Famotidine

Famotidine

Systematic (IUPAC) name
3-[({2-[(diaminomethylidene)amino]-1,3-thiazol-4-yl}methyl)sulfanyl]-N'-sulfamoylpropanimidamide
Clinical data
Pronunciation	/fəˈmɒtɪdiːn/
Trade names	Pepcid, others
AHFS/Drugs.com	monograph
MedlinePlus	a687011
License data	US FDA: Famotidine
Pregnancy category	AU: B1 US: B (No risk in non-human studies)
Routes of administration	Oral (tablets)
Legal status
Legal status	AU: Pharmacist only S3/S4 UK: General Availability (OTC) US: OTC
Pharmacokinetic data
Bioavailability	40–45% (oral)[1]
Protein binding	15–20%[1]
Metabolism	hepatic
Biological half-life	2.5–3.5 hours[1]
Excretion	Renal (25-30% unchanged [Oral])[1]
Identifiers
CAS Number	76824-35-6
ATC code	A02BA03 (WHO)
PubChem	CID 3325
IUPHAR/BPS	7074
DrugBank	DB00927
ChemSpider	3208
UNII	5QZO15J2Z8
KEGG	D00318
ChEBI	CHEBI:4975
ChEMBL	CHEMBL902
Chemical data
Formula	C8H15N7O2S3
Molar mass	337.449 g/mol
SMILES O=S(=O)(N=C(N)CCSCc1nc(/N=C(/N)N)sc1)N
InChI InChI=1S/C8H15N7O2S3/c9-6(15-20(12,16)17)1-2-18-3-5-4-19-8(13-5)14-7(10)11/h4H,1-3H2,(H2,9,15)(H2,12,16,17)(H4,10,11,13,14) Key:XUFQPHANEAPEMJ-UHFFFAOYSA-N
(verify)

Famotidine, sold under the trade name Pepcid among others is a histamine H₂ receptor antagonist that inhibits stomach acid production. It is commonly used in the treatment of peptic ulcer disease and gastroesophageal reflux disease.

Unlike cimetidine, the first H₂ antagonist, famotidine has no effect on the cytochrome P450 enzyme system, and does not appear to interact with other drugs.^[2]

It was discovered in 1979.^[3]

Medical uses

• Relief of heartburn, acid indigestion, and sour stomach
• Treatment for gastric and duodenal ulcers
• Treatment for pathologic gastrointestinal hypersecretory conditions such as Zollinger–Ellison syndrome and multiple endocrine adenomas
• Treatment for gastroesophageal reflux disease (GERD)
• Treatment for esophagitis
• Part of a multidrug regimen for Helicobacter pylori eradication, although omeprazole may be somewhat more effective.^{[4][5][6][7][8][9]}
• Prevention of NSAID-induced peptic ulcers.^[10][11]
• Given to surgery patients before operations to reduce the risk of aspiration pneumonitis.^[12][13][14]

Famotidine is also given to dogs and cats with acid reflux.^[15] Famotidine has been used in combination with an H₁ antagonist to treat and prevent urticaria caused by an acute allergic reaction.^[16]

Preparations

Certain preparations of famotidine are available over the counter (OTC) in various countries. In the United States and Canada, 10 mg and 20 mg tablets, sometimes in combination with an antacid,^[17][18] are available OTC. Larger doses still require a medical prescription.

Formulations of famotidine in combination with ibuprofen were marketed by Horizon Pharma under the trade name Duexis.^[19]

Side effects

Side effects associated with famotidine use include headache, dizziness, and constipation or diarrhea.^[20]

History

Famotidine was developed by Yamanouchi Pharmaceutical Co.^[21] It was licensed in the mid-80s by Merck & Co.^[22] and is marketed by a joint venture between Merck and Johnson & Johnson. The imidazole ring of cimetidine was replaced with a 2-guanidinothiazole ring. Famotidine proved to be 9 times more potent than ranitidine, and 32 times more potent than cimetidine.^[23]

It was first marketed in 1981. Pepcid RPD orally disintegrating tablets were released in 1999. Generic preparations became available in 2001, e.g. Fluxid (Schwarz) or Quamatel (Gedeon Richter Ltd.).

In the United States and Canada, a product called Pepcid Complete, which combines famotidine with an antacid in a chewable tablet to quickly relieve the symptoms of excess stomach acid, is available. In the UK, this product was known as Pepcidtwo prior to its discontinuation in April 2015.^[24]

Famotidine suffers from poor bioavailability (50%), as it is poorly soluble in the low pH of the stomach. When used in combination with antacids, it promotes local delivery of these drugs to the receptor of the parietal cell wall. Therefore, researchers are developing innovative formulations of tablets, such as gastroretentive drug delivery systems. Such tablets are retained in the stomach for a longer period of time, thereby improving the bioavailability of drugs. Local delivery also increases bioavailability at the stomach wall receptor site and increases the efficacy of drugs to reduce acid secretion.^[25]

Research

Famotidine has been investigated as an adjunct in treatment-resistant schizophrenia. In one trial, it caused a 10% reduction in schizophrenic symptom severity in treatment-resistant patients.^[26]

See also

• Ranitidine, another popular H₂ receptor antagonist
• Nizatidine

References

1. Truven Health Analytics, Inc. DRUGDEX® System (Internet) [cited 2013 Oct 10]. Greenwood Village, CO: Thomsen Healthcare; 2013.
2. Humphries TJ, Merritt GJ (August 1999). "Review article: drug interactions with agents used to treat acid-related diseases" (pdf). Aliment. Pharmacol. Ther. 13 (Suppl 3): 18–26. doi:10.1046/j.1365-2036.1999.00021.x. PMID 10491725.
3. Fischer, Janos (2010). Analogue-based Drug Discovery II. John Wiley & Sons. p. 4. ISBN 978-3-527-63212-1.
4. Kanayama, S (January 1999). "[Proton-pump inhibitors versus H2-receptor antagonists in triple therapy for Helicobacter pylori eradication].". Nihon rinsho. Japanese journal of clinical medicine 57 (1): 153–6. PMID 10036954.
5. Soga, T; Matsuura, M; Kodama, Y; Fujita, T; Sekimoto, I; Nishimura, K; Yoshida, S; Kutsumi, H; Fujimoto, S (August 1999). "Is a proton pump inhibitor necessary for the treatment of lower-grade reflux esophagitis?". Journal of gastroenterology 34 (4): 435–40. doi:10.1007/s005350050292. PMID 10452673.
6. Borody, TJ; Andrews, P; Fracchia, G; Brandl, S; Shortis, NP; Bae, H (October 1995). "Omeprazole enhances efficacy of triple therapy in eradicating Helicobacter pylori.". Gut 37 (4): 477–81. doi:10.1136/gut.37.4.477. PMID 7489931.
7. Hu, FL; Jia, JC; Li, YL; Yang, GB (2003). "Comparison of H2-receptor antagonist- and proton-pump inhibitor-based triple regimens for the eradication of Helicobacter pylori in Chinese patients with gastritis or peptic ulcer.". The Journal of international medical research 31 (6): 469–74. doi:10.1177/147323000303100601. PMID 14708410.
8. Kirika, NV; Bodrug, NI; Butorov, IV; Butorov, SI (2004). "[Efficacy of different schemes of anti-helicobacter therapy in duodenal ulcer].". Terapevticheskii arkhiv 76 (2): 18–22. PMID 15106408.
9. Fujiwara, Y; Higuchi, K; Nebiki, H; Chono, S; Uno, H; Kitada, K; Satoh, H; Nakagawa, K; Kobayashi, K; Tominaga, K; Watanabe, T; Oshitani, N; Arakawa, T (June 2005). "Famotidine vs. omeprazole: a prospective randomized multicentre trial to determine efficacy in non-erosive gastro-oesophageal reflux disease.". Alimentary pharmacology & therapeutics. 21 Suppl 2: 10–8. doi:10.1111/j.1365-2036.2005.02468.x. PMID 15943841.
10. La Corte, R; Caselli, M; Castellino, G; Bajocchi, G; Trotta, F (June 1999). "Prophylaxis and treatment of NSAID-induced gastroduodenal disorders.". Drug safety 20 (6): 527–43. doi:10.2165/00002018-199920060-00006. PMID 10392669.
11. Laine, L; Kivitz, AJ; Bello, AE; Grahn, AY; Schiff, MH; Taha, AS (March 2012). "Double-blind randomized trials of single-tablet ibuprofen/high-dose famotidine vs. ibuprofen alone for reduction of gastric and duodenal ulcers.". The American journal of gastroenterology 107 (3): 379–86. doi:10.1038/ajg.2011.443. PMID 22186979.
12. Escolano, F; Castaño, J; López, R; Bisbe, E; Alcón, A (October 1992). "Effects of omeprazole, ranitidine, famotidine and placebo on gastric secretion in patients undergoing elective surgery.". British journal of anaesthesia 69 (4): 404–6. doi:10.1093/bja/69.4.404. PMID 1419452.
13. Vila, P; Vallès, J; Canet, J; Melero, A; Vidal, F (November 1991). "Acid aspiration prophylaxis in morbidly obese patients: famotidine vs. ranitidine.". Anaesthesia 46 (11): 967–9. doi:10.1111/j.1365-2044.1991.tb09860.x. PMID 1750602.
14. Jahr, JS; Burckart, G; Smith, SS; Shapiro, J; Cook, DR (July 1991). "Effects of famotidine on gastric pH and residual volume in pediatric surgery.". Acta anaesthesiologica Scandinavica 35 (5): 457–60. doi:10.1111/j.1399-6576.1991.tb03328.x. PMID 1887750.
15. "Famotidine".
16. Fogg TB, Semple D (29 November 2007). "Combination therapy with H2 and H1 antihistamines in acute, non compromising allergic reactions". BestBets. Manchester, England: Manchester Royal Infirmary. Retrieved 26 April 2011.
17. Pepcid Complete
18. "Famotidine".
19. Drugs.com entry
20. "Pepcid Side Effects & Drug Interactions". RxList.com. 2008. Retrieved 2008-07-31.
21. US patent 4283408, HIRATA YASUFUMI; YANAGISAWA ISAO; ISHII YOSHIO; TSUKAMOTO SHINICHI; ITO NORIKI; ISOMURA YASUO; TAKEDA MASAAKI, "Guanidinothiazole compounds, process for preparation and gastric inhibiting compositions containing them", issued 1981-08-11 
22. "Sankyo Pharma". Skyscape Mediwire. 2002. Archived from the original on February 23, 2009. Retrieved 2009-10-30.
23. Howard, JM; Chremos, AN; Collen, MJ; McArthur, KE; Cherner, JA; Maton, PN; Ciarleglio, CA; Cornelius, MJ; Gardner, JD; Jensen, RT (April 1985). "Famotidine, a new, potent, long-acting histamine H2-receptor antagonist: comparison with cimetidine and ranitidine in the treatment of Zollinger-Ellison syndrome.". Gastroenterology 88 (4): 1026–33. PMID 2857672.
24. "PepcidTwo Chewable Tablet". Retrieved 7 June 2015.
25. "Formulation and Evaluation of Gastroretentive Floating Tablets of Famotidine". Farmavita.Net. 2008. Retrieved 2009-01-30.
26. Meskanen, K; Ekelund, H; Laitinen, J; Neuvonen, PJ; Haukka, J; Panula, P; Ekelund, J (August 2013). "A randomized clinical trial of histamine 2 receptor antagonism in treatment-resistant schizophrenia.". Journal of Clinical Psychopharmacology 33 (4): 472–478. doi:10.1097/JCP.0b013e3182970490. PMID 23764683.