Indications
Famotidine is prescribed for both pediatric and adult patients, weighing 40 kg or more, primarily to address active duodenal ulcers (DU), active gastric ulcers, and both symptomatic non-erosive and erosive esophagitis associated with gastroesophageal reflux disease (GERD) that has been confirmed via biopsy. In adult patients, it is also utilized for treating pathological hypersecretory conditions, such as Zollinger-Ellison Syndrome and multiple endocrine neoplasias, and for reducing the risk of DU recurrence. For hospitalized patients with pathological hypersecretory disorders, intractable ulcers, or those unable to take oral medications, an intravenous formulation of famotidine is available for short-term use. Over-the-counter famotidine can be used for managing and preventing heartburn related to gastroesophageal reflux in both children and adults. Additionally, off-label applications of the drug include mitigating gastrointestinal effects associated with NSAIDs, treating refractory urticaria, preventing stress ulcers in critically ill patients, and providing symptomatic relief for gastritis.
Pharmacodynamics
Famotidine operates by diminishing gastric acid production, thereby reducing the concentration of acid, the content of pepsin, and the volume of gastric secretions. It effectively inhibits both basal and nocturnal gastric acid secretion, as well as acid production induced by factors such as food, caffeine, insulin, and pentagastrin. The therapeutic effects of famotidine are dose-dependent, with higher doses correlated with prolonged duration and greater inhibitory impact on gastric acid secretion. When administered orally, the drug begins to take effect within one hour, with peak effects occurring within 1-3 hours, and a total duration of action lasting approximately 10-12 hours.
Absorption
Upon oral administration, famotidine's absorption is incomplete and varies with dosage. The oral bioavailability of the drug lies between 40-50%, reaching peak plasma concentration (Cmax) within 1-4 hours after dosing. Although its bioavailability can be slightly increased by food intake and diminished by antacids, these variations are not clinically significant.
Metabolism
Famotidine is subject to minimal first-pass metabolism, with approximately 25-30% of the drug undergoing hepatic metabolism. The S-oxide is the only metabolite identified within human pathways.
Mechanism of Action
Famotidine functions by targeting the H2 receptors on the basolateral membrane of gastric parietal cells, effectively inhibiting the action of histamine, a critical regulator of gastric acid secretion. Normally, histamine is released from enterochromaffin-like (ECL) cells, which lie in close proximity to parietal cells and are stimulated via a paracrine mechanism. This secretion can be further enhanced by acetylcholine and gastrin, the latter being released from G cells and acting on CCK2 receptors on ECL cells to stimulate histamine release. As histamine binds to H2 receptors on parietal cells, there is an increase in intracellular cyclic AMP (cAMP), which subsequently activates proton pumps, escalating gastric acid output. In clinical scenarios characterized by excessive acid production, such as peptic ulcers, regulatory mechanisms of acid secretion can become dysregulated. Famotidine's action in blocking H2 receptors disrupts this cascade, thereby reducing gastric acid secretion and alleviating these hypersecretion conditions.
