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Famotidine
Indications
Famotidine decreases the production of stomach acid, and its pharmacologic activity is used in the treatment of acid-related gastrointestinal conditions.[1][2] Famotidine is available both by prescription and over-the-counter (OTC). It is US Food and Drug Administration (FDA) approved and available through prescription for the treatment of duodenal ulcer, gastric ulcer, and gastroesophageal reflux disease (GERD) in adults and children, with a further indication for treatment of pathological hypersecretory conditions in adults.[3] Famotidine is also FDA approved for over-the-counter treatment and prevention of heartburn due to gastroesophageal reflux in adults and pediatrics.[4] Famotidine is used off-label for reducing gastrointestinal risks of NSAIDs.[5] It is also used off-label for the treatment of refractory urticarial, prevention of stress ulcer in critically-ill patients and symptomatic relief of gastritis.[6]
Mechanism of Action
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Mechanism of Action
Famotidine is a competitive histamine H-receptor antagonist (H2RA) that binds to the H-receptors located on the basolateral membrane of the parietal cell in the stomach, effectively blocking histamine actions. Its pharmacologic activity results in the inhibition of gastric secretion by suppressing acid concentration and volume of gastric secretion. Famotidine inhibits both basal and nocturnal gastric acid secretion as well as reduces gastric volume, acidity, and secretion stimulated by food, caffeine, insulin, and pentagastrin.[7][8][9]
Administration
Per famotidine's package insert, it is available in intravenous (IV) solution, oral suspension, and tablet formulations (10 mg, 20 mg, and 40 mg). The intravenous solution can be administered as an IV push over at least two minutes and as an IV infusion over 15 to 30 minutes. Over-the-counter formulations are available in gel capsules, tablets, and chewable tablets of 10 mg or 20 mg. The oral tablet is administered without regard to meals. The suspension formulation should be shaken vigorously before use. The over-the-counter tablet should not be chewed, and the dose may be taken 10 to 60 minutes before consuming food or drinks known to cause heartburn. Patients should not take over-the-counter famotidine for more than 2 weeks unless directed by their health care provider. Famotidine is metabolized by the hepatic cytochrome P450 enzymes, but it has a minimal inhibitory impact on other drugs metabolism.[10] Per package insert, the following medications should not be used concurrently with famotidine: cefuroxime, dasatinib, delavirdine, neratinib, pazopanib, and risedronate.
Adverse Effects
The adverse effects of the intravenous formulation occur locally as it may irritate the injection site; however, the frequency has not been defined. Most common adverse effects include agitation (infants equal to 14%; adults less than 1%), headache (5%), dizziness (1%), diarrhea (2%), and constipation (1%). Due to central nervous system (CNS) adverse effects, longer dosing intervals or reduced doses may be used instead to adjust for the resulting longer elimination half-life of famotidine.[10][11][12] An increased risk of developing community-acquired pneumonia and acute gastroenteritis have been linked to the use of famotidine as well as other gastric acid inhibitors in the pediatric population.[13] Patients who use over-the-counter famotidine must notify their health care provider if they experience frequent chest pain, frequent wheezing particularly with heartburn, unexplained weight loss, stomach pain, heartburn more than 3 months, heartburn with lightheadedness, sweating, or dizziness. Over-the-counter famotidine must be discontinued if a patient’s heartburn continues and/or worsens, or if they use it for more than 14 days.[14]
Contraindications
Famotidine is contraindicated for use by patients with serious hypersensitivity to famotidine itself or any component of the formulation. Cross-sensitivity of H2RAs has been observed; therefore, famotidine should not be administered to patients with a history of hypersensitivity to cimetidine. In addition, the over-the-counter tablets should not be used if the patient has trouble and/or pain when swallowing food, vomiting with blood, or bloody or black stools. The over-the-counter tablets should also not be used by patients who are allergic to other acid reducers, have renal impairment, or are currently taking other acid reducers.
Monitoring
Famotidine is substantially excreted by the kidney; thus, it may be useful for healthcare professionals to monitor renal function especially in elderly patients. A patient’s complete blood count (CBC), gastric pH and occult blood in patients with gastrointestinal (GI) bleeding should be monitored.
Toxicity
As famotidine is excreted mainly by the kidney, the risk of toxic reactions may be greater in patients with impaired renal function. Dose adjustment in patients who have moderate to severe renal impairment is necessary.[11][12] Per famotidine's package insert, oral doses outside of FDA-approved doses of up to 640 mg per day have been given to adult patients with pathological hypersecretory states with no serious adverse outcomes. Cases of overdose are similar to those encountered in normal clinical experience. Treatment of an overdose should include removing unabsorbed medications from the gastrointestinal tract, the patient should be monitored accordingly, and supportive therapy provided. Famotidine is classified as pregnancy category B and should be used during pregnancy only if needed. Famotidine is present in breast milk, and the decision for a mother to breastfeed during therapy should be based on the balance of risk to the infants and treatment benefits to the mother. Compared to other H2RAs, famotidine exhibit one of the lowest concentrations in break milk and is thus, maybe one of the preferred agents in this setting.[15][16]
Enhancing Healthcare Team Outcomes
The American Society of Health-System Pharmacists (ASHP) in 1999 released a guideline focusing on the prevention of stress ulcer in medical, surgical, respiratory, and pediatric intensive care unit (ICU) patients. Since then, and in recent years, the use of stress ulcer prophylaxis in a non-ICU setting, particularly in the general medical setting, have increased despite little to no evidence supporting its use. The use of acid-suppressive therapy (AST) is overused in hospital patients, with as many as 71% of patient's receiving treatment without an appropriate indication in the general medicine ward. Furthermore, a significant number of patients continue on acid-suppressive therapy when discharged from the hospital which can lead to increased medical cost and the risk of adverse drug reactions for patients. Health care professionals play an important role in enhancing patient's safety by minimizing the inappropriate use of AST. Physicians should carefully consider the need for AST in patients in the general medicine ward and pharmacist can communicate with physicians and ask about the unnecessary use of acid-suppressive therapy. Education about the proper use of acid-suppressive therapy in ICU settings per ASHP recommendations will help reduce its inappropriate use significantly.[17][18][19]
References
McCullough AJ, Graham DY, Knuff TE, Lanza FL, Levenson HL, Lyon DT, Munsell WP, Perozza J, Roufail WM, Sinar DR. Suppression of nocturnal acid secretion with famotidine accelerates gastric ulcer healing. Gastroenterology. 1989 Oct:97(4):860-6 [PubMed PMID: 2570730]
Level 1 (high-level) evidenceVinayek R, Howard JM, Maton PN, Wank SA, Slaff JI, Gardner JD, Jensen RT. Famotidine in the therapy of gastric hypersecretory states. The American journal of medicine. 1986 Oct 24:81(4B):49-59 [PubMed PMID: 2877575]
Keithley JK. Histamine H2-receptor antagonists. The Nursing clinics of North America. 1991 Jun:26(2):361-73 [PubMed PMID: 1675461]
. Nonprescription version of famotidine wins FDA approval. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists. 1995 Jul 1:52(13):1377 [PubMed PMID: 7671034]
Hudson N, Taha AS, Russell RI, Trye P, Cottrell J, Mann SG, Swanell AJ, Sturrock RD, Hawkey CJ. Famotidine for healing and maintenance in nonsteroidal anti-inflammatory drug-associated gastroduodenal ulceration. Gastroenterology. 1997 Jun:112(6):1817-22 [PubMed PMID: 9178671]
Level 1 (high-level) evidenceInalöz SS, Goral V, Sari I, Canberk Y, Ulak G. Omeprazole, nitrendipine, famotidine and stress-induced ulcers. Acta gastro-enterologica Belgica. 1997 Jul-Sep:60(3):192-6 [PubMed PMID: 9396173]
Level 3 (low-level) evidenceTalke PO, Solanki DR. Dose-response study of oral famotidine for reduction of gastric acidity and volume in outpatients and inpatients. Anesthesia and analgesia. 1993 Dec:77(6):1143-8 [PubMed PMID: 8250305]
Level 1 (high-level) evidenceBerlin RG, Clineschmidt BV, Majka JA. Famotidine: an appraisal of its mode of action and safety. The American journal of medicine. 1986 Oct 24:81(4B):8-12 [PubMed PMID: 2877577]
Level 3 (low-level) evidenceMiyata K, Kamato T, Nishida A, Honda K. Studies on the mechanism for the gastric mucosal protection by famotidine in rats. Japanese journal of pharmacology. 1991 Feb:55(2):211-22 [PubMed PMID: 2067140]
Level 3 (low-level) evidencePoluzzi E, Raschi E, Moretti U, De Ponti F. Drug-induced torsades de pointes: data mining of the public version of the FDA Adverse Event Reporting System (AERS). Pharmacoepidemiology and drug safety. 2009 Jun:18(6):512-8. doi: 10.1002/pds.1746. Epub [PubMed PMID: 19358226]
Echizen H, Ishizaki T. Clinical pharmacokinetics of famotidine. Clinical pharmacokinetics. 1991 Sep:21(3):178-94 [PubMed PMID: 1764869]
Lin JH, Chremos AN, Yeh KC, Antonello J, Hessey GA 2nd. Effects of age and chronic renal failure on the urinary excretion kinetics of famotidine in man. European journal of clinical pharmacology. 1988:34(1):41-6 [PubMed PMID: 2896129]
Canani RB, Cirillo P, Roggero P, Romano C, Malamisura B, Terrin G, Passariello A, Manguso F, Morelli L, Guarino A, Working Group on Intestinal Infections of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP). Therapy with gastric acidity inhibitors increases the risk of acute gastroenteritis and community-acquired pneumonia in children. Pediatrics. 2006 May:117(5):e817-20 [PubMed PMID: 16651285]
McRorie JW, Kirby JA, Miner PB. Histamine2-receptor antagonists: Rapid development of tachyphylaxis with repeat dosing. World journal of gastrointestinal pharmacology and therapeutics. 2014 May 6:5(2):57-62. doi: 10.4292/wjgpt.v5.i2.57. Epub [PubMed PMID: 24868486]
Richter JE. Review article: the management of heartburn in pregnancy. Alimentary pharmacology & therapeutics. 2005 Nov 1:22(9):749-57 [PubMed PMID: 16225482]
Garbis H, Elefant E, Diav-Citrin O, Mastroiacovo P, Schaefer C, Vial T, Clementi M, Valti E, McElhatton P, Smorlesi C, Rodriguez EP, Robert-Gnansia E, Merlob P, Peiker G, Pexieder T, Schueler L, Ritvanen A, Mathieu-Nolf M. Pregnancy outcome after exposure to ranitidine and other H2-blockers. A collaborative study of the European Network of Teratology Information Services. Reproductive toxicology (Elmsford, N.Y.). 2005 Mar-Apr:19(4):453-8 [PubMed PMID: 15749258]
Level 2 (mid-level) evidenceGrube RR, May DB. Stress ulcer prophylaxis in hospitalized patients not in intensive care units. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists. 2007 Jul 1:64(13):1396-400 [PubMed PMID: 17592004]
Farrell CP, Mercogliano G, Kuntz CL. Overuse of stress ulcer prophylaxis in the critical care setting and beyond. Journal of critical care. 2010 Jun:25(2):214-20. doi: 10.1016/j.jcrc.2009.05.014. Epub 2009 Aug 15 [PubMed PMID: 19683892]
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Hutchinson HM, Sayre BE, Prettyman T, King E. Evaluating Sterility of Single Dose Vials on an Automated Compounding Device. Hospital pharmacy. 2017 Apr:52(4):286-293. doi: 10.1310/hpj5204-286. Epub [PubMed PMID: 28515508]
Fukuda H, Kamidani R, Okada H, Kitagawa Y, Yoshida T, Yoshida S, Ogura S. Complex poisoning mainly with benzyl alcohol complicated by paralytic ileus: a case report. International journal of emergency medicine. 2022 Jul 4:15(1):31. doi: 10.1186/s12245-022-00434-4. Epub 2022 Jul 4 [PubMed PMID: 35787785]
Level 3 (low-level) evidence