Famotidine

Famotidine belongs to the Gastrointestinal Agent acts as a Histamine H₂ Receptor Antagonist.

Famotidine is a histamine H2 receptor antagonist used to treat duodenal ulcers, benign gastric ulcers, GERD, and Zollinger-Ellison syndrome.

Famotidine is incompletely absorbed. The bioavailability of oral doses is 40 to 45%. Bioavailability may be slightly increased by food, or slightly decreased by antacids; however, these effects are of no clinical consequence. Peak famotidine plasma levels occur in 1 to 3 hours. Plasma levels after multiple dosages are like those after single doses. Famotidine 15 to 20% of famotidine in plasma is protein bound. Famotidine undergoes minimal first-pass metabolism. 25% to 30% of an oral dose was recovered in the urine as unchanged compound. The only metabolite identified in humans is the S-oxide. Famotidine has an elimination half-life of 2.5-3.5 hours. Famotidine is eliminated by renal (65 to 70%) and metabolic (30 to 35%) routes. The renal clearance is 250 to 450 mL/minute, indicating some tubular excretion.

Famotidine shows side effects like Swelling of face, lips, eyelids, tongue, hands and feet, Difficulty in breathing, Skin rash, Breast pain and tenderness, Dry mouth, Chest pain, Dizziness and fainting, Extreme tiredness.

Famotidine is available in the form of Oral Tablet, Oral powder for reconstitution and Injectable solution.

Famotidine is available in India, Canada, US, China, Australia, France, Malaysia, Italy, Japan, and Germany.

Famotidine belongs to the Gastrointestinal Agent acts as a Histamine H₂ Receptor Antagonist.

Famotidine is a competitive inhibitor of histamine-2 (H2) receptors. The primary clinically important pharmacologic activity of famotidine is inhibition of gastric secretion. Both the acid concentration and volume of gastric secretion are suppressed by famotidine, while changes in pepsin secretion are proportional to volume output.

The Onset of action of Famotidine is within 1 hour.

The Duration of action of Famotidine is approximately 10-12 hours.

The Tmax of Famotidine is approximately 30 minutes (IV) and 1-30 hours (oral).

Famotidine is available in the form of Oral Tablet, Oral powder for reconstitution and Injectable solution.

Famotidine Tablet, Powder for reconstitution is taken orally, while injectable solution is given via intravenous route.

Famotidine is an anti-ulcer medicine that is used to treat stomach and intestine ulcers and reflux diseases (condition in which the stomach acid flows back into the food pipe). It is also used to treat and prevent indigestion, heartburn, and other acidity related symptoms. It works by decreasing the production of acid in your stomach.

Famotidine belongs to the Gastrointestinal Agent acts as a Histamine H₂ Receptor Antagonist.

Famotidine competitive inhibition of histamine at H₂ receptors of the gastric parietal cells, which inhibits gastric acid secretion.

Famotidine is approved for use in the following clinical indications

Adult indication

• Aspiration prophylaxis in patients undergoing anesthesia
• Chronic spontaneous urticaria
• Gastroesophageal reflux disease, treatment
• Infusion reaction, premedication
• Mastocytosis
• Stress ulcer prophylaxis in select critically ill patients

Pediatric indication

• GERD
• Heartburn, acid indigestion, or sour stomach
• Pathological hypersecretory conditions
• Peptic ulcer disease
• Stress ulcer prophylaxis, gastric acid suppression

Adult Dose

• Aspiration prophylaxis in patients undergoing anesthesia

IV: 20 mg as a single dose ~40 to 90 minutes prior to induction of anesthesia; may be given with a rapid-acting nonparticulate antacid (eg, oral sodium citrate and citric acid) and/or metoclopramide.

• Chronic spontaneous urticaria

Oral: 20 mg twice daily given in combination with H₁ antihistamine; a trial of 2 to 4 weeks is suggested to assess response.

• Gastroesophageal reflux disease, treatment

Mild and intermittent symptoms (<2 episodes/week), and no evidence of erosive esophagitis:

Oral: 10 mg twice daily as needed; if symptoms persist after 2 to 4 weeks, increase to 20 mg twice daily for 2 weeks; if symptoms improve, may continue therapy as needed.

Residual acid reflux symptoms despite maximal PPI therapy (adjunct):

Oral: 20 mg once daily given at bedtime in addition to PPI therapy; may also administer famotidine intermittently or on demand with scheduled PPI.

• Infusion reaction, premedication

IV, Oral: 20 mg typically administered 30 to 60 minutes prior to infusion of certain chemotherapy agents or biologics; usually given in conjunction with an H₁ antihistamine (eg, diphenhydramine) and glucocorticoid (refer to institutional protocols).

• Mastocytosis

Oral: 10 to 20 mg every 12 hours adjusted to achieve GI symptom relief. Typically used in combination with other appropriate agent(s) (eg, H₁ antihistamine and/or leukotriene inhibitor).

• Stress ulcer prophylaxis in select critically ill patients

Oral or via nasogastric (NG) tube (alternative to enteral PPI): 20 mg twice daily. Discontinue prophylaxis once risk factors have resolved.

IV: 20 mg twice daily. Discontinue prophylaxis once risk factors have resolved.

Pediatric Dose

• GERD

Oral Route:

Suspension:

Infants <3 months: 0.5 mg/kg/dose once daily for up to 8 weeks; if not effective after 2 weeks, increasing to 1 mg/kg/dose once daily has been suggested.

Infants ≥3 months, Children, and Adolescents ≤16 years: Initial: 0.5 mg/kg/dose twice daily; maximum dose: 40 mg/dose; doses up to 1 mg/kg/dose twice daily have been reported.

Tablets

Children and Adolescents ≥40 kg: 20 mg twice daily for up to 6 weeks; for esophagitis and accompanying symptoms due to GERD, may use 20 to 40 mg twice daily for up to 12 weeks.

IV Route:

Infants <3 months: 0.25 mg/kg/dose once daily; dosing based on a pharmacokinetic study which included 7 patients <3 months who received IV famotidine.

Infants ≥3 months: Initial: 0.25 mg/kg/dose every 12 hours; maximum dose: 20 mg/dose; dosing based on a pharmacokinetic study which included 11 patients >3 to 12 months who received IV famotidine.

Children and Adolescents: Initial: 0.25 mg/kg/dose every 12 hours; maximum dose: 20 mg/dose; doses up to 0.5 mg/kg/dose every 12 hours have been reported.

• Heartburn, acid indigestion, or sour stomach

Children ≥12 years and Adolescents: Oral: 10 to 20 mg every 12 hours; dose may be taken 15 to 60 minutes before eating foods known to cause heartburn; maximum daily dose: 2 tablets/day.

• Pathological hypersecretory conditions

Adolescents ≥17 years:

Oral: Initial: 20 mg every 6 hours, may increase up to 160 mg every 6 hours.

IV: 20 mg every 12 hours.

• Peptic ulcer disease

Oral Route:

Suspension: Children and Adolescents ≤16 years: 0.5 mg/kg/day at bedtime or divided twice daily; maximum daily dose: 40 mg/day; doses up to 1 mg/kg/day at bedtime or divided twice daily have been used.

Tablets: Children and Adolescents >40 kg:

Duodenal ulcer: Acute therapy: 40 mg once daily at bedtime or 20 mg twice daily for 4 to 8 weeks.

Gastric ulcer: Acute therapy: 40 mg once daily at bedtime for up to 8 weeks.

IV Route:

Children and Adolescents: Initial: 0.25 mg/kg/dose every 12 hours; maximum dose: 20 mg/dose; doses up to 0.5 mg/kg/dose every 12 hours have been reported.

• Stress ulcer prophylaxis, gastric acid suppression

Infants, Children, and Adolescents: IV: 1 to 2 mg/kg/day in divided doses every 8 to 12 hours; maximum daily dose: 40 mg/day.

Famotidine is available in various strengths as 20 mg; 40 mg; 20 mg/50 mL; 40 mg/5 mL; 10 mg/mL; 10 mg; 20 mg/10 mL-NaCl 0.9%; 20 mg/5 mL-NaCl 0.9%.

Famotidine is available in the form of Oral Tablet, Oral powder for reconstitution and Injectable solution.

• Dosage Adjustment in Kidney Patient

CrCl ≥50 mL/minute: No dosage adjustment necessary.

CrCl <50 mL/minute: Administer 50% of usual dose or continue usual dose but increase the dosing interval to every 36 to 48 hours.

Limit caffeine intake. Caffeine and other acidic beverages increase the risk of gastric irritation.

Famotidine is contraindicated in patients with

• Hypersensitivity to any component of these products. Cross sensitivity in this class of compounds has been observed. Therefore, Famotidine should not be administered to patients with a history of hypersensitivity to other H2-receptor antagonists.

• Vitamin B₁₂ deficiency: Famotidine and other H2RAs can reduce absorption of vitamin B₁₂ and thus decrease serum concentrations. It is unclear of its role in causing function or clinical deficiencies. Several studies have tried to determine the association of B₁₂ deficiency with H2RAs use; however, differences in diagnostic criteria have made this challenging.
• Gastric malignancy: Relief of symptoms does not preclude the presence of a gastric malignancy.
• Patients With Moderate or Severe Renal insufficiency: Since CNS adverse effects have been reported in patients with moderate and severe renal insufficiency, longer intervals between doses or lower doses may need to be used in patients with moderate (creatinine clearance < 50 mL/min) or severe (creatinine clearance < 10 mL/min) renal insufficiency to adjust for the longer elimination half-life of famotidine. Prolonged QT interval has been reported very rarely in patients with impaired renal function whose dose/dosing interval of famotidine may not have been adjusted appropriately.

Avoid excessive or chronic alcohol consumption. Alcohol increases the risk of gastric irritation.

Studies performed in lactating rats have shown that famotidine is secreted into breast milk. Transient growth depression was observed in young rats suckling from mothers treated with maternotoxic doses of at least 600 times the usual human dose. Famotidine is detectable in human milk. Because of the potential for serious adverse reactions in nursing infants from Famotidine, a decision should be made whether to discontinue nursing or discontinue the drug, considering the importance of the drug to the mother.

Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.

Limit caffeine intake. Caffeine and other acidic beverages increase the risk of gastric irritation.

Common Adverse effects

• Constipation, diarrhea, Dizziness, headache.

Rare Adverse effects

• Flushing, palpitations, Pruritus, skin rash, xeroderma, Decreased libido, Abdominal distress, anorexia, nausea, vomiting, xerostomia, Impotence, Thrombocytopenia, Increased liver enzymes, Anxiety, depression, drowsiness, fatigue, hallucination, insomnia, seizure, taste disorder, Arthralgia, asthenia, musculoskeletal pain, Conjunctival injection, periorbital edema, Tinnitus, Bronchospasm, Fever.

• Acalabrutinib: Histamine H2 Receptor Antagonists may decrease the serum concentration of Acalabrutinib. Management: Give acalabrutinib capsules 2 hours before a histamine H2 receptor antagonist (H2RA). No action is required if acalabrutinib tablets are coadministered with H2RAs.
• Atazanavir: Histamine H2 Receptor Antagonists may decrease the serum concentration of Atazanavir. Management: Specific dose limitations and administration guidelines exist; consult full interaction monograph or atazanavir prescribing information.
• Belumosudil: Histamine H2 Receptor Antagonists may decrease the serum concentration of Belumosudil.
• Bosutinib: Histamine H2 Receptor Antagonists may decrease the serum concentration of Bosutinib. Management: Administer histamine H2 receptor antagonists more than 2 hours before or after bosutinib.
• Cysteamine (Systemic): Histamine H2 Receptor Antagonists may diminish the therapeutic effect of Cysteamine (Systemic).
• Dacomitinib: Histamine H2 Receptor Antagonists may decrease the serum concentration of Dacomitinib. Management: Administer dacomitinib at least 6 hours before or 10 hours after a histamine H2-receptor antagonist (H2RA).
• Dasatinib: Histamine H2 Receptor Antagonists may decrease the absorption of Dasatinib. Management: Antacids (taken 2 hours before or after dasatinib administration) can be used in place of H2-antagonists if some acid-reducing therapy is needed.
• Erlotinib: Histamine H2 Receptor Antagonists may decrease the serum concentration of Erlotinib. Management: Avoid H2-antagonists in patients receiving erlotinib when possible. If concomitant treatment cannot be avoided, erlotinib should be dosed once daily, 10 hours after and at least 2 hours before H2-antagonist dosing.
• Fosamprenavir: Histamine H2 Receptor Antagonists may decrease the serum concentration of Fosamprenavir. Cimetidine may also inhibit the metabolism of the active metabolite amprenavir, making its effects on fosamprenavir/amprenavir concentrations difficult to predict.
• Infigratinib: Histamine H2 Receptor Antagonists may decrease serum concentrations of the active metabolite(s) of Infigratinib. Histamine H2 Receptor Antagonists may decrease the serum concentration of Infigratinib. Management: Avoid coadministration of infigratinib with histamine receptor antagonists (H2RAs) or other gastric acid-lowering agents. If H2RAs cannot be avoided, administer infigratinib 2 hours before or 10 hours after administration of H2RAs.
• Itraconazole: Histamine H2 Receptor Antagonists may increase the serum concentration of Itraconazole. Histamine H2 Receptor Antagonists may decrease the serum concentration of Itraconazole. Management: Administer Sporanox brand itraconazole at least 2 hours before or 2 hours after administration of any histamine H2 receptor antagonists (H2RAs). Exposure to Tolsura brand itraconazole may be increased by H2RAs; consider itraconazole dose reduction.
• Ketoconazole (Systemic): Histamine H2 Receptor Antagonists may decrease the serum concentration of Ketoconazole (Systemic). Management: Administer ketoconazole with an acidic beverage (eg, non-diet cola) and monitor for reduced efficacy if concomitant use with a H2RA is required. Increases in ketoconazole dose may be required.
• Ledipasvir: Histamine H2 Receptor Antagonists may decrease the serum concentration of Ledipasvir. Management: Administer H2 receptor antagonist doses less than or comparable to famotidine 40 mg twice daily simultaneously or 12 hours prior to ledipasvir. The effect of administering H2 receptor antagonists at other time intervals is unknown and not recommended.

The common side effect of Famotidine includes the following

Common

• Headache, dizziness, Constipation, diarrhea, fussiness (in babies who take famotidine).

Rare

• Hives, skin rash, Itching, swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs, Hoarseness, difficulty breathing or swallowing.

• Pregnancy

Pregnancy Category B

Reproductive studies have been performed in rats and rabbits at oral doses of up to 2000 and 500 mg/kg/day, respectively, and in both species at intravenous doses of up to 200 mg/kg/day and have revealed no significant evidence of impaired fertility or harm to the fetus due to Famotidine. While no direct fetotoxic effects have been observed, sporadic abortions occurring only in mothers displaying marked decreased food intake were seen in some rabbits at oral doses of 200 mg/kg/day (about 49 times the recommended human dose of 80 mg per day, based on body surface area) or higher. There are, however, no adequate or well-controlled studies in pregnant women. Because animal reproductive studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

• Nursing Mothers

Studies performed in lactating rats have shown that famotidine is secreted into breast milk. Transient growth depression was observed in young rats suckling from mothers treated with maternotoxic doses of at least 600 times the usual human dose. Famotidine is detectable in human milk. Because of the potential for serious adverse reactions in nursing infants from Famotidine, a decision should be made whether to discontinue nursing or discontinue the drug, considering the importance of the drug to the mother.

• Pediatric Use

In pediatric patients, the safety and effectiveness for the treatment of pathological hypersecretory conditions and reduction of risk of duodenal ulcer recurrence have not been established.

• Geriatric Use

Of the 1442 Famotidine -treated patients in clinical studies, approximately 10% were 65 and older. In these studies, no overall differences in safety or effectiveness were observed between elderly and younger patients. In post marketing experience, CNS adverse reactions have been reported in elderly patients with and without renal impairment receiving Famotidine.

The adverse reactions in overdose cases are like the adverse reactions encountered in normal clinical experience. Oral doses of up to 640 mg/day have been given to adult patients with pathological hypersecretory conditions with no serious adverse effects. In the event of overdosage, treatment should be symptomatic and supportive. Unabsorbed material should be removed from the gastrointestinal tract, the patient should be monitored, and supportive therapy should be employed.

Pharmacodynamic

Famotidine decreases the production of gastric acid, suppresses acid concentration and pepsin content, and decreases the volume of gastric secretion. Famotidine inhibits both basal and nocturnal gastric acid secretion, as well as acid secretion stimulated by food, caffeine, insulin, and pentagastrin. Famotidine has a dose-dependent therapeutic action, with the highest dose having the most extended duration of action and the highest inhibitory effect on gastric acid secretion. Following oral administration, the onset of action is within one hour, and the peak effect is reached within 1-3 hours. The duration of effect is about 10-12 hours.

Pharmacokinetics

• Absorption

Famotidine is incompletely absorbed. The bioavailability of oral doses is 40 to 45%. Bioavailability may be slightly increased by food, or slightly decreased by antacids; however, these effects are of no clinical consequence. Peak famotidine plasma levels occur in 1 to 3 hours. Plasma levels after multiple dosages are like those after single doses.

• Distribution

Famotidine 15 to 20% of famotidine in plasma is protein bound.

• Metabolism and Excretion

Famotidine undergoes minimal first-pass metabolism. 25% to 30% of an oral dose was recovered in the urine as unchanged compound. The only metabolite identified in humans is the S-oxide. Famotidine has an elimination half-life of 2.5-3.5 hours. Famotidine is eliminated by renal (65 to 70%) and metabolic (30 to 35%) routes. The renal clearance is 250 to 450 mL/minute, indicating some tubular excretion.

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