Famotidine

Famotidine

Systematic (IUPAC) name
3-([2-(diaminomethyleneamino)thiazol- 4-yl]methylthio)- N'-sulfamoylpropanimidamide
Clinical data
Trade names	Pepcid
AHFS/Drugs.com	monograph
MedlinePlus	a687011
Licence data	US FDA:link
Pregnancy cat.	B1 (Au), B (U.S.)
Legal status	S3/S4 (Au), POM/OTC (UK), OTC/℞-only (U.S.)
Routes	Oral, IV
Pharmacokinetic data
Bioavailability	20–66%
Protein binding	10–28%
Metabolism	hepatic-less than 30%
Half-life	2.5–4 hours (clinical half-life 8–12 hours)
Excretion	Principally excreted unchanged in urine
Identifiers
CAS number	76824-35-6 Y
ATC code	A02BA03
PubChem	CID 3325
DrugBank	APRD00296
ChemSpider	3208 Y
UNII	5QZO15J2Z8 Y
KEGG	D00318 Y
ChEBI	CHEBI:4975 Y
ChEMBL	CHEMBL902 Y
Chemical data
Formula	C8H15N7O2S3
Mol. mass	337.449 g/mol
SMILES	eMolecules & PubChem
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) Y Key:XUFQPHANEAPEMJ-UHFFFAOYSA-N Y
N(what is this?)  (verify)

Famotidine (INN) ( /fəˈmɒtɪdiːn/) is a histamine H₂-receptor antagonist that inhibits stomach acid production, and it is commonly used in the treatment of peptic ulcer disease (PUD) and gastroesophageal reflux disease (GERD/GORD). It is commonly marketed by Johnson & Johnson/Merck under the trade names Pepcidine and Pepcid and by Astellas under the trade name Gaster. 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.^[1]

History and development

Famotidine was developed by Yamanouchi Pharmaceutical Co.^[2] It was licensed in the mid-80s by Merck & Co.^[3] 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 30 times more active than cimetidine.^{[citation needed]}

It was first marketed in 1981. Pepcid RPD orally-disintegrating tablets (that are not swallowed) were released in 1999. Generic preparations became available in 2001, e.g. Fluxid (Schwarz) or Quamatel (Gedeon Richter Ltd.).

In the United States, a product called Pepcid Complete is available that combines famotidine with an antacid in a chewable tablet to ameliorate the relatively slow onset of effects. In the UK, this product is known as Pepcidtwo.

Famotidine suffers from poor bioavailability (50%), as it is poorly soluble in the low pH of the stomach. Famotidine used in combination with antacids 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 and thereby improve 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.^[4]

Clinical use

Main article: H2 antagonist

Certain preparations of famotidine are available over the counter (OTC) in various countries. In the United States, preparations of 10 mg and 20 mg tablets, sometimes in combination with a more traditional antacid, are available OTC. Larger doses still require a prescription.

Famotidine is given to surgery patients before operations to prevent postoperative nausea and to reduce the risk of aspiration pneumonitis. Famotidine is also given to some patients who take NSAIDs, to prevent peptic ulcers.^[5] It serves as an alternative to proton-pump inhibitors.^[6]

It is also given to dogs with acid reflux.

Famotidine has also been used in combination with an H1 antagonist to treat and prevent urticaria caused by an acute allergic reaction.^[7]

It has been found to decrease the debilitating effects of chronic heart failure by blocking histamine. ^[8]

Side effects

Side effects are associated with famotidine use. In clinical trials, the most common adverse effects were headache, dizziness, and constipation or diarrhea.^[9]

References

1. ^ Humphries TJ, Merritt GJ (August 1999). "Review article: drug interactions with agents used to treat acid-related diseases". Aliment. Pharmacol. Ther. 13 Suppl 3: 18–26. doi:10.1046/j.1365-2036.1999.00021.x. PMID 10491725. http://www3.interscience.wiley.com/cgi-bin/fulltext/119090200. 
2. ^ US patent 4283408, Hirata , et al., "Guanidinothiazole compounds, process for preparation and gastric inhibiting compositions containing them", issued 1981-08-11 
3. ^ "Sankyo Pharma". Skyscape Mediwire. 2002. http://mediwire.skyscape.com/main/Default.aspx?P=Content&ArticleID=23882. Retrieved 2009-10-30. 
4. ^ "Formulation and Evaluation of Gastroretentive Floating Tablets of Famotidine". Farmavita.Net. 2008. http://www.farmavita.net/content/view/1012/84/. Retrieved 2009-01-30. 
5. ^ "Horizon Pharma, Inc. Announces FDA Approval of DUEXIS(R) for the Relief of the Signs and Symptoms of Rheumatoid Arthritis and Osteoarthritis and to Decrease the Risk of Developing Upper Gastrointestinal Ulcers" (Press release). Horizon Pharma. 25 April 2011. http://www.clinicaspace.com/news_story.aspx?NewsEntityId=218076. Retrieved 26 April 2011. 
6. ^ http://www.medscape.com/viewarticle/705708 (membership required)
7. ^ TB Fogg; D Semple (29 November 2007). "Combination therapy with H2 and H1 antihistamines in acute, non compromising allergic reactions". BestBets. Manchester, England: Manchester Royal Infirmary. http://www.bestbets.org/bets/bet.php?id=353. Retrieved 26 April 2011. 
8. ^ http://www.rxpgnews.com/research/cardiology/congestive-heart-failure/article_5010.shtml
9. ^ "Pepcid Side Effects & Drug Interactions". RxList.com. 2008. http://www.rxlist.com/cgi/generic/famot_ad.htm. Retrieved 2008-07-31.