FAMOXINE

Famotidine is a competitive histamine-2 (H 2 ) receptor antagonist that works to inhibit gastric acid secretion.

It is commonly used in gastrointestinal conditions related to acid secretion, such as gastric ulcers and gastroesophageal reflux disease (GERD), in adults and children.

Compared to other

H 2 receptor antagonists, famotidine displays high selectivity towards this receptor; in a study consisting of healthy volunteers and patients with acid hypersecretory disease, famotidine was about 20-50 times more potent at inhibiting gastric acid secretion than cimetidine and eight times more potent than ranitidine on a weight basis.

Famotidine is used in various over-the-counter and off-label uses.

While oral formulations of famotidine are more commonly used, the intravenous solution of the drug is available for use in hospital settings.

Famotidine is indicated in pediatric and adult patients (with the bodyweight of 40 kg and above) for the management of active duodenal ulcer (DU), active gastric ulcer, symptomatic non-erosive gastroesophageal reflux disease (GERD), and erosive esophagitis due to GERD, diagnosed by biopsy.

It is also indicated in adult patients for the treatment of pathological hypersecretory conditions (e.g., Zollinger-Ellison Syndrome, multiple endocrine neoplasias) and reduction of the risk of DU recurrence.

The intravenous formulation of famotidine is available for some hospitalized patients with pathological hypersecretory conditions or intractable ulcers or as an alternative to the oral dosage form for short-term use in patients who are unable to take oral medication.

Over-the-counter famotidine is used for the management and prevention of heartburn caused by gastroesophageal reflux in children and adults.

Off-label uses of famotidine include the reduction of NSAIDs-associated gastrointestinal effects, treatment of refractory urticarial, prevention of stress ulcer in critically-ill patients, and symptomatic relief of gastritis. 8,

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. 5, 6 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.

Following oral administration, the absorption of famotidine is dose-dependent and incomplete.

The oral bioavailability ranges from 40-50%, and the Cmax is reached in 1-4 hours post-dosing. 1, 3 While the bioavailability can be slightly increased with the intake of food and decreased by antacids, there is no clinical significance.

The steady-state volume of distribution ranges from 1.0-1.3 L/kg.

Famotidine is found in breast milk; however, it is found in breast milk at the lowest concentrations compared to other H 2 receptor antagonists.

Famotidine undergoes minimal first-pass metabolism.

About 25-30% of the drug is eliminated through hepatic metabolism.

The only metabolite identified in humans is the S-oxide.

Hover over products below to view reaction partners Famotidine Famotidine S-oxide.

About 65-70% of the total administered dose of famotidine undergoes renal elimination, and 30-35% of the dose is cleared by metabolism.

Following intravenous administration, about 70% of the drug is eliminated in the urine as an unchanged drug.

The elimination half-life is about 2-4 hours.

The half-life is expected to increase nonlinearly in patients with decreased renal function.

Renal clearance is 250-450 mL/min, indicating some tubular excretion.

Because the renal clearance rate exceeds the glomerular filtration rate, famotidine is thought to be mainly eliminated via both glomerular filtration and renal tubular secretion.

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The oral

LD is 4049 mg/kg in rats and 4686 mg/kg in mice.

The subcutaneous

LD is 800 mg/kg in rats and mice.

The intraperitoneal

LD is 800 mg/kg in rats and 778 mg/kg in mice.

The intravenous

LD is 204 mg/kg in rats and 254 mg/kg in mice.

The lowest published toxic dose (TDLo) in man following oral administration is 4 mg/kg/7D.

Symptoms of overdose resemble the adverse events seen with the use of recommended doses, and they should be responded with supportive and symptomatic treatment.

Any unabsorbed drug should be removed from the gastrointestinal tract, and the patient should be monitored accordingly.

The use of hemodialysis to eliminate the drug from the systemic circulation is effective, but the experience of using hemodialysis in response to famotidine overdose is limited in clinical settings.

Famotidine tablets are contraindicated in patients with a history of serious hypersensitivity reactions (e.g., anaphylaxis) to famotidine or other histamine-2 (H 2 ) receptor antagonists.

History of serious hypersensitivity reactions (e.g., anaphylaxis) to famotidine or other H 2 receptor antagonists.

Indication Recommended Dosage Adult and Pediatric

Patients 40 kg and greater Active DU 40 mg once daily; or 20 mg twice daily Active Gastric Ulcer 40 mg once daily GERD 20 mg twice daily Erosive Esophagitis 20 mg twice daily; or 40 mg twice daily Adults Pathological Hypersecretory Conditions 20 mg every 6 hours; adjust to patient needs; maximum 160 mg every 6 hours Risk Reduction of DU Recurrence 20 mg once daily.

• See full prescribing information for complete dosing information, including dosing in renal impairment, and recommended treatment duration.

• Take once daily before bedtime or twice daily in the morning and before bedtime with or without food. 2.1 Recommended Dosage Table 1 shows the recommended dosage of famotidine 20 mg and 40 mg tablets in adult and pediatric patients weighing 40 kg and greater with normal renal function.

The use of famotidine 20 mg and 40 mg tablets is not recommended in pediatric patients weighing less than 40 kg because the lowest available strength (20 mg) exceeds the recommended dose for these patients.

Use another famotidine formulation for pediatric patients weighing less than 40 kg. Table 1: Recommended Dosage and Duration of Famotidine Tablets in Adult and Pediatric Patients 40 kg and Greater with Normal Renal Function Indication Recommended Dosage Recommended Duration Active duodenal ulcer (DU) 40 mg once daily; or 20 mg twice daily a Up to 8 weeks b,c Active gastric ulcer 40 mg once daily Up to 8 weeks c Symptomatic nonerosive GERD 20 mg twice daily Up to 6 weeks c Erosive esophagitis diagnosed by endoscopy 20 mg twice daily; or 40 mg twice daily a Up to 12 weeks Pathological hypersecretory conditions d Starting dosage: 20 mg every 6 hours; adjust dosage to individual patient needs Maximum dosage 160 mg every 6 hours As clinically indicated Reduction of the risk of DU recurrence d 20 mg once daily 1 year c or as clinically indicated a Both dosages demonstrated effectiveness in clinical trials. b In clinical trials, the majority of patients healed within 4 weeks.

For patients who do not heal after 4 weeks, consider an additional to 4 weeks of treatment. c Longer treatment durations have not been studied in clinical trials. d In pediatric patients, the safety and effectiveness of famotidine tablets have not been established for the reduction of the risk of duodenal ulcer recurrence or for treatment of pathological hypersecretory conditions. 2.2 Dosage in Renal Impairment Dosage adjustments of famotidine tablets are recommended for patients with moderate to severe renal impairment (creatinine clearance less than 60 mL/min) .

Table 2 shows the recommended maximum dosage of famotidine 20 mg or 40 mg tablets for patients with renal impairment, by indication.

Use the lowest effective dose.

Some dosage adjustments may require switching to other formulations of famotidine (e.g., oral suspension, lower dose tablet).

Table 2: Recommended Maximum Dosage of Famotidine Tablets in Adult and Pediatric Patients 40 kg and Greater with Moderate and Severe Renal Impairment Indication Recommended Maximum Dosages Creatinine clearance to 60 mL/minute Creatinine clearance less than 30 mL/minute Active duodenal ulcer (DU) 20 mg once daily; or 40 mg every other day 20 mg every other day a Active gastric ulcer 20 mg once daily; or 40 mg every other day 20 mg every other day a Symptomatic nonerosive GERD 20 mg once daily 20 mg every other day a Erosive esophagitis diagnosed by endoscopy b 20 mg once daily; or 40 mg every other day b 20 mg every other day a,b 40 mg once daily b 20 mg once daily b Pathological hypersecretory conditions c Avoid use d Reduction of the risk of DU recurrence c 20 mg every other day a e a An alternate dosage regimen is 10 mg once daily.

Since 20 mg or 40 mg tablet strength cannot be used for this dosage regimen, use an alternate famotidine formulation. b Dosage adjustments for renal impairment are provided for both dosing regimens (20 mg twice daily and 40 mg twice daily) which showed effectiveness for the treatment of erosive esophagitis in clinical trials. c In pediatric patients, the safety and effectiveness of famotidine tablets have not been established for the reduction of the risk of duodenal ulcer recurrence or for treatment of pathological hypersecretory conditions. d Doses required to treat pathological hypersecretory conditions may exceed the maximum doses evaluated in patients with impaired renal function.

The risk for increased adverse reactions in renally impaired patients treated with famotidine tablets for pathological hypersecretory conditions is unknown. e Recommended dosage regimen is 10 mg every other day. Since 20 mg or 40 mg tablet strength cannot be used for this dosage regimen, use an alternate famotidine formulation. 2.3 Administration Instructions.

• Take famotidine tablets once daily before bedtime or twice daily in the morning and before bedtime, as recommended.

• Famotidine tablets may be taken with or without food.

• Famotidine tablets may be given with antacids.

USP, 20 mg, are light yellow, round, biconvex, film-coated tablets debossed with “T” on one side and “11” on the other side.

They are supplied as follows

Bottles of 2 NDC 72789-331-02 Bottles of 20 NDC 72789-331-20 Bottles of 30 NDC 72789-331-30 Bottles of 60 NDC 72789-331-60 Bottles of 90 NDC 72789-331-90 Bottles of 180 NDC 72789-331-93 Storage Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) .

Dispense in a

USP tight, light-resistant container.

Risk Summary Available data with

H 2 -receptor antagonists, including famotidine, in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.

In animal reproduction studies, no adverse development effects were observed with oral administration of famotidine at doses up to approximately and 122 times, respectively, the recommended human dose of 80 mg per day for the treatment of erosive esophagitis.

The estimated background risk for major birth defects and miscarriage for the indicated population is unknown.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the

U.S. general population, the background risk of major birth defects and miscarriage in clinically recognized pregnancies is to 4% and to 20%, respectively.

Reproductive studies have been performed in rats and rabbits at oral doses of up to 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.

The safety and effectiveness of famotidine have been established in pediatric patients for the treatment of peptic ulcer disease (i.e., duodenal ulcer, gastric ulcer) and GERD (i.e., symptomatic nonerosive GERD, erosive esophagitis as diagnosed by endoscopy).

The use of famotidine and the recommended dosage of famotidine in these pediatric patients is supported by evidence from adequate and well-controlled studies of famotidine in adults and published pharmacokinetic and pharmacodynamic data in pediatric patients.

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.

Famotidine and 40 mg tablets are not recommended for use in pediatric patients weighing less than 40 kg because these tablet strengths exceed the recommended dose for these patients.

For pediatric patients weighing less than 40 kg, consider another famotidine formulation (e.g., oral suspension, lower dose tablet).

Of the 1442 famotidine-treated patients in clinical studies, approximately 10% were and older.

In these studies, no overall differences in safety or effectiveness were observed between elderly and younger patients.

In postmarketing experience, CNS adverse reactions have been reported in elderly patients with and without renal impairment receiving famotidine.

Famotidine is known to be substantially excreted by the kidney, and the risk of adverse reactions to famotidine may be greater in elderly patients, particularly those with impaired renal function.

In general, use the lowest effective dose of famotidine for an elderly patient and monitor renal function.