Famotidine

Last updated

Famotidine
Famotidine.svg
Famotidine-from-xtal-Mercury-3D-bs.png
Clinical data
Pronunciation /fəˈmɒtɪdiːn/
Trade names Pepcid, Zantac 360, others
AHFS/Drugs.com Monograph
MedlinePlus a687011
License data
Pregnancy
category
  • AU:B1
Routes of
administration 		By mouth, intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 40–45% (by mouth) [1]
Protein binding 15–20% [1]
Elimination half-life 2.5–3.5 hours [1]
Excretion Kidney (25–30% unchanged [Oral]) [1]
Identifiers
  • 3-[({2-[(diaminomethylidene)amino]-1,3-thiazol-4-yl}methyl)sulfanyl]-N-sulfamoylpropanimidamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard 100.116.793 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C8H15N7O2S3
Molar mass 337.44 g·mol−1
3D model (JSmol)
  • NS(=O)(=O)/N=C(\N)CCSCc1csc(n1)N=C(N)N
  • 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) Yes check.svgY
  • Key:XUFQPHANEAPEMJ-UHFFFAOYSA-N Yes check.svgY
   (verify)

Famotidine, sold under the brand name Pepcid among others, is a histamine H2 receptor antagonist medication that decreases stomach acid production. [3] It is used to treat peptic ulcer disease, gastroesophageal reflux disease, and Zollinger-Ellison syndrome. [3] It is taken by mouth or by injection into a vein. [3] It begins working within an hour. [3]

Contents

Common side effects include headache, intestinal upset, and dizziness. [3] Serious side effects may include pneumonia and seizures. [3] [4] Use in pregnancy appears safe but has not been well studied, while use during breastfeeding is not recommended. [5]

Famotidine was patented in 1979 and came into medical use in 1985. [6] It is available as a generic medication. [4] In 2021, it was the 57th most commonly prescribed medication in the United States, with more than 11 million prescriptions. [7] [8]

Medical uses

Pharmacokinetics

Famotidine has a delayed onset of action, beginning after 90 minutes. However, famotidine has a duration of effect of at least 540 minutes (9.0 h). At its peak effect, 210 minutes (3.5 h) after administration, famotidine reduces acid secretion by 7.3 mmol per 30 minutes. [20]

Side effects

The most common side effects associated with famotidine use include headache, dizziness, and constipation or diarrhea. [21] [22]

Famotidine may contribute to QT prolongation, [23] particularly when used with other QT-elongating drugs, or in people with poor kidney function. [24]

Mechanism of action

Activation of H2 receptors located on parietal cells stimulates proton pumps to secrete acid into the stomach lumen. Famotidine, an H2 antagonist, blocks the action of histamine on the parietal cells, ultimately reducing acid secretion into the stomach.

Interactions

Unlike cimetidine, the first H2 antagonist, famotidine has a minimal effect on the cytochrome P450 enzyme system, and does not appear to interact with as many drugs as other medications in its class. Some exceptions include antiretrovirals such as atazanavir, chemotherapeutics such as doxorubicin, and antifungal medications such as itraconazole. [25] [26] [27]

History

Famotidine was developed by Yamanouchi Pharmaceutical Co. [28] It was licensed in the mid-1980s by Merck & Co. [29] 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 nine times more potent than ranitidine, and thirty-two times more potent than cimetidine. [30]

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 until its discontinuation in April 2015. [31]

Famotidine has poor bioavailibility (50%) due to low gastroretention time. Famotidine is less soluble at higher pH, and when used in combination with antacids gastroretention time is increased. This promotes local delivery of these drugs to receptors in the parietal cell membrane and increases bioavailibility. Researchers are developing tablet formulations that rely on other gastroretentive drug delivery systems such as floating tablets to further increase bioavailibility. [32]

Society and culture

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, [33] [34] are available OTC. Larger doses still require a prescription.

Formulations of famotidine in combination with ibuprofen were marketed by Horizon Pharma under the trade name Duexis. [35]

Research

COVID-19

At the start of the COVID-19 pandemic, some doctors observed that anecdotally some hospitalized patients in China may have had better outcomes on famotidine than other patients that were not taking famotidine. This led to hypotheses about use of famotidine in treatment of COVID-19. [36] [37] Famotidine was considered a possible treatment for COVID-19 due to its potential anti-inflammatory effects. It was thought that famotidine could modify lung inflammation caused by coronaviruses. However, studies have shown that famotidine is not effective in reducing mortality or improving recovery in COVID-19 patients. [38] Famotidine primarily works by blocking the effects of histamine and has some potential mechanisms of action that may contribute to its anti-inflammatory properties, including the inhibition of the production of certain pro-inflammatory cytokines such as TNF-alpha and IL-6. [39] [40] Another hypothesis was that famotidine might activate the vagus nerve inflammatory reflex to attenuate cytokine storm. [40] Yet another hypothesis was that famotidine can reduce the activation of mast cells and the subsequent release of inflammatory mediators, therefore acting as a mast cell stabilizer. [41] [39] However, while famotidine may have some anti-inflammatory effects, there is currently insufficient evidence to support its use for treating inflammation associated with COVID-19. [38] Therefore, it is not recommended for this purpose. [42]

Other

Small-scale studies have shown inconsistent and inconclusive evidence of efficacy in treatment-refractory schizophrenia. [43]

Veterinary uses

Famotidine is given to dogs and cats with acid reflux. [44]

Related Research Articles

<span class="mw-page-title-main">Proton-pump inhibitor</span> Class of drugs for reducing stomach acid

Proton-pump inhibitors (PPIs) are a class of medications that cause a profound and prolonged reduction of stomach acid production. They do so by irreversibly inhibiting the stomach's H+/K+ ATPase proton pump.

H<sub>2</sub> receptor antagonist Class of medications

H2 antagonists, sometimes referred to as H2RAs and also called H2 blockers, are a class of medications that block the action of histamine at the histamine H2 receptors of the parietal cells in the stomach. This decreases the production of stomach acid. H2 antagonists can be used in the treatment of dyspepsia, peptic ulcers and gastroesophageal reflux disease. They have been surpassed by proton pump inhibitors (PPIs). The PPI omeprazole was found to be more effective at both healing and alleviating symptoms of ulcers and reflux oesophagitis than the H2 blockers ranitidine and cimetidine.

<span class="mw-page-title-main">Zollinger–Ellison syndrome</span> Condition in which tumours stimulate excessive gastric acid production

Zollinger–Ellison syndrome is rare disease in which tumors cause the stomach to produce too much acid, resulting in peptic ulcers. Symptoms include abdominal pain and diarrhea.

The histamine receptors are a class of G protein–coupled receptors which bind histamine as their primary endogenous ligand.

<span class="mw-page-title-main">Esomeprazole</span> Medication which reduces stomach acid

Esomeprazole, sold under the brand name Nexium [or Neksium] among others, is a medication which reduces stomach acid. It is used to treat gastroesophageal reflux disease, peptic ulcer disease, and Zollinger–Ellison syndrome. Its effectiveness is similar to that of other proton pump inhibitors (PPIs). It is taken by mouth or injection into a vein.

<span class="mw-page-title-main">Rabeprazole</span> Stomach acid suppressing medication

Rabeprazole, sold under the brand name Aciphex, among others, is a medication that decreases stomach acid. It is used to treat peptic ulcer disease, gastroesophageal reflux disease, and excess stomach acid production such as in Zollinger–Ellison syndrome. It may also be used in combination with other medications to treat Helicobacter pylori. Effectiveness is similar to other proton pump inhibitors (PPIs). It is taken by mouth.

<span class="mw-page-title-main">Cimetidine</span> Medication

Cimetidine, sold under the brand name Tagamet among others, is a histamine H2 receptor antagonist that inhibits stomach acid production. It is mainly used in the treatment of heartburn and peptic ulcers.

<span class="mw-page-title-main">Ranitidine</span> Medication that decreases stomach acid

Ranitidine, sold under the brand name Zantac among others, is a medication used to decrease stomach acid production. It is commonly used in treatment of peptic ulcer disease, gastroesophageal reflux disease, and Zollinger–Ellison syndrome. It can be given by mouth, injection into a muscle, or injection into a vein. In September 2019, the probable carcinogen N-nitrosodimethylamine (NDMA) was discovered in ranitidine products from a number of manufacturers, resulting in recalls.

<span class="mw-page-title-main">Nizatidine</span> Chemical compound

Nizatidine is a histamine H2 receptor antagonist that inhibits stomach acid production, and is commonly used in the treatment of peptic ulcer disease and gastroesophageal reflux disease.

<span class="mw-page-title-main">Metiamide</span> Chemical compound

Metiamide is a histamine H2 receptor antagonist developed from another H2 antagonist, burimamide. It was an intermediate compound in the development of the successful anti-ulcer drug cimetidine (Tagamet).

<span class="mw-page-title-main">Vagotomy</span> Surgical procedure

A vagotomy is a surgical procedure that involves removing part of the vagus nerve. It is performed in the abdomen.

<span class="mw-page-title-main">Antihistamine</span> Drug that blocks histamine or histamine agonists

Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic drug that can be bought without a prescription and provides relief from nasal congestion, sneezing, or hives caused by pollen, dust mites, or animal allergy with few side effects. Antihistamines are usually for short-term treatment. Chronic allergies increase the risk of health problems which antihistamines might not treat, including asthma, sinusitis, and lower respiratory tract infection. Consultation of a medical professional is recommended for those who intend to take antihistamines for longer-term use.

Lafutidine (INN) is a second generation histamine H2 receptor antagonist having multimodal mechanism of action and used to treat gastrointestinal disorders. It is marketed in South Korea, Japan and India.

<span class="mw-page-title-main">Troxipide</span> Chemical compound

Troxipide is a drug used in the treatment of gastroesophageal reflux disease. Troxipide is a systemic non-antisecretory gastric cytoprotective agent with anti-ulcer, anti-inflammatory and mucus secreting properties irrespective of pH of stomach or duodenum. Troxipide is currently marketed in Japan (Aplace), China (Shuqi), South Korea (Defensa), and India (Troxip). It is used for the management of gastric ulcers, and amelioration of gastric mucosal lesions in acute gastritis and acute exacerbation of chronic gastritis.

Ebrotidine is an H2 receptor antagonist with gastroprotective activity against ethanol-, aspirin- or stress-induced gastric mucosal damage. The antisecretory properties of ebrotidine are similar to those of ranitidine, and approximately 10-fold greater than those of cimetidine. Ebrotidine has anti-Helicobacter pylori activity via inhibition of the urease enzyme and the proteolytic and mucolytic activities of the bacterium. However, its activity is synergistic with a number of antibacterial agents. Ebrotidine counteracts the inhibitory effects of H. pylori lipopolysaccharides. Ebrotidine was withdrawn from the market due to risks of hepatotoxicity.

There are several classes of drugs for acid-related disorders, such as dyspepsia, peptic ulcer disease (PUD), gastroesophageal reflux disease (GORD/GERD), or laryngopharyngeal reflux.

Equine gastric ulcer syndrome (EGUS) is a common cause of colic and decreased performance in horses. Horses form ulcers in the mucosa of the stomach, leading to pain, decreased appetite, weight loss, and behavioral changes. Treatment generally involves reducing acid production of the stomach and dietary management. Unlike some animals, however, stomach rupture is rare, and the main goal of treating is to reduce pain and improve performance of animals used for showing or racing.

<span class="mw-page-title-main">Acid peptic diseases</span> Overview of the acid peptic diseases of the stomach and gastrointestinal tract

Acid peptic diseases, such as peptic ulcers, Zollinger-Ellison syndrome, and gastroesophageal reflux disease, are caused by distinct but overlapping pathogenic mechanisms involving acid effects on mucosal defense. Acid reflux damages the esophageal mucosa and may also cause laryngeal tissue injury, leading to the development of pulmonary symptoms.

Ranitidine bismuth citrate - drug, which has antisecretory and bactericidal action.

Ibuprofen/famotidine, sold under the brand name Duexis, is a fixed-dose combination medication used for the treatment of rheumatoid arthritis and osteoarthritis. It contains ibuprofen, a nonsteroidal anti-inflammatory drug (NSAID) and famotidine, a histamine H2-receptor antagonist.

References

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