Generic Name: FAMOTIDINE
Brand Name: Famotidine
- Substance Name(s):
Drug Interactions No drug interactions have been identified.
Studies with famotidine in man, in animal models, and in vitro have shown no significant interference with the disposition of compounds metabolized by the hepatic microsomal enzymes, e.g., cytochrome P450 system.
Compounds tested in man include warfarin, theophylline, phenytoin, diazepam, aminopyrine and antipyrine.
Indocyanine green as an index of hepatic drug extraction has been tested and no significant effects have been found.
The adverse reactions in overdose cases are similar to the adverse reactions encountered in normal clinical experience (see ADVERSE REACTIONS).
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.
The oral LD50 of famotidine in male and female rats and mice was greater than 3000 mg/kg and the minimum lethal acute oral dose in dogs exceeded 2000 mg/kg.
Famotidine did not produce overt effects at high oral doses in mice, rats, cats and dogs, but induced significant anorexia and growth depression in rabbits starting with 200 mg/kg/day orally.
The intravenous LD50 of famotidine for mice and rats ranged from 254-563 mg/kg and the minimum lethal single I.V.
dose in dogs was approximately 300 mg/kg.
Signs of acute intoxication in I.V.
treated dogs were emesis, restlessness, pallor of mucous membranes or redness of mouth and ears, hypotension, tachycardia and collapse.
The active ingredient in famotidine, is a histamine H2 -receptor antagonist.
Famotidine is N’-(aminosulfonyl)-3-[[[2-[(diamino-methylene)amino]-4- thiazolyl]methyl]thio]propanimidamide.
The empirical formula of famotidine is C8H15N7O2S3 and its molecular weight is 337.45.
Its structural formula is: Famotidine is a white to pale yellow crystalline compound that is freely soluble in glacial acetic acid, slightly soluble in methanol, very slightly soluble in water, and practically insoluble in ethanol.
Each tablet for oral administration contains either 20 mg or 40 mg of famotidine and the following inactive ingredients: hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycolate, sodium starch glycolate, modified corn starch (pregelatinized starch), talc, triacetin, titanium dioxide.
Clinical Studies Duodenal Ulcer In a U.S.
multicenter, double-blind study in outpatients with endoscopically confirmed duodenal ulcer, orally administered famotidine was compared to placebo.
As shown in Table 1, 70% of patients treated with Famotidine 40 mg h.s.
were healed by week 4.
Table 1 Outpatients with Endoscopically Confirmed Healed Duodenal Ulcers ** Statistically significantly different than placebo(p< 0.001) Famotidine 40 mg h.s.
(N=89) Famotidine 20 mg b.i.d.
(N=84) Placebo h.s.
(N=97) Week 2 ** 32% ** 38% 17% Week 4 ** 70% ** 67% 31% Patients not healed by week 4 were continued in the study.
By week 8, 83% of patients treated with famotidine had healed versus 45% of patients treated with placebo.
The incidence of ulcer healing with famotidine was significantly higher than with placebo at each time point based on proportion of endoscopically confirmed healed ulcers.
In this study, time to relief of daytime and nocturnal pain was significantly shorter for patients receiving famotidine than for patients receiving placebo; patients receiving famotidine also took less antacid than the patients receiving placebo.
Famotidine Tablets USP (white round tablets) containing 20mg of famotidine and engraved with .
Bottle of 1,000 (NDC 42291-281-10) Famotidine Tablets USP (white round tablets) containing 40mg of famotidine and engraved with .
Bottles of 1,000 (NDC 42291-282-10) CTI 121 CTI 122 STORAGE Store at 20° to 25°C (68° to 77°F).
[See USP Controlled Room Temperature.] Manufactured for: AvKARE, Inc.
Pulaski, TN 38478 Mfg.
06/12 AV Rev.
Geriatric Use Of the 4,966 subjects in clinical studies who were treated with famotidine, 488 subjects (9.8%) were 65 and older, and 88 subjects (1.7%) were greater than 75 years of age.
No overall differences in safety or effectiveness were observed between these subjects and younger subjects.
However, greater sensitivity of some older individuals cannot be ruled out.
No dosage adjustment is required based on age (see CLINICAL PHARMACOLOGY IN ADULTS , Pharmacokinetics ).
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function.
Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
Dosage adjustment in the case of moderate or severe renal impairment is necessary (see PRECAUTIONS, Patients with Moderate or Severe Renal Insufficiency and DOSAGE AND ADMINISTRATION, Dosage Adjustment for Patients with Moderate or Severe Renal Insufficiency ).
INDICATIONS AND USAGE
Famotidine is indicated in: Short term treatment of active duodenal ulcer.
Most adult patients heal within 4 weeks; there is rarely reason to use famotidine at full dosage for longer than 6 to 8 weeks.
Studies have not assessed the safety of famotidine in uncomplicated active duodenal ulcer for periods of more than eight weeks.
Maintenance therapy for duodenal ulcer patients at reduced dosage after healing of an active ulcer.
Controlled studies in adults have not extended beyond one year.
Short term treatment of active benign gastric ulcer.
Most adult patients heal within 6 weeks.
Studies have not assessed the safety or efficacy of famotidine in uncomplicated active benign gastric ulcer for periods of more than 8 weeks.
Short term treatment of gastroesophageal reflux disease (GERD).
Famotidine is indicated for short term treatment of patients with symptoms of GERD (see CLINICAL PHARMACOLOGY IN ADULTS, Clinical Studies ).
Famotidine is also indicated for the short term treatment of esophagitis due to GERD including erosive or ulcerative disease diagnosed by endoscopy (see CLINICAL PHARMACOLOGY IN ADULTS, Clinical Studies ).
Treatment of pathological hypersecretory conditions (e.g., Zollinger-Ellison Syndrome, multiple endocrine adenomas) (see CLINICAL PHARMACOLOGY IN ADULTS, Clinical Studies ).
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 I.V.
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 (250 times the usual human dose) 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, taking into account the importance of the drug to the mother.
DOSAGE AND ADMINISTRATION
Duodenal Ulcer Acute Therapy: The recommended adult oral dosage for active duodenal ulcer is 40 mg once a day at bedtime.
Most patients heal within 4 weeks; there is rarely reason to use famotidine at full dosage for longer than 6 to 8 weeks.
A regimen of 20 mg b.i.d.
is also effective.
Maintenance Therapy: The recommended adult oral dose is 20 mg once a day at bedtime.
Benign Gastric Ulcer Acute Therapy: The recommended adult oral dosage for active benign gastric ulcer is 40 mg once a day at bedtime.
Gastroesophageal Reflux Disease (GERD) The recommended oral dosage for treatment of adult patients with symptoms of GERD is 20 mg b.i.d.
for up to 6 weeks.
The recommended oral dosage for the treatment of adult patients with esophagitis including erosions and ulcerations and accompanying symptoms due to GERD is 20 or 40 mg b.i.d.
for up to 12 weeks (see CLINICAL PHARMACOLOGY IN ADULTS, Clinical Studies ).
Dosage for Pediatric Patients <1 year of age Gastroesophageal Reflux Disease (GERD) See PRECAUTIONS , Pediatric Patients <1 year of age.
The studies described in PRECAUTIONS , Pediatric Patients <1 year of age suggest the following starting doses in pediatric patients <1 year of age: Gastroesophageal Reflux Disease (GERD) – 0.5 mg/kg/dose of famotidine oral suspension for the treatment of GERD for up to 8 weeks once daily in patients <3 months of age and 0.5 mg/kg/dose twice daily in patients 3 months to <1 year of age.
Patients should also be receiving conservative measures (e.g., thickened feedings).
The use of intravenous famotidine in pediatric patients <1 year of age with GERD has not been adequately studied.
Dosage for Pediatric Patients 1-16 years of age See PRECAUTIONS , Pediatric Patients 1-16 years of age .
The studies described in PRECAUTIONS , Pediatric Patients 1-16 years of age suggest the following starting doses in pediatric patients 1-16 years of age: Peptic ulcer — 0.5 mg/kg/day p.o.
at bedtime or divided b.i.d.
up to 40 mg/day.
Gastroesophageal Reflux Disease with or without esophagitis including erosions and ulcerations — 1.0 mg/kg/day p.o.
up to 40 mg b.i.d.
While published uncontrolled studies suggest effectiveness of famotidine in the treatment of gastroesophageal reflux disease and peptic ulcer, data in pediatric patients are insufficient to establish percent response with dose and duration of therapy.
Therefore, treatment duration (initially based on adult duration recommendations) and dose should be individualized based on clinical response and/or pH determination (gastric or esophageal) and endoscopy.
Published uncontrolled clinical studies in pediatric patients 1-16 years of age have employed doses up to 1 mg/kg/day for peptic ulcer and 2 mg/kg/day for GERD with or without esophagitis including erosions and ulcerations.
Pathological Hypersecretory Conditions (e.g., Zollinger-Ellison Syndrome, Multiple Endocrine Adenomas) The dosage of famotidine in patients with pathological hypersecretory conditions varies with the individual patient.
The recommended adult oral starting dose for pathological hypersecretory conditions is 20 mg q 6 h.
In some patients, a higher starting dose may be required.
Doses should be adjusted to individual patient needs and should continue as long as clinically indicated.
Doses up to 160 mg q 6 h have been administered to some adult patients with severe Zollinger-Ellison Syndrome.
Concomitant Use of Antacids Antacids may be given concomitantly if needed.
Dosage Adjustment for Patients with Moderate or Severe Renal Insufficiency In adult patients with moderate (creatinine clearance <50 mL/min) or severe (creatinine clearance <10 mL/min) renal insufficiency, the elimination half-life of famotidine is increased.
For patients with severe renal insufficiency, it may exceed 20 hours, reaching approximately 24 hours in anuric patients.
Since CNS adverse effects have been reported in patients with moderate and severe renal insufficiency, to avoid excess accumulation of the drug in patients with moderate or severe renal insufficiency, the dose of famotidine may be reduced to half the dose or the dosing interval may be prolonged to 36-48 hours as indicated by the patient’s clinical response.
Based on the comparison of pharmacokinetic parameters for famotidine in adults and pediatric patients, dosage adjustment in pediatric patients with moderate or severe renal insufficiency should be considered.