Personal Information

Patient ID:                    # 06200601VC

Attending Physician:      xxxxxxxxxxxxxMD

Patient Name:               XXXXXXXXXXXX

Address:                       xxxxxxxxxxxxxxxx

City:                            xxxxxxxxxx

State:                            LA

Zipcode:                       xxxxx

Country:                       USA

Phone:                     (xxx) xxx-xxxx

____________________________________________________________________________________

 

Medical Information

____________________________________________________________________________________

 

General complaints not listed as diagnosis by your doctor:

                        Family reports patient is over-sedated

                        June 19, 2006

 

 

 

 

           

Letter sent to MD on June 20, 2006

Dear Dr. XXXXX,

                            First let me thank you for the vote of confidence in me in requesting this consult. As pre your request I have reviewed the records of  Mrs. xxxxx xxxxxx due to reports of over-sedation.

Her current medication regimen is:

Lasix 20mg  daily                        Restoril 7.5mg

Danazol 200mg daily                   Klonopin 0.5mg bid

Prevacid 30mg daily                     Lortab 10 1 po q 6 hrs

Senokot 1 po daily                      Cardizem 180mg daily*

Prednisone 20mg daily   

Exelon 3mg bid                                                                                                                                              

Calcium with vitamin D

Pepcid 20mg daily                                                    *Potentially  interacting drugs via CYP 450 pathways

 There are of course additive CNS effects from the items above which are in bold. This combination alone may be causing the patient’s over-sedation. Since her history of medication use isn’t available its also possible that a tolerance to CNS sedation had previously been developed if she didn’t display any signs or symptoms of over-sedation in the past on this combination.  However, with aging and decreased renal function this may have changed.

              Diltiazem (Cardizem) is metabolized via the CYP 450 3A4 pathway and will cause an increase in effects of benzodiazepines in patient with normal hepatic and renal function. Additionally, since this patient’s estimated creatinine clearance (CrCl) which  I calculated is 45.5ml/min and some of the CYP 450 pathway is also involved in the kidney this combination may be the cause of the oversedation in this patient as she’s on two benzodiaepines, Restoril and Klonopin.

Recommendations based on current complaint and medication regimen and diagnosis:

• Slowly titrate away both benzodiazepines and add an alternate anti-anxiety drug such as duloxetine (Cymbalta) venlafaxine(Effexor). I prefer, as you are well aware, the venlafaxine. These agents both act at both pre and post receptor sites (norepinephrine and serotonin sites) thus the preference for use of these agents as opposed to benzodiazepines. I prefer the venlafaxine because it has less risk of liver toxicity than does duloxetine.
• D/C Lortab and start APAP 650mg qid for pain.
• Use the Lortab q6hrs prn breakthrough pain

 

 

 

Suggestions:

• Start by decreasing the Restoril to qod hs x 1 week then D/C add Effexor XR 37.5mg hs now increase to 75mg hs when the Restoril is D/C’d in one week.
• Once Restoril titration is complete decrease Klonopin to 0.25mg am & 0.5mg hs x 1 week  and increase Effexor to 112.5mg hs then and monitor patient’s BP weekly. (This shouldn’t be a problem until we reach at least 300mg dose which shouldn’t be necessary.)
• Decrease the Klonopin to 0.25mg bid x 3 days then to 0.25mg hs x 3 days then D/C it.

 

Additional recommendations not related to over-sedation but which may improve current drug benefits your evaluation and consideration are sincerely appreciated.

• Due to patient’s current decreased kidney function and need for conservation of calcium consider changing from furosemide 20mg  daily to torsemide 10mg daily. Preservation of diuresis effects without rebound antidiuresis is much better with torsemide than with furosemide and torsemide is also less potassium, magnesium, and caclcium wasting  and this patient thas osteoporosis.
• Change the Calcium with Vitamin D to Calcium Citrate 600mg with vitamin D bid. This product is acid independent and has more reliable absorption in the geriatric patient than calcium carbonate which requires an acid stomach for absorption and the patient is on Prevacid 30mg daily and Pepcid.

Consider that: Long term use of proton pump inhibitors (beyond 4-8 weeks of therapy -  the duration of treatment recommended by all manufacturers for their PPIs in company  monographs and all current drug reference resources  for treatment of GERD) may lead to several serious conditions...

• Incidence of C. difficile diarrhea is 3 times higher for patient on long-term PPI therapy and twice as high for patients on H2 antagonist long term than control patients on neither.
• Rebound acidity –from the body’s attempt to regain the low gastric pH through more gastric acid secretions exacerbating the GI condition.
• Aspiration Pneumonia risk are increased (in the geriatric & ICU patient) -  raising the pH of the gut for long times produces a basic gut that complicates digestion, increase more gas and discomfort, slows down the breakdown of foods and many drugs and increase potential risk for aspiration of this basic fluid into the lungs.

 

• D/C Prevacid & Pepcid and start Zantac 75mg po bid x 1 month, use the H2 blocker in a step-down approach to reduce the potential for serious adverse events and implement non drug approaches as follows: 
• Prohibit spicy and difficult to digest foods after evening meal around 6 to 7 PM    
• Have the patient consume 3 oz buttermilk and saltine crackers or a container of plain yogurt amazingly helps this problem.  If these non-drug approaches are successful with this patient then begin tapering the H2 blocker as follows:

                    decrease Zantac to 75mg hs x 1 month then qod hs x 1 month then D/C

     

        Thank you for this very interesting consult,

 

________________________________________

Charles S. Feucht, PD,FASCP

 

____________________________________________________________________________________

 

Effexor XR

Venlafaxine extended-release capsules

What are venlafaxine extended-release capsules?

VENLAFAXINE (Effexor® XR) is an antidepressant, a medicine that helps to lift mental depression. Venlafaxine can help patients whose depression has not responded to other medications. Venlafaxine is also effective for the treatment of anxiety or other nervous conditions. Occasionally it is prescribed for other purposes. Generic venlafaxine tablets are not yet available.

What should my health care professional know before I take venlafaxine?

They need to know if you have any of these conditions:

.anorexia or weight loss

.attempted suicide

.high blood pressure, heart problems or a recent heart attack

.high cholesterol levels or receiving treatment for high cholesterol

.kidney disease

.liver disease

.mania or bipolar disorder

.seizures (convulsions)

.suicidal thoughts or a previous suicide attempt

.thyroid problems

.an unusual or allergic reaction to venlafaxine, other medicines, foods, dyes, or preservatives

.pregnant or trying to get pregnant

.breast-feeding

How should I take this medicine?

Take venlafaxine capsules by mouth. Follow the directions on the prescription label. Do not cut, crush, chew or divide the capsules; swallow them whole with plenty of water. Take venlafaxine capsules with food. Try to take your dose at about the same time each day, in the morning or evening. Do not take your medicine more often than directed. Do not stop taking the capsules except on your prescriber's advice.

Contact your pediatrician or health care professional regarding the use of this medicine in children. Special care may be needed.

What if I miss a dose?

If you miss a dose, take it as soon as you can. If it is less than two hours to your next dose, take only that dose and skip the missed dose. Do not take double or extra doses.

What drug(s) may interact with venlafaxine?

.alcohol

.amphetamine

.certain migraine headache medicines (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan)

.cimetidine

.clozapine

.dextroamphetamine

.furazolidone

.linezolid

.lithium

.medicines for heart rhythm or blood pressure

.medications for weight control or appetite

.medicines called MAO inhibitors-phenelzine (Nardil®), tranylcypromine (Parnate®), isocarboxazid (Marplan®)

.other medicines for mental depression, mania, psychosis, or anxiety

.procarbazine

.selegiline

.St. John's wort, Hypericum perforatum

.warfarin

Tell your prescriber or health care professional about all other medicines you are taking, including non-prescription medicines. Also tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs. These may affect the way your medicine works. Check with your health care professional before stopping or starting any of your medicines.

What side effects may I notice from taking venlafaxine?

Side effects that you should report to your prescriber or health care professional as soon as possible:

Rare or uncommon:

.abnormal body movements, for example, of your tongue or upper body

.bruising or bleeding

.difficulty breathing

.fainting spells

.mania (over-active behavior)

.problems passing urine (increase or decrease in frequency)

.rapid heartbeat, or palpitations

.seizures (convulsions)

More common:

.agitation, anxiety, or restlessness, especially in the first week of treatment or when doses are changed

.changes in vision (blurred vision)

.sexual difficulties (abnormal ejaculation or orgasm, difficult or painful erections, impotence)

.vomiting

Side effects that usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome):

.dry mouth

.constipation

.dizziness, drowsiness

.increased sweating

.loss of appetite, loss of weight

.nausea

.tremor

.weakness or tiredness

What should I watch for while taking venlafaxine?

Visit your prescriber or health care professional for regular checks on your progress. You may have to take venlafaxine for 4 weeks before you feel better. If you have been taking venlafaxine for some time, do not suddenly stop taking it. You must gradually reduce the dose to avoid side effects. Ask your prescriber or health care professional for advice.

Patients and their families should watch out for worsening depression or thoughts of suicide. Also watch out for sudden or severe changes in feelings such as feeling anxious, agitated, panicky, irritable, hostile, aggressive, impulsive, severely restless, overly excited and hyperactive, or not being able to sleep. If this happens, especially at the beginning of antidepressant treatment or after a change in dose, call your health care professional.

Venlafaxine can cause an increase in blood pressure or a faster heart beat. Check with your prescriber or health care professional; you may be able to measure your own blood pressure and pulse. Find out what your blood pressure and heart rate should be and when you should contact him or her.

You may get drowsy, dizzy or have blurred vision. Do not drive, use machinery, or do anything that needs mental alertness until you know how venlafaxine affects you. Do not stand or sit up quickly, especially if you are an older patient. This reduces the risk of dizzy or fainting spells. Alcohol may increase dizziness or drowsiness; avoid alcoholic drinks.

Venlafaxine can make your mouth dry. Chewing sugarless gum, sucking hard candy and drinking plenty of water will help.

Do not treat yourself for coughs, colds, or allergies without asking your prescriber or health care professional for advice. Some ingredients may increase possible side effects.

If you are going to have surgery, tell your prescriber or health care professional that you are taking venlafaxine.

Where can I keep my medicine?

Keep out of the reach of children in a container that small children cannot open.

Store at a controlled temperature between 20 degrees and 25 degrees C (68 degrees and 77 degrees F), in a dry place. Throw away any unused medicine after the expiration date.

 

Lansoprazole
Prevacid® | Prevacid® Granules for Oral Suspension | Prevacid® IV | Prevacid® SoluTab™

Classification:
• Gastrointestinal Agents
    • Antiulcer Agents
        • Proton pump inhibitors (PPIs)

Description, Mechanism of Action, Pharmacokinetics

Description: Lansoprazole is an antiulcer drug similar to omeprazole. Like omeprazole, lansoprazole is an acid proton-pump inhibitor. It is used for the short-term treatment of duodenal or gastric ulcers, gastroesophageal reflux disease (GERD), and erosive esophagitis. It is also indicated to maintain healing of duodenal ulcer and esophagitis, for NSAID-induced ulcer treatment or prophylaxis, and for long-term treatment of Zollinger-Ellison syndrome (pathological hypersecretory condition). In vitro data indicate that lansoprazole is significantly more potent than either omeprazole or pantoprazole against H. pylori.[1723] Clinically, lansoprazole is at least as effective as omeprazole in treating peptic ulcers and reflux esophagitis, and it has been shown to relieve reflux symptoms more quickly than either omeprazole or ranitidine.[757] Over a 4-week period, ulcer healing was greater with lansoprazole than ranitidine or placebo in a double-blind study of the treatment of active duodenal ulcer.[758] A comparative study of omeprazole and lansoprazole in the short-term treatment of reflux esophagitis showed no significant difference in healing after 4 or 8 weeks. Lansoprazole, however, showed greater improvement in heartburn and acid regurgitation symptoms after 4 weeks.[759] Lansoprazole has also been demonstrated to be safe and effective for chronic therapy of Zollinger-Ellison syndrome[760] and for Barrett's esophagus.[761] Lansoprazole is also available in a therapy pack which contains clarithromycin and amoxicillin (see Prevpac® monograph); this triple-drug regimen is indicated for the treatment of patients with duodenal ulcer and Helicobacter pylori infection. Lansoprazole was initially approved by the FDA May 10, 1995. A delayed-release oral suspension formulation of Prevacid® was approved by the FDA on May 3, 2001. Lansoprazole is approved for children >= 1 year and adolescents for short-term treatment of symptomatic GERD and erosive esophagitis. Prevacid® SoluTab™ Delayed-Release Orally Disintegrating Tablets were approved on August 30, 2002. All three oral Prevacid® dosage forms have delayed-release properties and contain lansoprazole within enteric-coated granules. An intravenous formulation of lansoprazole for the short-term treatment of erosive esophagitis was approved by the FDA on May 27, 2004. Oral Prevacid® is currently scheduled to go off patent by July 2005.

Mechanism of Action: Lansoprazole inhibits gastric acid secretion. It belongs to a new class of antisecretory agents, the substituted benzimidazoles, which suppress gastric acid secretion by inhibiting the H+/K+ ATPase enzyme system of gastric parietal cells. An acidic environment in the parietal cell is required for conversion of gastric-acid pump inhibitors, such as lansoprazole, to the active sulfenamide metabolite. The active metabolite then inhibits the ATPase enzyme required for gastric-acid pump activation, thereby blocking the final step of acid output from the parietal cells. A significant increase in gastric pH and decrease in basal acid output follow oral administration of lansoprazole. In hypersecretory conditions, lansoprazole has a marked effect on gastric acid secretion, both basal- and pentagastrin-stimulated. Lansoprazole exerts an inhibitory effect on gastric acid for at least 24 hours, which allows a once-daily dosing schedule. Lansoprazole does not antagonize H2 or cholinergic receptors.

Significant in vitro activity against Helicobacter pylori (H. Pylori) has been demonstrated for lansoprazole. Minimum inhibitory concentrations (MICs) for lansoprazole are lower than that for omeprazole. The clinical significance of this finding has not been established. Lansoprazole monotherapy increases the clearance rate of H. pylori; however, eradication does not occur without antimicrobial therapy.

Serum gastrin levels increase 50—100% from baseline in the fasting state, and these increases are greater during lansoprazole therapy than during ranitidine therapy.[758] Increases reach a plateau within 2 months and return to pretreatment levels within 4 weeks of discontinuation of lansoprazole therapy. Although prolonged hypergastrinemia has been associated with gastric tumors, a long-term study of lansoprazole for the treatment of Zollinger-Ellison syndrome did not reveal evidence to suggest that lansoprazole was implicated in tumor progression noted in two (10% of) patients.[760] Both patients already had extensive metastatic disease.

Short-term (i.e., 8-week) studies showed that lansoprazole had no effect on the endocrine system. Like omeprazole, however, lansoprazole also inhibits the hepatic cytochrome P450 oxidase system (see Drug Interactions).

Pharmacokinetics: Lansoprazole is administered orally and should be taken in the morning at least 30 minutes before a meal on a once-daily schedule, unless large doses must be divided for hypersecretory conditions. All lansoprazole dosage forms (capsules, oral suspension, and disintegrating tablets) contain delayed-release, enteric-coated granules that release drug after they leave the stomach. Absorption of lansoprazole is rapid; mean peak plasma levels occur after about 1.7 hours. The absolute bioavailability is over 80%, which can be reduced by 50% if lansoprazole is given 30 minutes after food. Lansoprazole is about 97% bound to plasma protein. Lansoprazole is excreted into animal breast milk and possibly into human breast milk. Lansoprazole is believed to be transformed into two active inhibitors of acid secretion in the gastric parietal cells.

Hepatic metabolism of lansoprazole is extensive. The two identified hepatic metabolites of lansoprazole have little antisecretory activity. Plasma elimination half-life, which is less than 2 hours, is not related to gastric antisecretory effect, which lasts more than 24 hours. Elimination is believed to occur via biliary excretion. Almost no unchanged lansoprazole is detected in urine after single-dose administration. After administration of a single dose of radio-labeled lansoprazole, one-third of the administered radiation was excreted in urine and two-thirds in the feces.

•Special populations: The pharmacokinetics of lansoprazole are similar for children (1—11 years) and adult subjects. The mean Cmax and AUC values are similar for two weight-adjusted dosage groups: 15 mg/day for weight <= 30 kg versus 30 mg/day for weight > 30 kg; pharmacokinetics are not affected by age or weight within these groups. Lansoprazole serum concentrations are increased in the elderly or patients with hepatic disease; but are not affected by gender, renal dysfunction or hemodialysis. In patients with various degrees of chronic hepatic disease, the mean plasma half-life of the drug was prolonged from 1.5 hours to 3.2—7.2 hours. An increase in the mean AUC of up to 500% was observed at steady-state in patients with hepatic impairment compared to healthy subjects in another study. Elderly patients have a reduced clearance and an increased elimination half-life (up to 2.9 hours) of lansoprazole; but drug accumulation was not observed during once-daily dosing. No clinically significant gender differences in clearance or AUC were determined. Pharmacokinetic parameters are not changed by the presence of renal impairment. Lansoprazole is not removed by hemodialysis.

Description, Mechanism of Action, Pharmacokinetics last revised 7/8/2004 11:22:00 AM

Indications

• duodenal ulcer	• Helicobacter pylori
• esophagitis	• NSAID-induced ulcer prophylaxis
• gastric ulcer	• pyrosis (heartburn)†
• gastroesophageal reflux disease (GERD)	• Zollinger-Ellison syndrome

† non-FDA-approved indication

Dosage

For the short-term treatment of frequent pyrosis (heartburn)† that occurs >= 2 times per week:
Oral dosage (capsules, disintegrating tablets, or oral suspension):
Adults and the elderly: 15 mg PO once daily for up to 14 days. Full relief may take 1—4 days. If frequent heartburn returns soon after the initial 14-day treatment regimen, patients should contact their health care provider.
Children: Safe and effective use has not been established.

For the short-term treatment of symptomatic non-erosive gastroesophageal reflux disease (GERD):
Oral dosage (capsules, disintegrating tablets, or oral suspension):
Adults, elderly and adolescents: 15 mg PO once daily in the morning at least 30 minutes before a meal, for up to 8 weeks. If the patient has symptomatic erosive or recurrent GERD, initially 30 mg PO once daily in the morning at least 30 minutes before a meal for up to 8 weeks. If healing is incomplete or recurs, a further 8 weeks of therapy can be considered.
Children 1—11 years: The FDA-approved initial dosage is 15—30 mg PO once daily in the morning at least 30 minutes before a meal for up to 12 weeks (15 mg/day for weight <= 30 kg; 30 mg/day for weight > 30 kg); the dosage was increased (up to 30 mg PO twice daily) in some children who were symptomatic after 2 weeks in trials. Based on published literature, initial starting doses of 1.4—1.5 mg/kg/day PO have also been suggested.[3636] [3637] Individualize dosage to attain clinical goals.

For the treatment of symptomatic erosive GERD, such as erosive esophagitis:
•for treatment of active disease:
Oral dosage (capsules, disintegrating tablets, or oral suspension):
Adults, elderly and adolescents: Initially, 30 mg PO once daily in the morning at least 30 minutes before a meal for up to 8 weeks. If healing is incomplete, a further 8 weeks of therapy can be administered. If erosive esophagitis recurs, an additional 8 week course of treatment can be considered.
Children 1—11 years: The FDA-approved initial dosage is 15—30 mg PO once daily in the morning at least 30 minutes before a meal for up to 12 weeks (15 mg/day for weight <= 30 kg; 30 mg/day for weight > 30 kg); the dosage was increased (up to 30 mg PO twice daily) in some children who were symptomatic after 2 weeks in trials. Based on published literature, initial starting doses of 1.4—1.5 mg/kg/day PO have also been suggested.[3636] [3637] Individualize dosage to attain clinical goals.
•for maintenance of remission:
Oral dosage (capsules, disintegrating tablets, or oral suspension):
Adults, elderly and adolescents: The recommended dosage is 15 mg PO once daily in the morning at least 30 minutes before a meal. Controlled studies do not extend beyond 12 months. In one clinical study, 173 patients were randomized to placebo, lansoprazole 15 mg, or lansoprazole 30 mg PO once daily before breakfast for 12 months. Lansoprazole was superior to placebo however there was no difference between the 2 lansoprazole doses.[1180]
Children: Safe and effective use has not been established.
•for the short-term treatment of erosive esophagitis in patients unable to take oral therapy:
Intravenous infusion dosage:
Adults and the elderly: 30 mg IV once daily given over 30 minutes for up to 7 days (see Administration for dilution and administration methods). Switch to oral therapy when feasible. Oral and IV lansoprazole equally suppress acid production.[5702]
Adolescents and children: Safe and effective use has not been established.

For the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome:
Oral dosage (capsules, disintegrating tablets, or oral suspension):
Adults, elderly and adolescents: Initially, 60 mg PO once daily in the morning at least 30 minutes before a meal. Dosage should be individualized and continued for as long as clinically indicated. Some patients with Z-E syndrome have been treated continuously for more than four years. Doses up to 90 mg PO twice daily have been used for this condition. If dosage is > 120 mg/day, give in divided doses.
Children: Safe and effective use has not been established.

For the treatment of active duodenal ulcer or active benign gastric ulcer:
•for the short-term treatment of active duodenal ulcer:
Oral dosage (capsules, disintegrating tablets, or oral suspension):
Adults, elderly and adolescents: 15 mg PO once daily in the morning at least 30 minutes before a meal, for up to 4 weeks.
Children: Safe and effective use has not been established.
•for maintenance of remission following treatment of active duodenal ulcer:
Oral dosage (capsules, disintegrating tablets, or oral suspension):
Adults, elderly and adolescents: 15 mg PO once daily in the morning at least 30 minutes before a meal. Controlled studies do not extend beyond 12 months.
Children: Safe and effective use has not been established.
•for the treatment of active benign gastric ulcer:
Oral dosage (capsules, disintegrating tablets, or oral suspension):
Adults, elderly and adolescents: 30 mg PO once daily in the morning at least 30 minutes before a meal, for up to 8 weeks.
Children: Safe and effective use has not been established.
•for triple therapy of Helicobacter pylori-positive duodenal ulcer in combination with clarithromycin and amoxicillin:
Oral dosage (capsules, disintegrating tablets, or oral suspension):
Adults, elderly and adolescents: The FDA-approved dosage is lansoprazole 30 mg PO twice daily, in combination with clarithromycin 500 mg PO twice daily plus amoxicillin 1 g PO twice daily, for 10—14 days. The American College of Gastroenterology (ACG) has previously recommended 14 days for triple regimens based on high H. pylori eradication rates.[2661]
Children: Safe and effective use has not been established.
•for dual therapy of Helicobacter pylori-positive duodenal ulcer in combination with amoxicillin in patients who are intolerant or resistant to clarithromycin:
Oral dosage (capsules, disintegrating tablets, or oral suspension):
Adults, elderly and adolescents: NOTE: More effective triple regimens are available.[2661] The FDA-approved dual regimen includes: lanzoprazole 30 mg PO three times daily plus amoxicillin 1 g PO three times daily, given for 14 days. H. pylori eradication rates are lower with this dual regimen (66—77%, per-protocol analysis) relative to the 2-week triple regimen containing clarithromycin (85—92%, per-protocol analysis).
Children: Safe and effective use has not been established.

For NSAID-induced ulcer prophylaxis or healing:
•to treat an NSAID-associated gastric ulcer in patients who continue NSAID use:
Oral dosage (capsules, disintegrating tablets, or oral suspension):
Adults, elderly and adolescents: 30 mg PO once daily in the morning at least 30 minutes before a meal for up to 8 weeks.
Children: Safe and effective use has not been established.
•to reduce the risk of NSAID-associated ulcers in patients with a prior documented gastric ulcer, who require NSAID therapy:
Oral dosage (capsules, disintegrating tablets, or oral suspension):
Adults, elderly and adolescents: 15 mg PO once daily in the morning at least 30 minutes before a meal for up to 12 weeks. A higher dosage of 30 mg once daily has been evaluated for risk-reduction of NSAID-induced ulcers in a large multicenter trial; the larger dose yielded no additional benefit compared to the 15 mg dose.
Children: Safe and effective use has not been established.

Maximum Dosage Limits:
•Adults: 30 mg/day PO for most indications; 90 mg/day PO for eradication of H. pylori; up to 180 mg/day PO for Zollinger-Ellison syndrome.
•Elderly: 30 mg/day PO for most indications; 90 mg/day PO for eradication of H. pylori; up to 180 mg/day PO for Zollinger-Ellison syndrome.
•Adolescents: 30 mg/day PO for most indications; 90 mg/day PO for eradication of H. pylori; up to 180 mg/day PO for Zollinger-Ellison syndrome.
•Children > 30 kg: 30 mg/day PO for GERD or erosive esophagitis, up to 60 mg/day PO has been used for refractory cases.
•Children <= 30 kg: 15 mg/day PO for GERD or erosive esophagitis; occasionally higher dosages used for refractory cases.
•Infants: Safe and effective use not established.

Patients with hepatic impairment:
Consider dosage reduction in patients with severe hepatic disease; specific recommendations are not available.

Patients with renal impairment:
No dosage adjustments are needed (manufacturer's information).

Intermittent hemodialysis:
Lansoprazole is not removed by hemodialysis.

†non-FDA-approved indication

Indications...Dosage last revised 8/22/2004 2:03:00 PM

Administration Guidelines

Oral Administration
•All dosage forms: Administer dosage 30 minutes prior to meal whenever possible. A once-daily dosage is usually administered prior to breakfast. The presence of a meal in the stomach decreases the bioavailability by about 50%. Antacids were used concomitantly with lansoprazole in clinical trials.
•Delayed-release capsules: Swallow delayed-release capsules intact; do not chew or crush. For patients with difficulty swallowing, the capsules may opened and the contents may be sprinkled on 1 tablespoonful (15 ml) of either applesauce, Ensure® liquid supplement, pudding, yogurt, or cottage cheese. Do not crush the capsule contents into the food. Swallow immediately. Do not chew the medication. Do not prepare doses before the time of administration. Alternatively, the capsule may be emptied into a small volume of either apple juice, orange juice or tomato juice (60 ml, approximately 2 ounces), mixed briefly and swallowed immediately. To ensure complete delivery of the dose, the glass should be rinsed with two or more volumes of juice and the contents swallowed immediately. The granules have been shown in vitro to remain intact when exposed to apple, cranberry, grape, orange, pineapple, prune, tomato, and V-8 vegetable juice and stored for up to 30 minutes.
•Delayed-release oral suspension: Packets containing the enteric-coated granules (15 or 30 mg doses) are mixed with 2 tablespoonfuls (30 ml) of water to form a strawberry-flavored suspension, intended for immediate administration after mixing. Do not use with other liquids or foods. Stir well and drink immediately. Do not crush or chew the granules. If any material remains after drinking, add more water, stir, and drink immediately.
•Delayed-release disintegrating tablets: Place the Prevacid® SoluTab™ on the tongue and allow it to disintegrate until the particles can be swallowed. The tablet will disintegrate rapidly (< 1 minute). Do not chew the tablets. For administration via an oral syringe, the tablet can be dissolved in water (4 ml for 15 mg tablet, 10 ml for 30 mg tablet) and should be administered within 15 minutes.
•Patients with a nasogastric tube: Prevacid® capsules or disintegrating tablets can be administered via a nasogastric tube. Capsules: Open the capsule and mix the intact granules in 40 ml of apple juice and inject through the nasogastric tube into the stomach. After administering the granules, the nasogastric tube should be flushed with additional apple juice to clear the tube. Nasogastric tube: Dissolve tablet in water (4 ml for 15 mg tablet, 10 ml for 30 mg tablet) and administer within 15 minutes. After administration, the tube should be flushed to clear the tube.

Intravenous Administration
•Lansoprazole is administered as an intravenous (IV) infusion either through a dedicated line or a Y-site. The drug should NOT be given by IV push or other parenteral routes other than IV infusion.
•Administer IV using the in-line filter provided. The filter MUST be used to remove precipitate.
•Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Reconstitution of vial:
•Reconstitute each 30 mg vial with 5 ml of Sterile Water for Injection, USP only. NOTE: Lansoprazole IV must be reconstituted with 5 ml of Sterile Water for Injection, USP. Failure to reconstitute with Sterile Water may result in formation of precipitation/particulates.
•Mix gently by swirling. The resulting solution will contain lansoprazole 6 mg/ml.
•The reconstituted solution can be held for 1 hour when stored at 25 degrees C (77 degrees F) prior to further dilution.
•Reconstituted vials and admixtures do not need to be protected from light. Do not freeze.

Preparation and Administration of IV infusion:
•Dilute the reconstituted vial in either 50 ml of 0.9% Sodium Chloride Injection (NS), Lactated Ringer's Injection (LR), or 5% Dextrose Injection (D5W). The admixture should be stored at 25 degrees C (77 degrees F). No refrigeration is required.
•If reconstituted with NS or LR, solution must be administered within 24 hours. If reconstituted with D5W, solution must be administered within 12 hours.
•Administer IV using the in-line filter provided. The filter MUST be used to remove precipitate.
•Lansoprazole IV infusion is administered either through a dedicated line or a Y-site. A dedicated line is not required; however, the intravenous line should be flushed before and after administration. When administered via a Y-site, immediately stop use if a precipitation or discoloration occurs.
•Infuse IV over 30 minutes.
•Do not administer lansoprazole IV with other drugs or diluents.

Administration last revised 4/15/2005 2:21:00 PM

Contraindications/Precautions

• proton pump inhibitors (PPIs) hypersensitivity	• hepatic disease
• breast-feeding	• infants
• children	• phenylketonuria
• gastric cancer	• pregnancy

• Absolute contraindications are in italics.

Lansoprazole is contraindicated in patients with known hypersensitivity to lansoprazole or other substituted benzimidazoles such as omeprazole or esomeprazole (i.e., known proton pump inhibitors (PPIs) hypersensitivity). Although rare, occasionally such reactions can be serious (e.g., result in anaphylaxis or angioedema). There has been evidence of PPI cross-sensitivity in some sensitive individuals in literature reports.

Lansoprazole is classified as pregnancy category B. Animal studies have shown no teratogenic effects. Adequate studies have not been undertaken in humans. Lansoprazole should be used during pregnancy only when clearly needed.

Animal studies have indicated that lansoprazole is excreted into breast milk. Although no studies have been done to determine if lansoprazole is similarly excreted into human milk, lansoprazole use is not recommended during breast-feeding. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions from lansoprazole in breast-fed infants, a decision should be made whether to discontinue breast-feeding or to discontinue the drug, taking into account the importance of the drug to the mother.

Lansoprazole elimination half-life is significantly prolonged in patients with hepatic disease. In patients with severe hepatic disease, dosage reduction of lansoprazole should be considered. Abnormal liver-function tests have been reported infrequently with lansoprazole use. No dosage adjustment is necessary in patients with renal insufficiency or the elderly (manufacturer's information).

Safety and efficacy of lansoprazole have not been established in infants (i.e., age < 1 year). The manufacturer has established safety and efficacy for lansoprazole use in children aged 1—17 years for short-term treatment of symptomatic GERD and erosive esophagitis. Safety and effectiveness in the pediatric population has been determined from adult clinical trials with additional clinical, pharmacokinetic, and pharmacodynamic studies in children.

Antimicrobials, lansoprazole, omeprazole, and bismuth preparations suppress H.pylori. Ingestion of these substances within four (4) weeks prior to performing urease or breath-tests for H. pylori detection may lead to false negative results. In the four weeks prior to performing the test, the patient must avoid the use lansoprazole and other agents which are known to suppress H.pylori.

Symptomatic response to therapy with lansoprazole does not preclude the presence of gastric cancer or other malignancy.

Patients with phenylketonuria should be made aware that lansoprazole disintegrating tablets contain phenylalanine (2.5 mg per 15 mg tablet; 5.1 mg per 30 mg tablet). The capsule and syrup formulations do not contain phenylalanine.

Contraindications last revised 7/6/2005 3:40:00 PM

Drug Interactions

• Ampicillin		• Iron Salts
	Antimuscarinics	• Itraconazole
• Atazanavir		• Ketoconazole
• Delavirdine		• Methylphenidate
• Dexmethylphenidate		• Misoprostol
• Digoxin		• Octreotide
• Fluvoxamine		• Sucralfate
• food		• Theophylline, Aminophylline
• Gefitinib		• Voriconazole
	H2-blockers	• Warfarin

NOTE: Lansoprazole is a substrate of the cytochrome P-450 system via the CYP2C19 and CYP3A4 isoenzymes.[4718] [5142]

Sucralfate has been shown to delay the absorption and reduce the bioavailability of oral lansoprazole by about 17%.[5142] Lansoprazole should be taken no less than 30 minutes before sucralfate if these drugs are to be used concomitantly. Concurrent administration of oral lansoprazole and antacids may reduce the bioavailability of lansoprazole; except when the antacids are given at least one hour before lansoprazole administration.[5142] The manufacturer states that antacids were given with lansoprazole in clinical trials, with the interpretation that concurrent antacids did not interfere with lansoprazole's effects.[5142]

Lansoprazole is metabolized by the hepatic cytochrome P450 system, specifically through the CYP3A and CYP2C19 isozymes.[4718] However, no interactions have been reported between lansoprazole and antipyrine, clarithromycin, diazepam, ibuprofen, indomethacin, oral contraceptives [763], phenytoin, prednisone, propranolol, or terfenadine in healthy subjects.[5142]

In a study of healthy subjects neither the pharmacokinetics of warfarin enantiomers nor prothrombin time were affected following single or multiple 60 mg doses of lansoprazole.[5142] However, there have been reports of increased INR and prothrombin time in patients receiving proton pump inhibitors, including lansoprazole, and warfarin concomitantly.[5142] It is prudent to monitor the INR more closely if a proton pump inhibitor is combined with warfarin.

Concomitant use of theophylline (CYP1A2 and CYP3A substrate) and lansoprazole has led to a small increase (10%) in theophylline clearance.[5142] Theophylline may require dosage adjustment when therapy with lansoprazole is initiated or discontinued.

Lansoprazole has a long-lasting effect on the secretion of gastric acid. For drugs whose bioavailability is influenced by gastric pH, the concomitant administration of lansoprazole can exert a significant effect on their absorption.[5142] Drugs that could be affected by lansoprazole in this way include ampicillin [5142], digoxin [5142], iron salts [5142] [6305], itraconazole [4700], and ketoconazole [4699] [5142]. The bioavailability of polysaccharide-iron complex and other oral iron salts is influenced by gastric pH, and the concomitant administration of a proton pump inhibitor can completely decrease iron absorption.[6924] The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Lansoprazole has been shown to lack a clinically significant interaction with amoxicillin. Gastric acid pump-inhibitors may increase digoxin bioavailability, however, the magnitude of the interaction is small. The potential interaction between lansoprazole and digoxin has not been specifically studied. Omeprazole increases the AUC of digoxin by about 10%. When rabeprazole is co-administered with digoxin, the AUC and Cmax for digoxin increases approximately 19% and 29%, respectively. Patients with digoxin serum levels at the upper end of the therapeutic range may need to be monitored for potential increases in serum digoxin levels when a gastric acid pump-inhibitor is coadministered with digoxin.

Lansoprazole is metabolized by the hepatic cytochrome P450 system, specifically via the CYP3A and CYP2C19 isozymes;[5142] voriconazole is a known inhibitor of these isozymes [4882]. The manufacturer for voriconazole has recommended that higher dosages of a related proton pump inhibitor, omeprazole, be reduced by one-half when initiating voriconazole therapy, due to increased omeprazole serum concentrations produced by this interaction.[4882] Although data are not available, theoretically a similar interaction may occur between lansoprazole and voriconazole. Higher daily doses of lansoprazole may need to be reduced when initiating voriconazole therapy.

Long-term treatment with lansoprazole in conjunction with diazepam therapy has been studied. Plasma elimination half-life, clearance, and volume of distribution of diazepam were not affected by concurrent use of lansoprazole.[762]

Proton pump inhibitors (PPIs), which increase gastric pH, may reduce the absorption of delavirdine. However, since these agents affect gastric pH for an extended period, separation of doses may not eliminate the interaction. Chronic use of proton pump inhibitors (PPIs) with delavirdine is not recommended.[5206]

Drugs that cause a significant sustained elevation in gastric pH [e.g., proton pump inhibitors (PPIs)] may reduce plasma concentrations of gefitinib and thus potentially may reduce gefitinib efficacy.[5012]

The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be decreased if given with other antisecretory agents (e.g., antimuscarinics, octreotide, H2-blockers, or misoprostol).[1569] Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.

Fluvoxamine is a major inhibitor of the cytochrome P450 enzyme (CYP) 2C19. Several proton pump inhibitors (PPIs), including lansoprazole, are primary substrates of the CYP2C19 enzyme. Reduced metabolism and resulting elevated plasma concentrations of these PPIs may occur if combined with fluvoxamine. A single-dose pharmacokinetic study has shown that the mean AUC of omeprazole 40 mg was increased 2- to 6-fold when given after fluvoxamine 50 mg/day for 6 days.[6481] Monitor patients for PPI toxicity, such as headache or GI distress if these drugs are combined.

A randomized, open-label, multiple-dose drug interaction study of atazanavir (300 mg) with ritonavir (100 mg) coadministered with omeprazole 40 mg, found a reduction in atazanavir AUC and Cmin of 76% and 78%, respectively. Based on these study results, atazanavir, with or without ritonavir, should not be coadministered with omeprazole due to the reduction in atazanavir exposure levels. It is not known whether the over-the-counter dose of omeprazole (20 mg once daily) would produce similar results; therefore, coadministration is not recommended. Increasing the atazanavir and ritonavir doses to 400 and 100 mg, respectively, with omeprazole did not result in atazanavir exposures comparable to those observed with a regimen of atazanavir 300 mg with ritonavir 100 mg without omeprazole. Due to similar mechanisms, other proton pump inhibitors (PPIs) (e.g., esomeprazole, pantoprazole, rabeprazole, and lansoprazole) should not be used with atazanavir. When such substantial reductions in atazanavir serum concentrations are seen, therapeutic failure and resistance development may be expected.[4865]

Administer a lansoprazole oral dosage 30 minutes prior to food whenever possible.[5142] The presence of a meal (food) in the stomach decreases the bioavailability by about 50%.

The effects of gastrointestinal pH alterations on the absorption of methylphenidate extended release capsules (Ritalin® LA) and dexmethylphenidate extended-release tablets (Focalin™ XR) have not been studied. Although the SODAS® system (drug delivery system utilized in Ritalin® LA and Focalin™ XR) is thought to be minimally affected by changes in pH,[8068] per the manufacturer, the modified release characteristics of both extended-release formulations are pH-dependent. It is possible that the administration of proton pump inhibitors (PPIs) or other acid suppressants could alter the release of dexmethylphenidate or methylphenidate.[8067] [8069] Patients receiving these extended-release products (Focalin™ XR or Ritalin® LA) with acid suppressants should be monitored for adverse effects and therapeutic efficacy.

Interactions last revised 6/30/2005 4:19:00 PM

Adverse Reactions

• abdominal pain	• hyperbilirubinemia
• agranulocytosis	• jaundice
• alopecia	• leukopenia
• anaphylactoid reactions	• nausea/vomiting
• anemia	• neutropenia
• aplastic anemia	• pancreatitis
• cholelithiasis	• pancytopenia
• constipation	• pernicious anemia
• diarrhea	• pruritus
• elevated hepatic enzymes	• rash (unspecified)
• erythema multiforme	• Stevens-Johnson syndrome
• gynecomastia	• thrombocytopenia
• headache	• thrombotic thrombocytopenic purpura (TTP)
• hemolysis	• toxic epidermal necrolysis
• hemolytic anemia	• urticaria
• hepatitis	• vitamin B<SUB>12</SUB> deficiency

The safety profile of lansoprazole is similar in adults and children 1—11 years old. Adverse reactions reported during lansoprazole clinical trials were mild and primarily related to the GI tract. The most frequent adverse reactions (> 1%) in adults which occurred at a greater frequency than placebo included: diarrhea (3.6% vs 2.6%), abdominal pain (1.8% vs 1.3%), and nausea/vomiting (1.5% vs 1.3%). The incidence of diarrhea was dose-related. At a daily dose of 60 mg of lansoprazole, 7.4% of patients experienced diarrhea compared with 1.4% at 15 mg/day and 4.2% at 15 mg/day (2.9% incidence in the placebo group). In children 1—11 years old, the most frequent side effect was constipation (5%). Other GI adverse events occurring infrequently (< 1%) in lansoprazole-treated patients during clinical trials or post-marketing experience and included: melena, anorexia, bezoar, constipation, xerostomia, dyspepsia, dysphagia, eructation, esophageal stenosis, esophageal ulcer, esophagitis, fecal discoloration, flatulence, gastric nodules/fundic gland polyps, gastroenteritis, gastrointestinal hemorrhage, hematemesis, increased appetite, increased salivation, rectal hemorrhage, stomatitis, tenesmus, and ulcerative colitis.

Headache was reported in > 1% of patients taking lansoprazole, but a higher percentage of patients taking placebo reported headache. During GERD trials with lansoprazole in pediatric patients, the frequency of headache in children 1—11 years old was 3%.

Hepatitis and/or jaundice have been associated with PPIs. Specifically, cholelithiasis (<1%), hepatoxicity (post-marketing data), hyperbilirubinemia, and elevated hepatic enzymes (increased AST and ALT) have been reported during lansoprazole therapy. In controlled clinical trials, 0.4% (1/250) placebo patients and 0.3% (2/795) lansoprazole patients had hepatic enzyme elevations > 3 times the upper limit of the normal range at the end of the study, but without evidence of jaundice. Pancreatitis has been reported post-marketing, but causal association and frequency are unknown.

Infrequent hematological reactions have been associated with lansoprazole therapy (<1%). These reactions have included agranulocytosis, anemia, aplastic anemia, hemolysis, hemolytic anemia, leukopenia, neutropenia, pancytopenia, thrombocytopenia, and thrombotic thrombocytopenic purpura (TTP). Generally, long-term (e.g., > 3 years) treatment with acid-suppressing agents can lead to malabsorption of vitamin B12 (cyanocobalamin). In a study of healthy volunteers, it was shown that omeprazole caused a significant reduction in cyanocobalamin absorption (vitamin B12 deficiency).[162] Although clinical data in lansoprazole is lacking, it may be prudent to monitor patients for signs of pernicious anemia. Neurological manifestations of pernicious anemia can occur in the absence of hematologic changes.

Allergic reactions, including rash (unspecified) and anaphylactoid reactions, have been reported infrequently with PPI therapy including lansoprazole (<1%). Specific dermatological reactions reported in < 1% of lansoprazole-treated patients included: acne, alopecia, pruritus, rash, and urticaria. Severe dermatological reactions reported during post-marketing experience include: erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis (some fatal).

Gynecomastia was reported in < 1% of patients receiving lansoprazole.

Significant elevations in serum gastrin have been reported with lansoprazole and is consistent with the effects of other PPIs; this effect may be dose-related. Although not specifically studied in patients receiving lansoprazole, the risk of carcinoid tumors during therapy with proton pump inhibitors is low based on cumulative safety experience. Monitoring of serum gastrin levels during PPI therapy is generally not necessary.[2859]

Other infrequent (< 1%) or rare adverse experiences reported without regard to causality are detailed in the prescribing information for lansoprazole.

Adverse Reactions last revised 3/12/2004 4:52:00 PM

Patient Education

Lansoprazole capsules

What are lansoprazole capsules?
LANSOPRAZOLE (Prevacid®) prevents the production of acid in the stomach. It reduces symptoms and prevents injury to the esophagus or stomach in patients with gastroesophageal reflux disease (GERD) or ulcers. Lansoprazole is also useful in conditions that produce too much stomach acid such as Zollinger-Ellison syndrome. Generic lansoprazole capsules are not yet available.

What should my health care professional know before I take lansoprazole?
They need to know if you have any of these conditions:
•liver disease
•an unusual or allergic reaction to lansoprazole, other medicines, foods, dyes, or preservatives
•pregnant or trying to get pregnant
•breast-feeding

How should I take this medicine?
Take lansoprazole capsules by mouth. Follow the directions on the prescription label. Swallow the capsules whole with a drink of water; do not crush or chew. Lansoprazole works best if taken on an empty stomach. It is best to take the capsules 30 to 60 minutes before food. Take your doses at regular intervals. Do not take your medicine more often than directed.

If you have difficulty swallowing the capsules, you may open the Prevacid® capsule and sprinkle the contents on a tablespoon of any of the following foods: applesauce, pudding, cottage cheese, yogurt, or a spoonful of Ensure® drink. Do not crush the contents of the capsule into the food. Swallow the dose immediately after preparing it; do not chew. Follow with a drink of water.

Contact your pediatrician or health care professional regarding the use of this medicine in children. Special care may be needed.

What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.

What drug(s) may interact with lansoprazole?
•ampicillin
•bisacodyl
•delavirdine
•digoxin
•fluvoxamine
•iron salts
•itraconazole
•ketoconazole
•sucralfate
•theophylline
•voriconazole

Tell your prescriber or health care professional about all other medicines you are taking, including non-prescription medicines, nutritional supplements, or herbal products. Also tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs. These may affect the way your medicine works. Check with your health care professional before stopping or starting any of your medicines.

What side effects may I notice from taking lansoprazole?
Side effects that you should report to your prescriber or health care professional as soon as possible.
Rare or uncommon:
•dark yellow or brown urine
•fever or sore throat
•unusual skin rash, blistering, or peeling
•unusual bleeding or bruising
•yellowing of the eyes or skin
•vomiting

Side effects that usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome):
•abdominal pain
•diarrhea or constipation
•headache
•nausea

What should I watch for while taking lansoprazole?
It can take several days of therapy with lansoprazole before your stomach pains improve. Check with your prescriber or health care professional if your condition does not improve, or if it gets worse. You can take antacids for the occasional relief of pain unless your prescriber or health care professional tells you otherwise.

Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.

Store at room temperature between 15 and 30 degrees C (59 and 86 degrees F). Protect from moisture. Throw away any unused medicine after the expiration date.

NOTE: This information is not intended to cover all possible uses, precautions, interactions, or adverse effects for this drug. If you have questions about the drug(s) you are taking, check with your health care professional.

 [Revised: 10/02/2002]

Lansoprazole disintegrating tablets

What are Lansoprazole disintegrating tablets?
LANSOPRAZOLE (Prevacid® SoluTab™) prevents the production of acid in the stomach. It reduces symptoms and prevents injury to the esophagus or stomach in patients with gastroesophageal reflux disease (GERD) or ulcers. Lansoprazole is also useful in conditions that produce too much stomach acid such as Zollinger-Ellison syndrome. Generic lansoprazole disintegrating tablets are not yet available.

What should my health care professional know before I receive Lansoprazole?
They need to know if you have any of these conditions:
•liver disease
•phenylketonuria
•an unusual reaction to lansoprazole, medicines, foods, dyes, or preservatives
•pregnant or trying to get pregnant
•breast-feeding

How should this medicine be used?
Take lansoprazole disintegrating tablets by mouth. Follow the directions on the prescription label. Place the tablet on your tongue and allow it to dissolve in your mouth. The tablet will dissolve rapidly, usually in less than one minute. Swallow the medicine once completely dissolved. Do not chew the tablets. Take your doses at regular intervals. Do not take your medicine more often than directed.

Contact your pediatrician or health care professional regarding the use of this medicine in children. Special care may be needed.

What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.

What drug(s) may interact with Lansoprazole?
•ampicillin
•bisacodyl
•delavirdine
•digoxin
•fluvoxamine
•iron salts
•itraconazole
•ketoconazole
•sucralfate
•theophylline
•voriconazole

Tell your prescriber or health care professional about all other medicines you are taking, including non-prescription medicines, nutritional supplements, or herbal products. Also tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs. These may affect the way your medicine works. Check with your health care professional before stopping or starting any of your medicines.

What side effects may I notice from receiving Lansoprazole?
Side effects that you should report to your prescriber or health care professional as soon as possible.
Rare or uncommon:
•dark yellow or brown urine
•fever or sore throat
•unusual skin rash, blistering, or peeling
•unusual bleeding or bruising
•yellowing of the eyes or skin
•vomiting

Side effects that usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome):
•abdominal pain
•diarrhea or constipation
•headache
•nausea

What should I watch for while taking Lansoprazole?
It can take several days of therapy with lansoprazole before your stomach pains improve. Check with your prescriber or health care professional if your condition does not improve, or if it gets worse. You can take antacids for the occasional relief of pain unless your prescriber or health care professional tells you otherwise.

If you have phenylketonuria, you should avoid taking the lansoprazole disintegrating tablets which contain phenylalanine. The capsules and syrup forms of lansoprazole are preferred because they do not contain phenylalanine.

Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.

Store at room temperature between 15 and 30 degrees C (59 and 86 degrees F). Protect from moisture. Throw away any unused medicine after the expiration date.

NOTE: This information is not intended to cover all possible uses, precautions, interactions, or adverse effects for this drug. If you have questions about the drug(s) you are taking, check with your health care professional.

 [Revised: 10/03/2002]

Lansoprazole Injection

What is lansoprazole Injection?
LANSOPRAZOLE (Prevacid® IV) prevents the production of acid in the stomach. It reduces symptoms and helps to heal injury to the esophagus in patients with erosive esophagitis (a severe reflux of stomach acid that damages the lining of the esophagitis). Generic lansoprazole injection is not yet available.

What should my health care professional know before I receive lansoprazole?
They need to know if you have any of these conditions:
•liver disease
•an unusual or allergic reaction to lansoprazole, other medicines, foods, dyes, or preservatives
•pregnant or trying to get pregnant
•breast-feeding

How should I take this medicine?
Lansoprazole injection is for infusion into a vein. It is given by a health care professional in a hospital or clinic setting.

Contact your pediatrician or health care professional regarding the use of this medicine in children. Special care may be needed.

What if I miss a dose?
This does not apply.

What drug(s) may interact with lansoprazole?
•ampicillin
•bisacodyl
•delavirdine
•digoxin
•fluvoxamine
•iron salts
•itraconazole
•ketoconazole
•theophylline
•voriconazole

Tell your prescriber or health care professional about all other medicines you are taking, including non-prescription medicines, nutritional supplements, or herbal products. Also tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs. These may affect the way your medicine works. Check with your health care professional before stopping or starting any of your medicines.

What side effects may I notice from taking lansoprazole?
Side effects that you should report to your prescriber or health care professional as soon as possible.
Rare or uncommon:
•dark yellow or brown urine
•fever or sore throat
•unusual skin rash, blistering, or peeling
•unusual bleeding or bruising
•yellowing of the eyes or skin
•vomiting

Side effects that usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome):
•abdominal pain
•diarrhea or constipation
•headache
•nausea

What should I watch for while taking lansoprazole?
It can take several days of therapy with lansoprazole before your stomach pains improve. Check with your prescriber or health care professional if your condition does not improve, or if it gets worse. You can take antacids for the occasional relief of pain unless your prescriber or health care professional tells you otherwise.

Where can I keep my medicine?
This does not apply. You will not be given lansoprazole injection to use at home.

NOTE: This information is not intended to cover all possible uses, precautions, interactions, or adverse effects for this drug. If you have questions about the drug(s) you are taking, check with your health care professional.

 [Revised: 08/04/2004]

Lansoprazole oral suspension

What is lansoprazole oral suspension?
LANSOPRAZOLE (Prevacid® Oral Suspension) prevents the production of acid in the stomach. It reduces symptoms and prevents injury to the esophagus or stomach in patients with gastroesophageal reflux disease (GERD) or ulcers. Lansoprazole is also useful in conditions that produce too much stomach acid such as Zollinger-Ellison syndrome. Generic lansoprazole oral suspension is not yet available.

What should my health care professional know before I take lansoprazole?
They need to know if you have any of these conditions:
•liver disease
•an unusual or allergic reaction to lansoprazole, other medicines, foods, dyes, or preservatives
•pregnant or trying to get pregnant
•breast-feeding

How should I take this medicine?
Take lansoprazole oral suspension by mouth. Follow the directions on the prescription label. First, mix the contents (granules) of the packets with 2 tablespoonfuls (30 ml) of water to form a strawberry-flavored suspension. Do not crush or chew the granules before mixing. Stir well and drink the liquid mixture immediately. If any material from the suspension remains after drinking, add more water, stir, and drink immediately. Do not take lansoprazole suspension with other liquids or foods. It is best to take the oral suspension at least 30 to 60 minutes before you eat any food. Take your doses at regular intervals. Do not take your medicine more often than directed.

Contact your pediatrician or health care professional regarding the use of this medicine in children. Special care may be needed.

What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.

What drug(s) may interact with lansoprazole?
•ampicillin
•bisacodyl
•delavirdine
•digoxin
•fluvoxamine
•iron salts
•itraconazole
•ketoconazole
•sucralfate
•theophylline
•voriconazole

Tell your prescriber or health care professional about all other medicines you are taking, including non-prescription medicines, nutritional supplements, or herbal products. Also tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs. These may affect the way your medicine works. Check with your health care professional before stopping or starting any of your medicines.

What side effects may I notice from taking lansoprazole?
Side effects that you should report to your prescriber or health care professional as soon as possible.
Rare or uncommon:
•dark yellow or brown urine
•fever or sore throat
•unusual skin rash, blistering, or peeling
•unusual bleeding or bruising
•yellowing of the eyes or skin
•vomiting

Side effects that usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome):
•abdominal pain
•diarrhea or constipation
•headache
•nausea

What should I watch for while taking lansoprazole?
It can take several days of therapy with lansoprazole before your stomach pains improve. Check with your prescriber or health care professional if your condition does not improve, or if it gets worse. You can take antacids for the occasional relief of pain unless your prescriber or health care professional tells you otherwise.

Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.

Store at room temperature between 15 and 30 degrees C (59 and 86 degrees F). Protect from moisture. Throw away any unused medicine after the expiration date.

NOTE: This information is not intended to cover all possible uses, precautions, interactions, or adverse effects for this drug. If you have questions about the drug(s) you are taking, check with your health care professional.

 [Revised: 10/02/2002]

 

Prednisone
Deltasone® | Predone™ | Sterapred® | Sterapred® DS

Classification:
• Biologic Response Modifiers
    • Immunosuppressives
        • Corticosteroids
• Hormones and Hormone Modifiers
    • Adrenal Agents
        • Corticosteroids
• Musculoskeletal Agents
    • Antiinflammatory Agents
        • Corticosteroids
• Respiratory Agents
    • Respiratory Antiinflammatory Agents
        • Corticosteroids

Description, Mechanism of Action, Pharmacokinetics

Description: Prednisone is the most commonly-prescribed oral corticosteroid. The drug is metabolized in the liver to its active form, prednisolone. Relative to hydrocortisone, prednisone is roughly 4 times as potent as a glucocorticoid. Prednisone is intermediate between hydrocortisone and dexamethasone in duration of action. Prednisone is used in many conditions, including allograft rejection, asthma, systemic lupus erythematosus, and many other inflammatory states. Prednisone has very little mineralocorticoid activity, so it is not used in the management of adrenal insufficiency unless a more potent mineralocorticoid is administered concomitantly. Prednisone was first approved by the FDA in 1955.

Mechanism of Action: Glucocorticoids are naturally occurring hormones that prevent or suppress inflammation and immune responses when administered at pharmacological doses. At a molecular level, unbound glucocorticoids readily cross cell membranes and bind with high affinity to specific cytoplasmic receptors. This binding induces a response by modifying transcription and, ultimately protein synthesis to achieve the steroid's intended action. Such actions may include: inhibition of leukocyte infiltration at the site of inflammation, interference in the function of mediators of inflammatory response, and suppression of humoral immune responses. Some of the net effects include reduction in edema or scar tissue, as well as a general suppression in immune response. The degree of clinical effect is normally related to the dose administered. The antiinflammatory actions of corticosteroids are thought to involve phospholipase A2 inhibitory proteins, collectively called lipocortins. Lipocortins, in turn, control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of the precursor molecule arachidonic acid. Likewise, the numerous adverse effects related to corticosteroid use are usually related to the dose administered and the duration of therapy.

Pharmacokinetics: Prednisone is rapidly absorbed across the GI membrane following oral administration. Peak effects can be observed after 1—2 hours. The circulating drug binds extensively to the plasma proteins albumin and transcortin, with only the unbound portion of a dose active. Systemic prednisone is quickly distributed into the kidneys, intestines, skin, liver and muscle. Corticosteroids distribute into the breast milk and cross the placenta. Prednisone is metabolized by the liver to the active metabolite prednisolone, which is then further metabolized to inactive compounds. These inactive metabolites, as well as a small portion of unchanged drug, are excreted in the urine. The plasma elimination half-life is 1 hour whereas the biological half-life of prednisone is 18—36 hours.

Description, Mechanism of Action, Pharmacokinetics last revised 5/22/2002

Indications

• acute lymphocytic leukemia (ALL)	• idiopathic thrombocytopenic purpura (ITP)
• acute respiratory distress syndrome (ARDS)	• iritis
• Addison's disease	• juvenile rheumatoid arthritis (JRA)
• adrenal hyperplasia	• keratitis
• adrenocortical insufficiency	• kidney transplant rejection prophylaxis
• allergic conjunctivitis	• Loeffler's syndrome
• amyloidosis†	• lupus nephritis
• angioedema	• mixed connective tissue disease†
• ankylosing spondylitis	• multiple myeloma
• anterior segment inflammation	• myasthenia gravis
• asthma	• mycosis fungoides
• atopic dermatitis	• nephrotic syndrome
• autoimmune hepatitis†	• optic neuritis
• Behcet's syndrome†	• osteoarthritis
• Bell's palsy†	• pemphigus
• berylliosis	• pericarditis†
• bone pain†	• pneumonia†
• bursitis	• pneumonitis
• carpal tunnel syndrome†	• polyarteritis nodosa†
• chorioretinitis	• polychondritis†
• chronic lymphocytic leukemia (CLL)	• polymyositis
• Churg-Strauss syndrome†	• psoriasis
• corneal ulcer	• pulmonary fibrosis†
• Crohn's disease	• rheumatic carditis
• dermatitis	• rheumatoid arthritis
• dermatomyositis†	• sarcoidosis
• Duchenne muscular dystrophy†	• severe pain
• endophthalmitis†	• Stevens-Johnson syndrome
• epicondylitis	• systemic lupus erythematosus (SLE)
• erythroblastopenia	• temporal arteritis†
• gout	• tenosynovitis
• gouty arthritis	• thrombocytopenia
• graft-versus-host disease (GVHD)	• thyroiditis
• headache	• tuberculosis
• hemolytic anemia	• ulcerative colitis
• Hodgkin's disease	• urticaria
• hypercalcemia	• uveitis
• hypoplastic anemia	• Wegener's granulomatosis†

† non-FDA-approved indication

Dosage

Equivalent Glucocorticoid dosages. These are general approximations and may not apply to all diseases or routes of administration.
Equivalent glucocorticoid dosages:
Cortisone--25 mg
Hydrocortisone--20 mg
Prednisolone--5 mg
Prednisone--5 mg
Methylprednisolone--4 mg
Triamcinolone--4 mg
Dexamethasone--0.75 mg
Betamethasone--0.6 mg

For maintenance therapy (i.e., replacement therapy) of primary (Addison's disease) or secondary adrenocortical insufficiency:
NOTE: Hydrocortisone and cortisone are the preferred agents for these conditions; prednisone has little to no mineralocorticoid properties.
NOTE: For acute conditions, parenteral steroid therapy is recommended initially.
Oral dosage:
Adults: 5 mg PO in the AM, and 2.5 mg PO in the PM.
Children: 4—5 mg/m2 PO given 1—4 times per day.

For the treatment of congenital adrenal hyperplasia:
NOTE: Hydrocortisone is the preferred glucocorticoid in infants.
Oral dosage:
Adults: 2.5—5 mg PO once daily at bedtime.
Children: 12—13 mg/m2/day PO administered in 2—3 divided doses.

For kidney transplant rejection prophylaxis:
Oral dosage:
Adults: Titrate to response. Usual range 5—30 mg PO once daily.

For the treatment of chronic graft-versus-host disease (GVHD):
Oral dosage:
Adults: Prednisone alternating with cyclosporine has been recommended at doses of prednisone 1 mg/kg/day PO plus cyclosporine (10 mg/kg/day PO in 2 divided doses) based on actual or ideal body weight, whichever is lower. After 2 weeks if no disease progression is noted, the prednisone dose is tapered by 25% per week to 1 mg/kg of prednisone on alternate days. Once the prednisone taper is completed without a flare, the cyclosporine dose is tapered to alternate day dosing such that the patient is taking prednisone one day and cyclosporine the next day. Once patients reach their maximal response, therapy is continued for another 3 months and then tapered.[3975]

For palliative management of acute lymphocytic leukemia (ALL):
Oral dosage:
Adults: 40—50 mg/m2 PO once daily indefinitely.

For palliative management of chronic lymphocytic leukemia (CLL) in combination with chlorambucil:
Oral dosage:
Adults: 80 mg PO once daily on days 1—5 in combination with chlorambucil. Administer every 2 weeks. Alternatively, prednisone 1 mg/kg/day PO on days 1—7, then 0.5 mg/kg/day PO on days 8—14, then DC; the cycle is repeated every 6 weeks.

For the short-term treatment of hypercalcemia secondary to neoplastic disease:
Oral dosage:
Adults: 50—100 mg/day PO for 3—5 days is usually effective for hypercalcemia due to hematologic cancers, lower doses may be effective for some tumors.[532]

For the treatment of multiple myeloma in combination with an alkylating agent:
Oral dosage:
Adults: 25—60 mg/m2 PO per day for 4—7 days; in combination with an alkylating agent. Repeat every 4—6 weeks. Other multi-drug regimens with prednisone exist.

For the treatment of inflammatory bowel disease:
•for short-term treatment of acute exacerbations of Crohn's disease:
Oral dosage:
Adults: Initially, 40—60 mg/day PO, adjusted to response. While evidence that maintenance therapy prevents recurrences is lacking, a substantial percentage of patients require chronic dosing (e.g., 5—15 mg/day PO). Corticosteroids for Crohn's disease are more effective for small-bowel involvement than for colonic involvement. Because of the potential complications of steroid use in this disease, steroids should be used selectively and in the lowest dose possible.
•for short-term treatment of acute exacerbations of ulcerative colitis:
Oral dosage:
Adults: Initially, 40—60 mg/day PO has been shown to be superior to 20 mg/day PO. Maximum dosage is 1 mg/kg/day PO. Improvement is usually noted after 7—10 days. Taper dose over the next 2—3 months and DC. Once clinical remission is achieved, corticosteroid therapy should be discontinued since there is no evidence that maintenance therapy prevents recurrences.

For the treatment of serious manifestations of Behcet's syndrome†:
Oral dosage:
Adults: A dosage of 1 mg/kg PO once daily is recommended in internal medicine texts.

For the treatment of rheumatic conditions such as rheumatoid arthritis, juvenile rheumatoid arthritis (JRA), severe psoriasis and psoriatic arthritis, ankylosing spondylitis, acute and subacute bursitis, acute non-specific tenosynovitis, acute gouty arthritis and gout, osteoarthritis, or epicondylitis:
Oral dosage:
Adults: Titrate to response. Usual dosage ranges 5—30 mg PO once daily.
Children: 0.05—2 mg/kg/day PO given in 1—4 divided doses.

For the symptomatic treatment of Duchenne muscular dystrophy†:
Oral dosage:
Children: Current practice guidelines issued by the American Academy of Neurology and the Child Neurology Society recommend 0.75 mg/kg/day PO. If side effects (e.g., weight gain and cushingoid facial appearance) outweigh benefits on muscle strength and function, gradual dose reduction to as low as 0.3 mg/kg/day PO can still be beneficial.[7443]

For adjunctive therapy in the treatment of carpal tunnel syndrome†:
NOTE: The definitive treatment for median-nerve entrapment is surgery. Corticosteroids are temporary measures; patients who have intermittent pain and paresthesias without any fixed motor-sensory deficits may respond to conservative therapy.
Oral dosage:
Adults: 20 mg PO once daily for 2 weeks, followed by 10 mg PO once daily for 2 additional weeks, has provided relief.

For the treatment of selected cases of collagen disorders and mixed connective tissue disease†:
•for the treatment of systemic lupus erythematosus (SLE):
Oral dosage:
Adults: Doses for the various manifestations of SLE vary widely. The usual starting dose is 20—40 mg/day PO for moderate illness and 60—100 mg/day PO for severe illness; some patients may initially require 200—300 mg/day PO in divided doses. After the disease is controlled, reduce the dose by 10% every 5—7 days; a more rapid reduction may result in relapse. Maintenance doses are usually 10—20 mg PO once daily or 20—40 mg PO every other day.
•for the treatment of lupus nephritis† in combination with cytotoxic agents (e.g., azathioprine, cyclophosphamide, chlorambucil):
Oral dosage:
Adults: 0.25 mg/kg/day PO is usually adequate for mesangial or mild focal proliferative disease. In patients with diffuse proliferative or severe focal proliferative disease, 1 mg/kg/day PO for 2 months followed by gradual tapering has been recommended.[997] In combination with azathioprine or cyclophosphamide, doses of 60 mg PO once daily have been used. Prednisone should be tapered over a 6 month period to 30—60 mg once every other day.[213] In a comparison of oral prednisone and cytotoxic agents, prednisone was inferior to cytotoxic agents in ability to prevent decline in renal function. In this study, prednisone was dosed at 1 mg/kg/day for the first 4—8 weeks, followed by gradual tapering as tolerated.[670] Some clinicians believe that chronic renal failure is cause to discontinue therapy since serum creatinine concentrations > 3—4 mg/dL suggest limited probability of reversibility.[213]
•for the treatment of systemic dermatomyositis† (polymyositis†) in combination with azathioprine:
Oral dosage:
Adults: Initially, large doses (e.g., 60 mg PO once daily) are used, once the muscle disease is controlled, prednisone should be tapered to 5—10 mg PO every other day.[213]
•for the treatment of nonrheumatic† or rheumatic carditis, Churg-Strauss syndrome†, polymyalgia rheumatica†, polyarteritis nodosa†, relapsing polychondritis†, temporal arteritis†, vasculitis†, Wegener's granulomatosis†:
Oral dosage:
Adults: Titrate to response. Initial dose should be high (60—100 mg/day PO). After symptoms controlled, decrease dose by 10% every 5—7 days. Maintenance doses are usually 10—20 mg PO once daily or 20—40 mg PO every other day.
Children: 0.05—2 mg/kg/day PO in 1—4 divided doses.

For the treatment of autoimmune hepatitis†:
Oral dosage:
Adults: Initially, 20—30 mg PO once daily has been recommended. Some experts give a combination of prednisone and azathioprine. For maintenance, prednisone 5—15 mg PO once daily has been recommended.[1164]

For the treatment of primary amyloidosis† not associated with familial Mediterranean fever:
Oral dosage:
Adults: 0.8 mg/kg PO once daily for 7 days, in combination with melphalan; repeated every 6 weeks. The treatment combination demonstrated superior results over colchicine alone in the treatment of primary amyloidosis. [1366]

For the treatment of other systemic autoimmune conditions such as acquired hemolytic anemia, congenital hypoplastic anemia, mycosis fungoides, pemphigus, symptomatic sarcoidosis, or nonsuppurative thyroiditis:
Oral dosage:
Adults: Titrate to response. Usual dosage ranges 5—30 mg PO once daily.

For the treatment of asthma:
•for the treatment of a moderate-severe asthma exacerbation in the emergency department or the hospital:
Oral dosage:
Adults: The National Asthma Education and Prevention Expert Panel recommends 120—180 mg/day PO in 3—4 divided doses for 48 hours, then 60—80 mg/day PO until the peak expiratory flow (PEF) reaches 70% of predicted or personal best.[1515]
Children: The National Asthma Education and Prevention Expert Panel recommends 1 mg/kg PO every 6 hours for 48 hours, then 1—2 mg/kg/day (max: 60 mg/day) PO in 2 divided doses until peak expiratory flow (PEF) reaches 70% of predicted or personal best.[1515]
•for the treatment of an acute asthma exacerbation on an outpatient basis in selected patients:
Oral dosage:
Adults: The National Asthma Education and Prevention Expert Panel recommends 40—60 mg PO as a single dose or in 2 divided doses for 3—10 days.[1515]
Children: The National Asthma Education and Prevention Program Expert Panel recommends 1—2 mg/kg/day (max: 60 mg/day) PO as a single dose or in 2 divided doses for 3—10 days.[1515]
•for long-term prevention of symptoms in severe persistent asthma:
Oral dosage:
Adults and children: The National Asthma Education and Prevention Expert Panel recommends 7.5—60 mg PO administered once daily in the AM or every other day. Taper to the lowest effective dose. One study indicates that administering the dose in the afternoon at 3:00 pm may increase efficacy, with no increase in adrenal suppression.[1943]

For the treatment of thrombocytopenia:
•in patients with chronic idiopathic thrombocytopenic purpura (ITP):
Oral dosage:
Adults: Initially, 1 mg/kg PO once daily[533] ; however, lower doses of 5—10 mg/day PO are preferable for long-term treatment.[1342]
•for the treatment of autoimmune thrombocytopenia associated with SLE:
Oral dosage:
Adults and children: 0.25 mg/kg/day PO was as effective as higher doses of 1 mg/kg/day.[997]

For the treatment of acute, severe urticaria or angioedema associated with systemic symptoms in patients who fail to respond to epinephrine or histamine blockers including angioedema associated with ACE inhibitor therapy:
Oral dosage:
Adults: Short courses of 30—50 mg/day can be given PO during the late phase of an acute reaction.[570]

For the treatment of myasthenia gravis in patients who are poorly controlled with cholinesterase inhibitor therapy:
Oral dosage:
Adults: Initially, 15—20 mg/day PO. Increase by 5 mg every 2—3 days as needed up to 60 mg/day PO maximum. Then change to every other day therapy.[540]

For the treatment of idiopathic or viral pericarditis†:
Oral dosage:
Adults: 20—80 mg PO once daily. Corticosteroids are contraindicated in pericarditis after MI; corticosteroids retard myocardial scar formation and the incidence of rupture may increase.

For the treatment of nephrotic syndrome:
Oral dosage:
Adults: 40—80 mg/day PO until urine is protein-free; slowly taper as indicated. Some patients may require long-term dosing.
Children: 2 mg/kg/day or 60 mg/m2/day (maximum 80 mg) PO once daily until urine is protein-free for 3 consecutive days. Then 1—1.5 mg/kg or 40 mg/m2 PO every other day for 4 weeks. If needed, the long-term maintenance dose is 0.5—1 mg/kg PO every other day for 3—6 months.[1944]

For the treatment of Stevens-Johnson syndrome:
Oral dosage:
Adults: High-dose corticosteroids are controversial; administration has been associated with decreased survival.[534] [535] Prednisone doses of 60—250 mg/day PO are equivalent to the recommended hydrocortisone doses of 240—1000 mg/day.

For adjunctive treatment in selected cases of pneumonia† or pneumonitis:
•for adjunctive treatment of AIDS-associated Pneumocystis carinii pneumonia† (PCP):
Oral dosage:
Adults: 40 mg PO twice daily for 5 days, then 40 mg PO daily for 5 days, then 20 mg PO daily for 11 days, during anti-infective therapy. Begin prednisone within 24—72 hours of the initiation of anti-infectives for PCP; use is associated with improved outcomes.
Children: Safe dosage has not been established.
•for adjunctive treatment of aspiration pneumonitis:
Oral dosage:
Adults: 5—60 mg/day PO; administered in 1—4 divided doses. Gradually taper after 1—2 weeks and discontinue by 4—6 weeks, guided by symptoms.
Children: 0.14—2 mg/kg PO daily or 4—60 mg/m2 PO daily, given in 4 divided doses. Gradually taper after 1—2 weeks and discontinue by 4—6 weeks, as guided by symptoms.

For the systemic treatment of ophthalmic inflammatory conditions such as endophthalmitis†, optic neuritis, allergic conjunctivitis, keratitis, allergic corneal ulcer, iritis, chorioretinitis, anterior segment inflammation, uveitis, choroiditis, or sympathetic ophthalmia:
NOTE: Topically applied corticosteroids are as effective as systemic corticosteroids for anterior ocular inflammation.
Oral dosage:
Adults: 5—60 mg/day PO administered in 1—4 divided doses, depending upon disease being treated.
Children: 0.14—2 mg/kg/day PO or 4—60 mg/m2/day PO, given in 4 divided doses.

For the short-term treatment of acute, severe headache:
Oral dosage:
Adults: 80 mg PO per day for several days.[351] Taper rapidly.

For the adjunctive management of severe pain associated with bone pain†, brain metastases and epidural spinal cord compression:
Oral dosage:
Adults: 10—50 mg/day PO has been used for bone pain. A range of 40—80 mg/day PO is suggested for spinal cord compression.[1171]

For the treatment of the acute respiratory distress syndrome (ARDS) in patients with severe disease and no signs of improvement 7—14 days after onset of the condition:
Oral dosage:
Adults: Corticosteroid use in ARDS is controversial. If there are no signs of improvement 7—14 days after ARDS onset, 2—4 mg/kg/day PO for 7—14 days has been recommended.[564]

For the treatment of other conditions not listed above including atopic dermatitis, Loeffler's syndrome, berylliosis, erythroblastopenia, or trichinosis:
Oral dosage:
Adults: 5—60 mg/day PO, administered in 1—4 divided doses, depending upon disease being treated. Depending on the indication, the initial dose may be gradually tapered after 1—2 weeks and DC'd by 4—6 weeks, as guided by symptoms.
Children: 0.14—2 mg/kg/day POor 4—60 mg/m2/day PO, given in 4 divided doses. Depending on indication, gradually taper the initial dose after 1—2 weeks and DC by 4—6 weeks, guided by symptoms.

For the treatment of tuberculosis† meningitis or pulmonary tuberculosis† controlled by appropriate antituberculosis chemotherapy:
Oral dosage:
Adults: 5—60 mg/day PO, administered in 1—4 divided doses, depending upon disease being treated. For TB meningitis, initially 60—80 mg PO once daily; experts recommend corticosteroid use in stage 2 (confusion or the presence of focal neurological defects) or stage 3 (stuporous or dense paraplegia or hemiplegia). Alternatively, initial doses of 0.5—1 mg/kg/day PO have been used.[1945] Gradually taper after 1—2 weeks and DC by 4—6 weeks, as guided by the patient's symptoms.
Children: 0.14—2 mg/kg/day PO or 4—60 mg/m2/day PO, given in 4 divided doses.

For the treatment of idiopathic pulmonary fibrosis†:
Oral dosage:
Adults: 0.5 mg/kg/day PO for 4 weeks, then 0.25 mg/kg/day PO for 8 weeks. Taper to 0.125 mg/kg/day or 0.25 mg/kg/day PO on alternate days. Guidelines suggest treatment should be in combination with cyclophosphamide or azathioprine and continued for a minimum of 6 months. Objective responses may not be noted until the patient has received >= 3 months of therapy. Exact duration of treatment and need for long-term maintenance should be individualized based on clinical response and tolerance to therapy. Chronic doses of prednisone (15—20 mg PO once daily) may be adequate as maintenance therapy.[3164]

For the treatment of Hodgkin's disease in combination with antineoplastic agents:
•in combination with mechlorethamine, vincristine, vinblastine, and procarbazine (MVVPP regimen):
Oral dosage:
Adults: 40 mg/m2/day PO on days 1—22, then taper. Chemotherapy cycle is repeated every 57 days.
•in combination with mechlorethamine, vincristine, procarbazine, doxorubicin, bleomycin, and vinblastine (MOPP/APB regimen):
Oral dosage:
Adults: 40 mg/m2/day PO on days 1—14; cycle is repeated every 28 days.

For the treatment of Bell's palsy†:
Oral dosage:
Adults: 10 mg/kg (up to 80 mg) PO once per day for 7 to 14 days, with an HSV antiviral agent (i.e., acyclovir, valacyclovir, or famciclovir), has been recommended.[7250] If treatment is continued for 14 days, the prednisone dose can be tapered in the second week of treatment.[7251]

Maximum Dosage Limits:
Dosage must be individualized and is highly variable depending on the nature and severity of the disease, and on patient response. Although there is no absolute maximum dosage, the Boston Collaborative Drug Study found that psychiatric events occurred in fewer than 1% of patients when prednisone was prescribed in doses of 30 mg/day or less, whereas the incidence rose to 18% in patients receiving 80 mg/day.[243]

Patients with hepatic impairment:
Specific guidelines for dosage adjustments in hepatic impairment are not available; prednisone is converted to prednisolone, the active moiety, by the liver. The use of oral prednisolone instead of oral prednisone may be preferred in patients with significant hepatic dysfunction (see Prednisolone monograph); doses are equivalent (i.e., 1 mg prednisone is equivalent to 1 mg of prednisolone).

Patients with renal impairment:
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

†non-FDA-approved indication

Indications...Dosage last revised 1/19/2005 6:26:00 PM

Administration Guidelines

NOTE: Dosage must be individualized and is highly variable depending on the nature and severity of the disease, and on patient response. If therapy is continuous for more than several days, withdrawal should generally be gradual.

Oral Administration
•All oral dosage forms: Administer with meals to minimize indigestion or GI irritation. If given once daily or every other day, administer in the morning to coincide with the body's normal cortisol secretion.
•Oral solution or syrup: Administer using a calibrated measuring device for accurate measurement of the dose.

†non-FDA approved

Administration last revised 7/1/2002

†non-FDA-approved indication

Contraindications/Precautions

• abrupt discontinuation	• infection
• Cushing's syndrome	• inflammatory bowel disease
• fungal infection	• lactase deficiency
• measles	• myasthenia gravis
• varicella	• myocardial infarction
• breast-feeding	• osteoporosis
• cataracts	• peptic ulcer disease
• children	• pregnancy
• coagulopathy	• psychosis
• corticosteroid hypersensitivity	• renal disease
• diabetes mellitus	• seizure disorder
• diverticulitis	• surgery
• GI disease	• thromboembolic disease
• glaucoma	• tuberculosis
• heart failure	• ulcerative colitis
• hepatic disease	• vaccination
• herpes infection	• viral infection
• hypertension	• visual disturbance
• hypothyroidism

• Absolute contraindications are in italics.

The manufacturers state that prednisone is contraindicated in patients with systemic fungal infection, but many clinicians believe that corticosteroids can be administered to patients with any type of known infection as long as appropriate antifungal therapy is administered simultaneously.

Corticosteroid therapy can mask the symptoms of infection and should not be used in cases of viral infection or bacterial infection which are not adequately controlled by anti-infective agents. Secondary infections are common during corticosteroid therapy. Corticosteroids may reactivate tuberculosis, and should not be used in patients with a history of active tuberculosis except when chemoprophylaxis is instituted concomitantly. Patients receiving immunosuppressive doses of corticosteroids should be advised to avoid exposure to measles or varicella, and if exposed to these diseases, to seek medical advice immediately. In general, corticosteroids should not be used in patients with herpes infection.

Patients should be instructed to notify their physician immediately if signs of infection or injury occur, both during treatment, or up to 12 months following cessation of therapy. Dosages should be adjusted, or glucocorticoid therapy reintroduced, if required. If surgery is required, patients should advise the attending physician of the corticosteroid they have received within the last 12 months, and the disease for which they were being treated. Identification cards which include the name of the patient's disease, the currently administered type and dose of corticosteroid, and the patient's physician should be carried with the patient at all times.

Corticosteroid therapy has been associated with left ventricular free-wall rupture in patients with recent myocardial infarction, and should therefore be used cautiously in these patients.

Corticosteroids cause edema, which may exacerbate congestive heart failure or hypertension, and should be used with caution in these patients.

Corticosteroids should be used cautiously in patients with glaucoma or other visual disturbance. Corticosteroids are well known to cause cataracts and can exacerbate glaucoma during long-term administration. Patients receiving topical or systemic corticosteroids chronically should be periodically assessed for cataract formation.

Corticosteroids should be used with caution in patients with GI disease, diverticulitis, intestinal anastomosis (because of the possibility of perforation), or hepatic disease causing hypoalbuminemia such as cirrhosis. While used for the short-term treatment of acute exacerbations of chronic inflammatory bowel disease such as ulcerative colitis and Crohn's disease, corticosteroids should not be used in patients where there is a possibility of impending GI perforation, abscess, or pyogenic infection. Some patients may require long-term corticosteroid therapy to suppress disease activity, but generally this practice is not recommended. Corticosteroids should not be used in patients with peptic ulcer disease except under life-threatening circumstances.

Corticosteroids should be used with extreme caution in patients with psychosis, emotional instability, herpes simplex ocular infections, renal disease, osteoporosis, diabetes mellitus, and seizure disorder, because the drugs may exacerbate these conditions. Patients with hypothyroidism may have an exaggerated response to corticosteroids, thus any steroid should be used with caution in these patients.

Glucocorticoids should be used with caution in patients with myasthenia gravis who are being treated with anticholinesterase agents (see Interactions). Muscle weakness may be transiently increased during the initiation of glucocorticoid therapy in patients with myasthenia gravis, necessitating respiratory support.

Glucocorticoids may rarely increase blood coagulability and cause intravascular thrombosis, thrombophlebitis, and thromboembolism. Therefore, corticosteroids should be used with caution in patients with coagulopathy or thromboembolic disease.

Increased dosages of rapid-acting corticosteroids may be necessary for patients undergoing physiologic stress, such as major surgery, acute infection, or blood loss. The corticosteroid should be administered before, during, and after the stressful situation.

Complications including cleft palate, still birth, and premature abortion have been reported when corticosteroids were administered during pregnancy. If these drugs must be used during pregnancy, the potential risks should be discussed with the patient. Babies born to women receiving large doses of corticosteroids during pregnancy should be monitored for signs of adrenal insufficiency and appropriate therapy initiated, if necessary. Prednisone is classified as FDA pregnancy risk category C but cortisone is classified as pregnancy category D. This probably reflects the fact that cortisone is more commonly used during pregnancy than is prednisone and therefore, more reports of problems have been associated with cortisone than prednisone and not the fact that it is a more potent teratogen. Corticosteroids distribute into breast milk, and the manufacturer states that women receiving pharmacological dosages of corticosteroids should not practice breast-feeding.

Corticosteroid therapy usually does not contraindicate vaccination with live-virus vaccines when such therapy is of short-term (< 2 weeks); low to moderate dose; long-term alternate day treatment with short-acting preparations; maintenance physiologic doses (replacement therapy); or via topical administration (skin or eye), by aerosol, or by intra-articular, bursal or tendon injection. The immunosuppressive effects of steroid treatment differ, but many clinicians consider a dose equivalent to either 2 mg/kg/day or 20 mg/day of prednisone as sufficiently immunosuppressive to raise concern about the safety of immunization with live-virus vaccines. In general, patients with severe immunosuppression due to large doses of corticosteroids should not receive vaccination with live-virus vaccines. When cancer chemotherapy or immunosuppressive therapy is being considered (e.g., for patients with Hodgkin's disease or organ transplantation), vaccination should precede the initiation of chemotherapy or immunotherapy by >= 2 weeks. Patients vaccinated while on immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated at least 3 months after discontinuation of therapy. In patients who have received high-dose, systemic corticosteroids for >= 2 weeks, it is recommended to wait at least 3 months after discontinuation of therapy before administering a live-virus vaccine.

Prolonged therapy with corticosteroids should be avoided in children, as the drug may retard bone growth. Children receiving corticosteroids are immunosuppressed, and are therefore more susceptible to infection. Normally innocuous infections can become fatal in these children, and care should be taken to avoid exposure to these diseases.

As glucocorticoids can produce or aggravate Cushing's syndrome, glucocorticoids should be avoided in patients with Cushing's disease.

Pharmacologic doses of corticosteroids administered for prolonged periods may result in hypothalamic-pituitary-adrenal (HPA) suppression. Acute adrenal insufficiency and even death may occur following abrupt discontinuation. Withdrawal from prolonged oral corticosteroid therapy should be gradual; HPA suppression can last for up to 12 months following cessation of therapy, and patients may need supplemental corticosteroid treatment during periods of physiologic stress, such as surgery, acute blood loss, or infection, even after the drug has been discontinued. Also, a non-HPA withdrawal syndrome may occur following abrupt discontinuation of corticosteroid therapy, and is apparently unrelated to adrenocortical insufficiency. These effects are thought to be due to the sudden change in glucocorticoid concentration rather than to low corticosteroid levels (see Adverse Reactions).

Although true corticosteroid hypersensitivity is rare, patients who have demonstrated a prior hypersensitivity reaction to prednisone should not receive any form of prednisone or prednisolone. It is possible, though also rare, that such patients will display cross-hypersensitivity to other corticosteroids. It is advisable that patients who have a hypersensitivity reaction to any corticosteroid undergo skin testing, which, although not a conclusive predictor, may help to determine if hypersensitivity to another corticosteroid exists. Such patients should be carefully monitored during and following the administration of any corticosteroid.[4323]

Prednisone is contraindicated in patients with a hypersensitivity to prednisone or to any components of the formulation.[8143] As prednisone tablets contain lactose, appropriate precautions should be taken when administered to patients with lactase deficiency.

Contraindications last revised 11/29/2005 1:24:00 PM

Drug Interactions

• Amphotericin B		• Mecasermin, Recombinant, rh-IGF-1
	Antidiabetic Agents	• Mifepristone, RU-486
	Antineoplastic Agents		Neuromuscular blockers
	Antithyroid agents	• Nevirapine
	Barbiturates		Nonsteroidal antiinflammatory drugs (NSAIDs)
• Bosentan		• Pegaspargase
• Calcium Carbonate		• Phenytoin
	Cardiac glycosides		Photosensitizing Agents
	Cholinesterase Inhibitors	• Rifabutin
	Diuretics	• Rifampin
• Dofetilide		• Ritonavir
• Ephedra, Ma Huang			Salicylates
	Estrogens	• Sodium Iodide I-131
• Ethotoin			Thyroid hormones
• Fosphenytoin			Toxoids
	Immunosuppressives		Vaccines
• Infliximab			Vitamin D analogs
• Isoproterenol		• Warfarin
• L-Asparaginase

Hepatic microsomal enzyme inducers including barbiturates [4722], bosentan [4739], phenytoin [4742] or fosphenytoin, and possibly ethotoin [4741], rifabutin [5948] and rifampin [4742] may increase the metabolism of glucocorticoids. Rifabutin and rifampin are particularly potent enzyme inducers. Despite the fact that prednisone is converted in the liver to its active form, prednisolone, prednisolone is also metabolized by the liver and susceptible to accelerated clearance if any of these drugs are added. Dosages of prednisone may require adjustment if these agents, especially rifabutin or rifampin, are initiated or withdrawn during therapy.

Estrogens have been associated with elevated serum concentrations of corticosteroid binding globulin (CBG), leading to increased circulating corticosteroids.[4744] In addition, estrogens have been shown to decrease the clearance of prednisolone. Since prednisone is metabolized to prednisolone, this interaction should also apply to prednisone. Therefore, the effects of corticosteroids may be altered by the concurrent administration of estrogen, requiring the adjustment of corticosteroid dosages if estrogen is added to or withdrawn during therapy.

Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs.[1162] Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.

The potassium-wasting effects of corticosteroid therapy [6524] may be exacerbated by concomitant administration of other potassium depleting drugs including diuretics and amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.

Patients receiving cardiac glycosides and corticosteroids concomitantly are at an increased risk for developing arrhythmias or digitalis toxicity due to corticosteroid-induced hypokalemia.[4999] [6115] Corticosteroid-induced hypokalemia could also enhance the proarrhythmic effects of dofetilide.[4947]

Glucocorticoids may interact with cholinesterase inhibitors, including ambenonium, neostigmine, and pyridostigmine, occasionally causing severe muscle weakness in patients with myasthenia gravis.[6524] [7895] Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis.[7896] In such patients it is recommended that corticosteroid therapy be initiated at low dosages (i.e., 10—25 mg/day of prednisone or equivalent) and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.[7895] [7896]

Killed or inactivated vaccines and toxoids do not represent a danger to immunocompromised persons and generally should be administered as recommended for healthy persons. The immune response of immunocompromised persons to vaccines is not as good as healthy persons; higher doses or more frequent boosters may be required, although the immune response still may be suboptimal. Live-virus vaccines should not be given to immunocompromised individuals due to the potentiation of virus replication and adverse reactions to the virus.[3957] Those undergoing high-dose corticosteroid therapy should not be exposed to others who have recently received the oral poliovirus vaccine (OPV). Measles-mumps-rubella (MMR) vaccination is not contraindicated for the close contacts, including health care professionals, of immunocompromised patients. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination. When exposed to a vaccine-preventable disease such as measles, severely immunocompromised children should be considered susceptible regardless of their vaccination history.

The effect of corticosteroids on oral anticoagulants (e.g., warfarin) is variable. There are reports of enhanced as well as diminished effects of anticoagulants when given concurrently with corticosteroids [6524]; however, limited published data exist, and the mechanism of the interaction is not well described. High-dose corticosteroids appear to pose a greater risk for increased anticoagulant effect.[6525] [6526] In addition, corticosteroids have been associated with a risk of peptic ulcer and gastrointestinal bleeding.[6524] [6527] Thus corticosteroids should be used cautiously and with appropriate clinical monitoring in patients receiving oral anticoagulants; coagulation indices (e.g., INR, etc.) should be monitored to maintain the desired anticoagulant effect. During high-dose corticosteroid administration, daily laboratory monitoring may be desirable.[6525]

The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism.[6524] Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.

Systemic corticosteroids increase blood glucose levels [4751]; a potential pharmacodynamic interaction exists between corticosteroids and all antidiabetic agents. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent. Blood lactate concentrations and the lactate to pyruvate ratio increased when metformin was coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with an increased risk of lactic acidosis, so patients on metformin concurrently with systemic steroids should be monitored closely.

Concomitant use of L-asparaginase or pegaspargase with corticosteroids can result in additive hyperglycemia.[6639] L-Asparaginase transiently inhibits insulin production contributing to hyperglycemia seen during concurrent corticosteroid therapy. Insulin therapy may be required in some cases. Administration of L-asparaginase or pegaspargase after rather than before corticosteroids reportedly has produced fewer hypersensitivity reactions.

Corticosteroids can cause increases in blood pressure, sodium and water retention, and hypokalemia [6524], predisposing patients to interactions with certain other medications. Hypokalemia is known to potentiate neuromuscular blockade associated with nondepolarizing neuromuscular blockers. In addition, case reports and clinical studies have reported myopathy and weakness, sometimes prolonged, with the combined use of neuromuscular blocking agents with corticosteroids in critically ill patients. Many cases involved patients with no underlying risk factors. The term 'blocking agent-corticosteroid myopathy' (BACM) has been applied to this syndrome.[7893] When given concomitantly for prolonged periods these agents appear to confer a greater risk of myopathy versus the use of either agent alone, and the pathology of the effect is not known.[7893] When combined use is necessary for prolonged periods, careful monitoring of the patient is recommended.

Corticosteroids administered systemically prior to or concomitantly with photosensitizing agents may decrease the efficacy of photodynamic therapy.[6625]

The risk of cardiac toxicity with isoproterenol in asthma patients appears to be increased with the coadministration of corticosteroids or methylxanthines. Intravenous infusions of isoproterenol in refractory asthmatic children at rates of 0.05—2.7 mcg/kg/min have caused clinical deterioration, myocardial infarction (necrosis), congestive heart failure and death.[4721]

Mifepristone, RU-486 exhibits antiglucocorticoid activity [4720] that may antagonize the corticosteroids. In rats, the activity of dexamethasone was inhibited by oral mifepristone doses of 10—25 mg/kg. A mifepristone dose of 4.5 mg/kg in humans resulted in compensatory increases in ACTH and cortisol. Mifepristone is contraindicated in patients on long-term corticosteroid therapy.

Due to ritonavir's inhibitory effects on various hepatic isoenzymes (especially CYP2D6 and CYP3A4) [4194], a drug interaction may occur with prednisone. Monitoring of therapeutic and adverse effects is required when prednisone is coadministered with ritonavir; dosage reduction may be needed.

In a clinical trial, concomitant use of prednisone (40 mg/day for the first 14 days of nevirapine administration) was associated with an increase in incidence and severity of rash during the first 6 weeks of nevirapine therapy. Therefore, the use of prednisone to prevent nevirapine-associated rash is not recommended.[5222]

Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods [7714], additive effects may be seen with other immunosuppressives or antineoplastic agents. While therapy is designed to take advantage of this effect, patients may be predisposed to over-immunosuppression resulting in an increased risk for the development of severe infections.[7714] Close clinical monitoring is advised with concurrent use; in the presence of serious infections, continuation of the corticosteroid or immunosuppressive agent may be necessary but should be accompanied by appropriate antimicrobial therapies as indicated.

Many serious infections during infliximab therapy have occurred in patients who received concurrent immunosuppressives that, in addition to their underlying Crohn's disease or rheumatoid arthritis, predisposed patients to infections.[4711] The impact of concurrent infliximab therapy and immunosuppression on the development of malignancies is unknown. In clinical trials, the use of concomitant immunosuppressant agents appeared to reduce the frequency of antibodies to infliximab and appeared to reduce infusion reactions.[4711]

Ephedra, ma huang may increase the metabolism and lead to subtherapeutic levels of corticosteroids. Ephedrine, an ephedra alkaloid may result in higher liver clearance or metabolism of corticosteroids. Patients requiring corticosteroids, especially those with asthma or immunosuppression, should avoid ma huang.[3649]

Vitamin D plus calcium supplements are generally recommended for the prevention of osteoporosis in patients taking long-term corticosteroids.[6905] A relationship of functional antagonism exists between vitamin D analogs, which promote calcium absorption, and corticosteroids, which inhibit calcium absorption.[6902] [1441] Therapeutic effect of vitamin D analogs should be monitored when used concomitantly with corticosteroids.

Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function.[8256] [8255]

Additional monitoring may be required when coadministering systemic or inhaled corticosteroids and mecasermin, recombinant, rh-IGF-1. In animal studies, corticosteroids impair the growth-stimulating effects of growth hormone (GH) through interference with the physiological stimulation of epiphyseal chondrocyte proliferation exerted by GH and IGF-1. Dexamethasone administration on long bone tissue in vitro resulted in a decrease of local synthesis of IGF-1.[8314] Similar counteractive effects are expected in humans. If systemic or inhaled glucocorticoid therapy is required, the steroid dose should be carefully adjusted and growth rate monitored.[8315]

Corticosteroids are known to decrease the uptake of iodide into thyroid tissue.[8683] In order to increase thyroid uptake and optimize exposure of thyroid tissue to the radionucleotide sodium iodide I-131, consider withholding prednisone prior to treatment with sodium iodide I-131.

Interactions last revised 2/13/2006 3:13:00 PM

Adverse Reactions

• abdominal pain	• immunosuppression
• acne vulgaris	• impaired wound healing
• adrenocortical insufficiency	• increased intracranial pressure
• amenorrhea	• infection
• angina	• insomnia
• angioedema	• lethargy
• anorexia	• menstrual irregularity
• anxiety	• metabolic alkalosis
• appetite stimulation	• myalgia
• arthralgia	• myocardial infarction
• avascular necrosis	• myopathy
• bone fractures	• nausea/vomiting
• cataracts	• ocular hypertension
• constipation	• optic neuritis
• Cushing's syndrome	• osteoporosis
• depression	• palpitations
• diabetes mellitus	• pancreatitis
• diaphoresis	• papilledema
• diarrhea	• peptic ulcer
• dysmenorrhea	• peripheral neuropathy
• ecchymosis	• petechiae
• edema	• phlebitis
• EEG changes	• physiological dependence
• emotional lability	• pseudotumor cerebri
• erythema	• psychosis
• esophageal ulceration	• restlessness
• euphoria	• retinopathy
• exfoliative dermatitis	• seizures
• exophthalmos	• sinus tachycardia
• fever	• skin atrophy
• fluid retention	• sodium retention
• gastritis	• stomatitis
• glossitis	• striae
• growth inhibition	• stroke
• headache	• thromboembolism
• heart failure	• thrombosis
• hirsutism	• urinary incontinence
• hypercholesterolemia	• urinary urgency
• hyperglycemia	• urticaria
• hypernatremia	• vertigo
• hypertension	• visual impairment
• hypocalcemia	• weakness
• hypokalemia	• weight gain
• hypotension	• weight loss
• hypothalamic-pituitary-adrenal (HPA) suppression	• withdrawal

NOTE: Prolonged administration of physiologic replacement dosages of glucocorticoids does not usually cause adverse effects. The severity of the adverse effects associated with prolonged administration of pharmacological dosages of corticosteroids increases with duration of therapy. Short term administration of large doses typically does not cause adverse effects, but long term administration can lead to adrenocortical atrophy and generalized protein depletion.

Glucocorticoids are responsible for protein metabolism, and prolonged therapy can result in various musculoskeletal manifestations, including: myopathy (myalgia, muscle wasting, muscle weakness), impaired wound healing, bone matrix atrophy (osteoporosis), bone fractures such as vertebral compression fractures or fractures of long bones, and avascular necrosis of femoral or humoral heads. These effects are more likely to occur in older or debilitated patients. Glucocorticoids interact with calcium metabolism at many sites, including: decreasing the synthesis by osteoblasts of the principle proteins of bone matrix, malabsorption of calcium in both the nephron and the gut, and reduction of sex hormone concentrations. Although all of these actions probably contribute to glucocorticoid-induced osteoporosis, the actions on osteoblasts is most important. Glucocorticoids do not modify vitamin D metabolism.[1441] Postmenopausal women, in particular, should be monitored for signs of osteoporosis during corticosteroid therapy. Because of retardation of bone growth, children receiving prolonged corticosteroid therapy may have growth inhibition.

Corticosteroid therapy can mask the symptoms of infection and should be avoided during an acute viral or bacterial infection. Immunosuppression is most likely to occur in patients receiving high-dose (e.g., equivalent to 1 mg/kg or more of prednisone daily), systemic corticosteroid therapy for any period of time, particularly in conjunction with corticosteroid sparing drugs (e.g., troleandomycin) and/or concomitant immunosuppressant agents; however, patients receiving moderate dosages of systemic corticosteroids for short periods or low dosages for prolonged periods also may be at risk. Corticosteroids can reactivate tuberculosis and should not be used in patients with a history of active tuberculosis except when chemoprophylaxis is instituted concomitantly. Patients receiving immunosuppressive doses of corticosteroids should be advised to avoid exposure to measles or varicella (chickenpox) and, if exposed to these diseases, to seek medical advice immediately.

Corticosteroids are divided into two classes: mineralocorticoids and glucocorticoids. Mineralocorticoids alter electrolyte and fluid balance by facilitating sodium retention and hydrogen and potassium excretion at the level of the distal renal tubule, resulting in edema and hypertension. Mineralocorticoid properties can cause fluid retention; electrolyte disturbances (hypokalemia, hypokalemic metabolic alkalosis, hypernatremia, hypocalcemia), edema, and hypertension. Prolonged administration of glucocorticoids may also result in edema and hypertension. In a review of 93 studies of corticosteroid use, hypertension was found to develop 4 times as often in steroid recipients compared to control groups.[938]
Although corticosteroids are used to treat Graves' ophthalmopathy, ocular effects, such as exophthalmos, posterior subcapsular cataracts, retinopathy, or ocular hypertension, can result from prolonged use of glucocorticoids and could result in glaucoma or ocular nerve damage including optic neuritis. Temporary or permanent visual impairment, including blindness, has been reported with glucocorticoid administration by several routes of administration including intranasal and ophthalmic administration. Secondary fungal and viral infections of the eye can be exacerbated by corticosteroid therapy.

Prolonged corticosteroid therapy may adversely affect the endocrine system, resulting in hypercorticism (Cushing's syndrome), menstrual irregularity including dysmenorrhea or amenorrhea, hyperglycemia, and aggravation of diabetes mellitus in susceptible patients. In a recently-published review of 93 studies of corticosteroid use, the development of diabetes mellitus was determined to occur 4 times more frequently in steroid recipients compared to control groups.[938] In patients with preexisting diabetes mellitus, insulin or oral hypoglycemic dosages may require adjustment during steroid administration.

Adverse GI effects associated with corticosteroid administration include nausea/vomiting and anorexia with subsequent weight loss. Appetite stimulation with weight gain, diarrhea, constipation, abdominal pain, esophageal ulceration, gastritis, and pancreatitis have also been reported. Although it was once believed that corticosteroids contributed to the development of peptic ulcer disease, in a published review of 93 studies of corticosteroid use, the incidence of peptic ulcer disease was not found to be higher in steroid recipients compared to control groups.[938] While most of these studies did not utilize endoscopy, it is unlikely that corticosteroids contribute to the development of peptic ulcer disease.

Adverse neurologic effects have been reported during prolonged corticosteroid administration and include headache, insomnia, vertigo, restlessness, ischemic peripheral neuropathy, seizures, and EEG changes. Mental disturbances, including depression, anxiety, euphoria, personality changes, and psychosis, have also been reported; emotional lability and psychotic problems can be exacerbated by corticosteroid therapy.

Various adverse dermatologic effects reported during corticosteroid therapy include skin atrophy, acne vulgaris, diaphoresis, impaired wound healing, facial erythema, striae, petechiae, hirsutism, ecchymosis, and easy bruising. Hypersensitivity reactions may manifest as allergic dermatitis, urticaria, and/or angioedema.

Pharmacologic doses of corticosteroids administered for prolonged periods may result in physiological dependence due to hypothalamic-pituitary-adrenal (HPA) suppression. Exogenous corticosteroids exert negative feedback on the pituitary, inhibiting the secretion of adrenocorticotropin (ACTH). This results in a decrease in ACTH-mediated synthesis of endogenous corticosteroids and androgens by the adrenal cortex. The severity of glucocorticoid-induced secondary adrenocortical insufficiency varies among individuals, and is dependent upon the dose, frequency, time of administration, and duration of therapy. Administering the drug on alternate days may help to alleviate this adverse effect. Patients with HPA suppression will require increased doses of corticosteroid therapy during periods of physiologic stress. Acute adrenal insufficiency and even death may occur if sudden withdrawal of the drugs is undertaken. Withdrawal from prolonged oral corticosteroid therapy should be gradual; HPA suppression can last for up to 12 months following cessation of therapy, and patients may need supplemental corticosteroid treatment during periods of physiologic stress, such as surgery, acute blood loss, or infection, even after the drug has been discontinued. Also, a non-HAP withdrawal syndrome may occur following abrupt discontinuance of corticosteroid therapy, and is apparently unrelated to adrenocortical insufficiency. This syndrome includes symptoms such as anorexia, lethargy, nausea/vomiting, headache, fever, arthralgia, myalgia, exfoliative dermatitis, weight loss, and hypotension. These effects are thought to be due to the sudden change in glucocorticoid concentration rather than to low corticosteroid levels. Increased intracranial pressure with papilledema (i.e., pseudotumor cerebri) has also been reported with withdrawal of glucocorticoid therapy.

Hypercholesterolemia, atherosclerosis, fat embolism, thrombosis, thromboembolism, and phlebitis, specifically, thrombophlebitis have been associated with corticosteroid therapy. Glucocorticoid use appears to increase the risk of cardiovascular events such as myocardial infarction, angina, angioplasty, coronary revascularization, stroke, transient ischemic attack, congestive heart failure, or cardiovascular death. As determined from observational data, the rate of cardiovascular events was 17 per 1000 person-years among 82,202 non-users of glucocorticoids. In contrast, the rate was 23.9 per 1000 person-years among 68,781 glucocorticoid users. Furthermore, the rate of cardiovascular events was 76.5 per 1000 person-years for high exposure patients. After adjustment for known covariates by multivariate analysis, high-dose glucocorticoid use was associated with a 2.56-fold increased risk of cardiovascular events as compared with nonuse. An increased risk of heart failure was also observed for medium-dose glucocorticoid use as compared with nonuse. At the beginning of the study, patients were at least 40 years of age and had not been hospitalized for cardiovascular disease. High glucocorticoid exposure was defined as at least 7.5 mg daily of prednisolone or the equivalent given orally, rectally, or parenterally whereas medium exposure was defined as less than the above dosage by any of the 3 routes. Low-dose exposure was defined as inhaled, topical, or nasal usage only.[7459]

Palpitations, sinus tachycardia, glossitis, stomatitis, urinary incontinence, and urinary urgency have been rarely reported. Corticosteroids may also decrease serum concentrations of vitamin C (ascorbic acid) and vitamin A which may rarely produce symptoms of vitamin A deficiency or vitamin C deficiency.

Adverse Reactions last revised 1/19/2005 7:53:00 PM

Patient Education

Prednisone oral solution or syrup

What is prednisone oral solution?
PREDNISONE (Prednisone Intensol®) is a corticosteroid. It helps to reduce swelling, redness, itching, and allergic reactions and can be used to treat severe allergies, skin problems, asthma, arthritis and other conditions. Generic prednisone oral solution is available.

What should my health care professional know before I take prednisone?
They need to know if you have any of these conditions:
•cataracts or glaucoma
•Cushing's syndrome
•diabetes
•heart problems, or previous heart attack
•high blood pressure or blood clotting disorder
•infection, such as herpes, measles, tuberculosis or chickenpox
•myasthenia gravis
•pschosis
•osteoporosis
•recent surgery
•seizures (convulsions)
•stomach or intestinal disease, including colitis
•under-active thyroid
•an unusual or allergic reaction to prednisone, other corticosteroids, medicines, foods, dyes, or preservatives
•pregnant or trying to get pregnant
•breast-feeding

How should I take this medicine?
Take prednisone oral solution by mouth. Follow the directions on the prescription label. Shake well before using. Use a specially marked spoon or container to measure your medicine. Ask your pharmacist if you do not have one; household spoons are not always accurate. Take with food or milk to avoid stomach upset. If you are only taking prednisone once a day, take it in the morning, which is the time your body normally secretes cortisol. Take your doses at regular intervals. Do not take your medicine more often than directed.

Contact your pediatrician or health care professional regarding the use of this medicine in children. Special care may be needed.

What if I miss a dose?
If you miss a dose, take it a soon as you can. If it is almost time for your next dose, consult your prescriber or health care professional. You may need to miss a dose or take a double dose, depending on your condition and treatment. Do not take double or extra doses without advice.

What drug(s) may interact with prednisone?
•acetazolamide
•antiinflammatory drugs (NSAIDs, such as ibuprofen)
•barbiturate medicines for inducing sleep or treating seizures
•bosentan
•certain heart medicines
•female hormones, including contraceptives or birth control pills
•live virus vaccines, and other toxoids and vaccines
•medicines for diabetes
•mifepristone
•phenytoin
•rifabutin
•rifampin
•water pills
•warfarin

Tell your prescriber or health care professional about all other medicines you are taking, including non-prescription medicines, nutritional supplements, or herbal products. Also tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs. These may affect the way your medicine works. Check with your health care professional before stopping or starting any of your medicines.

What side effects may I notice from taking prednisone?
Side effects that you should report to your prescriber or health care professional as soon as possible:
•bloody or black, tarry stools
•confusion, excitement, restlessness, a false sense of well-being
•eye pain, decreased or blurred vision, or bulging eyes
•fever, sore throat, sneezing, cough, or other signs of infection, wounds that will not heal
•frequent passing of urine
•increased thirst
•irregular heartbeat
•menstrual problems
•mental depression, mood swings, mistaken feelings of self-importance or of being mistreated
•muscle cramps or weakness
•nausea, vomiting
•pain in hips, back, ribs, arms, shoulders, or legs
•rounding out of face
•skin problems, acne, thin and shiny skin
•stomach pain
•swelling of feet or lower legs
•unusual bruising, pinpoint red spots on the skin
•unusual tiredness or weakness
•weight gain or weight loss

Side effects that usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome):
•diarrhea or constipation
•headache
•increased or decreased appetite
•increased sweating
•nervousness, restlessness, or difficulty sleeping
•upset stomach
•unusual increased growth of hair on the face or body

What should I watch for while taking prednisone?
Visit your prescriber or health care professional for regular checks on your progress. If you are taking prednisone over a prolonged period, carry an identification card with your name and address, the type and dose of your medicine, and your prescriber's name and address. Do not suddenly stop taking prednisone. You may need to gradually reduce the dose, so that your body can adjust. Follow the advice of your prescriber or health care professional.

If you are taking prednisone regularly, avoid contact with people who have an infection. You will have an increased risk from infection while taking prednisone. Tell your prescriber or health care professional if you are exposed to anyone with measles or chickenpox, or if you develop sores or blisters that do not heal properly.

People who are taking certain dosages of prednisone may need to avoid immunization with certain vaccines or may need to have changes in their vaccination schedules to ensure adequate protection from certain diseases. Make sure to tell your prescriber or health care professional that you are taking prednisone before receiving any vaccine.

If you are going to have surgery, tell your prescriber or health care professional that you have received prednisone within the last twelve months.

If you receive prednisone every day, you may need to watch your diet. Your body can lose potassium while you are taking this medicine. Ask your prescriber or health care professional about your diet.

Prednisone can affect your blood sugar. If you are diabetic check with your prescriber or health care professional if you need help adjusting the dose of your diabetic medicine.

Alcohol can increase the risk of getting serious side effects while you are taking prednisone. Avoid alcoholic drinks.

Prednisone can interfere with certain lab tests and can cause false skin test results.

Where can I keep my medicine?
Keep out of the reach of children.

Store at room temperature between 15 and 30 degrees C (59 and 86 degrees F); do not freeze. Throw away any unused medicine after the expiration date.

NOTE: This information is not intended to cover all possible uses, precautions, interactions, or adverse effects for this drug. If you have questions about the drug(s) you are taking, check with your health care professional.

 [Revised: 11/29/2005]

Prednisone tablets

What are prednisone tablets?
PREDNISONE (Deltasone®) is a corticosteroid. It helps to reduce swelling, redness, itching, and allergic reactions and can be used to treat severe allergies, skin problems, asthma, arthritis and other conditions. Generic prednisone tablets are available.

What should my health care professional know before I take prednisone?
They need to know if you have any of these conditions:
•cataracts or glaucoma
•Cushing's syndrome
•diabetes
•heart problems, or previous heart attack
•high blood pressure or blood clotting disorder
•infection, such as herpes, measles, tuberculosis or chickenpox
•myasthenia gravis
•pschosis
•osteoporosis
•recent surgery
•seizures (convulsions)
•stomach or intestinal disease, including colitis
•under-active thyroid
•an unusual or allergic reaction to lactose, prednisone, other corticosteroids, medicines, foods, dyes, or preservatives
•pregnant or trying to get pregnant
•breast-feeding

How should I take this medicine?
Take prednisone tablets by mouth. Follow the directions on the prescription label. Swallow the tablets with a drink of water. Take with food or milk to avoid stomach upset. If you are only taking prednisone once a day, take it in the morning, which is the time your body normally secretes cortisol. Take your doses at regular intervals. Do not take your medicine more often than directed.

Contact your pediatrician or health care professional regarding the use of this medicine in children. Special care may be needed.

What if I miss a dose?
If you miss a dose, take it a soon as you can. If it is almost time for your next dose, consult your prescriber or health care professional. You may need to miss a dose or take a double dose, depending on your condition and treatment. Do not take double or extra doses without advice.

What drug(s) may interact with prednisone?
•acetazolamide
•antiinflammatory drugs (NSAIDs, such as ibuprofen)
•barbiturate medicines for inducing sleep or treating seizures
•bosentan
•calcium supplements
•certain heart medicines
•female hormones, including contraceptives or birth control pills
•live virus vaccines, and other toxoids and vaccines
•medicines for diabetes
•mifepristone
•phenytoin
•rifabutin
•rifampin
•water pills
•warfarin

Tell your prescriber or health care professional about all other medicines you are taking, including non-prescription medicines, nutritional supplements, or herbal products. Also tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs. These may affect the way your medicine works. Check with your health care professional before stopping or starting any of your medicines.

What side effects may I notice from taking prednisone?
Side effects that you should report to your prescriber or health care professional as soon as possible:
•bloody or black, tarry stools
•confusion, excitement, restlessness, a false sense of well-being
•eye pain, decreased or blurred vision, or bulging eyes
•fever, sore throat, sneezing, cough, or other signs of infection, wounds that will not heal
•frequent passing of urine
•increased thirst
•irregular heartbeat
•menstrual problems
•mental depression, mood swings, mistaken feelings of self-importance or of being mistreated
•muscle cramps or weakness
•nausea, vomiting
•pain in hips, back, ribs, arms, shoulders, or legs
•rounding out of face
•skin problems, acne, thin and shiny skin
•stomach pain
•swelling of feet or lower legs
•unusual bruising, pinpoint red spots on the skin
•unusual tiredness or weakness
•weight gain or weight loss

Side effects that usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome):
•diarrhea or constipation
•headache
•increased or decreased appetite
•increased sweating
•nervousness, restlessness, or difficulty sleeping
•upset stomach
•unusual increased growth of hair on the face or body

What should I watch for while taking prednisone?
Visit your prescriber or health care professional for regular checks on your progress. If you are taking prednisone over a prolonged period, carry an identification card with your name and address, the type and dose of your medicine, and your prescriber's name and address. Do not suddenly stop taking prednisone. You may need to gradually reduce the dose, so that your body can adjust. Follow the advice of your prescriber or health care professional.

If you are taking prednisone regularly, avoid contact with people who have an infection. You will have an increased risk from infection while taking prednisone. Tell your prescriber or health care professional if you are exposed to anyone with measles or chickenpox, or if you develop sores or blisters that do not heal properly.

People who are taking certain dosages of prednisone may need to avoid immunization with certain vaccines or may need to have changes in their vaccination schedules to ensure adequate protection from certain diseases. Make sure to tell your prescriber or health care professional that you are taking prednisone before receiving any vaccine.

If you are going to have surgery, tell your prescriber or health care professional that you have received prednisone within the last twelve months.

If you receive prednisone every day, you may need to watch your diet. Your body can lose potassium while you are taking this medicine. Ask your prescriber or health care professional about your diet.

Prednisone can affect your blood sugar. If you are diabetic check with your prescriber or health care professional if you need help adjusting the dose of your diabetic medicine.

Alcohol can increase the risk of getting serious side effects while you are taking prednisone. Avoid alcoholic drinks.

Prednisone can interfere with certain lab tests and can cause false skin test results.

Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.

Store at room temperature between 15 and 30 degrees C (59 and 86 degrees F). Throw away any unused medicine after the expiration date.

NOTE: This information is not intended to cover all possible uses, precautions, interactions, or adverse effects for this drug. If you have questions about the drug(s) you are taking, check with your health care professional.

 [Revised: 11/29/2005]

Famotidine
Heartburn Relief | Mylanta® AR | Pepcid® | Pepcid® AC

Classification:
• Antihistamines
    • H2-blockers
• Gastrointestinal Agents
    • Antiulcer Agents
        • H2-blockers

Description, Mechanism of Action, Pharmacokinetics

Description: Famotidine is an oral and parenteral histamine type 2-receptor antagonist similar to cimetidine and ranitidine. The actions and indications of famotidine differ little from the other agents, except that famotidine is less likely than cimetidine to interact with other drugs. Famotidine is used in the treatment of gastrointestinal disorders such as gastric or duodenal ulcer, gastroesophageal reflux disease, and pathological hypersecretory conditions. It was approved by the FDA in October 1986. In 1994, the manufacturer filed an NDA for a non-prescription form of famotidine and on April 30, 1995, Pepcid® AC (10 mg) became available for OTC use. Maximum Strength Pepcid® AC (20 mg) became available for OTC use in September 2003.

Mechanism of Action: Famotidine competitively inhibits the binding of histamine to H2-receptors on the gastric basolateral membrane of parietal cells, reducing basal and nocturnal gastric acid secretions. The drug also decreases the gastric acid response to stimuli such as food, caffeine, insulin, betazole, or pentagastrin. Famotidine reduces the total volume of gastric juice, thus indirectly decreasing pepsin secretion. The drug does not appear to alter gastric motility, gastric emptying, esophageal pressures, biliary secretions, or pancreatic secretions. Famotidine may aid in gastromucosal healing, and it may protect the mucosa from the irritant effects caused by aspirin and nonsteroidal antiinflammatory agents.

Pharmacokinetics: Famotidine is administered orally and parenterally. Bioavailability of famotidine is approximately 40—45%. Famotidine tablets, oral suspension, and orally disintegrating tablets are bioequivalent. Food may slightly increase and antacids may slightly decrease the bioavailability of famotidine, however, the effects are considered clinically insignificant. The drug distributes widely throughout the body tissues, although only minimally into CSF. Plasma protein binding is approximately 15—20%. The onset of action is usually within 1 hour after oral administration with maximum effects occurring within 1—3 hours depending on the dose. The duration of action is roughly 10—12 hours. There is no cumulative effect with repeat doses; plasma concentrations after multiple doses are similar to those after single doses.

Famotidine undergoes minimal first-pass metabolism. The majority (65—70%) of a famotidine dose is excreted in the urine; 30—35% of the dose is metabolized by the liver. Twenty-five to 30% of an oral dose and 65—70% of an intravenous dose are excreted in urine as unchanged drug. The S-oxide metabolite is the only one identified in humans. Famotidine elimination half-life is 2.5—3.5 hours in adults with normal renal function.

•Special Populations: There is a close relationship between famotidine elimination half-life and creatinine clearance (CrCl). Famotidine elimination half-life increases to roughly 24 hours in anuric patients. Dosage adjustment is recommended based on CrCl (see Dosage). In infants 0—3 months of age, plasma clearance is reduced and elimination half-life is prolonged compared to children and adolescents age 1—15 years. The duration of action of famotidine is also longer in infants less than 1 month of age. Pharmacokinetic parameters for children and adolescents are comparable to those of adults. There are no clinically significant age-related changes in famotidine pharmacokinetics in elderly patients versus younger adults. However, in elderly patients with decreased renal function, the clearance of famotidine may be reduced.

Description, Mechanism of Action, Pharmacokinetics last revised 9/26/2003 3:39:00 PM

Indications

• aspiration prophylaxis†	• multiple endocrine adenoma syndrome
• duodenal ulcer	• NSAID-induced ulcer prophylaxis†
• dyspepsia	• pyrosis (heartburn)
• esophagitis	• stress gastritis prophylaxis†
• gastric ulcer	• systemic mastocytosis
• gastroesophageal reflux disease (GERD)	• Zollinger-Ellison syndrome
• Helicobacter pylori

† non-FDA-approved indication

Dosage

For stress gastritis prophylaxis† in critically-ill patients:
Intermittent intravenous dosage:
Adults: 20 mg IV every 12 hours. This dosage adequately maintains intragastric pH above 4.0.[2674]
Continuous IV infusion dosage:
Adults and adolescents: Give 10 mg as a single IV initially, follow with an infusion of 1.7 mg/hr IV by continuous infusion (i.e., total daily dosage of 40 mg/day). At least one study has verified that this dosage adequately maintains intragastric pH above 4.0.[2674]

For the treatment of peptic ulcer disease (duodenal ulcer or gastric ulcer):
•for treatment of acute duodenal ulcer or gastric ulcer:
Oral dosage:
Adults: 40 mg PO once daily at bedtime. Most duodenal ulcer patients heal within 4 weeks and full-dose therapy is rarely needed for longer than 6—8 weeks.
Adolescents and children: The suggested starting dose is 0.5 mg/kg/day PO at bedtime or 0.25 mg/kg PO twice daily. Individualize treatment duration and dose based on clinical response and/or pH determination (gastric or esophageal) and endoscopy. Doses up to 1 mg/kg/day PO have been used. In one small study, a treatment duration of 8 weeks was effective for the treatment of gastric or duodenal ulcer.[1648] Maximum dosage is 40 mg/day.
Intravenous dosage:
Adults: 20 mg IV every 12 hours.
Children: 1—2 mg/kg/day IV given in 1—2 divided doses has been used. Pharmacokinetic and pharmacodynamic data support an initial dosage of 0.5 mg/kg IV every 8—12 hours.[1649] Maximum dosage is 40 mg/day.
•for maintenance therapy of duodenal ulcer after the initial treatment phase has been completed:
Oral dosage:
Adults: 20 mg PO once daily at bedtime.
Adolescents and children: Maintenance dose and duration of therapy have not been determined in this age group.
•for the active treatment of Helicobacter pylori-positive duodenal ulcer or gastric ulcer in combination with bismuth subsalicylate, metronidazole, and tetracycline (e.g., Helidac® or equivalent dosage of these individual drugs in combination):
NOTE: Famotidine is not effective as a single agent for the eradication of H. pylori. However, 4-drug regimens which include a H2-blocker as an anti-secretory agent are approved regimens, but are associated with lower compliance and efficacy rates than other recommended regimens.[2661] It is not acceptable to subsitute an H2-blocker for a PPI in any current 2- or 3-drug H.pylori treatment regimen.[2661]
Oral dosage:
Adults: 20 mg PO twice daily or 40 mg PO once daily at bedtime with bismuth subsalicylate, metronidazole, and tetracycline (e.g., Helidac®) at their currently recommended dosages for 14 days. Subsequently, famotidine should be continued at this dosage for an additional 2—4 weeks after the discontinuation of the antibiotic therapy to ensure appropriate healing of the active ulcer. This drug combination is expected to result in eradication of H. pylori in 80—90% of patients.
•for the active treatment of Helicobacter pylori-positive duodenal ulcer or gastric ulcer in combination with bismuth subsalicylate, metronidazole, and amoxicillin†:
Oral dosage:
Adults: 20 mg PO twice daily or 40 mg PO once daily at bedtime with bismuth subsalicylate, metronidazole, and amoxicillin† at their currently recommended dosages for 14 days.[2661] Subsequently, famotidine should be continued at this dosage for an additional 2—4 weeks after the discontinuation of the antibiotic therapy to ensure appropriate healing of the active ulcer. This drug combination is expected to result in eradication of H. pylori in 70—80% of patients.

For NSAID-induced ulcer prophylaxis†:
Oral dosage:
Adults: Patients receiving a NSAID for either rheumatoid arthritis or osteoarthritis were given famotidine 20 mg PO twice daily, famotidine 40 mg PO twice daily, or placebo for 24 weeks. The cumulative incidence of gastric ulcer was significantly reduced by famotidine 40 mg but not the lower dose compared to placebo. The cumulative incidence of duodenal ulcer was significantly reduced by both famotidine doses relative to placebo.[1188]

For pathologic GI hypersecretory conditions such as Zollinger-Ellison syndrome, systemic mastocytosis, or multiple endocrine adenoma syndrome:
Oral dosage:
Adults: 20 mg PO every 6 hours, up to a maximum of 160 mg PO every 6 hours per the manufacturer; doses have been reported as high as 200 mg PO every 6 hours.
Intravenous dosage:
Adults: 20 mg IV every 6 hours when oral therapy is not feasible; higher doses may be needed and therapy should be individualized based on patient response.

For the treatment of gastroesophageal reflux disease (GERD) or esophagitis associated with gastroesophageal reflux disease (GERD):
Oral dosage:
Adults: 20 mg PO twice daily for up to 6 weeks. If esophagitis has developed, a dose of 20—40 mg PO twice daily for up to 12 weeks is recommended.
Adolescents and children: The suggested starting dose is 0.5 mg/kg PO twice daily up to 40 mg PO twice daily. Maintenance dose and duration of therapy have not been determined in this age group. Individualize treatment duration and dose based on clinical response and/or pH determination (gastric or esophageal) and endoscopy. Doses up to 2 mg/kg/day PO have been used for GERD with or without esophagitis including erosions and ulcerations.
Infants 3 months to < 1 year: 0.5 mg/kg PO twice daily for up to 8 weeks in addition to conservative measures such as thickened feedings.
Infants < 3 months: 0.5 mg/kg PO once daily of the oral suspension for up to 8 weeks in addition to conservative measures such as thickened feedings.
Intravenous dosage:
Children: Pharmacokinetic and pharmacodynamic data support an initial dosage of 0.5 mg/kg IV every 8—12 hours.[1649]
Infants: Use of IV famotidine in infants for the treatment of GERD has not been adequately studied.

For acid aspiration prophylaxis† prior to anesthesia:
IM dosage:
Adults: 20 mg IM the night before or the morning of surgery, prior to induction of anesthesia.

For the self-medication (OTC products) of pyrosis (heartburn), acid dyspepsia (acid indigestion), or sour stomach:
•for OTC prophylaxis of heartburn, acid dyspepsia (acid indigestion), or sour stomach:
Oral dosage (Pepcid® AC):
Adults and children >= 12 years: 10 mg PO given 15 minutes to 1 hour prior to eating a meal which is expected to cause symptoms. Maximum daily dose is 20 mg/day. Patients should not take the maximum dose for > 2 weeks without consulting their physician.
Children < 12 years: Do not self-medicate. Use only if advised by qualified health care prescriber.
•for self-treatment of heartburn, acid dyspepsia (acid indigestion), or sour stomach:
Oral dosage (Pepcid® AC):
Adults and children >= 12 years: 10 PO given 1—2 times per day. Maximum dose is 20 mg/day. Patients should not take the maximum dose for > 2 weeks without consulting their physician.
Oral dosage (Maximum Strength Pepcid® AC):
Adults and children >= 12 years: 20 mg PO once per day. Maximum dose is 20 mg/day. Patients should not take the maximum dose for > 2 weeks without consulting their physician.
Children < 12 years: Do not self-medicate. Use only if advised by qualified health care prescriber.

Maximum Dosage Limits:
•Adults: 40 mg/day PO or IV for active duodenal or benign gastric ulcer; 20 mg/day PO for ulcer maintenance; 40 mg/day PO for GERD; 80 mg/day PO for esophagitis; doses may go as high as 640 mg/day or 800 mg/day (rare) PO or 80 mg/day IV for hypersecretory conditions such as Zollinger-Ellison; 20 mg/day PO for self-medication (OTC).
•Elderly: 40 mg/day PO or IV for active duodenal or benign gastric ulcer healing; 20 mg/day PO for ulcer maintenance; 40 mg/day PO for GERD; 80 mg/day PO for esophagitis; doses may go as high as 640 mg/day or 800 mg/day (rare) PO or 80 mg/day IV for hypersecretory conditions such as Zollinger-Ellison; 20 mg/day PO for self-medication (OTC).
•Adolescents: 40 mg/day PO or IV for active duodenal or benign gastric ulcer healing; 20 mg/day PO for ulcer maintenance; 40 mg/day PO for GERD; 80 mg/day PO for esophagitis; 20 mg/day PO for self-medication (OTC).
•Children: 2 mg/kg/day PO, usually not to exceed 40 mg/day PO or IV for active duodenal or benign gastric ulcer healing; 40 mg/day PO for GERD; 80 mg/day PO for esophagitis; do not self-medicate (OTC) if < 12 years.
•Infants 3 months to < 1 year: 1 mg/kg/day PO.
•Infants < 3 months: 0.5 mg/kg/day PO.

Patients with hepatic impairment:
No dosage adjustment needed, unless decreased renal elimination is also present.

Patients with renal impairment:
CrCl >= 50 ml/min: no dosage adjustment needed.
CrCl < 50 ml/min: reduce recommended dose by 50% (or extend dosing interval to 36—48 hours according to clinical response and degree of renal impairment).

†non-FDA-approved indication

Indications...Dosage last revised 11/9/2004 10:03:00 AM

Administration Guidelines

Oral Administration
NOTE: Pepcid® Oral Suspension or Pepcid® RPD™ Orally Disintegrating Tablets may be substituted for Pepcid® Tablets in any of the indications below at the same recommended dosages.
•All dosage forms: May be administered without regard to meals. Administer with food, water, or milk to minimize gastric irritation.
•Oral suspension: Reconstitute by slowly adding 46 ml of purified water. Shake vigorously for 5—10 seconds after adding water and again immediately prior to administration. After reconstitution, each 5 ml contains 40 mg of famotidine. Unused constituted oral suspension should be discarded after 30 days. Measure dosage with calibrated device for accuracy.
•Orally disintegrating tablets: No water is needed for administration. Patients should be instructed to open the tablet blister pack with dry hands, place the tablet on the tongue, allow to disintegrate, then swallow with saliva.

Intravenous Administration
•Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Intermittent IV injection:
•Dilute dosage, not to exceed 20 mg, to a total of 5 or 10 ml with NS or other compatible solution to give concentrations of 4 or 2 mg/ml, respectively.
•Inject appropriate dose at a rate no greater than 10 mg/minute.

Intermittent intravenous (IV) infusion:
•Dilute 20 mg of famotidine in 100 ml of D5W or other compatible IV solution to give a concentration of 0.2 mg/ml. The diluted solution is stable for up to 48 hours at room temperature.
•Infuse over 15—30 minutes.

Continuous 24-hour IV infusion:
•For adults, dilute 40 mg of famotidine in 250 ml of D5W or NS or other compatible solution. The diluted solution is stable for up to 48 hours at room temperature. Infuse over 24 hours at a rate of 11 ml/hr or as specified by physician.
•Use a controlled-rate infusion device.
•Alternatively, the dosage may be added to a compatible TPN solution for administration over 24 hours.

Administration last revised 11/5/2004 3:12:00 PM

Contraindications/Precautions

• breast-feeding	• infection
• children	• phenylketonuria
• elderly	• pregnancy
• gastric cancer	• renal disease
• GI bleeding	• renal failure
• H2-blocker hypersensitivity	• renal impairment
• hepatic disease	• tobacco smoking

Famotidine is contraindicated in any patient hypersensitive to the drug or its components. Cross-sensitivity in this class of compounds has been observed, so famotidine should be administered with caution to patients with a history of H2-blocker hypersensitivity. An incidence of cross-reactivity among this class of agents is not currently available.

Symptomatic response to therapy with famotidine does not preclude the presence of gastric cancer. In the patient who is self-medicating with OTC formulations, the continuation of heartburn, acid indigestion, or dyspepsia beyond 2 weeks signals the need to consult a health-care professional for evaluation. Patients using the the OTC famotidine products should seek immediate medical advice if any sign of GI bleeding (e.g., blood in vomit, stools) or difficult or painful swallowing (dysphagia) becomes evident.

Symptomatic response to therapy with famotidine does not preclude the presence of H. pylori infection. Famotidine therapy does not appear to interfere with the sensitivity of gastric urease biopsy or urea breath-tests for the detection of H. pylori in most patients. H2-blockers, as single agents, will not eradicate H. pylori infection, if present.

Famotidine should be used cautiously in patients with hepatic disease, renal impairment or renal failure (renal disease), because the drug can accumulate, causing toxicity. There is a close relationship between elimination half-life and creatinine clearance. Dosages of famotidine should be adjusted in patients with a creatinine clearance of <50 ml/min. No special precautions have been advised for the elderly, but some older patients may exhibit decreased renal function. Dosage adjustments may be necessary in some older individuals based on renal function. If critically ill, the elderly have been noted in some uncontrolled studies to be more likely to exhibit central nervous system (CNS) reactions to the H2-blockers.

Famotidine is secreted into breast milk. Animal studies have documented transient growth depression in immature animals receiving famotidine via breast milk. Famotidine should not be used in women who are breast-feeding.

Famotidine should not be used for self-medication in children younger than 12 years of age unless directed by a clinician.

Famotidine is classified in FDA pregnancy category B. However, self-medication during pregnancy is not recommended. Pregnant patients should see their health care professional for a proper diagnosis and for treatment recommendations.

Tobacco smoking appears to contribute to an increased risk of developing PUD and may also impair ulcer healing or increase the risk of ulcer recurrence.

Pepcid® AC Chewable Tablets contain phenylalanine 1.4 mg/tablet and should be used cautiously in patients with phenylketonuria.

Contraindications last revised 1/25/2005 5:04:00 PM

Drug Interactions

• Bismuth Subsalicylate	• Gefitinib
• Cefditoren	• Itraconazole
• Cefpodoxime	• Ketoconazole
• Cefuroxime	• Metformin
• Delavirdine	• Methylphenidate
• Dexmethylphenidate	• Theophylline, Aminophylline
• Ethanol

Famotidine does not affect the cytochrome hepatic oxidative metabolism pathway in the same manner as cimetidine does and therefore does not interact with drugs that are metabolized via this pathway. Nevertheless, a small study documented a significant decrease in theophylline clearance with a corresponding increase in theophylline half-life after therapy with famotidine.[321]

H2-blockers can affect the pharmacokinetics of some orally-administered cephalosporins. In a pharmacokinetic study, famotidine reduced cefpodoxime AUC by 40% and ranitidine reduced cefpodoxime AUC by 29%.[7798] A similar interaction has been reported between ranitidine and cefuroxime.[7796] The interactions are probably due to increased gastric pH and subsequent pH-induced changes in the oral absorption of these cephalosporins. Clinicians should watch for antibiotic failure in patients receiving cefpodoxime or cefuroxime who are concurrently receiving H2-blockers. Co-administration of a single dose of an intravenous H2-blocker (famotidine) reduced the oral absorption of a single 400 mg dose of cefditoren pivoxil administered after a meal. There was a 27% and 22% decrease in mean Cmax and AUC, respectively.[5253] Although the clinical significance is not known, it is recommended that cefditoren pivoxil not be taken concomitantly with any H2-blockers.

Ketoconazole and itraconazole are weak bases. Both require an acidic environment for oral absorption and therapy with famotidine can reduce the bioavailability of these drugs. The mechanism involves decreased ionization and dissolution of the antifungals. Due to the sustained action of H2-blockers, a clinically-significant drug interaction with these azole antifungals may still occur even if administration times are adjusted. Also, ketoconazole and itraconazole are potent inhibitors of hepatic CYP3A4, and clinicians should be aware that drug interactions may occur after discontinuation of famotidine due to increased ketoconazole or itraconazole serum concentrations. When possible, concurrent use of H2-blockers with either ketoconazole or itraconazole should be avoided.[4699] [4700] Fluconazole absorption is not affected by gastric pH.

Although some studies have suggested that H2-receptor antagonists inhibit gastric alcohol dehydrogenase and thus decrease the first pass metabolism of ethanol [5305], a small study of patients receiving treatment for duodenal ulcer with either famotidine or ranitidine did not demonstrate altered ethanol pharmacokinetics.[135] A meta-analysis evaluating the effects of H2-blockers on blood ethanol concentrations reported that only cimetidine and ranitidine, but not other H2-blockers, caused small elevations in serum ethanol levels. However, it was reported that larger studies were less likely to show an effect and that these elevations were not likely to be clinically relevant.[5305]

H2-blockers appear to increase the systemic absorption of bismuth from bismuth-containing compounds like bismuth subsalicylate.[7825] The clinical significance of this finding is uncertain.

Famotidine may decrease the renal clearance of metformin [7775] secondary to competition for renal tubular transport systems. Such an interaction has been observed when cimetidine was administered with metformin. The decrease in renal excretion led to a 40% increase in metformin AUC. Although interactions with cationic drugs remain theoretical (except for cimetidine), caution is warranted when famotidine and metformin are prescribed concurrently. Famotidine may be less likely to interact with metformin versus cimetidine or ranitidine because of less tubular excretion.

Sucralfate does not appear to reduce the bioavailability of famotidine. Drugs that reduce gastric acidity (e.g. H2-blockers) were formerly thought to decrease the ability of sucralfate to bind to ulcerated tissues in the GI tract; however, in vitro animal studies have not supported this type of an interaction between the H2-antagonists and sucralfate. The concurrent use of H2-blockers does not appear to interfere with the appropriate action of sucralfate.

Drugs that cause a significant sustained elevation in gastric pH (e.g., H2-blockers, gastric acid-pump inhibitors) may reduce plasma concentrations of gefitinib and thus potentially may reduce gefitinib efficacy. Concurrent administration of high doses of ranitidine with sodium bicarbonate to maintain the gastric pH > 5 reduced the mean gefitinib AUC by 44%.[5012]

Coadministration of delavirdine with antacids results in decreased absorption of delavirdine. When given in combination with an antacid (Maalox TC®), the Cmax of delavirdine was decreased by 52% and the delavirdine AUC was decreased by 44%. Administration of delavirdine and antacids should be separated by at least 1 hour. H2-blockers and proton pump inhibitors (PPIs), which increase gastric pH, may also reduce the absorption of delavirdine. However, since these agents affect gastric pH for an extended period, separation of doses may not eliminate the interaction. Chronic use of H2-blockers and proton pump inhibitors (PPIs) with delavirdine is not recommended.[5206]

The effects of gastrointestinal pH alterations on the absorption of methylphenidate extended release capsules (Ritalin® LA) and dexmethylphenidate extended-release tablets (Focalin™ XR) have not been studied. Although the SODAS® system (drug delivery system utilized in Ritalin® LA and Focalin™ XR) is thought to be minimally affected by changes in pH [8068], per the manufacturer, the modified release characteristics of both extended-release formulations are pH-dependent. It is possible that the administration of H2-blockers or other acid suppressants could alter the release of dexmethylphenidate or methylphenidate.[8067] [8069] Patients receiving these extended-release products (Focalin™ XR or Ritalin® LA) with acid suppressants should be monitored for adverse effects and therapeutic efficacy.

Interactions last revised 6/30/2005 4:19:00 PM

Adverse Reactions

• agitation	• dizziness
• alopecia	• hallucinations
• confusion	• headache
• constipation	• insomnia
• delirium	• paranoia
• depression	• pruritus
• diarrhea	• urticaria

Similar to other H2-antagonists, famotidine causes infrequent adverse reactions. In controlled clinical trials, the incidence of adverse reactions in patients who received famotidine 40 mg at bedtime was similar to that in the placebo group. The following reactions have occurred in greater than 1% of patients and may be causally related to the drug: headache (4.7%) and dizziness (1.3%), constipation (1.2%), and diarrhea (1.7%).

Reversible mental status changes, including agitation, confusion, delirium, hallucinations, hostility, paranoia, depression, insomnia, and disorientation have been reported rarely following famotidine therapy. A review of central nervous system reactions to H2-blockers revealed that the incidence varies widely depending on the specific report, and that no single H2-antagonist is more likely to induce CNS reactions than another.[34] Central nervous system reactions are more likely to occur in elderly patients and/or those with renal impairment. In a clinical study of famotidine in 35 infants < 1 year of age with GERD symptoms, agitation was reported in 5 patients that resolved when famotidine was discontinued.

Dermatologic reactions are rarely reported with famotidine therapy and include urticaria, pruritus, and alopecia. Although a causal relationship has not been established, both acne and xerosis have been reported.

Impotence and gynecomastia have been reported rarely during famotidine therapy; however, in controlled clinical trials, the incidences were not greater than those seen with placebo.

A number of other adverse reactions have been reported with famotidine, although a causal relationship has not been established. These reactions include myalgias, tinnitus, dysgeusia, paresthesias, seizure (1 report), flushing, fever, asthenia, palpitations, orbital edema, and conjunctival injection.

Adverse Reactions last revised 8/19/2002 1:41:00 PM

Patient Education

Famotidine oral suspension

What is famotidine oral suspension?
FAMOTIDINE (Pepcid®) is a type of antihistamine that blocks the release of stomach acid. Famotidine is used to treat stomach and intestinal ulcers. It can relieve ulcer pain and discomfort. Famotidine is also used to control acid reflux (heartburn). Generic famotidine oral suspension is not yet available.

What should my health care professional know before I take famotidine?
They need to know if you have any of these conditions:
•an alcohol abuse probem
•kidney disease
•liver disease
•other chronic illness
•an unusual or allergic reaction to famotidine, other medicines, foods, dyes, or preservatives
•pregnant or trying to get pregnant
•breast-feeding

How should I take this medicine?
Take famotidine oral suspension by mouth. Follow the directions on the prescription label. Shake the bottle for 5 to 10 seconds. Use a specially marked spoon or container to measure your medicine. Ask your pharmacist if you do not have one; household spoons are not always accurate. If you only take famotidine once a day, take it at bedtime. Take your doses at regular intervals. Do not take your medicine more often than directed.

Contact your pediatrician or health care professional regarding the use of this medicine in children. Special care may be needed.

What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.

What drug(s) may interact with famotidine?
•cefditoren
•cefpodoxime
•cefuroxime
•delavirdine
•itraconazole
•ketoconazole
•metformin
•theophylline

Tell your prescriber or health care professional about all other medicines you are taking, including non-prescription medicines, nutritional supplements, or herbal products. Also tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs. These may affect the way your medicine works. Check with your health care professional before stopping or starting any of your medicines.

What side effects may I notice from taking famotidine?
Side effects that you should report to your prescriber or health care professional as soon as possible:
Rare or uncommon:
•confusion
•hallucinations
•skin rash, itching

Side effects that usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome):
•agitation, nervousness
•constipation
•diarrhea
•dizziness
•headache
•nausea

What should I watch for while taking famotidine?
Tell your prescriber or health care professional if your condition does not improve or gets worse. Finish the full course of suspension prescribed, even if you feel better.

Do not self-medicate with aspirin, ibuprofen or other antiinflammatory medicines; these can aggravate your condition.

Do not smoke cigarettes or drink alcohol; these increase irritation in your stomach and can lengthen the time it will take for ulcers to heal. Cigarettes and alcohol can also worsen acid reflux or heartburn.

If you need to take an antacid you should take it at least 1 hour before or 1 hour after famotidine. Famotidine will not be as effective if taken at the same time as an antacid.

If you get black, tarry stools or vomit up what looks like coffee grounds, call your prescriber or health care professional at once. You may have a bleeding ulcer.

Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.

Store at room temperatures below 30 degrees C (86 degrees F) after the suspension is prepared; do not freeze. Throw away any unused suspension after thirty days.

NOTE: This information is not intended to cover all possible uses, precautions, interactions, or adverse effects for this drug. If you have questions about the drug(s) you are taking, check with your health care professional.

 [Revised: 01/30/2002]

Famotidine tablets or gelcaps

What are famotidine tablets or gelcaps?
FAMOTIDINE (Mylanta-AR®, Fluxid® Orally Disintegrating Tablets, Pepcid®, Pepcid® AC Gelcaps, Tablets or Chewable Tablets, Pepcid® RPD™ Orally Disintegrating Tablets) is a type of antihistamine that blocks the release of stomach acid. Famotidine is used to treat stomach and intestinal ulcers. It can relieve ulcer pain and discomfort. Famotidine is also used to control acid reflux (heartburn). Generic famotidine tablets are available; generic gelcaps are not available.

What should my health care professional know before I take famotidine?
They need to know if you have any of these conditions:
•an alcohol abuse problem
•bleeding, such as in your stool or any vomiting with blood
•kidney disease
•liver disease
•other chronic illness
•phenylketonuria
•trouble swallowing
•an unusual or allergic reaction to famotidine, other medicines, foods, dyes, or preservatives
•pregnant or trying to get pregnant
•breast-feeding

How should I take this medicine?
Take famotidine tablets or gelcaps by mouth. Follow the directions on the prescription label. Swallow the tablets or gelcaps with a drink of water. If you only take famotidine once a day, take it at bedtime. Take your doses at regular intervals. Do not take your medicine more often than directed.

If you are taking Fluxid® or Pepcid® orally disintegrating tablets: Place the tablet on your tongue, allow to dissolve completely and then swallow. You can take the orally disintegrating tablets with or without water.

Contact your pediatrician or health care professional regarding the use of this medicine in children. Special care may be needed.

What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.

What drug(s) may interact with famotidine?
•cefditoren
•cefpodoxime
•cefuroxime
•delavirdine
•itraconazole
•ketoconazole
•metformin
•theophylline

Tell your prescriber or health care professional about all other medicines you are taking, including non-prescription medicines, nutritional supplements, or herbal products. Also tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs. These may affect the way your medicine works. Check with your health care professional before stopping or starting any of your medicines.

What side effects may I notice from taking famotidine?
Side effects that you should report to your prescriber or health care professional as soon as possible:
Rare or uncommon:
•confusion
•hallucinations
•skin rash, itching

Side effects that usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome):
•agitation, nervousness
•constipation
•diarrhea
•dizziness
•headache
•nausea

What should I watch for while taking famotidine?
Tell your prescriber or health care professional if your condition does not improve or gets worse. Finish the full course of tablets prescribed, even if you feel better.

Do not self-medicate with aspirin, ibuprofen or other antiinflammatory medicines; these can aggravate your condition.

Do not smoke cigarettes or drink alcohol; these increase irritation in your stomach and can lengthen the time it will take for ulcers to heal. Cigarettes and alcohol can also worsen acid reflux or heartburn.

If you need to take an antacid, you should take it at least 1 hour before or 1 hour after famotidine. Famotidine will not be as effective if taken at the same time as an antacid.

If you get black, tarry stools or vomit up what looks like coffee grounds, call your prescriber or health care professional at once. You may have a bleeding ulcer.

If you have phenylketonuria you should not use Pepcid® AC chewable tablets as they contain 1.4 mg of phenylalanine per tablet.

Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.

Store at room temperatures below 40 degrees C (104 degrees F). Throw away any unused medicine after the expiration date.

NOTE: This information is not intended to cover all possible uses, precautions, interactions, or adverse effects for this drug. If you have questions about the drug(s) you are taking, check with your health care professional.

 [Revised: 11/09/2004]

Famotidine
Heartburn Relief | Mylanta® AR | Pepcid® | Pepcid® AC

Classification:
• Antihistamines
    • H2-blockers
• Gastrointestinal Agents
    • Antiulcer Agents
        • H2-blockers

Description, Mechanism of Action, Pharmacokinetics

Description: Famotidine is an oral and parenteral histamine type 2-receptor antagonist similar to cimetidine and ranitidine. The actions and indications of famotidine differ little from the other agents, except that famotidine is less likely than cimetidine to interact with other drugs. Famotidine is used in the treatment of gastrointestinal disorders such as gastric or duodenal ulcer, gastroesophageal reflux disease, and pathological hypersecretory conditions. It was approved by the FDA in October 1986. In 1994, the manufacturer filed an NDA for a non-prescription form of famotidine and on April 30, 1995, Pepcid® AC (10 mg) became available for OTC use. Maximum Strength Pepcid® AC (20 mg) became available for OTC use in September 2003.

Mechanism of Action: Famotidine competitively inhibits the binding of histamine to H2-receptors on the gastric basolateral membrane of parietal cells, reducing basal and nocturnal gastric acid secretions. The drug also decreases the gastric acid response to stimuli such as food, caffeine, insulin, betazole, or pentagastrin. Famotidine reduces the total volume of gastric juice, thus indirectly decreasing pepsin secretion. The drug does not appear to alter gastric motility, gastric emptying, esophageal pressures, biliary secretions, or pancreatic secretions. Famotidine may aid in gastromucosal healing, and it may protect the mucosa from the irritant effects caused by aspirin and nonsteroidal antiinflammatory agents.

Pharmacokinetics: Famotidine is administered orally and parenterally. Bioavailability of famotidine is approximately 40—45%. Famotidine tablets, oral suspension, and orally disintegrating tablets are bioequivalent. Food may slightly increase and antacids may slightly decrease the bioavailability of famotidine, however, the effects are considered clinically insignificant. The drug distributes widely throughout the body tissues, although only minimally into CSF. Plasma protein binding is approximately 15—20%. The onset of action is usually within 1 hour after oral administration with maximum effects occurring within 1—3 hours depending on the dose. The duration of action is roughly 10—12 hours. There is no cumulative effect with repeat doses; plasma concentrations after multiple doses are similar to those after single doses.

Famotidine undergoes minimal first-pass metabolism. The majority (65—70%) of a famotidine dose is excreted in the urine; 30—35% of the dose is metabolized by the liver. Twenty-five to 30% of an oral dose and 65—70% of an intravenous dose are excreted in urine as unchanged drug. The S-oxide metabolite is the only one identified in humans. Famotidine elimination half-life is 2.5—3.5 hours in adults with normal renal function.

•Special Populations: There is a close relationship between famotidine elimination half-life and creatinine clearance (CrCl). Famotidine elimination half-life increases to roughly 24 hours in anuric patients. Dosage adjustment is recommended based on CrCl (see Dosage). In infants 0—3 months of age, plasma clearance is reduced and elimination half-life is prolonged compared to children and adolescents age 1—15 years. The duration of action of famotidine is also longer in infants less than 1 month of age. Pharmacokinetic parameters for children and adolescents are comparable to those of adults. There are no clinically significant age-related changes in famotidine pharmacokinetics in elderly patients versus younger adults. However, in elderly patients with decreased renal function, the clearance of famotidine may be reduced.

Description, Mechanism of Action, Pharmacokinetics last revised 9/26/2003 3:39:00 PM

Indications

• aspiration prophylaxis†	• multiple endocrine adenoma syndrome
• duodenal ulcer	• NSAID-induced ulcer prophylaxis†
• dyspepsia	• pyrosis (heartburn)
• esophagitis	• stress gastritis prophylaxis†
• gastric ulcer	• systemic mastocytosis
• gastroesophageal reflux disease (GERD)	• Zollinger-Ellison syndrome
• Helicobacter pylori

† non-FDA-approved indication

Dosage

For stress gastritis prophylaxis† in critically-ill patients:
Intermittent intravenous dosage:
Adults: 20 mg IV every 12 hours. This dosage adequately maintains intragastric pH above 4.0.[2674]
Continuous IV infusion dosage:
Adults and adolescents: Give 10 mg as a single IV initially, follow with an infusion of 1.7 mg/hr IV by continuous infusion (i.e., total daily dosage of 40 mg/day). At least one study has verified that this dosage adequately maintains intragastric pH above 4.0.[2674]

For the treatment of peptic ulcer disease (duodenal ulcer or gastric ulcer):
•for treatment of acute duodenal ulcer or gastric ulcer:
Oral dosage:
Adults: 40 mg PO once daily at bedtime. Most duodenal ulcer patients heal within 4 weeks and full-dose therapy is rarely needed for longer than 6—8 weeks.
Adolescents and children: The suggested starting dose is 0.5 mg/kg/day PO at bedtime or 0.25 mg/kg PO twice daily. Individualize treatment duration and dose based on clinical response and/or pH determination (gastric or esophageal) and endoscopy. Doses up to 1 mg/kg/day PO have been used. In one small study, a treatment duration of 8 weeks was effective for the treatment of gastric or duodenal ulcer.[1648] Maximum dosage is 40 mg/day.
Intravenous dosage:
Adults: 20 mg IV every 12 hours.
Children: 1—2 mg/kg/day IV given in 1—2 divided doses has been used. Pharmacokinetic and pharmacodynamic data support an initial dosage of 0.5 mg/kg IV every 8—12 hours.[1649] Maximum dosage is 40 mg/day.
•for maintenance therapy of duodenal ulcer after the initial treatment phase has been completed:
Oral dosage:
Adults: 20 mg PO once daily at bedtime.
Adolescents and children: Maintenance dose and duration of therapy have not been determined in this age group.
•for the active treatment of Helicobacter pylori-positive duodenal ulcer or gastric ulcer in combination with bismuth subsalicylate, metronidazole, and tetracycline (e.g., Helidac® or equivalent dosage of these individual drugs in combination):
NOTE: Famotidine is not effective as a single agent for the eradication of H. pylori. However, 4-drug regimens which include a H2-blocker as an anti-secretory agent are approved regimens, but are associated with lower compliance and efficacy rates than other recommended regimens.[2661] It is not acceptable to subsitute an H2-blocker for a PPI in any current 2- or 3-drug H.pylori treatment regimen.[2661]
Oral dosage:
Adults: 20 mg PO twice daily or 40 mg PO once daily at bedtime with bismuth subsalicylate, metronidazole, and tetracycline (e.g., Helidac®) at their currently recommended dosages for 14 days. Subsequently, famotidine should be continued at this dosage for an additional 2—4 weeks after the discontinuation of the antibiotic therapy to ensure appropriate healing of the active ulcer. This drug combination is expected to result in eradication of H. pylori in 80—90% of patients.
•for the active treatment of Helicobacter pylori-positive duodenal ulcer or gastric ulcer in combination with bismuth subsalicylate, metronidazole, and amoxicillin†:
Oral dosage:
Adults: 20 mg PO twice daily or 40 mg PO once daily at bedtime with bismuth subsalicylate, metronidazole, and amoxicillin† at their currently recommended dosages for 14 days.[2661] Subsequently, famotidine should be continued at this dosage for an additional 2—4 weeks after the discontinuation of the antibiotic therapy to ensure appropriate healing of the active ulcer. This drug combination is expected to result in eradication of H. pylori in 70—80% of patients.

For NSAID-induced ulcer prophylaxis†:
Oral dosage:
Adults: Patients receiving a NSAID for either rheumatoid arthritis or osteoarthritis were given famotidine 20 mg PO twice daily, famotidine 40 mg PO twice daily, or placebo for 24 weeks. The cumulative incidence of gastric ulcer was significantly reduced by famotidine 40 mg but not the lower dose compared to placebo. The cumulative incidence of duodenal ulcer was significantly reduced by both famotidine doses relative to placebo.[1188]

For pathologic GI hypersecretory conditions such as Zollinger-Ellison syndrome, systemic mastocytosis, or multiple endocrine adenoma syndrome:
Oral dosage:
Adults: 20 mg PO every 6 hours, up to a maximum of 160 mg PO every 6 hours per the manufacturer; doses have been reported as high as 200 mg PO every 6 hours.
Intravenous dosage:
Adults: 20 mg IV every 6 hours when oral therapy is not feasible; higher doses may be needed and therapy should be individualized based on patient response.

For the treatment of gastroesophageal reflux disease (GERD) or esophagitis associated with gastroesophageal reflux disease (GERD):
Oral dosage:
Adults: 20 mg PO twice daily for up to 6 weeks. If esophagitis has developed, a dose of 20—40 mg PO twice daily for up to 12 weeks is recommended.
Adolescents and children: The suggested starting dose is 0.5 mg/kg PO twice daily up to 40 mg PO twice daily. Maintenance dose and duration of therapy have not been determined in this age group. Individualize treatment duration and dose based on clinical response and/or pH determination (gastric or esophageal) and endoscopy. Doses up to 2 mg/kg/day PO have been used for GERD with or without esophagitis including erosions and ulcerations.
Infants 3 months to < 1 year: 0.5 mg/kg PO twice daily for up to 8 weeks in addition to conservative measures such as thickened feedings.
Infants < 3 months: 0.5 mg/kg PO once daily of the oral suspension for up to 8 weeks in addition to conservative measures such as thickened feedings.
Intravenous dosage:
Children: Pharmacokinetic and pharmacodynamic data support an initial dosage of 0.5 mg/kg IV every 8—12 hours.[1649]
Infants: Use of IV famotidine in infants for the treatment of GERD has not been adequately studied.

For acid aspiration prophylaxis† prior to anesthesia:
IM dosage:
Adults: 20 mg IM the night before or the morning of surgery, prior to induction of anesthesia.

For the self-medication (OTC products) of pyrosis (heartburn), acid dyspepsia (acid indigestion), or sour stomach:
•for OTC prophylaxis of heartburn, acid dyspepsia (acid indigestion), or sour stomach:
Oral dosage (Pepcid® AC):
Adults and children >= 12 years: 10 mg PO given 15 minutes to 1 hour prior to eating a meal which is expected to cause symptoms. Maximum daily dose is 20 mg/day. Patients should not take the maximum dose for > 2 weeks without consulting their physician.
Children < 12 years: Do not self-medicate. Use only if advised by qualified health care prescriber.
•for self-treatment of heartburn, acid dyspepsia (acid indigestion), or sour stomach:
Oral dosage (Pepcid® AC):
Adults and children >= 12 years: 10 PO given 1—2 times per day. Maximum dose is 20 mg/day. Patients should not take the maximum dose for > 2 weeks without consulting their physician.
Oral dosage (Maximum Strength Pepcid® AC):
Adults and children >= 12 years: 20 mg PO once per day. Maximum dose is 20 mg/day. Patients should not take the maximum dose for > 2 weeks without consulting their physician.
Children < 12 years: Do not self-medicate. Use only if advised by qualified health care prescriber.

Maximum Dosage Limits:
•Adults: 40 mg/day PO or IV for active duodenal or benign gastric ulcer; 20 mg/day PO for ulcer maintenance; 40 mg/day PO for GERD; 80 mg/day PO for esophagitis; doses may go as high as 640 mg/day or 800 mg/day (rare) PO or 80 mg/day IV for hypersecretory conditions such as Zollinger-Ellison; 20 mg/day PO for self-medication (OTC).
•Elderly: 40 mg/day PO or IV for active duodenal or benign gastric ulcer healing; 20 mg/day PO for ulcer maintenance; 40 mg/day PO for GERD; 80 mg/day PO for esophagitis; doses may go as high as 640 mg/day or 800 mg/day (rare) PO or 80 mg/day IV for hypersecretory conditions such as Zollinger-Ellison; 20 mg/day PO for self-medication (OTC).
•Adolescents: 40 mg/day PO or IV for active duodenal or benign gastric ulcer healing; 20 mg/day PO for ulcer maintenance; 40 mg/day PO for GERD; 80 mg/day PO for esophagitis; 20 mg/day PO for self-medication (OTC).
•Children: 2 mg/kg/day PO, usually not to exceed 40 mg/day PO or IV for active duodenal or benign gastric ulcer healing; 40 mg/day PO for GERD; 80 mg/day PO for esophagitis; do not self-medicate (OTC) if < 12 years.
•Infants 3 months to < 1 year: 1 mg/kg/day PO.
•Infants < 3 months: 0.5 mg/kg/day PO.

Patients with hepatic impairment:
No dosage adjustment needed, unless decreased renal elimination is also present.

Patients with renal impairment:
CrCl >= 50 ml/min: no dosage adjustment needed.
CrCl < 50 ml/min: reduce recommended dose by 50% (or extend dosing interval to 36—48 hours according to clinical response and degree of renal impairment).

†non-FDA-approved indication

Indications...Dosage last revised 11/9/2004 10:03:00 AM

Administration Guidelines

Oral Administration
NOTE: Pepcid® Oral Suspension or Pepcid® RPD™ Orally Disintegrating Tablets may be substituted for Pepcid® Tablets in any of the indications below at the same recommended dosages.
•All dosage forms: May be administered without regard to meals. Administer with food, water, or milk to minimize gastric irritation.
•Oral suspension: Reconstitute by slowly adding 46 ml of purified water. Shake vigorously for 5—10 seconds after adding water and again immediately prior to administration. After reconstitution, each 5 ml contains 40 mg of famotidine. Unused constituted oral suspension should be discarded after 30 days. Measure dosage with calibrated device for accuracy.
•Orally disintegrating tablets: No water is needed for administration. Patients should be instructed to open the tablet blister pack with dry hands, place the tablet on the tongue, allow to disintegrate, then swallow with saliva.

Intravenous Administration
•Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Intermittent IV injection:
•Dilute dosage, not to exceed 20 mg, to a total of 5 or 10 ml with NS or other compatible solution to give concentrations of 4 or 2 mg/ml, respectively.
•Inject appropriate dose at a rate no greater than 10 mg/minute.

Intermittent intravenous (IV) infusion:
•Dilute 20 mg of famotidine in 100 ml of D5W or other compatible IV solution to give a concentration of 0.2 mg/ml. The diluted solution is stable for up to 48 hours at room temperature.
•Infuse over 15—30 minutes.

Continuous 24-hour IV infusion:
•For adults, dilute 40 mg of famotidine in 250 ml of D5W or NS or other compatible solution. The diluted solution is stable for up to 48 hours at room temperature. Infuse over 24 hours at a rate of 11 ml/hr or as specified by physician.
•Use a controlled-rate infusion device.
•Alternatively, the dosage may be added to a compatible TPN solution for administration over 24 hours.

Administration last revised 11/5/2004 3:12:00 PM

Contraindications/Precautions

• breast-feeding	• infection
• children	• phenylketonuria
• elderly	• pregnancy
• gastric cancer	• renal disease
• GI bleeding	• renal failure
• H2-blocker hypersensitivity	• renal impairment
• hepatic disease	• tobacco smoking

Famotidine is contraindicated in any patient hypersensitive to the drug or its components. Cross-sensitivity in this class of compounds has been observed, so famotidine should be administered with caution to patients with a history of H2-blocker hypersensitivity. An incidence of cross-reactivity among this class of agents is not currently available.

Symptomatic response to therapy with famotidine does not preclude the presence of gastric cancer. In the patient who is self-medicating with OTC formulations, the continuation of heartburn, acid indigestion, or dyspepsia beyond 2 weeks signals the need to consult a health-care professional for evaluation. Patients using the the OTC famotidine products should seek immediate medical advice if any sign of GI bleeding (e.g., blood in vomit, stools) or difficult or painful swallowing (dysphagia) becomes evident.

Symptomatic response to therapy with famotidine does not preclude the presence of H. pylori infection. Famotidine therapy does not appear to interfere with the sensitivity of gastric urease biopsy or urea breath-tests for the detection of H. pylori in most patients. H2-blockers, as single agents, will not eradicate H. pylori infection, if present.

Famotidine should be used cautiously in patients with hepatic disease, renal impairment or renal failure (renal disease), because the drug can accumulate, causing toxicity. There is a close relationship between elimination half-life and creatinine clearance. Dosages of famotidine should be adjusted in patients with a creatinine clearance of <50 ml/min. No special precautions have been advised for the elderly, but some older patients may exhibit decreased renal function. Dosage adjustments may be necessary in some older individuals based on renal function. If critically ill, the elderly have been noted in some uncontrolled studies to be more likely to exhibit central nervous system (CNS) reactions to the H2-blockers.

Famotidine is secreted into breast milk. Animal studies have documented transient growth depression in immature animals receiving famotidine via breast milk. Famotidine should not be used in women who are breast-feeding.

Famotidine should not be used for self-medication in children younger than 12 years of age unless directed by a clinician.

Famotidine is classified in FDA pregnancy category B. However, self-medication during pregnancy is not recommended. Pregnant patients should see their health care professional for a proper diagnosis and for treatment recommendations.

Tobacco smoking appears to contribute to an increased risk of developing PUD and may also impair ulcer healing or increase the risk of ulcer recurrence.

Pepcid® AC Chewable Tablets contain phenylalanine 1.4 mg/tablet and should be used cautiously in patients with phenylketonuria.

Contraindications last revised 1/25/2005 5:04:00 PM

Drug Interactions

• Bismuth Subsalicylate	• Gefitinib
• Cefditoren	• Itraconazole
• Cefpodoxime	• Ketoconazole
• Cefuroxime	• Metformin
• Delavirdine	• Methylphenidate
• Dexmethylphenidate	• Theophylline, Aminophylline
• Ethanol

Famotidine does not affect the cytochrome hepatic oxidative metabolism pathway in the same manner as cimetidine does and therefore does not interact with drugs that are metabolized via this pathway. Nevertheless, a small study documented a significant decrease in theophylline clearance with a corresponding increase in theophylline half-life after therapy with famotidine.[321]

H2-blockers can affect the pharmacokinetics of some orally-administered cephalosporins. In a pharmacokinetic study, famotidine reduced cefpodoxime AUC by 40% and ranitidine reduced cefpodoxime AUC by 29%.[7798] A similar interaction has been reported between ranitidine and cefuroxime.[7796] The interactions are probably due to increased gastric pH and subsequent pH-induced changes in the oral absorption of these cephalosporins. Clinicians should watch for antibiotic failure in patients receiving cefpodoxime or cefuroxime who are concurrently receiving H2-blockers. Co-administration of a single dose of an intravenous H2-blocker (famotidine) reduced the oral absorption of a single 400 mg dose of cefditoren pivoxil administered after a meal. There was a 27% and 22% decrease in mean Cmax and AUC, respectively.[5253] Although the clinical significance is not known, it is recommended that cefditoren pivoxil not be taken concomitantly with any H2-blockers.

Ketoconazole and itraconazole are weak bases. Both require an acidic environment for oral absorption and therapy with famotidine can reduce the bioavailability of these drugs. The mechanism involves decreased ionization and dissolution of the antifungals. Due to the sustained action of H2-blockers, a clinically-significant drug interaction with these azole antifungals may still occur even if administration times are adjusted. Also, ketoconazole and itraconazole are potent inhibitors of hepatic CYP3A4, and clinicians should be aware that drug interactions may occur after discontinuation of famotidine due to increased ketoconazole or itraconazole serum concentrations. When possible, concurrent use of H2-blockers with either ketoconazole or itraconazole should be avoided.[4699] [4700] Fluconazole absorption is not affected by gastric pH.

Although some studies have suggested that H2-receptor antagonists inhibit gastric alcohol dehydrogenase and thus decrease the first pass metabolism of ethanol [5305], a small study of patients receiving treatment for duodenal ulcer with either famotidine or ranitidine did not demonstrate altered ethanol pharmacokinetics.[135] A meta-analysis evaluating the effects of H2-blockers on blood ethanol concentrations reported that only cimetidine and ranitidine, but not other H2-blockers, caused small elevations in serum ethanol levels. However, it was reported that larger studies were less likely to show an effect and that these elevations were not likely to be clinically relevant.[5305]

H2-blockers appear to increase the systemic absorption of bismuth from bismuth-containing compounds like bismuth subsalicylate.[7825] The clinical significance of this finding is uncertain.

Famotidine may decrease the renal clearance of metformin [7775] secondary to competition for renal tubular transport systems. Such an interaction has been observed when cimetidine was administered with metformin. The decrease in renal excretion led to a 40% increase in metformin AUC. Although interactions with cationic drugs remain theoretical (except for cimetidine), caution is warranted when famotidine and metformin are prescribed concurrently. Famotidine may be less likely to interact with metformin versus cimetidine or ranitidine because of less tubular excretion.

Sucralfate does not appear to reduce the bioavailability of famotidine. Drugs that reduce gastric acidity (e.g. H2-blockers) were formerly thought to decrease the ability of sucralfate to bind to ulcerated tissues in the GI tract; however, in vitro animal studies have not supported this type of an interaction between the H2-antagonists and sucralfate. The concurrent use of H2-blockers does not appear to interfere with the appropriate action of sucralfate.

Drugs that cause a significant sustained elevation in gastric pH (e.g., H2-blockers, gastric acid-pump inhibitors) may reduce plasma concentrations of gefitinib and thus potentially may reduce gefitinib efficacy. Concurrent administration of high doses of ranitidine with sodium bicarbonate to maintain the gastric pH > 5 reduced the mean gefitinib AUC by 44%.[5012]

Coadministration of delavirdine with antacids results in decreased absorption of delavirdine. When given in combination with an antacid (Maalox TC®), the Cmax of delavirdine was decreased by 52% and the delavirdine AUC was decreased by 44%. Administration of delavirdine and antacids should be separated by at least 1 hour. H2-blockers and proton pump inhibitors (PPIs), which increase gastric pH, may also reduce the absorption of delavirdine. However, since these agents affect gastric pH for an extended period, separation of doses may not eliminate the interaction. Chronic use of H2-blockers and proton pump inhibitors (PPIs) with delavirdine is not recommended.[5206]

The effects of gastrointestinal pH alterations on the absorption of methylphenidate extended release capsules (Ritalin® LA) and dexmethylphenidate extended-release tablets (Focalin™ XR) have not been studied. Although the SODAS® system (drug delivery system utilized in Ritalin® LA and Focalin™ XR) is thought to be minimally affected by changes in pH [8068], per the manufacturer, the modified release characteristics of both extended-release formulations are pH-dependent. It is possible that the administration of H2-blockers or other acid suppressants could alter the release of dexmethylphenidate or methylphenidate.[8067] [8069] Patients receiving these extended-release products (Focalin™ XR or Ritalin® LA) with acid suppressants should be monitored for adverse effects and therapeutic efficacy.

Interactions last revised 6/30/2005 4:19:00 PM

Adverse Reactions

• agitation	• dizziness
• alopecia	• hallucinations
• confusion	• headache
• constipation	• insomnia
• delirium	• paranoia
• depression	• pruritus
• diarrhea	• urticaria

Similar to other H2-antagonists, famotidine causes infrequent adverse reactions. In controlled clinical trials, the incidence of adverse reactions in patients who received famotidine 40 mg at bedtime was similar to that in the placebo group. The following reactions have occurred in greater than 1% of patients and may be causally related to the drug: headache (4.7%) and dizziness (1.3%), constipation (1.2%), and diarrhea (1.7%).

Reversible mental status changes, including agitation, confusion, delirium, hallucinations, hostility, paranoia, depression, insomnia, and disorientation have been reported rarely following famotidine therapy. A review of central nervous system reactions to H2-blockers revealed that the incidence varies widely depending on the specific report, and that no single H2-antagonist is more likely to induce CNS reactions than another.[34] Central nervous system reactions are more likely to occur in elderly patients and/or those with renal impairment. In a clinical study of famotidine in 35 infants < 1 year of age with GERD symptoms, agitation was reported in 5 patients that resolved when famotidine was discontinued.

Dermatologic reactions are rarely reported with famotidine therapy and include urticaria, pruritus, and alopecia. Although a causal relationship has not been established, both acne and xerosis have been reported.

Impotence and gynecomastia have been reported rarely during famotidine therapy; however, in controlled clinical trials, the incidences were not greater than those seen with placebo.

A number of other adverse reactions have been reported with famotidine, although a causal relationship has not been established. These reactions include myalgias, tinnitus, dysgeusia, paresthesias, seizure (1 report), flushing, fever, asthenia, palpitations, orbital edema, and conjunctival injection.

Adverse Reactions last revised 8/19/2002 1:41:00 PM

Patient Education

Famotidine oral suspension

What is famotidine oral suspension?
FAMOTIDINE (Pepcid®) is a type of antihistamine that blocks the release of stomach acid. Famotidine is used to treat stomach and intestinal ulcers. It can relieve ulcer pain and discomfort. Famotidine is also used to control acid reflux (heartburn). Generic famotidine oral suspension is not yet available.

What should my health care professional know before I take famotidine?
They need to know if you have any of these conditions:
•an alcohol abuse probem
•kidney disease
•liver disease
•other chronic illness
•an unusual or allergic reaction to famotidine, other medicines, foods, dyes, or preservatives
•pregnant or trying to get pregnant
•breast-feeding

How should I take this medicine?
Take famotidine oral suspension by mouth. Follow the directions on the prescription label. Shake the bottle for 5 to 10 seconds. Use a specially marked spoon or container to measure your medicine. Ask your pharmacist if you do not have one; household spoons are not always accurate. If you only take famotidine once a day, take it at bedtime. Take your doses at regular intervals. Do not take your medicine more often than directed.

Contact your pediatrician or health care professional regarding the use of this medicine in children. Special care may be needed.

What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.

What drug(s) may interact with famotidine?
•cefditoren
•cefpodoxime
•cefuroxime
•delavirdine
•itraconazole
•ketoconazole
•metformin
•theophylline

Tell your prescriber or health care professional about all other medicines you are taking, including non-prescription medicines, nutritional supplements, or herbal products. Also tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs. These may affect the way your medicine works. Check with your health care professional before stopping or starting any of your medicines.

What side effects may I notice from taking famotidine?
Side effects that you should report to your prescriber or health care professional as soon as possible:
Rare or uncommon:
•confusion
•hallucinations
•skin rash, itching

Side effects that usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome):
•agitation, nervousness
•constipation
•diarrhea
•dizziness
•headache
•nausea

What should I watch for while taking famotidine?
Tell your prescriber or health care professional if your condition does not improve or gets worse. Finish the full course of suspension prescribed, even if you feel better.

Do not self-medicate with aspirin, ibuprofen or other antiinflammatory medicines; these can aggravate your condition.

Do not smoke cigarettes or drink alcohol; these increase irritation in your stomach and can lengthen the time it will take for ulcers to heal. Cigarettes and alcohol can also worsen acid reflux or heartburn.

If you need to take an antacid you should take it at least 1 hour before or 1 hour after famotidine. Famotidine will not be as effective if taken at the same time as an antacid.

If you get black, tarry stools or vomit up what looks like coffee grounds, call your prescriber or health care professional at once. You may have a bleeding ulcer.

Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.

Store at room temperatures below 30 degrees C (86 degrees F) after the suspension is prepared; do not freeze. Throw away any unused suspension after thirty days.

NOTE: This information is not intended to cover all possible uses, precautions, interactions, or adverse effects for this drug. If you have questions about the drug(s) you are taking, check with your health care professional.

 [Revised: 01/30/2002]

Famotidine tablets or gelcaps

What are famotidine tablets or gelcaps?
FAMOTIDINE (Mylanta-AR®, Fluxid® Orally Disintegrating Tablets, Pepcid®, Pepcid® AC Gelcaps, Tablets or Chewable Tablets, Pepcid® RPD™ Orally Disintegrating Tablets) is a type of antihistamine that blocks the release of stomach acid. Famotidine is used to treat stomach and intestinal ulcers. It can relieve ulcer pain and discomfort. Famotidine is also used to control acid reflux (heartburn). Generic famotidine tablets are available; generic gelcaps are not available.

What should my health care professional know before I take famotidine?
They need to know if you have any of these conditions:
•an alcohol abuse problem
•bleeding, such as in your stool or any vomiting with blood
•kidney disease
•liver disease
•other chronic illness
•phenylketonuria
•trouble swallowing
•an unusual or allergic reaction to famotidine, other medicines, foods, dyes, or preservatives
•pregnant or trying to get pregnant
•breast-feeding

How should I take this medicine?
Take famotidine tablets or gelcaps by mouth. Follow the directions on the prescription label. Swallow the tablets or gelcaps with a drink of water. If you only take famotidine once a day, take it at bedtime. Take your doses at regular intervals. Do not take your medicine more often than directed.

If you are taking Fluxid® or Pepcid® orally disintegrating tablets: Place the tablet on your tongue, allow to dissolve completely and then swallow. You can take the orally disintegrating tablets with or without water.

Contact your pediatrician or health care professional regarding the use of this medicine in children. Special care may be needed.

What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.

What drug(s) may interact with famotidine?
•cefditoren
•cefpodoxime
•cefuroxime
•delavirdine
•itraconazole
•ketoconazole
•metformin
•theophylline

Tell your prescriber or health care professional about all other medicines you are taking, including non-prescription medicines, nutritional supplements, or herbal products. Also tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs. These may affect the way your medicine works. Check with your health care professional before stopping or starting any of your medicines.

What side effects may I notice from taking famotidine?
Side effects that you should report to your prescriber or health care professional as soon as possible:
Rare or uncommon:
•confusion
•hallucinations
•skin rash, itching

Side effects that usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome):
•agitation, nervousness
•constipation
•diarrhea
•dizziness
•headache
•nausea

What should I watch for while taking famotidine?
Tell your prescriber or health care professional if your condition does not improve or gets worse. Finish the full course of tablets prescribed, even if you feel better.

Do not self-medicate with aspirin, ibuprofen or other antiinflammatory medicines; these can aggravate your condition.

Do not smoke cigarettes or drink alcohol; these increase irritation in your stomach and can lengthen the time it will take for ulcers to heal. Cigarettes and alcohol can also worsen acid reflux or heartburn.

If you need to take an antacid, you should take it at least 1 hour before or 1 hour after famotidine. Famotidine will not be as effective if taken at the same time as an antacid.

If you get black, tarry stools or vomit up what looks like coffee grounds, call your prescriber or health care professional at once. You may have a bleeding ulcer.

If you have phenylketonuria you should not use Pepcid® AC chewable tablets as they contain 1.4 mg of phenylalanine per tablet.

Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.

Store at room temperatures below 40 degrees C (104 degrees F). Throw away any unused medicine after the expiration date.

NOTE: This information is not intended to cover all possible uses, precautions, interactions, or adverse effects for this drug. If you have questions about the drug(s) you are taking, check with your health care professional.

 [Revised: 11/09/2004]

Prednisone
Deltasone® | Predone™ | Sterapred® | Sterapred® DS

Classification:
• Biologic Response Modifiers
    • Immunosuppressives
        • Corticosteroids
• Hormones and Hormone Modifiers
    • Adrenal Agents
        • Corticosteroids
• Musculoskeletal Agents
    • Antiinflammatory Agents
        • Corticosteroids
• Respiratory Agents
    • Respiratory Antiinflammatory Agents
        • Corticosteroids

Description, Mechanism of Action, Pharmacokinetics

Description: Prednisone is the most commonly-prescribed oral corticosteroid. The drug is metabolized in the liver to its active form, prednisolone. Relative to hydrocortisone, prednisone is roughly 4 times as potent as a glucocorticoid. Prednisone is intermediate between hydrocortisone and dexamethasone in duration of action. Prednisone is used in many conditions, including allograft rejection, asthma, systemic lupus erythematosus, and many other inflammatory states. Prednisone has very little mineralocorticoid activity, so it is not used in the management of adrenal insufficiency unless a more potent mineralocorticoid is administered concomitantly. Prednisone was first approved by the FDA in 1955.

Mechanism of Action: Glucocorticoids are naturally occurring hormones that prevent or suppress inflammation and immune responses when administered at pharmacological doses. At a molecular level, unbound glucocorticoids readily cross cell membranes and bind with high affinity to specific cytoplasmic receptors. This binding induces a response by modifying transcription and, ultimately protein synthesis to achieve the steroid's intended action. Such actions may include: inhibition of leukocyte infiltration at the site of inflammation, interference in the function of mediators of inflammatory response, and suppression of humoral immune responses. Some of the net effects include reduction in edema or scar tissue, as well as a general suppression in immune response. The degree of clinical effect is normally related to the dose administered. The antiinflammatory actions of corticosteroids are thought to involve phospholipase A2 inhibitory proteins, collectively called lipocortins. Lipocortins, in turn, control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of the precursor molecule arachidonic acid. Likewise, the numerous adverse effects related to corticosteroid use are usually related to the dose administered and the duration of therapy.

Pharmacokinetics: Prednisone is rapidly absorbed across the GI membrane following oral administration. Peak effects can be observed after 1—2 hours. The circulating drug binds extensively to the plasma proteins albumin and transcortin, with only the unbound portion of a dose active. Systemic prednisone is quickly distributed into the kidneys, intestines, skin, liver and muscle. Corticosteroids distribute into the breast milk and cross the placenta. Prednisone is metabolized by the liver to the active metabolite prednisolone, which is then further metabolized to inactive compounds. These inactive metabolites, as well as a small portion of unchanged drug, are excreted in the urine. The plasma elimination half-life is 1 hour whereas the biological half-life of prednisone is 18—36 hours.

Description, Mechanism of Action, Pharmacokinetics last revised 5/22/2002

Indications

• acute lymphocytic leukemia (ALL)	• idiopathic thrombocytopenic purpura (ITP)
• acute respiratory distress syndrome (ARDS)	• iritis
• Addison's disease	• juvenile rheumatoid arthritis (JRA)
• adrenal hyperplasia	• keratitis
• adrenocortical insufficiency	• kidney transplant rejection prophylaxis
• allergic conjunctivitis	• Loeffler's syndrome
• amyloidosis†	• lupus nephritis
• angioedema	• mixed connective tissue disease†
• ankylosing spondylitis	• multiple myeloma
• anterior segment inflammation	• myasthenia gravis
• asthma	• mycosis fungoides
• atopic dermatitis	• nephrotic syndrome
• autoimmune hepatitis†	• optic neuritis
• Behcet's syndrome†	• osteoarthritis
• Bell's palsy†	• pemphigus
• berylliosis	• pericarditis†
• bone pain†	• pneumonia†
• bursitis	• pneumonitis
• carpal tunnel syndrome†	• polyarteritis nodosa†
• chorioretinitis	• polychondritis†
• chronic lymphocytic leukemia (CLL)	• polymyositis
• Churg-Strauss syndrome†	• psoriasis
• corneal ulcer	• pulmonary fibrosis†
• Crohn's disease	• rheumatic carditis
• dermatitis	• rheumatoid arthritis
• dermatomyositis†	• sarcoidosis
• Duchenne muscular dystrophy†	• severe pain
• endophthalmitis†	• Stevens-Johnson syndrome
• epicondylitis	• systemic lupus erythematosus (SLE)
• erythroblastopenia	• temporal arteritis†
• gout	• tenosynovitis
• gouty arthritis	• thrombocytopenia
• graft-versus-host disease (GVHD)	• thyroiditis
• headache	• tuberculosis
• hemolytic anemia	• ulcerative colitis
• Hodgkin's disease	• urticaria
• hypercalcemia	• uveitis
• hypoplastic anemia	• Wegener's granulomatosis†

† non-FDA-approved indication

Dosage

Equivalent Glucocorticoid dosages. These are general approximations and may not apply to all diseases or routes of administration.
Equivalent glucocorticoid dosages:
Cortisone--25 mg
Hydrocortisone--20 mg
Prednisolone--5 mg
Prednisone--5 mg
Methylprednisolone--4 mg
Triamcinolone--4 mg
Dexamethasone--0.75 mg
Betamethasone--0.6 mg

For maintenance therapy (i.e., replacement therapy) of primary (Addison's disease) or secondary adrenocortical insufficiency:
NOTE: Hydrocortisone and cortisone are the preferred agents for these conditions; prednisone has little to no mineralocorticoid properties.
NOTE: For acute conditions, parenteral steroid therapy is recommended initially.
Oral dosage:
Adults: 5 mg PO in the AM, and 2.5 mg PO in the PM.
Children: 4—5 mg/m2 PO given 1—4 times per day.

For the treatment of congenital adrenal hyperplasia:
NOTE: Hydrocortisone is the preferred glucocorticoid in infants.
Oral dosage:
Adults: 2.5—5 mg PO once daily at bedtime.
Children: 12—13 mg/m2/day PO administered in 2—3 divided doses.

For kidney transplant rejection prophylaxis:
Oral dosage:
Adults: Titrate to response. Usual range 5—30 mg PO once daily.

For the treatment of chronic graft-versus-host disease (GVHD):
Oral dosage:
Adults: Prednisone alternating with cyclosporine has been recommended at doses of prednisone 1 mg/kg/day PO plus cyclosporine (10 mg/kg/day PO in 2 divided doses) based on actual or ideal body weight, whichever is lower. After 2 weeks if no disease progression is noted, the prednisone dose is tapered by 25% per week to 1 mg/kg of prednisone on alternate days. Once the prednisone taper is completed without a flare, the cyclosporine dose is tapered to alternate day dosing such that the patient is taking prednisone one day and cyclosporine the next day. Once patients reach their maximal response, therapy is continued for another 3 months and then tapered.[3975]

For palliative management of acute lymphocytic leukemia (ALL):
Oral dosage:
Adults: 40—50 mg/m2 PO once daily indefinitely.

For palliative management of chronic lymphocytic leukemia (CLL) in combination with chlorambucil:
Oral dosage:
Adults: 80 mg PO once daily on days 1—5 in combination with chlorambucil. Administer every 2 weeks. Alternatively, prednisone 1 mg/kg/day PO on days 1—7, then 0.5 mg/kg/day PO on days 8—14, then DC; the cycle is repeated every 6 weeks.

For the short-term treatment of hypercalcemia secondary to neoplastic disease:
Oral dosage:
Adults: 50—100 mg/day PO for 3—5 days is usually effective for hypercalcemia due to hematologic cancers, lower doses may be effective for some tumors.[532]

For the treatment of multiple myeloma in combination with an alkylating agent:
Oral dosage:
Adults: 25—60 mg/m2 PO per day for 4—7 days; in combination with an alkylating agent. Repeat every 4—6 weeks. Other multi-drug regimens with prednisone exist.

For the treatment of inflammatory bowel disease:
•for short-term treatment of acute exacerbations of Crohn's disease:
Oral dosage:
Adults: Initially, 40—60 mg/day PO, adjusted to response. While evidence that maintenance therapy prevents recurrences is lacking, a substantial percentage of patients require chronic dosing (e.g., 5—15 mg/day PO). Corticosteroids for Crohn's disease are more effective for small-bowel involvement than for colonic involvement. Because of the potential complications of steroid use in this disease, steroids should be used selectively and in the lowest dose possible.
•for short-term treatment of acute exacerbations of ulcerative colitis:
Oral dosage:
Adults: Initially, 40—60 mg/day PO has been shown to be superior to 20 mg/day PO. Maximum dosage is 1 mg/kg/day PO. Improvement is usually noted after 7—10 days. Taper dose over the next 2—3 months and DC. Once clinical remission is achieved, corticosteroid therapy should be discontinued since there is no evidence that maintenance therapy prevents recurrences.

For the treatment of serious manifestations of Behcet's syndrome†:
Oral dosage:
Adults: A dosage of 1 mg/kg PO once daily is recommended in internal medicine texts.

For the treatment of rheumatic conditions such as rheumatoid arthritis, juvenile rheumatoid arthritis (JRA), severe psoriasis and psoriatic arthritis, ankylosing spondylitis, acute and subacute bursitis, acute non-specific tenosynovitis, acute gouty arthritis and gout, osteoarthritis, or epicondylitis:
Oral dosage:
Adults: Titrate to response. Usual dosage ranges 5—30 mg PO once daily.
Children: 0.05—2 mg/kg/day PO given in 1—4 divided doses.

For the symptomatic treatment of Duchenne muscular dystrophy†:
Oral dosage:
Children: Current practice guidelines issued by the American Academy of Neurology and the Child Neurology Society recommend 0.75 mg/kg/day PO. If side effects (e.g., weight gain and cushingoid facial appearance) outweigh benefits on muscle strength and function, gradual dose reduction to as low as 0.3 mg/kg/day PO can still be beneficial.[7443]

For adjunctive therapy in the treatment of carpal tunnel syndrome†:
NOTE: The definitive treatment for median-nerve entrapment is surgery. Corticosteroids are temporary measures; patients who have intermittent pain and paresthesias without any fixed motor-sensory deficits may respond to conservative therapy.
Oral dosage:
Adults: 20 mg PO once daily for 2 weeks, followed by 10 mg PO once daily for 2 additional weeks, has provided relief.

For the treatment of selected cases of collagen disorders and mixed connective tissue disease†:
•for the treatment of systemic lupus erythematosus (SLE):
Oral dosage:
Adults: Doses for the various manifestations of SLE vary widely. The usual starting dose is 20—40 mg/day PO for moderate illness and 60—100 mg/day PO for severe illness; some patients may initially require 200—300 mg/day PO in divided doses. After the disease is controlled, reduce the dose by 10% every 5—7 days; a more rapid reduction may result in relapse. Maintenance doses are usually 10—20 mg PO once daily or 20—40 mg PO every other day.
•for the treatment of lupus nephritis† in combination with cytotoxic agents (e.g., azathioprine, cyclophosphamide, chlorambucil):
Oral dosage:
Adults: 0.25 mg/kg/day PO is usually adequate for mesangial or mild focal proliferative disease. In patients with diffuse proliferative or severe focal proliferative disease, 1 mg/kg/day PO for 2 months followed by gradual tapering has been recommended.[997] In combination with azathioprine or cyclophosphamide, doses of 60 mg PO once daily have been used. Prednisone should be tapered over a 6 month period to 30—60 mg once every other day.[213] In a comparison of oral prednisone and cytotoxic agents, prednisone was inferior to cytotoxic agents in ability to prevent decline in renal function. In this study, prednisone was dosed at 1 mg/kg/day for the first 4—8 weeks, followed by gradual tapering as tolerated.[670] Some clinicians believe that chronic renal failure is cause to discontinue therapy since serum creatinine concentrations > 3—4 mg/dL suggest limited probability of reversibility.[213]
•for the treatment of systemic dermatomyositis† (polymyositis†) in combination with azathioprine:
Oral dosage:
Adults: Initially, large doses (e.g., 60 mg PO once daily) are used, once the muscle disease is controlled, prednisone should be tapered to 5—10 mg PO every other day.[213]
•for the treatment of nonrheumatic† or rheumatic carditis, Churg-Strauss syndrome†, polymyalgia rheumatica†, polyarteritis nodosa†, relapsing polychondritis†, temporal arteritis†, vasculitis†, Wegener's granulomatosis†:
Oral dosage:
Adults: Titrate to response. Initial dose should be high (60—100 mg/day PO). After symptoms controlled, decrease dose by 10% every 5—7 days. Maintenance doses are usually 10—20 mg PO once daily or 20—40 mg PO every other day.
Children: 0.05—2 mg/kg/day PO in 1—4 divided doses.

For the treatment of autoimmune hepatitis†:
Oral dosage:
Adults: Initially, 20—30 mg PO once daily has been recommended. Some experts give a combination of prednisone and azathioprine. For maintenance, prednisone 5—15 mg PO once daily has been recommended.[1164]

For the treatment of primary amyloidosis† not associated with familial Mediterranean fever:
Oral dosage:
Adults: 0.8 mg/kg PO once daily for 7 days, in combination with melphalan; repeated every 6 weeks. The treatment combination demonstrated superior results over colchicine alone in the treatment of primary amyloidosis. [1366]

For the treatment of other systemic autoimmune conditions such as acquired hemolytic anemia, congenital hypoplastic anemia, mycosis fungoides, pemphigus, symptomatic sarcoidosis, or nonsuppurative thyroiditis:
Oral dosage:
Adults: Titrate to response. Usual dosage ranges 5—30 mg PO once daily.

For the treatment of asthma:
•for the treatment of a moderate-severe asthma exacerbation in the emergency department or the hospital:
Oral dosage:
Adults: The National Asthma Education and Prevention Expert Panel recommends 120—180 mg/day PO in 3—4 divided doses for 48 hours, then 60—80 mg/day PO until the peak expiratory flow (PEF) reaches 70% of predicted or personal best.[1515]
Children: The National Asthma Education and Prevention Expert Panel recommends 1 mg/kg PO every 6 hours for 48 hours, then 1—2 mg/kg/day (max: 60 mg/day) PO in 2 divided doses until peak expiratory flow (PEF) reaches 70% of predicted or personal best.[1515]
•for the treatment of an acute asthma exacerbation on an outpatient basis in selected patients:
Oral dosage:
Adults: The National Asthma Education and Prevention Expert Panel recommends 40—60 mg PO as a single dose or in 2 divided doses for 3—10 days.[1515]
Children: The National Asthma Education and Prevention Program Expert Panel recommends 1—2 mg/kg/day (max: 60 mg/day) PO as a single dose or in 2 divided doses for 3—10 days.[1515]
•for long-term prevention of symptoms in severe persistent asthma:
Oral dosage:
Adults and children: The National Asthma Education and Prevention Expert Panel recommends 7.5—60 mg PO administered once daily in the AM or every other day. Taper to the lowest effective dose. One study indicates that administering the dose in the afternoon at 3:00 pm may increase efficacy, with no increase in adrenal suppression.[1943]

For the treatment of thrombocytopenia:
•in patients with chronic idiopathic thrombocytopenic purpura (ITP):
Oral dosage:
Adults: Initially, 1 mg/kg PO once daily[533] ; however, lower doses of 5—10 mg/day PO are preferable for long-term treatment.[1342]
•for the treatment of autoimmune thrombocytopenia associated with SLE:
Oral dosage:
Adults and children: 0.25 mg/kg/day PO was as effective as higher doses of 1 mg/kg/day.[997]

For the treatment of acute, severe urticaria or angioedema associated with systemic symptoms in patients who fail to respond to epinephrine or histamine blockers including angioedema associated with ACE inhibitor therapy:
Oral dosage:
Adults: Short courses of 30—50 mg/day can be given PO during the late phase of an acute reaction.[570]

For the treatment of myasthenia gravis in patients who are poorly controlled with cholinesterase inhibitor therapy:
Oral dosage:
Adults: Initially, 15—20 mg/day PO. Increase by 5 mg every 2—3 days as needed up to 60 mg/day PO maximum. Then change to every other day therapy.[540]

For the treatment of idiopathic or viral pericarditis†:
Oral dosage:
Adults: 20—80 mg PO once daily. Corticosteroids are contraindicated in pericarditis after MI; corticosteroids retard myocardial scar formation and the incidence of rupture may increase.

For the treatment of nephrotic syndrome:
Oral dosage:
Adults: 40—80 mg/day PO until urine is protein-free; slowly taper as indicated. Some patients may require long-term dosing.
Children: 2 mg/kg/day or 60 mg/m2/day (maximum 80 mg) PO once daily until urine is protein-free for 3 consecutive days. Then 1—1.5 mg/kg or 40 mg/m2 PO every other day for 4 weeks. If needed, the long-term maintenance dose is 0.5—1 mg/kg PO every other day for 3—6 months.[1944]

For the treatment of Stevens-Johnson syndrome:
Oral dosage:
Adults: High-dose corticosteroids are controversial; administration has been associated with decreased survival.[534] [535] Prednisone doses of 60—250 mg/day PO are equivalent to the recommended hydrocortisone doses of 240—1000 mg/day.

For adjunctive treatment in selected cases of pneumonia† or pneumonitis:
•for adjunctive treatment of AIDS-associated Pneumocystis carinii pneumonia† (PCP):
Oral dosage:
Adults: 40 mg PO twice daily for 5 days, then 40 mg PO daily for 5 days, then 20 mg PO daily for 11 days, during anti-infective therapy. Begin prednisone within 24—72 hours of the initiation of anti-infectives for PCP; use is associated with improved outcomes.
Children: Safe dosage has not been established.
•for adjunctive treatment of aspiration pneumonitis:
Oral dosage:
Adults: 5—60 mg/day PO; administered in 1—4 divided doses. Gradually taper after 1—2 weeks and discontinue by 4—6 weeks, guided by symptoms.
Children: 0.14—2 mg/kg PO daily or 4—60 mg/m2 PO daily, given in 4 divided doses. Gradually taper after 1—2 weeks and discontinue by 4—6 weeks, as guided by symptoms.

For the systemic treatment of ophthalmic inflammatory conditions such as endophthalmitis†, optic neuritis, allergic conjunctivitis, keratitis, allergic corneal ulcer, iritis, chorioretinitis, anterior segment inflammation, uveitis, choroiditis, or sympathetic ophthalmia:
NOTE: Topically applied corticosteroids are as effective as systemic corticosteroids for anterior ocular inflammation.
Oral dosage:
Adults: 5—60 mg/day PO administered in 1—4 divided doses, depending upon disease being treated.
Children: 0.14—2 mg/kg/day PO or 4—60 mg/m2/day PO, given in 4 divided doses.

For the short-term treatment of acute, severe headache:
Oral dosage:
Adults: 80 mg PO per day for several days.[351] Taper rapidly.

For the adjunctive management of severe pain associated with bone pain†, brain metastases and epidural spinal cord compression:
Oral dosage:
Adults: 10—50 mg/day PO has been used for bone pain. A range of 40—80 mg/day PO is suggested for spinal cord compression.[1171]

For the treatment of the acute respiratory distress syndrome (ARDS) in patients with severe disease and no signs of improvement 7—14 days after onset of the condition:
Oral dosage:
Adults: Corticosteroid use in ARDS is controversial. If there are no signs of improvement 7—14 days after ARDS onset, 2—4 mg/kg/day PO for 7—14 days has been recommended.[564]

For the treatment of other conditions not listed above including atopic dermatitis, Loeffler's syndrome, berylliosis, erythroblastopenia, or trichinosis:
Oral dosage:
Adults: 5—60 mg/day PO, administered in 1—4 divided doses, depending upon disease being treated. Depending on the indication, the initial dose may be gradually tapered after 1—2 weeks and DC'd by 4—6 weeks, as guided by symptoms.
Children: 0.14—2 mg/kg/day POor 4—60 mg/m2/day PO, given in 4 divided doses. Depending on indication, gradually taper the initial dose after 1—2 weeks and DC by 4—6 weeks, guided by symptoms.

For the treatment of tuberculosis† meningitis or pulmonary tuberculosis† controlled by appropriate antituberculosis chemotherapy:
Oral dosage:
Adults: 5—60 mg/day PO, administered in 1—4 divided doses, depending upon disease being treated. For TB meningitis, initially 60—80 mg PO once daily; experts recommend corticosteroid use in stage 2 (confusion or the presence of focal neurological defects) or stage 3 (stuporous or dense paraplegia or hemiplegia). Alternatively, initial doses of 0.5—1 mg/kg/day PO have been used.[1945] Gradually taper after 1—2 weeks and DC by 4—6 weeks, as guided by the patient's symptoms.
Children: 0.14—2 mg/kg/day PO or 4—60 mg/m2/day PO, given in 4 divided doses.

For the treatment of idiopathic pulmonary fibrosis†:
Oral dosage:
Adults: 0.5 mg/kg/day PO for 4 weeks, then 0.25 mg/kg/day PO for 8 weeks. Taper to 0.125 mg/kg/day or 0.25 mg/kg/day PO on alternate days. Guidelines suggest treatment should be in combination with cyclophosphamide or azathioprine and continued for a minimum of 6 months. Objective responses may not be noted until the patient has received >= 3 months of therapy. Exact duration of treatment and need for long-term maintenance should be individualized based on clinical response and tolerance to therapy. Chronic doses of prednisone (15—20 mg PO once daily) may be adequate as maintenance therapy.[3164]

For the treatment of Hodgkin's disease in combination with antineoplastic agents:
•in combination with mechlorethamine, vincristine, vinblastine, and procarbazine (MVVPP regimen):
Oral dosage:
Adults: 40 mg/m2/day PO on days 1—22, then taper. Chemotherapy cycle is repeated every 57 days.
•in combination with mechlorethamine, vincristine, procarbazine, doxorubicin, bleomycin, and vinblastine (MOPP/APB regimen):
Oral dosage:
Adults: 40 mg/m2/day PO on days 1—14; cycle is repeated every 28 days.

For the treatment of Bell's palsy†:
Oral dosage:
Adults: 10 mg/kg (up to 80 mg) PO once per day for 7 to 14 days, with an HSV antiviral agent (i.e., acyclovir, valacyclovir, or famciclovir), has been recommended.[7250] If treatment is continued for 14 days, the prednisone dose can be tapered in the second week of treatment.[7251]

Maximum Dosage Limits:
Dosage must be individualized and is highly variable depending on the nature and severity of the disease, and on patient response. Although there is no absolute maximum dosage, the Boston Collaborative Drug Study found that psychiatric events occurred in fewer than 1% of patients when prednisone was prescribed in doses of 30 mg/day or less, whereas the incidence rose to 18% in patients receiving 80 mg/day.[243]

Patients with hepatic impairment:
Specific guidelines for dosage adjustments in hepatic impairment are not available; prednisone is converted to prednisolone, the active moiety, by the liver. The use of oral prednisolone instead of oral prednisone may be preferred in patients with significant hepatic dysfunction (see Prednisolone monograph); doses are equivalent (i.e., 1 mg prednisone is equivalent to 1 mg of prednisolone).

Patients with renal impairment:
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

†non-FDA-approved indication

Indications...Dosage last revised 1/19/2005 6:26:00 PM

Administration Guidelines

NOTE: Dosage must be individualized and is highly variable depending on the nature and severity of the disease, and on patient response. If therapy is continuous for more than several days, withdrawal should generally be gradual.

Oral Administration
•All oral dosage forms: Administer with meals to minimize indigestion or GI irritation. If given once daily or every other day, administer in the morning to coincide with the body's normal cortisol secretion.
•Oral solution or syrup: Administer using a calibrated measuring device for accurate measurement of the dose.

†non-FDA approved

Administration last revised 7/1/2002

†non-FDA-approved indication

Contraindications/Precautions

• abrupt discontinuation	• infection
• Cushing's syndrome	• inflammatory bowel disease
• fungal infection	• lactase deficiency
• measles	• myasthenia gravis
• varicella	• myocardial infarction
• breast-feeding	• osteoporosis
• cataracts	• peptic ulcer disease
• children	• pregnancy
• coagulopathy	• psychosis
• corticosteroid hypersensitivity	• renal disease
• diabetes mellitus	• seizure disorder
• diverticulitis	• surgery
• GI disease	• thromboembolic disease
• glaucoma	• tuberculosis
• heart failure	• ulcerative colitis
• hepatic disease	• vaccination
• herpes infection	• viral infection
• hypertension	• visual disturbance
• hypothyroidism

• Absolute contraindications are in italics.

The manufacturers state that prednisone is contraindicated in patients with systemic fungal infection, but many clinicians believe that corticosteroids can be administered to patients with any type of known infection as long as appropriate antifungal therapy is administered simultaneously.

Corticosteroid therapy can mask the symptoms of infection and should not be used in cases of viral infection or bacterial infection which are not adequately controlled by anti-infective agents. Secondary infections are common during corticosteroid therapy. Corticosteroids may reactivate tuberculosis, and should not be used in patients with a history of active tuberculosis except when chemoprophylaxis is instituted concomitantly. Patients receiving immunosuppressive doses of corticosteroids should be advised to avoid exposure to measles or varicella, and if exposed to these diseases, to seek medical advice immediately. In general, corticosteroids should not be used in patients with herpes infection.

Patients should be instructed to notify their physician immediately if signs of infection or injury occur, both during treatment, or up to 12 months following cessation of therapy. Dosages should be adjusted, or glucocorticoid therapy reintroduced, if required. If surgery is required, patients should advise the attending physician of the corticosteroid they have received within the last 12 months, and the disease for which they were being treated. Identification cards which include the name of the patient's disease, the currently administered type and dose of corticosteroid, and the patient's physician should be carried with the patient at all times.

Corticosteroid therapy has been associated with left ventricular free-wall rupture in patients with recent myocardial infarction, and should therefore be used cautiously in these patients.

Corticosteroids cause edema, which may exacerbate congestive heart failure or hypertension, and should be used with caution in these patients.

Corticosteroids should be used cautiously in patients with glaucoma or other visual disturbance. Corticosteroids are well known to cause cataracts and can exacerbate glaucoma during long-term administration. Patients receiving topical or systemic corticosteroids chronically should be periodically assessed for cataract formation.

Corticosteroids should be used with caution in patients with GI disease, diverticulitis, intestinal anastomosis (because of the possibility of perforation), or hepatic disease causing hypoalbuminemia such as cirrhosis. While used for the short-term treatment of acute exacerbations of chronic inflammatory bowel disease such as ulcerative colitis and Crohn's disease, corticosteroids should not be used in patients where there is a possibility of impending GI perforation, abscess, or pyogenic infection. Some patients may require long-term corticosteroid therapy to suppress disease activity, but generally this practice is not recommended. Corticosteroids should not be used in patients with peptic ulcer disease except under life-threatening circumstances.

Corticosteroids should be used with extreme caution in patients with psychosis, emotional instability, herpes simplex ocular infections, renal disease, osteoporosis, diabetes mellitus, and seizure disorder, because the drugs may exacerbate these conditions. Patients with hypothyroidism may have an exaggerated response to corticosteroids, thus any steroid should be used with caution in these patients.

Glucocorticoids should be used with caution in patients with myasthenia gravis who are being treated with anticholinesterase agents (see Interactions). Muscle weakness may be transiently increased during the initiation of glucocorticoid therapy in patients with myasthenia gravis, necessitating respiratory support.

Glucocorticoids may rarely increase blood coagulability and cause intravascular thrombosis, thrombophlebitis, and thromboembolism. Therefore, corticosteroids should be used with caution in patients with coagulopathy or thromboembolic disease.

Increased dosages of rapid-acting corticosteroids may be necessary for patients undergoing physiologic stress, such as major surgery, acute infection, or blood loss. The corticosteroid should be administered before, during, and after the stressful situation.

Complications including cleft palate, still birth, and premature abortion have been reported when corticosteroids were administered during pregnancy. If these drugs must be used during pregnancy, the potential risks should be discussed with the patient. Babies born to women receiving large doses of corticosteroids during pregnancy should be monitored for signs of adrenal insufficiency and appropriate therapy initiated, if necessary. Prednisone is classified as FDA pregnancy risk category C but cortisone is classified as pregnancy category D. This probably reflects the fact that cortisone is more commonly used during pregnancy than is prednisone and therefore, more reports of problems have been associated with cortisone than prednisone and not the fact that it is a more potent teratogen. Corticosteroids distribute into breast milk, and the manufacturer states that women receiving pharmacological dosages of corticosteroids should not practice breast-feeding.

Corticosteroid therapy usually does not contraindicate vaccination with live-virus vaccines when such therapy is of short-term (< 2 weeks); low to moderate dose; long-term alternate day treatment with short-acting preparations; maintenance physiologic doses (replacement therapy); or via topical administration (skin or eye), by aerosol, or by intra-articular, bursal or tendon injection. The immunosuppressive effects of steroid treatment differ, but many clinicians consider a dose equivalent to either 2 mg/kg/day or 20 mg/day of prednisone as sufficiently immunosuppressive to raise concern about the safety of immunization with live-virus vaccines. In general, patients with severe immunosuppression due to large doses of corticosteroids should not receive vaccination with live-virus vaccines. When cancer chemotherapy or immunosuppressive therapy is being considered (e.g., for patients with Hodgkin's disease or organ transplantation), vaccination should precede the initiation of chemotherapy or immunotherapy by >= 2 weeks. Patients vaccinated while on immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated at least 3 months after discontinuation of therapy. In patients who have received high-dose, systemic corticosteroids for >= 2 weeks, it is recommended to wait at least 3 months after discontinuation of therapy before administering a live-virus vaccine.

Prolonged therapy with corticosteroids should be avoided in children, as the drug may retard bone growth. Children receiving corticosteroids are immunosuppressed, and are therefore more susceptible to infection. Normally innocuous infections can become fatal in these children, and care should be taken to avoid exposure to these diseases.

As glucocorticoids can produce or aggravate Cushing's syndrome, glucocorticoids should be avoided in patients with Cushing's disease.

Pharmacologic doses of corticosteroids administered for prolonged periods may result in hypothalamic-pituitary-adrenal (HPA) suppression. Acute adrenal insufficiency and even death may occur following abrupt discontinuation. Withdrawal from prolonged oral corticosteroid therapy should be gradual; HPA suppression can last for up to 12 months following cessation of therapy, and patients may need supplemental corticosteroid treatment during periods of physiologic stress, such as surgery, acute blood loss, or infection, even after the drug has been discontinued. Also, a non-HPA withdrawal syndrome may occur following abrupt discontinuation of corticosteroid therapy, and is apparently unrelated to adrenocortical insufficiency. These effects are thought to be due to the sudden change in glucocorticoid concentration rather than to low corticosteroid levels (see Adverse Reactions).

Although true corticosteroid hypersensitivity is rare, patients who have demonstrated a prior hypersensitivity reaction to prednisone should not receive any form of prednisone or prednisolone. It is possible, though also rare, that such patients will display cross-hypersensitivity to other corticosteroids. It is advisable that patients who have a hypersensitivity reaction to any corticosteroid undergo skin testing, which, although not a conclusive predictor, may help to determine if hypersensitivity to another corticosteroid exists. Such patients should be carefully monitored during and following the administration of any corticosteroid.[4323]

Prednisone is contraindicated in patients with a hypersensitivity to prednisone or to any components of the formulation.[8143] As prednisone tablets contain lactose, appropriate precautions should be taken when administered to patients with lactase deficiency.

Contraindications last revised 11/29/2005 1:24:00 PM

Drug Interactions

• Amphotericin B		• Mecasermin, Recombinant, rh-IGF-1
	Antidiabetic Agents	• Mifepristone, RU-486
	Antineoplastic Agents		Neuromuscular blockers
	Antithyroid agents	• Nevirapine
	Barbiturates		Nonsteroidal antiinflammatory drugs (NSAIDs)
• Bosentan		• Pegaspargase
• Calcium Carbonate		• Phenytoin
	Cardiac glycosides		Photosensitizing Agents
	Cholinesterase Inhibitors	• Rifabutin
	Diuretics	• Rifampin
• Dofetilide		• Ritonavir
• Ephedra, Ma Huang			Salicylates
	Estrogens	• Sodium Iodide I-131
• Ethotoin			Thyroid hormones
• Fosphenytoin			Toxoids
	Immunosuppressives		Vaccines
• Infliximab			Vitamin D analogs
• Isoproterenol		• Warfarin
• L-Asparaginase

Hepatic microsomal enzyme inducers including barbiturates [4722], bosentan [4739], phenytoin [4742] or fosphenytoin, and possibly ethotoin [4741], rifabutin [5948] and rifampin [4742] may increase the metabolism of glucocorticoids. Rifabutin and rifampin are particularly potent enzyme inducers. Despite the fact that prednisone is converted in the liver to its active form, prednisolone, prednisolone is also metabolized by the liver and susceptible to accelerated clearance if any of these drugs are added. Dosages of prednisone may require adjustment if these agents, especially rifabutin or rifampin, are initiated or withdrawn during therapy.

Estrogens have been associated with elevated serum concentrations of corticosteroid binding globulin (CBG), leading to increased circulating corticosteroids.[4744] In addition, estrogens have been shown to decrease the clearance of prednisolone. Since prednisone is metabolized to prednisolone, this interaction should also apply to prednisone. Therefore, the effects of corticosteroids may be altered by the concurrent administration of estrogen, requiring the adjustment of corticosteroid dosages if estrogen is added to or withdrawn during therapy.

Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs.[1162] Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.

The potassium-wasting effects of corticosteroid therapy [6524] may be exacerbated by concomitant administration of other potassium depleting drugs including diuretics and amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.

Patients receiving cardiac glycosides and corticosteroids concomitantly are at an increased risk for developing arrhythmias or digitalis toxicity due to corticosteroid-induced hypokalemia.[4999] [6115] Corticosteroid-induced hypokalemia could also enhance the proarrhythmic effects of dofetilide.[4947]

Glucocorticoids may interact with cholinesterase inhibitors, including ambenonium, neostigmine, and pyridostigmine, occasionally causing severe muscle weakness in patients with myasthenia gravis.[6524] [7895] Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis.[7896] In such patients it is recommended that corticosteroid therapy be initiated at low dosages (i.e., 10—25 mg/day of prednisone or equivalent) and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.[7895] [7896]

Killed or inactivated vaccines and toxoids do not represent a danger to immunocompromised persons and generally should be administered as recommended for healthy persons. The immune response of immunocompromised persons to vaccines is not as good as healthy persons; higher doses or more frequent boosters may be required, although the immune response still may be suboptimal. Live-virus vaccines should not be given to immunocompromised individuals due to the potentiation of virus replication and adverse reactions to the virus.[3957] Those undergoing high-dose corticosteroid therapy should not be exposed to others who have recently received the oral poliovirus vaccine (OPV). Measles-mumps-rubella (MMR) vaccination is not contraindicated for the close contacts, including health care professionals, of immunocompromised patients. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination. When exposed to a vaccine-preventable disease such as measles, severely immunocompromised children should be considered susceptible regardless of their vaccination history.

The effect of corticosteroids on oral anticoagulants (e.g., warfarin) is variable. There are reports of enhanced as well as diminished effects of anticoagulants when given concurrently with corticosteroids [6524]; however, limited published data exist, and the mechanism of the interaction is not well described. High-dose corticosteroids appear to pose a greater risk for increased anticoagulant effect.[6525] [6526] In addition, corticosteroids have been associated with a risk of peptic ulcer and gastrointestinal bleeding.[6524] [6527] Thus corticosteroids should be used cautiously and with appropriate clinical monitoring in patients receiving oral anticoagulants; coagulation indices (e.g., INR, etc.) should be monitored to maintain the desired anticoagulant effect. During high-dose corticosteroid administration, daily laboratory monitoring may be desirable.[6525]

The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism.[6524] Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.

Systemic corticosteroids increase blood glucose levels [4751]; a potential pharmacodynamic interaction exists between corticosteroids and all antidiabetic agents. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent. Blood lactate concentrations and the lactate to pyruvate ratio increased when metformin was coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with an increased risk of lactic acidosis, so patients on metformin concurrently with systemic steroids should be monitored closely.

Concomitant use of L-asparaginase or pegaspargase with corticosteroids can result in additive hyperglycemia.[6639] L-Asparaginase transiently inhibits insulin production contributing to hyperglycemia seen during concurrent corticosteroid therapy. Insulin therapy may be required in some cases. Administration of L-asparaginase or pegaspargase after rather than before corticosteroids reportedly has produced fewer hypersensitivity reactions.

Corticosteroids can cause increases in blood pressure, sodium and water retention, and hypokalemia [6524], predisposing patients to interactions with certain other medications. Hypokalemia is known to potentiate neuromuscular blockade associated with nondepolarizing neuromuscular blockers. In addition, case reports and clinical studies have reported myopathy and weakness, sometimes prolonged, with the combined use of neuromuscular blocking agents with corticosteroids in critically ill patients. Many cases involved patients with no underlying risk factors. The term 'blocking agent-corticosteroid myopathy' (BACM) has been applied to this syndrome.[7893] When given concomitantly for prolonged periods these agents appear to confer a greater risk of myopathy versus the use of either agent alone, and the pathology of the effect is not known.[7893] When combined use is necessary for prolonged periods, careful monitoring of the patient is recommended.

Corticosteroids administered systemically prior to or concomitantly with photosensitizing agents may decrease the efficacy of photodynamic therapy.[6625]

The risk of cardiac toxicity with isoproterenol in asthma patients appears to be increased with the coadministration of corticosteroids or methylxanthines. Intravenous infusions of isoproterenol in refractory asthmatic children at rates of 0.05—2.7 mcg/kg/min have caused clinical deterioration, myocardial infarction (necrosis), congestive heart failure and death.[4721]

Mifepristone, RU-486 exhibits antiglucocorticoid activity [4720] that may antagonize the corticosteroids. In rats, the activity of dexamethasone was inhibited by oral mifepristone doses of 10—25 mg/kg. A mifepristone dose of 4.5 mg/kg in humans resulted in compensatory increases in ACTH and cortisol. Mifepristone is contraindicated in patients on long-term corticosteroid therapy.

Due to ritonavir's inhibitory effects on various hepatic isoenzymes (especially CYP2D6 and CYP3A4) [4194], a drug interaction may occur with prednisone. Monitoring of therapeutic and adverse effects is required when prednisone is coadministered with ritonavir; dosage reduction may be needed.

In a clinical trial, concomitant use of prednisone (40 mg/day for the first 14 days of nevirapine administration) was associated with an increase in incidence and severity of rash during the first 6 weeks of nevirapine therapy. Therefore, the use of prednisone to prevent nevirapine-associated rash is not recommended.[5222]

Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods [7714], additive effects may be seen with other immunosuppressives or antineoplastic agents. While therapy is designed to take advantage of this effect, patients may be predisposed to over-immunosuppression resulting in an increased risk for the development of severe infections.[7714] Close clinical monitoring is advised with concurrent use; in the presence of serious infections, continuation of the corticosteroid or immunosuppressive agent may be necessary but should be accompanied by appropriate antimicrobial therapies as indicated.

Many serious infections during infliximab therapy have occurred in patients who received concurrent immunosuppressives that, in addition to their underlying Crohn's disease or rheumatoid arthritis, predisposed patients to infections.[4711] The impact of concurrent infliximab therapy and immunosuppression on the development of malignancies is unknown. In clinical trials, the use of concomitant immunosuppressant agents appeared to reduce the frequency of antibodies to infliximab and appeared to reduce infusion reactions.[4711]

Ephedra, ma huang may increase the metabolism and lead to subtherapeutic levels of corticosteroids. Ephedrine, an ephedra alkaloid may result in higher liver clearance or metabolism of corticosteroids. Patients requiring corticosteroids, especially those with asthma or immunosuppression, should avoid ma huang.[3649]

Vitamin D plus calcium supplements are generally recommended for the prevention of osteoporosis in patients taking long-term corticosteroids.[6905] A relationship of functional antagonism exists between vitamin D analogs, which promote calcium absorption, and corticosteroids, which inhibit calcium absorption.[6902] [1441] Therapeutic effect of vitamin D analogs should be monitored when used concomitantly with corticosteroids.

Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function.[8256] [8255]

Additional monitoring may be required when coadministering systemic or inhaled corticosteroids and mecasermin, recombinant, rh-IGF-1. In animal studies, corticosteroids impair the growth-stimulating effects of growth hormone (GH) through interference with the physiological stimulation of epiphyseal chondrocyte proliferation exerted by GH and IGF-1. Dexamethasone administration on long bone tissue in vitro resulted in a decrease of local synthesis of IGF-1.[8314] Similar counteractive effects are expected in humans. If systemic or inhaled glucocorticoid therapy is required, the steroid dose should be carefully adjusted and growth rate monitored.[8315]

Corticosteroids are known to decrease the uptake of iodide into thyroid tissue.[8683] In order to increase thyroid uptake and optimize exposure of thyroid tissue to the radionucleotide sodium iodide I-131, consider withholding prednisone prior to treatment with sodium iodide I-131.

Interactions last revised 2/13/2006 3:13:00 PM

Adverse Reactions

• abdominal pain	• immunosuppression
• acne vulgaris	• impaired wound healing
• adrenocortical insufficiency	• increased intracranial pressure
• amenorrhea	• infection
• angina	• insomnia
• angioedema	• lethargy
• anorexia	• menstrual irregularity
• anxiety	• metabolic alkalosis
• appetite stimulation	• myalgia
• arthralgia	• myocardial infarction
• avascular necrosis	• myopathy
• bone fractures	• nausea/vomiting
• cataracts	• ocular hypertension
• constipation	• optic neuritis
• Cushing's syndrome	• osteoporosis
• depression	• palpitations
• diabetes mellitus	• pancreatitis
• diaphoresis	• papilledema
• diarrhea	• peptic ulcer
• dysmenorrhea	• peripheral neuropathy
• ecchymosis	• petechiae
• edema	• phlebitis
• EEG changes	• physiological dependence
• emotional lability	• pseudotumor cerebri
• erythema	• psychosis
• esophageal ulceration	• restlessness
• euphoria	• retinopathy
• exfoliative dermatitis	• seizures
• exophthalmos	• sinus tachycardia
• fever	• skin atrophy
• fluid retention	• sodium retention
• gastritis	• stomatitis
• glossitis	• striae
• growth inhibition	• stroke
• headache	• thromboembolism
• heart failure	• thrombosis
• hirsutism	• urinary incontinence
• hypercholesterolemia	• urinary urgency
• hyperglycemia	• urticaria
• hypernatremia	• vertigo
• hypertension	• visual impairment
• hypocalcemia	• weakness
• hypokalemia	• weight gain
• hypotension	• weight loss
• hypothalamic-pituitary-adrenal (HPA) suppression	• withdrawal

NOTE: Prolonged administration of physiologic replacement dosages of glucocorticoids does not usually cause adverse effects. The severity of the adverse effects associated with prolonged administration of pharmacological dosages of corticosteroids increases with duration of therapy. Short term administration of large doses typically does not cause adverse effects, but long term administration can lead to adrenocortical atrophy and generalized protein depletion.

Glucocorticoids are responsible for protein metabolism, and prolonged therapy can result in various musculoskeletal manifestations, including: myopathy (myalgia, muscle wasting, muscle weakness), impaired wound healing, bone matrix atrophy (osteoporosis), bone fractures such as vertebral compression fractures or fractures of long bones, and avascular necrosis of femoral or humoral heads. These effects are more likely to occur in older or debilitated patients. Glucocorticoids interact with calcium metabolism at many sites, including: decreasing the synthesis by osteoblasts of the principle proteins of bone matrix, malabsorption of calcium in both the nephron and the gut, and reduction of sex hormone concentrations. Although all of these actions probably contribute to glucocorticoid-induced osteoporosis, the actions on osteoblasts is most important. Glucocorticoids do not modify vitamin D metabolism.[1441] Postmenopausal women, in particular, should be monitored for signs of osteoporosis during corticosteroid therapy. Because of retardation of bone growth, children receiving prolonged corticosteroid therapy may have growth inhibition.

Corticosteroid therapy can mask the symptoms of infection and should be avoided during an acute viral or bacterial infection. Immunosuppression is most likely to occur in patients receiving high-dose (e.g., equivalent to 1 mg/kg or more of prednisone daily), systemic corticosteroid therapy for any period of time, particularly in conjunction with corticosteroid sparing drugs (e.g., troleandomycin) and/or concomitant immunosuppressant agents; however, patients receiving moderate dosages of systemic corticosteroids for short periods or low dosages for prolonged periods also may be at risk. Corticosteroids can reactivate tuberculosis and should not be used in patients with a history of active tuberculosis except when chemoprophylaxis is instituted concomitantly. Patients receiving immunosuppressive doses of corticosteroids should be advised to avoid exposure to measles or varicella (chickenpox) and, if exposed to these diseases, to seek medical advice immediately.

Corticosteroids are divided into two classes: mineralocorticoids and glucocorticoids. Mineralocorticoids alter electrolyte and fluid balance by facilitating sodium retention and hydrogen and potassium excretion at the level of the distal renal tubule, resulting in edema and hypertension. Mineralocorticoid properties can cause fluid retention; electrolyte disturbances (hypokalemia, hypokalemic metabolic alkalosis, hypernatremia, hypocalcemia), edema, and hypertension. Prolonged administration of glucocorticoids may also result in edema and hypertension. In a review of 93 studies of corticosteroid use, hypertension was found to develop 4 times as often in steroid recipients compared to control groups.[938]
Although corticosteroids are used to treat Graves' ophthalmopathy, ocular effects, such as exophthalmos, posterior subcapsular cataracts, retinopathy, or ocular hypertension, can result from prolonged use of glucocorticoids and could result in glaucoma or ocular nerve damage including optic neuritis. Temporary or permanent visual impairment, including blindness, has been reported with glucocorticoid administration by several routes of administration including intranasal and ophthalmic administration. Secondary fungal and viral infections of the eye can be exacerbated by corticosteroid therapy.

Prolonged corticosteroid therapy may adversely affect the endocrine system, resulting in hypercorticism (Cushing's syndrome), menstrual irregularity including dysmenorrhea or amenorrhea, hyperglycemia, and aggravation of diabetes mellitus in susceptible patients. In a recently-published review of 93 studies of corticosteroid use, the development of diabetes mellitus was determined to occur 4 times more frequently in steroid recipients compared to control groups.[938] In patients with preexisting diabetes mellitus, insulin or oral hypoglycemic dosages may require adjustment during steroid administration.

Adverse GI effects associated with corticosteroid administration include nausea/vomiting and anorexia with subsequent weight loss. Appetite stimulation with weight gain, diarrhea, constipation, abdominal pain, esophageal ulceration, gastritis, and pancreatitis have also been reported. Although it was once believed that corticosteroids contributed to the development of peptic ulcer disease, in a published review of 93 studies of corticosteroid use, the incidence of peptic ulcer disease was not found to be higher in steroid recipients compared to control groups.[938] While most of these studies did not utilize endoscopy, it is unlikely that corticosteroids contribute to the development of peptic ulcer disease.

Adverse neurologic effects have been reported during prolonged corticosteroid administration and include headache, insomnia, vertigo, restlessness, ischemic peripheral neuropathy, seizures, and EEG changes. Mental disturbances, including depression, anxiety, euphoria, personality changes, and psychosis, have also been reported; emotional lability and psychotic problems can be exacerbated by corticosteroid therapy.

Various adverse dermatologic effects reported during corticosteroid therapy include skin atrophy, acne vulgaris, diaphoresis, impaired wound healing, facial erythema, striae, petechiae, hirsutism, ecchymosis, and easy bruising. Hypersensitivity reactions may manifest as allergic dermatitis, urticaria, and/or angioedema.

Pharmacologic doses of corticosteroids administered for prolonged periods may result in physiological dependence due to hypothalamic-pituitary-adrenal (HPA) suppression. Exogenous corticosteroids exert negative feedback on the pituitary, inhibiting the secretion of adrenocorticotropin (ACTH). This results in a decrease in ACTH-mediated synthesis of endogenous corticosteroids and androgens by the adrenal cortex. The severity of glucocorticoid-induced secondary adrenocortical insufficiency varies among individuals, and is dependent upon the dose, frequency, time of administration, and duration of therapy. Administering the drug on alternate days may help to alleviate this adverse effect. Patients with HPA suppression will require increased doses of corticosteroid therapy during periods of physiologic stress. Acute adrenal insufficiency and even death may occur if sudden withdrawal of the drugs is undertaken. Withdrawal from prolonged oral corticosteroid therapy should be gradual; HPA suppression can last for up to 12 months following cessation of therapy, and patients may need supplemental corticosteroid treatment during periods of physiologic stress, such as surgery, acute blood loss, or infection, even after the drug has been discontinued. Also, a non-HAP withdrawal syndrome may occur following abrupt discontinuance of corticosteroid therapy, and is apparently unrelated to adrenocortical insufficiency. This syndrome includes symptoms such as anorexia, lethargy, nausea/vomiting, headache, fever, arthralgia, myalgia, exfoliative dermatitis, weight loss, and hypotension. These effects are thought to be due to the sudden change in glucocorticoid concentration rather than to low corticosteroid levels. Increased intracranial pressure with papilledema (i.e., pseudotumor cerebri) has also been reported with withdrawal of glucocorticoid therapy.

Hypercholesterolemia, atherosclerosis, fat embolism, thrombosis, thromboembolism, and phlebitis, specifically, thrombophlebitis have been associated with corticosteroid therapy. Glucocorticoid use appears to increase the risk of cardiovascular events such as myocardial infarction, angina, angioplasty, coronary revascularization, stroke, transient ischemic attack, congestive heart failure, or cardiovascular death. As determined from observational data, the rate of cardiovascular events was 17 per 1000 person-years among 82,202 non-users of glucocorticoids. In contrast, the rate was 23.9 per 1000 person-years among 68,781 glucocorticoid users. Furthermore, the rate of cardiovascular events was 76.5 per 1000 person-years for high exposure patients. After adjustment for known covariates by multivariate analysis, high-dose glucocorticoid use was associated with a 2.56-fold increased risk of cardiovascular events as compared with nonuse. An increased risk of heart failure was also observed for medium-dose glucocorticoid use as compared with nonuse. At the beginning of the study, patients were at least 40 years of age and had not been hospitalized for cardiovascular disease. High glucocorticoid exposure was defined as at least 7.5 mg daily of prednisolone or the equivalent given orally, rectally, or parenterally whereas medium exposure was defined as less than the above dosage by any of the 3 routes. Low-dose exposure was defined as inhaled, topical, or nasal usage only.[7459]

Palpitations, sinus tachycardia, glossitis, stomatitis, urinary incontinence, and urinary urgency have been rarely reported. Corticosteroids may also decrease serum concentrations of vitamin C (ascorbic acid) and vitamin A which may rarely produce symptoms of vitamin A deficiency or vitamin C deficiency.

Adverse Reactions last revised 1/19/2005 7:53:00 PM

Patient Education

Prednisone oral solution or syrup

What is prednisone oral solution?
PREDNISONE (Prednisone Intensol®) is a corticosteroid. It helps to reduce swelling, redness, itching, and allergic reactions and can be used to treat severe allergies, skin problems, asthma, arthritis and other conditions. Generic prednisone oral solution is available.

What should my health care professional know before I take prednisone?
They need to know if you have any of these conditions:
•cataracts or glaucoma
•Cushing's syndrome
•diabetes
•heart problems, or previous heart attack
•high blood pressure or blood clotting disorder
•infection, such as herpes, measles, tuberculosis or chickenpox
•myasthenia gravis
•pschosis
•osteoporosis
•recent surgery
•seizures (convulsions)
•stomach or intestinal disease, including colitis
•under-active thyroid
•an unusual or allergic reaction to prednisone, other corticosteroids, medicines, foods, dyes, or preservatives
•pregnant or trying to get pregnant
•breast-feeding

How should I take this medicine?
Take prednisone oral solution by mouth. Follow the directions on the prescription label. Shake well before using. Use a specially marked spoon or container to measure your medicine. Ask your pharmacist if you do not have one; household spoons are not always accurate. Take with food or milk to avoid stomach upset. If you are only taking prednisone once a day, take it in the morning, which is the time your body normally secretes cortisol. Take your doses at regular intervals. Do not take your medicine more often than directed.

Contact your pediatrician or health care professional regarding the use of this medicine in children. Special care may be needed.

What if I miss a dose?
If you miss a dose, take it a soon as you can. If it is almost time for your next dose, consult your prescriber or health care professional. You may need to miss a dose or take a double dose, depending on your condition and treatment. Do not take double or extra doses without advice.

What drug(s) may interact with prednisone?
•acetazolamide
•antiinflammatory drugs (NSAIDs, such as ibuprofen)
•barbiturate medicines for inducing sleep or treating seizures
•bosentan
•certain heart medicines
•female hormones, including contraceptives or birth control pills
•live virus vaccines, and other toxoids and vaccines
•medicines for diabetes
•mifepristone
•phenytoin
•rifabutin
•rifampin
•water pills
•warfarin

Tell your prescriber or health care professional about all other medicines you are taking, including non-prescription medicines, nutritional supplements, or herbal products. Also tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs. These may affect the way your medicine works. Check with your health care professional before stopping or starting any of your medicines.

What side effects may I notice from taking prednisone?
Side effects that you should report to your prescriber or health care professional as soon as possible:
•bloody or black, tarry stools
•confusion, excitement, restlessness, a false sense of well-being
•eye pain, decreased or blurred vision, or bulging eyes
•fever, sore throat, sneezing, cough, or other signs of infection, wounds that will not heal
•frequent passing of urine
•increased thirst
•irregular heartbeat
•menstrual problems
•mental depression, mood swings, mistaken feelings of self-importance or of being mistreated
•muscle cramps or weakness
•nausea, vomiting
•pain in hips, back, ribs, arms, shoulders, or legs
•rounding out of face
•skin problems, acne, thin and shiny skin
•stomach pain
•swelling of feet or lower legs
•unusual bruising, pinpoint red spots on the skin
•unusual tiredness or weakness
•weight gain or weight loss

Side effects that usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome):
•diarrhea or constipation
•headache
•increased or decreased appetite
•increased sweating
•nervousness, restlessness, or difficulty sleeping
•upset stomach
•unusual increased growth of hair on the face or body

What should I watch for while taking prednisone?
Visit your prescriber or health care professional for regular checks on your progress. If you are taking prednisone over a prolonged period, carry an identification card with your name and address, the type and dose of your medicine, and your prescriber's name and address. Do not suddenly stop taking prednisone. You may need to gradually reduce the dose, so that your body can adjust. Follow the advice of your prescriber or health care professional.

If you are taking prednisone regularly, avoid contact with people who have an infection. You will have an increased risk from infection while taking prednisone. Tell your prescriber or health care professional if you are exposed to anyone with measles or chickenpox, or if you develop sores or blisters that do not heal properly.

People who are taking certain dosages of prednisone may need to avoid immunization with certain vaccines or may need to have changes in their vaccination schedules to ensure adequate protection from certain diseases. Make sure to tell your prescriber or health care professional that you are taking prednisone before receiving any vaccine.

If you are going to have surgery, tell your prescriber or health care professional that you have received prednisone within the last twelve months.

If you receive prednisone every day, you may need to watch your diet. Your body can lose potassium while you are taking this medicine. Ask your prescriber or health care professional about your diet.

Prednisone can affect your blood sugar. If you are diabetic check with your prescriber or health care professional if you need help adjusting the dose of your diabetic medicine.

Alcohol can increase the risk of getting serious side effects while you are taking prednisone. Avoid alcoholic drinks.

Prednisone can interfere with certain lab tests and can cause false skin test results.

Where can I keep my medicine?
Keep out of the reach of children.

Store at room temperature between 15 and 30 degrees C (59 and 86 degrees F); do not freeze. Throw away any unused medicine after the expiration date.

NOTE: This information is not intended to cover all possible uses, precautions, interactions, or adverse effects for this drug. If you have questions about the drug(s) you are taking, check with your health care professional.

 [Revised: 11/29/2005]

Prednisone tablets

What are prednisone tablets?
PREDNISONE (Deltasone®) is a corticosteroid. It helps to reduce swelling, redness, itching, and allergic reactions and can be used to treat severe allergies, skin problems, asthma, arthritis and other conditions. Generic prednisone tablets are available.

What should my health care professional know before I take prednisone?
They need to know if you have any of these conditions:
•cataracts or glaucoma
•Cushing's syndrome
•diabetes
•heart problems, or previous heart attack
•high blood pressure or blood clotting disorder
•infection, such as herpes, measles, tuberculosis or chickenpox
•myasthenia gravis
•pschosis
•osteoporosis
•recent surgery
•seizures (convulsions)
•stomach or intestinal disease, including colitis
•under-active thyroid
•an unusual or allergic reaction to lactose, prednisone, other corticosteroids, medicines, foods, dyes, or preservatives
•pregnant or trying to get pregnant
•breast-feeding

How should I take this medicine?
Take prednisone tablets by mouth. Follow the directions on the prescription label. Swallow the tablets with a drink of water. Take with food or milk to avoid stomach upset. If you are only taking prednisone once a day, take it in the morning, which is the time your body normally secretes cortisol. Take your doses at regular intervals. Do not take your medicine more often than directed.

Contact your pediatrician or health care professional regarding the use of this medicine in children. Special care may be needed.

What if I miss a dose?
If you miss a dose, take it a soon as you can. If it is almost time for your next dose, consult your prescriber or health care professional. You may need to miss a dose or take a double dose, depending on your condition and treatment. Do not take double or extra doses without advice.

What drug(s) may interact with prednisone?
•acetazolamide
•antiinflammatory drugs (NSAIDs, such as ibuprofen)
•barbiturate medicines for inducing sleep or treating seizures
•bosentan
•calcium supplements
•certain heart medicines
•female hormones, including contraceptives or birth control pills
•live virus vaccines, and other toxoids and vaccines
•medicines for diabetes
•mifepristone
•phenytoin
•rifabutin
•rifampin
•water pills
•warfarin

Tell your prescriber or health care professional about all other medicines you are taking, including non-prescription medicines, nutritional supplements, or herbal products. Also tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs. These may affect the way your medicine works. Check with your health care professional before stopping or starting any of your medicines.

What side effects may I notice from taking prednisone?
Side effects that you should report to your prescriber or health care professional as soon as possible:
•bloody or black, tarry stools
•confusion, excitement, restlessness, a false sense of well-being
•eye pain, decreased or blurred vision, or bulging eyes
•fever, sore throat, sneezing, cough, or other signs of infection, wounds that will not heal
•frequent passing of urine
•increased thirst
•irregular heartbeat
•menstrual problems
•mental depression, mood swings, mistaken feelings of self-importance or of being mistreated
•muscle cramps or weakness
•nausea, vomiting
•pain in hips, back, ribs, arms, shoulders, or legs
•rounding out of face
•skin problems, acne, thin and shiny skin
•stomach pain
•swelling of feet or lower legs
•unusual bruising, pinpoint red spots on the skin
•unusual tiredness or weakness
•weight gain or weight loss

Side effects that usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome):
•diarrhea or constipation
•headache
•increased or decreased appetite
•increased sweating
•nervousness, restlessness, or difficulty sleeping
•upset stomach
•unusual increased growth of hair on the face or body

What should I watch for while taking prednisone?
Visit your prescriber or health care professional for regular checks on your progress. If you are taking prednisone over a prolonged period, carry an identification card with your name and address, the type and dose of your medicine, and your prescriber's name and address. Do not suddenly stop taking prednisone. You may need to gradually reduce the dose, so that your body can adjust. Follow the advice of your prescriber or health care professional.

If you are taking prednisone regularly, avoid contact with people who have an infection. You will have an increased risk from infection while taking prednisone. Tell your prescriber or health care professional if you are exposed to anyone with measles or chickenpox, or if you develop sores or blisters that do not heal properly.

People who are taking certain dosages of prednisone may need to avoid immunization with certain vaccines or may need to have changes in their vaccination schedules to ensure adequate protection from certain diseases. Make sure to tell your prescriber or health care professional that you are taking prednisone before receiving any vaccine.

If you are going to have surgery, tell your prescriber or health care professional that you have received prednisone within the last twelve months.

If you receive prednisone every day, you may need to watch your diet. Your body can lose potassium while you are taking this medicine. Ask your prescriber or health care professional about your diet.

Prednisone can affect your blood sugar. If you are diabetic check with your prescriber or health care professional if you need help adjusting the dose of your diabetic medicine.

Alcohol can increase the risk of getting serious side effects while you are taking prednisone. Avoid alcoholic drinks.

Prednisone can interfere with certain lab tests and can cause false skin test results.

Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.

Store at room temperature between 15 and 30 degrees C (59 and 86 degrees F). Throw away any unused medicine after the expiration date.

NOTE: This information is not intended to cover all possible uses, precautions, interactions, or adverse effects for this drug. If you have questions about the drug(s) you are taking, check with your health care professional.

 [Revised: 11/29/2005]

Temazepam
Restoril®

Classification:
• Psychotropic Agents
    • Anxiolytics, Sedatives, and Hypnotics
        • Benzodiazepines

Description, Mechanism of Action, Pharmacokinetics

NOTE: Temazepam is a schedule C-IV controlled substance.

Description: Temazepam is an oral benzodiazepine used as a hypnotic agent in the short-term management of insomnia. Temazepam is often preferable to flurazepam for insomnia, particularly in the elderly or patients with liver disease, because temazepam has a shorter half-life and does not have active metabolites. Some clinicians, however, prefer flurazepam when a hypnotic is needed due to its more rapid onset of action. Temazepam was approved by the FDA in 1981.

Mechanism of Action: Benzodiazepines act at the level of the limbic, thalamic, and hypothalamic regions of the CNS and can produce any level of CNS depression required including sedation, hypnosis, skeletal muscle relaxation, and anticonvulsant activity. Recent evidence indicates that benzodiazepines exert their effects through enhancement of the gamma-aminobutyric acid (GABA)-benzodiazepine receptor complex. GABA is an inhibitory neurotransmitter that exerts its effects at specific receptor subtypes designated GABA-A and GABA-B. GABA-A is the primary receptor subtype in the CNS and is thought to be involved in the actions of anxiolytics and sedatives.

Specific benzodiazepine receptor subtypes are thought to be coupled to GABA-A receptors. Three types of BNZ receptors are located in the CNS and other tissues; the BNZ1 receptors are located in the cerebellum and cerebral cortex, the BNZ2 receptors in the cerebral cortex and spinal cord, and the BNZ3 receptors in peripheral tissues. Activation of the BNZ1 receptor is thought to mediate sleep while the BNZ2 receptor affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. Benzodiazepines bind nonspecifically to BNZ1 and BNZ2 which ultimately enhances the effects of GABA. Unlike barbiturates which augment GABA responses by increasing the length of time that chloride channels are open, benzodiazepines enhance the effects of GABA by increasing GABA affinity for the GABA receptor. Binding of GABA to the site opens the chloride channel resulting in a hyperpolarized cell membrane that prevents further excitation of the cell.

Benzodiazepines alleviate insomnia by decreasing the latency to sleep and increasing sleep continuity and total sleep time through their effects on GABA.

Pharmacokinetics: Temazepam is administered orally and is rapidly absorbed. The onset of action occurs within 30—60 minutes. The drug is widely distributed and is 98% protein-bound. Temazepam crosses the placenta and may be distributed into breast milk (see Contraindications). The half-life of the parent compound is 8—15 hours. Temazepam is metabolized by direct conjugation with glucuronic acid to inactive metabolites, which are then excreted in the urine.

Description, Mechanism of Action, Pharmacokinetics last revised 2/15/2001

Indications

• insomnia

Dosage

For the short-term treatment of insomnia:
Oral dosage:
Adults: The usual dose is 15 mg PO 30 minutes before bedtime. If this dose is inadequate, then the dose may be increased to 30 mg PO before bedtime. In some patients, 7.5 mg may be sufficient to treat transient insomnia.
Elderly or debilitated patients: Initiate therapy at 7.5 mg PO 30 minutes before bedtime and titrate to response, up to 30 mg PO before bedtime. OBRA guidelines for long-term care residents recommend maximum dose of 15 mg PO before bedtime in the majority of patients; dosage up to 30 mg/day at bedtime should be limited.[4460]
Children: Safe and effective use has not been established.

Maximum Dosage Limits:
•Adults: 30 mg/day PO.
•Elderly: 30 mg/day PO; OBRA guidelines state maximum dose is 15 mg/day PO for skilled care residents.
•Adolescents: Safe and effective use has not been established.
•Children: Safe and effective use has not been established.

Patients with hepatic impairment:
It appears no dosage adjustment is needed. Although a slight decrease in clearance is apparent in patients with cirrhosis, the difference is not enough to warrant changes in the normal dosing of the drug. Adjust to patient response and tolerance.

Patients with renal impairment:
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Indications...Dosage last revised 2/25/2004 2:27:00 PM

Administration Guidelines

Oral Administration
•Temazepam is administered at bedtime.

†non-FDA approved

Administration last revised 7/1/2002

†non-FDA-approved indication

Contraindications/Precautions

• abrupt discontinuation	• infants
• benzodiazepine hypersensitivity	• mania
• breast-feeding	• myasthenia gravis
• ethanol intoxication	• obstetric delivery
• pregnancy	• pain
• alcoholism	• Parkinson's disease
• benzodiazepine dependence	• porphyria
• bipolar disorder	• psychosis
• children	• pulmonary disease
• chronic obstructive pulmonary disease (COPD)	• renal failure
• closed-angle glaucoma	• renal impairment
• CNS depression	• respiratory depression
• coma	• seizure disorder
• dementia	• seizures
• depression	• shock
• driving or operating machinery	• sleep apnea
• elderly	• status epilepticus
• hepatic disease	• substance abuse
• hypotension	• suicidal ideation

• Absolute contraindications are in italics.

Temazepam is contraindicated in any patient with a known or suspected hypersensitivity to temazepam, other benzodiazepine hypersensitivity, or with sensitivity to any component of the formulation.

Occasionally, pre-existing depression may emerge or worsen with the use of benzodiazepines; therefore, temazepam should be used prudently in patients with major depression or psychosis. Temazepam should be administered cautiously and prescribed in the smallest amount possible to patients with suicidal ideation or a history of suicide attempt. In bipolar disorder, mania and hypomania have been reported in conjunction with the use of benzodiazepines. Use caution in patients with a neuromuscular disease, such as muscular dystrophy, myotonia, or myasthenia gravis as these conditions can be exacerbated. Patients with late stage Parkinson's disease may experience worsening of their psychosis or impaired cognition with administration of benzodiazepines. Benzodiazepines may also cause incoordination or paradoxical reactions that may worsen symptoms of Parkinson's disease.

The use of benzodiazepines may worsen severe pain. Benzodiazepines do not provide analgesic, antidepressant or antipsychotic effects.

Due to CNS depression, patients should be cautioned against driving or operating machinery until they know how temazepam may affect them. Some patients may experience excessive sedation and impaired ability to perform tasks. Increased CNS effects may be seen with concurrent use of temazepam and other CNS depressant agents (see Drug Interactions), and in patients with acute ethanol intoxication or organic brain syndromes (i.e., dementia). Patients with ethanol intoxication who have also consumed temazepam have an increased risk of respiratory suppression, hypotension and coma; avoid use in patients with alcoholism. Temazepam should not be used in patients with preexisting respiratory depression or in cases of shock or coma because the drug can worsen respiratory and central depression. Temazepam should not be used in patients with pulmonary disease that may decrease respiratory function such as chronic obstructive pulmonary disease (COPD) or sleep apnea. Temazepam should be used cautiously in patients who snore regularly, because partial airway obstruction may convert to obstructive sleep apnea with benzodiazepine administration.

Temazepam can cause physical and psychological dependence, and should be used with extreme caution in patients with known, suspected or a history of substance abuse. Tolerance (or tachyphylaxis) may develop to the sedative effects of benzodiazepines. Abrupt discontinuation of temazepam after prolonged use should be avoided. Abrupt discontinuation of benzodiazepine therapy has been reported to cause withdrawal symptoms, seizures and status epilepticus, especially following high dose or prolonged therapy (see Adverse Effects). However, benzodiazepine dependence can occur following administration of therapeutic doses for as few as 1—2 weeks, and withdrawal symptoms may be seen following the discontinuation of therapy. Patients with a history of a seizure disorder or who are taking other drugs that lower the seizure threshold (i.e., TCAs, phenothiazines) should not be withdrawn abruptly from benzodiazepines due to the risk of precipitating a seizure. Temazepam should be withdrawn slowly, using a gradual dosage-tapering schedule. During benzodiazepine withdrawal in general, the greatest risk of seizure appears to be during the first 24 to 72 hours.

According to most manufacturers, benzodiazepines are contraindicated in patients with acute closed-angle glaucoma. The mechanistic rational for this contraindication has been questioned, as benzodiazepines do not have antimuscarinic activity and do not raise intraocular pressure. Benzodiazepines may be used in patients with open-angle glaucoma who are receiving appropriate therapy.[3958] The manufacturers of temazepam do not contraindicate its use in patients with closed-angle glaucoma.

The administration of temazepam can exacerbate acute intermittent porphyria, so the drug should be used with caution in patients with this condition.

Temazepam is classified in FDA pregnancy risk category X. Temazepam should not be used during pregnancy. The possibility that a woman of child-bearing potential may be pregnant should be ruled out prior to initiating temazepam. Adequate birth control measures should be instituted. Positive evidence of human fetal risk exists based on investigational, marketing, or human studies. Fetal abnormalities have been reported in infants whose mothers used benzodiazepines during the first trimester of pregnancy. There may also be non-teratogenic risks associated with benzodiazepines during the perinatal period, including neonatal flaccidity, respiratory suppression, feeding difficulties, and hypothermia in infants born to mothers who received benzodiazepines late in pregnancy. Abrupt withdrawal of temazepam may lead to seizure activity in the mother. Even a mild seizure may pose hazards to the developing fetus. If a woman becomes pregnant while taking temazepam, she should be counseled regarding the potential risks to the fetus. Temazepam has no established use in labor or obstetric delivery, including cesarean section.

Temazepam is excreted into breast milk. Temazepam is contraindicated in women who are breast-feeding due to the possibility of CNS and respiratory suppression, feeding difficulties and weight loss in the nursing infant.

Temazepam should be administered cautiously to patients with severe hepatic disease because the elimination half-life of the drug can be prolonged, possibly resulting in toxicity. Patients with hepatic disease are more likely to experience adverse CNS reactions and should receive reduced initial dosages.

Temazepam should be administered cautiously to patients with renal impairment or renal failure; in general, initial dose selection should be in the lower range and dosage titration should proceed cautiously. Assess renal function during prolonged therapy and adjust dosage as clinically indicated. No active metabolites are excreted renally during temazepam use; therefore, it may be a more appropriate benzodiazepine in patients with renal impairment.

The clearance and/or elimination of many drugs are reduced in the elderly. Delayed elimination can either intensify or prolong the actions of adverse reactions of the drug. Benzodiazepines have been associated with an increased incidence of falls in the elderly. The impairment of cognitive and motor function may be more marked in this patient group and lower initial dosage is recommended together with close monitoring (see Dosage). In the elderly, the use of a benzodiazepine without active metabolites (i.e., estazolam, lorazepam, temazepam) will help to prevent accumulation and worsened toxicity. Federal OBRA regulations recommend dosage limits for anxiolytic and hypnotic use in the elderly nursing home resident (see Dosage).[4460]

Flumazenil, a benzodiazepine receptor antagonist, is indicated for partial or complete reversal of the depressive effects of benzodiazepines, and may be useful in overdose situations (see Flumazenil monograph). The prescriber should be aware of the risk for seizure activity with flumazenil use, particularly in long-term users of benzodiazepines or patients presenting with a cyclic antidepressant overdose.

The safe and effective use of temazepam in children under 18 years old has not been established. Children are generally more sensitive to the CNS effects of the benzodiazepines.

Contraindications last revised 2/25/2004 2:27:00 PM

Drug Interactions

	Anxiolytics, Sedatives, and Hypnotics	• Melatonin
	Barbiturates	• Nalbuphine
• Buprenorphine			Opiate agonists
• Butorphanol			Oral contraceptives
• Caffeine		• Pentazocine
• Clozapine			Phenothiazines
• Dronabinol, THC		• Phenytoin
• Entacapone		• Pregabalin
• Ethanol		• Probenecid
• Ethotoin			Radiopaque Contrast Agents
• Flumazenil			Sedating H1-blockers
• Fosphenytoin		• Theophylline, Aminophylline
	General Anesthetics	• Tolcapone
• Green Tea		• Tramadol
• Guarana			Tricyclic antidepressants
• Kava Kava, Piper methysticum		• Valerian, Valeriana officinalis

Benzodiazepines should be combined cautiously with clozapine because they could cause additive CNS depressant effects. Severe confusion, hypotension and respiratory depression have occurred rarely in those patients receiving clozapine concurrently or following benzodiazepine therapy. A single case report is noted where the addition of clozapine to maintenance therapy with clonazepam lead to somnolence, confusion, disorientation, and ataxia. The symptoms cleared after clonazepam was discontinued. In patients receiving concomitant clozapine, the starting doses of the benzodiazepine should be approximately one-half of the usual dose until experience with the patient has been gained.[4989] [7490] [7491]

Concomitant administration of temazepam with CNS-depressant drugs [7168], including opiate agonists [7187], buprenorphine, butorphanol, nalbuphine, pentazocine, phenothiazines [5732], barbiturates [4718], dronabinol, THC [7185], entacapone [5769], ethanol, sedating H1-blockers [3321], general anesthetics [6892], pregabalin [7523], tolcapone [5578], tramadol [5043], tricyclic antidepressants, or other anxiolytics, sedatives, and hypnotics [7168], can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent.[6729]

Oral contraceptives can decrease the effects of temazepam because oral contraceptives enhance glucuronidation, thereby decreasing serum concentrations of concomitantly administered benzodiazepines that undergo glucuronidation. Patients receiving oral contraceptive therapy should be observed for evidence of decreased response to temazepam.[7486]

Probenecid may inhibit the hepatic metabolism of temazepam based on studies conducted with lorazepam and midazolam. Patients receiving benzodiazepines should be monitored for signs of an exaggerated response if probenecid is used concomitantly.[5035]

Ethotoin [4622], phenytoin [4718] (or fosphenytoin) may increase the hepatic clearance of benzodiazepines.[4718] Interactions have been documented with benzodiazepines metabolized by oxidation or conjugation (e.g., chlordiazepoxide, diazepam, midazolam, oxazepam).

Flumazenil and benzodiazepines are pharmacological opposites. Flumazenil is specifically used to reverse the actions of benzodiazepines.[6149] Clinicians should note that the duration of action for some benzodiazepines may be much longer than that of flumazenil and repeat doses of flumazenil may be necessary.

It appears prudent to recommend caution when temazepam is prescribed in conjunction with melatonin. In animal studies, melatonin has been shown to increase benzodiazepine binding to receptor sites, and this may result in clinically significant drug interactions. Case reports exist of concomitant benzodiazepine and melatonin use in humans; the cases resulted in lethargy, short-term amnestic responses, or prolonged benzodiazepine activity. These apparent interactions could have been the result of a pharmacokinetic or pharmacodynamic enhancement of benzodiazepine activity by melatonin.[2106] [2107]

The German Commission E warns that any substances that act on the CNS, including psychotropic agents, may interact with kava kava.[5559] While the interactions can be pharmacodynamic in nature, kava kava has been reported to inhibit many CYP isozymes (i.e., CYP1A2, 2C9, 2C19, 2D6, 3A4, and 4A9/11) and important pharmacokinetic interactions with agents that undergo oxidative metabolism (e.g., selected benzodiazepines) are also possible.[5569] Patients on benzodiazepine therapy should avoid concomitant administration of kava kava. Patients should discuss the use of herbal supplements with their health care professional prior to consuming kava kava and should not abruptly stop taking their prescribed medications.

Any substances that act on the CNS, including benzodiazepines, may interact with valerian, Valeriana officinalis. These interactions are probably pharmacodynamic in nature. [5565] Patients who are on temazepam should avoid concomitant administration of valerian.

Theophylline has been reported to counteract the pharmacodynamic effects (e.g., sedative and anxiolytic effects) of diazepam. A proposed mechanism is competitive binding of theophylline to adenosine receptors in the brain. Whether a similar interaction occurs with other benzodiazepines is not known. If theophylline therapy is initiated or discontinued, monitor the clinical response to benzodiazepines.[4764]

Patients taking benzodiazepines for insomnia should not use caffeine-containing products (e.g., coffee, green tea, other teas, guarana, or colas) prior to going to bed as these products may antagonize the sedative effects of the benzodiazepine.[4764]

The use of intrathecal radiopaque contrast agents is associated with a risk of seizures. Patients should be instructed to continue using benzodiazepines during procedures or exams that require the use of intrathecal radiopaque contrast agents as abrupt discontinuation of benzodiazepines may also increase seizure risk. [5422] [5698]

Interactions last revised 2/21/2005 5:03:00 PM

Adverse Reactions

• anxiety	• insomnia
• ataxia	• mania
• confusion	• nightmares
• depression	• physiological dependence
• dizziness	• syncope
• drowsiness	• teratogenesis
• euphoria	• tremor
• fatigue	• vertigo
• headache	• withdrawal

Most of the adverse effects associated with temazepam therapy are dose-dependent and CNS-related including headache, drowsiness, ataxia, dizziness, confusion, depression, syncope, fatigue, tremor, and vertigo.

Daytime anxiety or wakefulness during the last third of the night may develop during several weeks of consistent nightly dosing with temazepam. These effects are thought to be due to the development of tolerance, which leads to a deficiency of benzodiazepine binding sites.

CNS stimulation can occur in as many as 10% of patients receiving benzodiazepines and is of particular significance in psychiatric patients and hyperactive children. This paradoxical effect is possibly due to disinhibition of previously inhibited responses. Symptoms of CNS stimulation include nightmares, talkativeness, excitement, mania, tremor, insomnia, anxiety, restlessness, euphoria, acute rage reactions, and hyperactivity. Benzodiazepine therapy usually should be discontinued if signs of CNS stimulation occur.

Physiological dependence on temazepam is evidenced by manifestation of withdrawal symptoms. Abrupt withdrawal of benzodiazepine therapy has been reported to cause withdrawal symptoms such as irritability, nervousness, and insomnia. Benzodiazepine withdrawal is more likely to occur following abrupt cessation of excessive or prolonged doses, but it can occur following the discontinuance of therapeutic doses administered for as few as 1—2 weeks. Abdominal cramps, confusion, depression, perceptual disturbances, sweating, nausea, vomiting, parasthesias, photophobia, hyperacusis, tachycardia, and trembling also occur during benzodiazepine withdrawal, but the incidence of these reactions is lower. Convulsions, hallucinations, delirium, and paranoia also can occur. Benzodiazepines should be withdrawn cautiously and slowly, using a very gradual dosage-tapering schedule.

Temazepam is classified as FDA pregnancy risk category X. Many benzodiazepines have been associated with teratogenesis. Use of benzodiazepines during pregnancy, particularly in the first trimester, increases the risk of congenital malformations and decreases viability.

Adverse Reactions last revised 7/1/2002

Patient Education

Temazepam tablets or capsules

What are temazepam tablets or capsules?
TEMAZEPAM (Restoril®) is a benzodiazepine. Benzodiazepines belong to a group of medicines that slow down the central nervous system. Temazepam helps to treat insomnia (difficulty sleeping at night). Federal law prohibits the transfer of temazepam to any person other than the patient for whom it was prescribed. Do not share this medicine with anyone else. Generic temazepam tablets and capsules are available.

What should my health care professional know before I take temazepam?
They need to know if you have any of these conditions:
•an alcohol or drug abuse problem
•bipolar disorder, depression, psychosis or other mental health condition
•glaucoma
•kidney disease
•liver disease
•lung disease, such as chronic obstructive pulmonary disease (COPD), sleep apnea or other breathing difficulties
•myasthenia gravis
•Parkinson's disease
•porphyria
•seizures or a history of seizures
•shortness of breath
•snoring
•suicidal thoughts
•uncontrolled pain
•an unusual or allergic reaction to temazepam, other benzodiazepines, other medicines, foods, dyes, or preservatives
•pregnant or trying to get pregnant
•breast-feeding

How should I take this medicine?
Take temazepam tablets or capsules by mouth. Temazepam is only for use at bedtime. Follow the directions on the prescription label. Swallow the tablets or capsules with a drink of water. If temazepam upsets your stomach, take it with food or milk. Do not take your medicine more often than directed. Do not stop taking except on your prescriber's advice.

Contact your pediatrician or health care professional regarding the use of this medicine in children. Special care may be needed.

What if I miss a dose?
If you miss a dose, take it as soon as you can. It can take up to 2 hours for drowsiness to occur; never repeat the dose before 2 hours have passed. Do not take double or extra doses.

What drug(s) may interact with temazepam?
•alcohol
•barbiturate medicines for inducing sleep or treating seizures (convulsions), like phenobarbital
•caffeine
•female hormones, including contraceptive or birth control pills
•herbal or dietary supplements such as kava kava, melatonin, or valerian
•medicines for anxiety or sleeping problems, such as alprazolam, diazepam, lorazepam or triazolam
•medicines for depression, mental problems or psychiatric disturbances
•phenytoin
•prescription pain medicines
•probenecid
•some medicines for colds, hay fever or other allergies
•theophylline

Tell your prescriber or health care professional about all other medicines you are taking, including non-prescription medicines, nutritional supplements, or herbal products. Also tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs. These may affect the way your medicine works. Check with your health care professional before stopping or starting any of your medicines.

What side effects may I notice from taking temazepam?
Side effects that you should report to your prescriber or health care professional as soon as possible:
•confusion
•depression
•lightheadedness or fainting spells
•mood changes, excitability or aggressive behavior
•movement difficulty, staggering or jerky movements
•muscle cramps
•tremors
•weakness or tiredness

Side effects that usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome):
•dizziness, drowsiness, clumsiness, or unsteadiness; a 'hangover' effect
•headache
•increased dreaming
•nausea, vomiting

What should I watch for while taking temazepam?
Visit your prescriber or health care professional for regular checks on your progress. Temazepam is for short-term periods of use. If sleep medicine is taken every night for a long time it may no longer help you to sleep. Your body can become dependent on temazepam, ask your prescriber or health care professional if you still need to take it. However, if you have been taking temazepam regularly for some time, do not suddenly stop taking it. You must gradually reduce the dose or you may get severe side effects. Ask your prescriber or health care professional for advice. Even after you stop taking temazepam it can still affect your body for several days.

You may get drowsy or dizzy. Do not drive, use machinery, or do anything that needs mental alertness until you know how temazepam affects you. To reduce the risk of dizzy and fainting spells, do not stand or sit up quickly, especially if you are an older patient. Alcohol may increase dizziness and drowsiness. Avoid alcoholic drinks.

Do not treat yourself for coughs, colds or allergies without asking your prescriber or health care professional for advice. Some ingredients can increase possible side effects.

If you are going to have surgery, tell your prescriber or health care professional that you are taking temazepam.

Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.

Store at room temperature below 30 degrees C (86 degrees F). Protect from light. Keep container tightly closed. Throw away any unused medicine after the expiration date.

NOTE: This information is not intended to cover all possible uses, precautions, interactions, or adverse effects for this drug. If you have questions about the drug(s) you are taking, check with your health care professional.

 [Revised: 03/13/2003]

Furosemide
Delone™ | Furocot™ | Lasix®

Classification:
• Cardiovascular Agents
    • Antihypertensive Agents
        • Diuretics
• Electrolytic and Renal Agents
    • Diuretics
        • Loop diuretics
• Electrolytic and Renal Agents
    • Diuretics
        • Thiazide diuretics

Description, Mechanism of Action, Pharmacokinetics

Description: Furosemide is a sulfonamide-type loop diuretic used in the management of edema associated with congestive heart failure, cirrhosis, and renal disease, including the nephrotic syndrome. Other uses include mild to moderate hypertension and as an adjunct in hypertensive crisis and acute pulmonary edema. Furosemide is also useful in treating hypercalcemia, although it is not FDA approved for this indication. Furosemide is especially effective in managing edema associated with congestive heart failure, and it may be particularly useful in patients who are unresponsive to other diuretics or who have severe renal impairment. Furosemide was approved by the FDA in 1966.

Mechanism of Action: Furosemide is a loop diuretic that acts to inhibit the reabsorption of sodium and chloride in the ascending limb of the loop of Henle by interfering with the chloride-binding of the Na+/K+/2Cl- cotransport system, altering electrolyte transfer in the proximal tubule. A profound diuresis results from the increased urinary excretion of sodium, chloride, potassium, and hydrogen ions. In addition, furosemide increases the excretion of calcium, magnesium, bicarbonate, ammonium, and phosphate. The diuresis caused by furosemide can lead to increased aldosterone production, resulting in increased sodium resorption, and increased potassium and hydrogen excretion. Excessive loss of these electrolytes can lead to metabolic alkalosis.

Furosemide's effectiveness is independent of the acid-base status of the patient. Renal vasodilation occurs following administration of furosemide; renal vascular resistance decreases, and renal blood flow is enhanced. Reduced peripheral vascular resistance and increased peripheral venous capacitance also occur, and the subsequent decrease in left ventricular filling pressure may contribute to the drug's beneficial effect in patients with congestive heart failure. Initially, diuretics lower blood pressure by causing hypovolemia (decreased plasma and extracellular fluid), a temporary increase in glomerular filtration rate, and a decreased cardiac output. Cardiac output eventually returns to normal, but peripheral resistance is now reduced, resulting in lower blood pressure. In general, diuretics worsen LVH and glucose tolerance, and exert detrimental effects on the lipid profile.

Pharmacokinetics: Furosemide is administered orally and intravenously. It is absorbed erratically following an oral dose, and food will delay this absorption but will not alter the diuretic response. Diuresis generally begins 30 to 60 minutes after oral administration and about 5 minutes after IV administration. The drug is 95% plasma protein-bound, crosses the placenta, and appears in breast milk. Furosemide undergoes minimal metabolism in the liver, with 50—80% of a dose excreted in the urine within 24 hours. The remainder of the drug is eliminated through nonrenal mechanisms including being excreted unchanged in the feces. In patients with significant renal impairment, nonrenal elimination can increase to 98%. The half-life of furosemide is approximately 0.5—1 hour. However, in neonates and in patients with renal and hepatic impairment, half-lives are prolonged. NOTE: Larger doses may be necessary in patients with renal impairment.

Description, Mechanism of Action, Pharmacokinetics last revised 11/19/2002 12:46:00 PM

Indications

• ascites†	• hypertensive emergency†
• edema	• hypertensive urgency†
• heart failure	• nephrotic syndrome
• hypercalcemia†	• pulmonary edema
• hypertension

† non-FDA-approved indication

Dosage

For the treatment of peripheral edema, or edema associated with heart failure or nephrotic syndrome:
Oral dosage:
Adults: Initially, 20—80 mg PO as a single dose, which may be repeated in 6—8 hours. Titrate doses upward in 20—40 mg increments. The usual dosage is 40—120 mg/day PO. Maximum dosage is 600 mg/day PO.
Elderly: See adult dosage. Elderly patients may be more sensitive to the effects of the usual adult dosage.
Children and infants: Initially, 1—2 mg/kg PO every 6—12 hours. Maximum dosage is 6 mg/kg/dose PO.
Premature neonates: Doses of 1—4 mg/kg PO, given 1—2 times daily, have been used. Bioavailability is poor.
Parenteral dosage:
Adults: Initially, 20—40 mg IV or IM, increasing by 20 mg every 2 hours as needed to attain clinical response. IV doses should be given slowly. A maximum infusion rate of 4 mg/min has been recommended for patients receiving IV doses greater than 120 mg or for patients with cardiac or renal failure.[52]
Elderly: See adult dosage. Elderly patients may be more sensitive to the effects of the usual adult dosage.
Children and infants: 1—2 mg/kg IV or IM every 6—12 hours. Maximum dosage is 6 mg/kg/dose IV or IM.
Premature neonates: 1—2 mg/kg IV or IM every 12—24 hours.

For adjunctive treatment of acute pulmonary edema:
Parenteral dosage:
Adults: Initially, 40 mg IV injected slowly; then 80 mg IV injected slowly in 2 hours if needed.
Elderly: See adult dosage. Elderly patients may be more sensitive to the effects of the usual adult dosage.
Children: Initially, 1—2 mg/kg IV or IM, every 6—12 hours. Maximum dosage is 6 mg/kg/dose.
Premature neonates: 1—2 mg/kg IV or IM every 12—24 hours.

For the treatment of hypertension:
Oral dosage:
Adults: Initially, 40 mg PO twice daily. Adjust dosage according to response. Alternative dosage regimen is 10—20 mg PO twice daily, then adjusting dosage according to response. Maximum dosage is 600 mg/day PO.
Elderly: See adult dosage. Elderly patients may be more sensitive to the effects of the usual adult dosage.
Children and infants: Initially, 1—2 mg/kg PO every 6—12 hours. Maximum dosage is 6 mg/kg/dose PO.
Premature neonates: Doses of 1—4 mg/kg PO, given 1—2 times daily, have been used. Bioavailability is poor.

For adjunctive treatment of hypertensive urgency† or hypertensive emergency†:
Intravenous dosage:
Adults: Doses of 40—80 mg IV have been used in patients with normal renal function.
Elderly: See adult dosage. Elderly patients may be more sensitive to the effects of the usual adult dosage.

For adjunctive treatment of edema in patients with acute or chronic renal failure:
Oral dosage:
Adults: Initially, 80 mg PO once daily, increasing dose in increments of 80—120 mg/day until desired clinical response. For immediate diuresis, 320—400 mg PO once daily has been suggested.
Elderly: See adult dosage. Elderly patients may be more sensitive to the effects of the usual adult dosage.
Intravenous dosage:
Adults: Initially, 100—200 mg IV. Traditionally, it has been recommended that doses can be doubled every 2—24 hours until desired clinical response, however, most clinicians would probably consider 600—800 mg IV a maximum dose and either administer a different loop-active agent, or add a second agent in combination with furosemide. A maximum infusion rate of 4 mg/min has been recommended for patients receiving doses greater than 120 mg or for patients with cardiac or renal failure.[52]
Elderly: See adult dosage. Elderly patients may be more sensitive to the effects of the usual adult dosage.

For the acute treatment of hypercalcemia† associated with neoplastic disease in combination with intravenous saline:
Parenteral dosage:
Adults: Initially, 80—100 mg IVor IM with the dose being repeated every 1—2 hours as needed based on clinical response. Less severe cases may use smaller doses every 2—4 hours. Saline administration should begin before the first dose of furosemide is administered to avoid volume contraction which may limit the desired calciuric response.
Elderly: See adult dosage. Elderly patients may be more sensitive to the effects of the usual adult dosage.
Neonates, infants, and children: Initially, 25—50 mg IV or IM. The dose may be repeated every 4 hours as needed based on clinical response. Saline administration should begin before the first dose of furosemide is administered to avoid volume contraction which may limit the desired calciuric response.

For the treatment of ascites† in combination with spironolactone or amiloride:
Oral dosage:
Adults: Initially, 40 mg PO once daily, in the morning in combination with spironolactone; dosage may be increased after 2—3 days if no clinical response.[602]
Elderly: See adult dosage. Elderly patients may be more sensitive to the effects of the usual adult dosage.

Maximum Dosage Limits:
•Adults: 600 mg/day PO or 6 g/day IV infusion. Up to 4 g/day PO has been given to treat chronic renal failure.
•Elderly: 600 mg/day PO or 6 g/day IV infusion. Up to 4 g/day PO has been given to treat chronic renal failure.
•Adolescents: 6 mg/kg/dose PO.
•Children: 6 mg/kg/dose PO.
•Infants: 6 mg/kg/dose PO.
•Neonates: No maximum dosage information is available.

Patients with hepatic impairment:
No specific dosage adjustment is needed; see the dosage for the treatment of ascites. Diuretics should be used with caution in patients with hepatic disease since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

Patients with renal impairment:
No specific dosage adjustments are recommended. Higher doses with extended dosage intervals may be effective in patients with end-stage renal disease (ESRD).

†non-FDA-approved indication

Indications...Dosage last revised 3/22/2005 11:30:00 AM

Administration Guidelines

NOTE: In patients with acute or chronic renal failure, larger doses of oral or IV furosemide have been used.
NOTE: The risk of ototoxicity increases with larger doses and/or more rapid parenteral administration of furosemide.[51] A maximum infusion rate of 4 mg/min has been recommended for patients receiving IV doses greater than 120 mg or for patients with cardiac or renal failure.[52]
NOTE: Half-life in neonates will be prolonged. Increasing the dosage interval is suggested to help prevent toxicity. Elderly patients may be more sensitive to the effects of normal adult doses.

Oral Administration
•Administer with meals to minimize indigestion or GI irritation. If patient has difficulty swallowing, the tablets may be crushed.

Parenteral Administration
•The maximum concentration for administration is 10 mg/ml.
•Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Intramuscular injection:
•No dilution necessary.
•Inject deeply into a large muscle. Aspirate prior to injection to avoid injection into a blood vessel.

Direct IV injection:
•Inject each 20 mg slowly IV over 1—2 minutes.

Intermittent IV infusion:
•Dilute in NS, lactated Ringer's, or D5W injection solution; adjust pH to greater than 5.5 when necessary.
•Infuse intravenously at a rate not to exceed 4 mg/minute in adults or 0.5 mg/kg/minute in children.

Administration last revised 7/1/2002

Contraindications/Precautions

• anuria	• hypochloremia
• electrolyte imbalance	• hypokalemia
• acute myocardial infarction	• hypomagnesemia
• breast-feeding	• hyponatremia
• diabetes mellitus	• neonatal prematurity
• diarrhea	• pancreatitis
• eclampsia	• preeclampsia
• elderly	• pregnancy
• gout	• renal disease
• hearing impairment	• renal failure
• heart failure	• renal impairment
• hepatic disease	• sulfonamide hypersensitivity
• hyperglycemia	• systemic lupus erythematosus (SLE)
• hyperuricemia	• thiazide diuretic hypersensitivity
• hypocalcemia	• ventricular arrhythmias

• Absolute contraindications are in italics.

Furosemide is contraindicated in severe preexisting electrolyte imbalance such as hyponatremia, hypokalemia, hypocalcemia, hypochloremia, and hypomagnesemia. Furosemide-induced fluctuations in serum electrolyte concentrations can occur rapidly and precipitate coma in susceptible patients. Therefore, furosemide should be used with caution in patients with hepatic disease such as cirrhosis. Furosemide is contraindicated in patients with hepatic coma until this condition is corrected.

Blood and urine glucose levels should be assessed in patients with diabetes mellitus or hyperglycemia during treatment with furosemide; loop diuretics can impair glucose tolerance.

Patients with neonatal prematurity who receive furosemide in the first few weeks of life can have an increased risk of persistent patent ductus arteriosus.

Patients with ventricular arrhythmias, heart failure, potassium-losing nephropathy, aldosterone excess, or diarrhea should be monitored closely since furosemide-induced hypokalemia can exacerbate these conditions.

Excessive diuresis with furosemide should be avoided in patients with acute myocardial infarction due to the risk of precipitating shock.

Furosemide should not be used in anuria. It should be used cautiously in any patient with renal disease such as severe renal impairment or renal failure. Drug-induced hypovolemia can precipitate azotemia in these patients. Furosemide is an effective diuretic for many patients with renal impairment. Renal impairment may reduce clearance and warrant the use of higher doses with extended dosing intervals. Furosemide may be less effective in these patients and delayed excretion of drug may increase the risk of toxicity.

Greater sensitivity to the hypotensive and diuretic effects of furosemide is possible in elderly patients.

Due to similarities in chemical structure and the fact that haptens of both compounds can become covalently bound to macromolecules, patients with sulfonamide hypersensitivity or thiazide diuretic hypersensitivity may also be hypersensitive to furosemide. A case report, published in 1987, documents an anaphylactic reaction to IV furosemide. This patient was subsequently skin-tested with furosemide, bumetanide, ethacrynic acid, chlorothiazide, and sulfamethoxazole-trimethoprim and a positive reaction was elicited to all except ethacrynic acid.[3520] This case appears to be one of the only published reports of its kind. Prior to this, neither the FDA nor the manufacturer of Lasix® had received any reports of cross-sensitivity between furosemide and sulfonamide antibiotics.[178] [3520] Considering the widespread use of furosemide, the absolute risk of an allergic reaction in a patient with sulfonamide or thiazide diuretic hypertensively appears to be very low.[53] [178] Regarding cross-sensitivities within the loop diuretic group, Hansbrough and colleagues documented cross-reactivity between furosemide and bumetanide,[3520] but torsemide was not commercially available at that time. When evaluating the potential for cross-sensitivities between drugs in these categories, clinicians should consider not only similarities in chemical structure, but also metabolic intermediates and the potential of those molecules to serve as haptens and bind with tissue macromolecules.[53]

Furosemide has been reported to activate or exacerbate systemic lupus erythematosus (SLE), although the association is less certain than with procainamide or other drugs.

Since loop diuretics can reduce the clearance of uric acid, patients with gout or hyperuricemia can have exacerbations of their disease.

High doses and accumulation of furosemide may cause ototoxicity (see Adverse Reactions). Furosemide should be used with caution in patients with hearing impairment. The recommended rate of infusion should not be exceeded when IV doses are administered (see Dosage).

Furosemide has been reported to cause pancreatitis. It should be used with caution in patients with a history of pancreatitis.

Because no well-controlled studies have been performed with furosemide in pregnant women, it is classified as pregnancy category C. After the first trimester, it has been used for edema and hypertension. However, it is important to note that diuretics are generally not recommended for the treatment of pregnancy-induced hypertension (preeclampsia, eclampsia) since they do not alter the course of toxemia and may exacerbate maternal hypovolemia associated with this condition.

Because furosemide appears in breast milk, caution should be exercised when furosemide is administered to a breast-feeding mother. In addition, diuretics such as furosemide may suppress lactation.

Contraindications last revised 3/31/2004 5:21:00 PM

Drug Interactions

• Alendronate		• Horse Chestnut, Aesculus hippocastanum
	Aminoglycosides	• Ibandronate
• Amphotericin B		• Levomethadyl
	Angiotensin-converting enzyme inhibitors (ACE inhibitors)	• Lithium
	Antidiabetic Agents	• Metformin
	Antihypertensive Agents	• Methazolamide
• Arsenic Trioxide		• Metolazone
	Beta-agonists		Neuromuscular blockers
	Cardiac glycosides	• Nitroglycerin
• Cholestyramine			Nonsteroidal antiinflammatory drugs (NSAIDs)
• Cisplatin		• Norepinephrine
• Colestipol		• Palonosetron
	Corticosteroids	• Pamidronate
• Dofetilide		• Phenytoin
• Ephedra, Ma Huang			Potassium-sparing diuretics
• Ethacrynic Acid			Radiopaque Contrast Agents
• Ethanol			Salicylates
• Ginseng, Panax ginseng		• Sucralfate
• Hawthorn, Crataegus laevigata		• Zoledronic Acid

Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of loop diuretics, including furosemide.[5159] Hypokalemia increases the potential for proarrhythmic effects (e.g., torsade de pointes) due to arsenic trioxide, cardiac glycosides, dofetilide [4947], or levomethadyl. Potassium levels should be within the normal range prior and during administration of these agents. In the absence of electrolyte imbalances, furosemide and these agents can be used together safely.

Concomitant use of metolazone with a loop diuretic can cause severe electrolyte loss.[6135] Metolazone should only be used in combination with furosemide in patients who are refractory to loop diuretics alone. Close monitoring of serum electrolytes and cardiac function is advised. In patients with creatinine clearances > 30 ml/min, the combination of a loop diuretic with a thiazide diuretic may also lead to profound fluid and electrolyte loss. Thus, furosemide should be used very cautiously in combination with either metolazone or thiazide diuretics. Conversely, potassium-sparing diuretics (amiloride, spironolactone, and triamterene) can counteract furosemide-induced hypokalemia.[5159] These agents have been used as therapeutic alternatives to potassium supplements in patients receiving loop diuretics. In addition, amiloride and triamterene may counteract the magnesium wasting actions of furosemide.

Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus,[5159] probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between furosemide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely. Also, an pharmacokinetic interaction has been noted between furosemide and metformin. In pharmacokinetic studies, furosemide increased the plasma and blood maximum concentrations of metformin by 22% and blood AUC by 15%, without any significant change in metformin renal clearance.[5280] On the other hand, metformin decreased furosemide plasma and blood maximum concentrations by 31% and 12%, respectively, than when administered alone. Furosemide's terminal half-life was also decreased by 32% without any significant change in furosemide renal clearance.

Additive hypotension is possible if furosemide used in combination with any other antihypertensive agents,[5159] including drugs such as nitroglycerin. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative.

Ethanol interacts with antihypertensive agents by potentiating their hypotensive effect.[5944] Ethanol, since it also possesses diuretic properties, should be taken in small quantities in patients receiving loop diuretics. The diuretic properties may be additive, leading to dehydration in some patients.