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Famotidine

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Famotidine
Clinical data
Pronunciation/fəˈmɒtɪdn/
Trade namesPepcid, Zantac 360, others
AHFS/Drugs.comMonograph
MedlinePlusa687011
License data
Pregnancy
category
Routes of
administration
By mouth, intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability40–45% (by mouth)[2]
Protein binding15–20%[2]
Elimination half-life2.5–3.5 hours[2]
ExcretionKidney (25–30% unchanged [Oral])[2]
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 InfoCard100.116.793 Edit this at Wikidata
Chemical and physical data
FormulaC8H15N7O2S3
Molar mass337.44 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) checkY
  • Key:XUFQPHANEAPEMJ-UHFFFAOYSA-N checkY
  (verify)

Famotidine, sold under the brand name Pepcid among others, is a histamine H2 receptor antagonist medication that decreases stomach acid production.[4] It is used to treat peptic ulcer disease, gastroesophageal reflux disease, and Zollinger-Ellison syndrome.[4] It is taken by mouth or by injection into a vein.[4] It begins working within an hour.[4]

Common side effects include headache, intestinal upset, and dizziness.[4] Serious side effects may include pneumonia and seizures.[4][5] Use in pregnancy appears safe but has not been well studied, while use during breastfeeding is not recommended.[1]

Famotidine was patented in 1979 and came into medical use in 1985.[6] It is available as a generic medication.[5] In 2021, it was the 57th most commonly prescribed medication in the United States, with more than 11 million prescriptions.[7][8]

Medical uses

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Pharmacokinetics

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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

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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

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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

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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

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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

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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

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COVID-19

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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

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

Veterinary uses

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

References

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  2. ^ a b c d e "Famotidine tablet". DailyMed. Archived from the original on 31 March 2024. Retrieved 6 March 2021.
  3. ^ "Zantac 360- famotidine tablet, film coated". DailyMed. 17 May 2022. Archived from the original on 6 July 2022. Retrieved 6 July 2022.
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  5. ^ a b British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. pp. 74–75. ISBN 9780857113382.
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  25. ^ Wang X, Boffito M, Zhang J, Chung E, Zhu L, Wu Y, et al. (September 2011). "Effects of the H2-receptor antagonist famotidine on the pharmacokinetics of atazanavir-ritonavir with or without tenofovir in HIV-infected patients". AIDS Patient Care and STDs. 25 (9): 509–515. doi:10.1089/apc.2011.0113. PMC 3157302. PMID 21770762.
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  28. ^ US patent 4283408, Yasufumi Hirata, Isao Yanagisawa, Yoshio Ishii, Shinichi Tsukamoto, Noriki Ito, Yasuo Isomura and Masaaki Takeda, "Guanidinothiazole compounds, process for preparation and gastric inhibiting compositions containing them", issued 11 August 1981 
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  33. ^ Pepcid Complete
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  35. ^ "Duexis". Drugs.com. Archived from the original on 26 November 2020. Retrieved 28 April 2020.
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  38. ^ a b Cheema HA, Shafiee A, Athar M, Shahid A, Awan RU, Afifi AM, et al. (February 2023). "No evidence of clinical efficacy of famotidine for the treatment of COVID-19: a systematic review and meta-analysis". J Infect. 86 (2): 154–225. doi:10.1016/j.jinf.2022.11.022. PMC 9711899. PMID 36462586.
  39. ^ a b Kow CS, Ramachandram DS, Hasan SS (September 2023). "Famotidine: A potential mitigator of mast cell activation in post-COVID-19 cognitive impairment". J Psychosom Res. 172: 111425. doi:10.1016/j.jpsychores.2023.111425. PMC 10292911. PMID 37399740.
  40. ^ a b Yang H, George SJ, Thompson DA, Silverman HA, Tsaava T, Tynan A, et al. (May 2022). "Famotidine activates the vagus nerve inflammatory reflex to attenuate cytokine storm". Mol Med. 28 (1): 57. doi:10.1186/s10020-022-00483-8. PMC 9109205. PMID 35578169.
  41. ^ Salvucci F, Codella R, Coppola A, Zacchei I, Grassi G, Anti ML, et al. (2023). "Antihistamines improve cardiovascular manifestations and other symptoms of long-COVID attributed to mast cell activation". Front Cardiovasc Med. 10: 1202696. doi:10.3389/fcvm.2023.1202696. PMC 10388239. PMID 37529714.
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  43. ^ Andrade C (2013). "Famotidine Augmentation in Schizophrenia: Hope or Hype?". The Journal of Clinical Psychiatry. 74 (9): e855–e858. doi:10.4088/JCP.13f08707. PMID 24107771. Archived from the original on 11 January 2024. Retrieved 11 January 2024.
  44. ^ "Famotidine". PetMD. Archived from the original on 19 May 2015. Retrieved 7 June 2015.
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