|
This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or
standards of non-Merck sources.
Pronunciation
(fa MOE ti deen)
Generic Available (U.S.)
Yes: Infusion, Injection, oral suspension, tablet
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Maintenance therapy and treatment of duodenal ulcer; treatment of gastroesophageal reflux disease (GERD), active benign gastric ulcer; pathological hypersecretory conditions
OTC labeling: Relief of heartburn, acid indigestion, and sour stomach
Use: Unlabeled
Part of a multidrug regimen for H. pylori eradication to reduce the risk of duodenal ulcer recurrence; stress ulcer prophylaxis in critically-ill patients; symptomatic relief in gastritis
Pregnancy Risk Factor
B
Pregnancy Considerations
Adverse events have not been observed in animal reproduction studies; therefore, famotidine is classified as pregnancy category B. Famotidine crosses the placenta. An increased risk of congenital malformations or adverse events in the newborn has generally not been observed following maternal use of famotidine during pregnancy. Histamine H2 antagonists have been evaluated for the treatment of gastroesophageal reflux disease (GERD), as well as gastric and duodenal ulcers, during pregnancy. Although if needed, famotidine is not the agent of choice. Histamine H2 antagonists may be used for aspiration prophylaxis prior to cesarean delivery.
Lactation
Enters breast milk/not recommended
Breast-Feeding Considerations
Famotidine is excreted into breast milk with peak concentrations occurring ~6 hours after the maternal dose. According to the manufacturer, the decision to continue or discontinue breast-feeding during therapy should take into account the risk of exposure to the infant and the benefits of treatment to the mother.
Contraindications
Hypersensitivity to famotidine, other H2 antagonists, or any component of the formulation
Warnings/Precautions
Concerns related to adverse effects.
• Confusion: Reversible confusional states, usually clearing within 3-4 days after discontinuation, have been linked to use. Increased age (>50 years) and renal or hepatic impairment are thought to be associated.
• ECG changes: Prolonged QT interval has been reported in patients with renal dysfunction. The FDA has received reports of torsade de pointes occurring with famotidine (Poluzzi, 2009).
Disease-related concerns:
• Gastric malignancy: Relief of symptoms does not preclude the presence of a gastric malignancy.
• Renal impairment: Use with caution in patients with moderate-to-severe renal impairment (Clcr <50 mL/minute); dosage adjustment recommended.
Dosage form specific issues:
• Benzyl alcohol: Multidose vials for injection contain benzyl alcohol which has been associated with "gasping syndrome" in neonates.
Other warnings/precautions:
• OTC labeling: When used for self-medication, patients should be instructed not to use if they have difficulty swallowing, are vomiting blood, or have bloody or black stools. Not for use with other acid reducers.
Adverse Reactions
Note: Agitation and vomiting have been reported in up to 14% of pediatric patients <1 year of age.
1% to 10%:
Central nervous system: Headache (5%), dizziness (1%)
Gastrointestinal: Diarrhea (2%), constipation (1%), necrotizing enterocolitis (VLBW neonates; Guillet, 2006)
<1% (Limited to important or life-threatening): Abdominal discomfort, acne, agitation, agranulocytosis, allergic reaction, alopecia, anaphylaxis, angioedema, anorexia, anxiety, arrhythmia, arthralgia, AV block, bronchospasm, cholestatic jaundice, confusion, conjunctival injection, depression, dry skin, facial edema, fatigue, fever, flushing, hallucinations, hepatitis, injection site reactions, insomnia, interstitial pneumonia, leukopenia, libido decreased, liver function tests increased, muscle cramps, nausea, palpitation, pancytopenia, paresthesia, pruritus, QT-interval prolongation, rash, seizure, somnolence, Stevens-Johnson syndrome, taste disorder, tinnitus, thrombocytopenia, torsade de pointes, toxic epidermal necrolysis, urticaria, vomiting, weakness, xerostomia
Metabolism/Transport Effects
None known.
Drug Interactions
Atazanavir: H2-Antagonists may decrease the absorption of Atazanavir. Management: Specific dose limitations and administration guidelines exist; consult full interaction monograph or atazanavir prescribing information. Risk D: Consider therapy modification
Cefditoren: H2-Antagonists may decrease the serum concentration of Cefditoren. Management: Concomitant use of cefditoren with H2-antagonists and antacids is not recommended. Consider alternative methods to control acid reflux (eg, diet modification) or alternative antimicrobial therapy if use of H2-antagonists can not be avoided. Risk D: Consider therapy modification
Cefpodoxime: H2-Antagonists may decrease the absorption of Cefpodoxime. Separate oral doses by at least 2 hours. Risk C: Monitor therapy
Cefuroxime: H2-Antagonists may decrease the absorption of Cefuroxime. Separate oral doses by at least 2 hours. Risk C: Monitor therapy
Dasatinib: H2-Antagonists may decrease the absorption of Dasatinib. Management: Avoid concurrent use of H2-receptor antagonists with dasatinib. Antacids (taken 2 hours before or after dasatinib administration) should be used in place of these agents if some acid-reducing therapy is needed. Risk D: Consider therapy modification
Delavirdine: H2-Antagonists may decrease the serum concentration of Delavirdine. Management: Chronic therapy with H2-antagonists should be avoided in patients who are being treated with delavirdine. The clinical significance of short-term H2-antagonist therapy with delavirdine is uncertain, but such therapy should be undertaken with caution. Risk X: Avoid combination
Dexmethylphenidate: H2-Antagonists may increase the absorption of Dexmethylphenidate. Specifically, H2-antagonists may interfere with the normal release of drug from the extended-release capsules (Focalin XR brand), which could result in both increased absorption (early) and decreased delayed absorption. Risk C: Monitor therapy
Erlotinib: H2-Antagonists may decrease the serum concentration of Erlotinib. Management: Avoid H2-antagonists in patients receiving erlotinib when possible. If concomitant treatment cannot be avoided, erlotinib should be dosed once daily, 10 hours after and at least 2 hours before H2-antagonist dosing. Risk D: Consider therapy modification
Fosamprenavir: H2-Antagonists may decrease the serum concentration of Fosamprenavir. Cimetidine may also inhibit the metabolism of the active metabolite amprenavir, making its effects on fosamprenavir/amprenavir concentrations difficult to predict. Risk C: Monitor therapy
Gefitinib: H2-Antagonists may decrease the serum concentration of Gefitinib. Risk C: Monitor therapy
Indinavir: H2-Antagonists may decrease the serum concentration of Indinavir. Risk C: Monitor therapy
Iron Salts: H2-Antagonists may decrease the absorption of Iron Salts. Exceptions: Ferric Gluconate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose. Risk C: Monitor therapy
Itraconazole: H2-Antagonists may decrease the serum concentration of Itraconazole. Management: When this combination is used, the itraconazole should be administered with a cola beverage (8 ounces). Itraconazole oral suspension may be less sensitive to this interaction. Monitor patient response to itraconazole closely. Risk D: Consider therapy modification
Ketoconazole: H2-Antagonists may decrease the serum concentration of Ketoconazole. Management: Administer oral ketoconazole at least 2 hours prior to use of any H2-receptor antagonist. Monitor patients closely for signs of inadequate clinical response to ketoconazole. Risk D: Consider therapy modification
Ketoconazole (Systemic): H2-Antagonists may decrease the serum concentration of Ketoconazole (Systemic). Management: Administer oral ketoconazole at least 2 hours prior to use of any H2-receptor antagonist. Monitor patients closely for signs of inadequate clinical response to ketoconazole. Risk D: Consider therapy modification
Mesalamine: H2-Antagonists may diminish the therapeutic effect of Mesalamine. Histamine H2-Antagonist-mediated increases in gastrointestinal pH may cause the premature release of mesalamine from specific sustained-release mesalamine products. Management: Consider avoiding concurrent administration of high-dose histamine H2-receptor antagonists with sustained-release mesalamine products. Risk D: Consider therapy modification
Methylphenidate: H2-Antagonists may increase the absorption of Methylphenidate. Specifically, H2-antagonists may interfere with the normal release of drug from the extended-release capsules (Ritalin LA brand), which could result in both increased absorption (early) and decreased delayed absorption. Risk C: Monitor therapy
Nelfinavir: H2-Antagonists may decrease the serum concentration of Nelfinavir. Concentrations of the active M8 metabolite may also be reduced. Risk C: Monitor therapy
Posaconazole: H2-Antagonists may decrease the serum concentration of Posaconazole. Management: Avoid concurrent use whenever possible. Monitor patients closely for decreased antifungal effects if this combination is used. Consider using a noninteracting antifungal as appropriate. Risk D: Consider therapy modification
Rilpivirine: H2-Antagonists may decrease the serum concentration of Rilpivirine. Management: Administer histamine H2 receptor antagonists at least 12 hours before or 4 hours after rilpivirine. Risk D: Consider therapy modification
Saquinavir: H2-Antagonists may increase the serum concentration of Saquinavir. Risk C: Monitor therapy
Varenicline: H2-Antagonists may increase the serum concentration of Varenicline. Management: Monitor for increased varenicline adverse effects with concomitant use of cimetidine or other H2-antagonists, particulary in patients with severe renal impairment. International product labeling recommendations vary. Consult appropriate labeling. Risk C: Monitor therapy
Vismodegib: H2-Antagonists may decrease the serum concentration of Vismodegib. Management: Carefully consider the need for any medication that increases the pH of the upper GI tract (PPIs, H2RAs, antacids), as these could significantly reduce vismodegib systemic exposure. Vismodegib dose increases are unlikely to compensate for this effect. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (may cause gastric mucosal irritation).
Food: Famotidine bioavailability may be increased if taken with food.
Storage
Oral:
Powder for oral suspension: Prior to mixing, dry powder should be stored at controlled room temperature of 25°C (77°F). Reconstituted oral suspension is stable for 30 days at room temperature; do not freeze.
Tablet: Store controlled room temperature. Protect from moisture.
I.V.:
Solution for injection: Prior to use, store at 2°C to 8°C (36°F to 46°F). If solution freezes, allow to solubilize at controlled room temperature. May be stored at room temperature for up to 3 months (data on file [Bedford Laboratories, 2011]).
I.V. push: Following preparation, solutions for I.V. push should be used immediately, or may be stored in refrigerator and used within 48 hours.
Infusion: Following preparation, the manufacturer states may be stored for up to 48 hours under refrigeration; however, solutions for infusion have been found to be physically and chemically stable for 7 days at room temperature.
Solution for injection, premixed bags: Store at controlled room temperature of 25°C (77°F); avoid excessive heat.
Reconstitution
Solution for injection:
I.V. push: Dilute famotidine with NS (or another compatible solution) to a total of 5-10 mL (some centers also administer undiluted).
Infusion: Dilute with D5W 100 mL or another compatible solution.
Compatibility
Stable in D5W, D10W, LR, fat emulsion 10%, NS, sodium bicarbonate 5%; variable stability (consult detailed reference) in TPN.
Y-site administration: Compatible: Acyclovir, allopurinol, amifostine, aminophylline, amiodarone, ampicillin, ampicillin/sulbactam, amsacrine, anakinra, anidulafungin, atropine, aztreonam, bivalirudin, calcium gluconate, caspofungin, cefazolin, cefotaxime, cefotetan, cefoxitin, ceftazidime, cefuroxime, chlorpromazine, cisatracurium, cisplatin, cladribine, clindamycin, cyanocobalamin, cyclosporine, cyclophosphamide, cytarabine, dexamethasone sodium phosphate, dexmedetomidine, dextran 40, digoxin, diphenhydramine, dobutamine, docetaxel, dopamine, doripenem, doxorubicin, doxorubicin liposome, doxycycline, droperidol, enalaprilat, ephedrine, epinephrine, erythromycin lactobionate, esmolol, etoposide phosphate, fenoldopam, filgrastim, fluconazole, fludarabine, folic acid, gemcitabine, gentamicin, granisetron, haloperidol, heparin, hetastarch in lactate electrolyte injection (Hextend®), hydrocortisone sodium succinate, hydromorphone, hydroxyzine, imipenem/cilastatin, inamrinone, insulin (regular), isoproterenol, labetalol, lidocaine, linezolid, lorazepam, magnesium sulfate, melphalan, meperidine, methotrexate, methylprednisolone sodium succinate, metoclopramide, midazolam, morphine, nafcillin, nicardipine, nitroglycerin, nitroprusside, norepinephrine, ondansetron, oxacillin, oxaliplatin, oxytocin, paclitaxel, palonosetron, pemetrexed, phenylephrine, phytonadione, phenytoin, piperacillin, potassium chloride, potassium phosphate, procainamide, propofol, remifentanil, sargramostim, sodium bicarbonate, telavancin, teniposide, theophylline, thiamine, thiotepa, ticarcillin/clavulanate potassium, tirofiban, verapamil, vinorelbine. Incompatible: Amphotericin B cholesteryl sulfate complex, azithromycin, cefepime, piperacillin/tazobactam, sulfamethoxazole/trimethoprim. Variable (consult detailed reference): Furosemide.
Compatibility in syringe: Incompatible: Ceftriaxone, dexamethasone sodium phosphate.
Mechanism of Action
Competitive inhibition of histamine at H2 receptors of the gastric parietal cells, which inhibits gastric acid secretion
Pharmacodynamics/Kinetics
Onset of action: Antisecretory effect: Oral: Within 1 hour; I.V.: Within 30 minutes
Peak effect: Antisecretory effect: Oral: Within 1-3 hours (dose-dependent)
Duration: Antisecretory effect: I.V., Oral: 10-12 hours
Absorption: Oral: Incompletely absorbed
Distribution: Vd:
Infants: 0-3 months: ~1.4-1.8 L/kg; >3-12 months: ~2.3 L/kg
Children: ~2 L/kg
Adults: ~1 L/kg
Protein binding: 15% to 20%
Metabolism: Minimal first-pass metabolism; forms one metabolite (S-oxide)
Bioavailability: Oral: 40% to 45%
Half-life elimination:
Infants: 0-3 months: ~8-10.5 hours; >3-12 months: ~4.5 hours
Children: 3.4 hours
Adults: 2.5-3.5 hours; prolonged with renal impairment; Oliguria: >20 hours
Time to peak, serum: Oral: ~1-3 hours
Excretion: Urine (25% to 30% [oral], 65% to 70% [I.V.] as unchanged drug)
Dosage
Children: Treatment duration and dose should be individualized
Peptic ulcer: 1-16 years:
Oral: 0.5 mg/kg/day at bedtime or divided twice daily (maximum dose: 40 mg/day); doses of up to 1 mg/kg/day have been used in clinical studies
I.V.: 0.25 mg/kg every 12 hours (maximum dose: 40 mg/day); doses of up to 0.5 mg/kg have been used in clinical studies
GERD: Oral:
<3 months: 0.5 mg/kg once daily
3-12 months: 0.5 mg/kg twice daily
1-16 years: 1 mg/kg/day divided twice daily (maximum dose: 40 mg twice daily); doses of up to 2 mg/kg/day have been used in clinical studies
Children ≥12 years and Adults: Heartburn, indigestion, sour stomach: OTC labeling: Oral: 10-20 mg every 12 hours; dose may be taken 15-60 minutes before eating foods known to cause heartburn
Adults:
Duodenal ulcer: Oral: Acute therapy: 40 mg/day at bedtime (or 20 mg twice daily) for 4-8 weeks; maintenance therapy: 20 mg/day at bedtime
Helicobacter pylori eradication (unlabeled use): Oral: 40 mg once daily; requires combination therapy with antibiotics
Gastric ulcer: Oral: Acute therapy: 40 mg/day at bedtime
Hypersecretory conditions: Oral: Initial: 20 mg every 6 hours, may increase in increments up to 160 mg every 6 hours
GERD: Oral: 20 mg twice daily for 6 weeks
Esophagitis and accompanying symptoms due to GERD: Oral: 20 mg or 40 mg twice daily for up to 12 weeks
Patients unable to take oral medication: I.V.: 20 mg every 12 hours
Dosing adjustment in renal impairment: Clcr <50 mL/minute: Manufacturer recommendation: Administer 50% of dose or increase the dosing interval to every 36-48 hours (to limit potential CNS adverse effects).
Administration: Oral
May administer with antacids.
Suspension: Shake vigorously before use. May be taken without regard to meals.
Tablet: May be taken without regard to meals.
Administration: I.V.
I.V. push: Inject over at least 2 minutes.
Solution for infusion: Administer over 15-30 minutes.
Administration: I.V. Detail
pH: 5.7-6.4 (premixed solution); 5.0-5.6 (injection)
Dietary Considerations
May be taken without regard to meals.
Patient Education
OTC: Do not use for more than 14 days unless recommended by prescriber. May cause drowsiness, dizziness, constipation, or diarrhea. Report acute headache, unresolved constipation or diarrhea, palpitations, black tarry stools, abdominal pain, rash, worsening of condition being treated, or recurrence of symptoms after therapy is completed.
Geriatric Considerations
H2 blockers are the preferred drugs for treating PUD in the elderly due to cost and ease of administration. They are no less or more effective than any other therapy. Famotidine is one of the preferred agents (due to side effects, drug interaction profile, and pharmacokinetics). Treatment for PUD in the elderly is recommended for 12 weeks since their lesions are typically larger; therefore, take longer to heal. Always adjust dose based upon creatinine clearance, since slight accumulation may result in CNS side effects, mainly confusion.
Anesthesia and Critical Care Concerns/Other Considerations
Evidence-Based Information: The 2008 Surviving Sepsis Campaign guidelines recommend that stress ulcer prophylaxis using an H2 blocker (Grade 1A) or proton pump inhibitor (Grade 1B) be given to patients with severe sepsis to prevent upper GI bleed. Benefit of prevention of upper GI bleed must be weighed against potential effect of increased stomach pH on development of ventilator-associated pneumonia.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause dizziness or drowsiness; may rarely cause insomnia
Mental Health: Effects on Psychiatric Treatment
May cause agranulocytosis; use caution with clozapine and carbamazepine
Nursing: Physical Assessment/Monitoring
Teach patient proper timing of administration.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Infusion, premixed in NS [preservative free]: 20 mg (50 mL)
Injection, solution: 10 mg/mL (4 mL, 20 mL, 50 mL)
Injection, solution [preservative free]: 10 mg/mL (2 mL)
Powder for suspension, oral: 40 mg/5 mL (50 mL)
Pepcid®: 40 mg/5 mL (50 mL) [contains sodium benzoate; cherry-banana-mint flavor]
Tablet, oral: 10 mg, 20 mg, 40 mg
Heartburn Relief: 10 mg
Heartburn Relief Maximum Strength: 20 mg
Pepcid®: 20 mg, 40 mg
Pepcid® AC: 10 mg
Pepcid® AC Maximum Strength: 20 mg
Tablet, chewable, oral:
Pepcid® AC Maximum Strength: 20 mg [berries 'n' cream flavor]
Pepcid® AC Maximum Strength: 20 mg [cool mint flavor]
Pricing: U.S. (www.drugstore.com)
Suspension (reconstituted) (Famotidine)
40 mg/5 mL (50): $155.98
Suspension (reconstituted) (Pepcid)
40 mg/5 mL (50): $175.99
Tablets (Famotidine)
20 mg (30): $19.99
40 mg (90): $18.98
Tablets (Pepcid)
20 mg (30): $71.99
40 mg (30): $125.99
Tablets (Pepcid AC)
10 mg (30): $19.99
Extemporaneously Prepared
An 8 mg/mL oral suspension may be made with tablets. Crush seventy 40 mg tablets in a mortar and reduce to a fine powder. Add small portions of sterile water and mix to a uniform paste. Mix while adding a 1:1 mixture of Ora-Plus® and Ora-Sweet® in incremental proportions to almost 350 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 350 mL. Label "shake well". Stable for 95 days at room temperature.
Dentinger PJ, Swenson CF, and Anaizi NH, "Stability of Famotidine in an Extemporaneously Compounded Oral Liquid," Am J Health Syst Pharm, 2000, 57(14):1340-2.
References
Ahmad S, “Famotidine and Cardiac Arrhythmia,” DICP, 1991, 25(3):315.
Broussard CN and Richter JE, “Treating Gastro-oesophageal Reflux Disease During Pregnancy and Lactation: What Are the Safest Therapy Options,” Drug Saf, 1998, 19(4):325-37.
Chey WD and Wong B, “American College of Gastroenterology Guideline on the Management of Helicobacter pylori Infection,” Am J Gastroenterol, 2007 102(8):1808-25.
Dellinger RP, Levy MM, Carlet JM, et al, “Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2008,” [published correction appears in Crit Care Med, 2008, 36(4):1394-6], Crit Care Med, 2008, 36(1):296-327.
Fennerty MD and Higbee M, “Drug Therapy of Gastrointestinal Disease,” Geriatric Pharmacology, Bressler R and Katz MD, eds, New York, NY: McGraw-Hill, 1993, 585-608.
Fish DN, “Safety and Cost of Rapid I.V. Injection of Famotidine in Critically Ill Patients,” Am J Health Syst Pharm, 1995, 52(17):1889-94.
Gottlieb S, Decktor DL, Eckert JM, et al, “Efficacy and Tolerability of Famotidine in Preventing Heartburn and Related Symptoms of Upper Gastrointestinal Discomfort,” Am J Ther, 1995, 2:314-9.
Guillet R, Stoll BJ, Cotten CM, et al, "Association of H2-Blocker Therapy and Higher Incidence of Necrotizing Enterocolitis in Very Low Birth Weight Infants," Pediatrics, 2006, 117(2):137-42.
Inotsume N, Mishimura M, Nakano M, et al, “Removal of Famotidine by Haemodialysis in Elderly Anuric Patients,” Eur J Clin Pharmacol, 1990, 38(3):313-4.
James LP and Kearns GL, “Pharmacokinetics and Pharmacodynamics of Famotidine in Paediatric Patients,” Clin Pharmacokinet, 1996, 31(2):103-10.
Lipsy RJ and Freeman CD, “Hemodynamic Effects of Intravenous Famotidine in Critically Ill Patients,” Pharmacotherapy,1995, 15(1):48-51.
Poluzzi E, Raschi E, Moretti U, et al, “Drug-Induced Torsades de Pointes: Data Mining of the Public Version of the FDA Adverse Event Reporting System (AERS),” Pharmacoepidemiol Drug Saf, 2009, 18(6):512-8.
Simon TJ, Berlin RG, Gardner AH, et al, “Self-Directed Treatment of Intermittent Heartburn: A Randomized, Multicenter, Double-Blind, Placebo-Controlled Evaluation of Antacid and Low Doses of an H2-Receptor Antagonist (Famotidine),” Am J Ther, 1995, 2:304-13.
Treem WR, Davis PM, and Hyams JS, “Suppression of Gastric Acid Secretion by Intravenous Administration of Famotidine in Children,” J Pediatr, 1991, 118(5):812-6.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
|
