Famotidine

Description

The active ingredient in famotidine tablets, USP, is a histamine H2-receptor antagonist. Famotidine is chemically defined as N'-(aminosulfonyl)-3-[[[2-(diaminomethylene)amino-4-thiazolyl]methyl] thio]propanimidamide, with an empirical formula of C8H15N7O2S3 and a molecular weight of 337.43. It appears as a white to pale yellow crystalline compound. Famotidine 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. Inactive ingredients include colloidal silicon dioxide, yellow iron oxide, red iron oxide, lecithin, macrogel/PEG 3350, magnesium stearate, microcrystalline cellulose, polyvinyl alcohol, pregelatinized starch, talc, and titanium dioxide.

Uses and Indications

Famotidine is indicated for the short-term treatment of active duodenal ulcer, with most adult patients healing within 4 weeks. It is recommended that famotidine not be used at full dosage for longer than 6 to 8 weeks, as studies have not assessed the safety of famotidine in uncomplicated active duodenal ulcer beyond this duration.

Additionally, famotidine is indicated for maintenance therapy in patients with duodenal ulcers at a reduced dosage following the healing of an active ulcer. Controlled studies in adults have not extended beyond one year for this indication.

Famotidine is also indicated for the short-term treatment of active benign gastric ulcer, with most adult patients healing within 6 weeks. Similar to the indication for duodenal ulcers, studies have not assessed the safety or efficacy of famotidine in uncomplicated active benign gastric ulcer for periods exceeding 8 weeks.

Furthermore, famotidine is indicated for the short-term treatment of gastroesophageal reflux disease (GERD), including the treatment of esophagitis due to GERD, such as erosive or ulcerative disease diagnosed by endoscopy.

Lastly, famotidine is indicated for the treatment of pathological hypersecretory conditions, including Zollinger-Ellison Syndrome and multiple endocrine adenomas.

No teratogenic or nonteratogenic effects have been reported.

Dosage and Administration

The recommended adult oral dosage for the treatment of active duodenal ulcer is 40 mg once daily at bedtime. Most patients typically achieve healing within 4 weeks; however, there is generally no need to continue famotidine at the full dosage for longer than 6 to 8 weeks. An alternative regimen of 20 mg administered twice daily (b.i.d.) is also effective. For maintenance therapy, the recommended adult oral dose is 20 mg once daily at bedtime.

For the treatment of active benign gastric ulcer, the recommended adult oral dosage is 40 mg once daily at bedtime.

In adult patients with gastroesophageal reflux disease (GERD), the recommended oral dosage for symptomatic treatment is 20 mg b.i.d. for up to 6 weeks. For patients with esophagitis, including erosions and ulcerations due to GERD, the recommended oral dosage is either 20 mg or 40 mg b.i.d. for up to 12 weeks.

For pediatric patients under 1 year of age with GERD, the starting doses are as follows: for those less than 3 months of age, 0.5 mg/kg/dose of famotidine oral suspension is recommended once daily for up to 8 weeks. For patients aged 3 months to less than 1 year, the dose is 0.5 mg/kg/dose administered twice daily.

In pediatric patients aged 1 to 16 years, the dosage for peptic ulcer is 0.5 mg/kg/day orally at bedtime or divided b.i.d., not exceeding 40 mg/day. For gastroesophageal reflux disease, with or without esophagitis including erosions and ulcerations, the recommended dosage is 1 mg/kg/day orally, divided b.i.d., up to a maximum of 40 mg b.i.d.

For pathological hypersecretory conditions such as Zollinger-Ellison Syndrome and Multiple Endocrine Adenomas, the recommended adult oral starting dose is 20 mg every 6 hours (q 6 h). Some patients may require a higher starting dose, and adjustments should be made based on individual patient needs. Doses up to 160 mg q 6 h have been administered to certain adult patients with severe Zollinger-Ellison Syndrome.

In patients with moderate (creatinine clearance <50 mL/min) or severe (creatinine clearance <10 mL/min) renal insufficiency, the dose of famotidine may be reduced to half the standard dose, or the dosing interval may be extended to 36 to 48 hours, depending on the patient's clinical response.

Contraindications

Use of this product is contraindicated in patients with hypersensitivity to any component of the formulation. Cross-sensitivity among H2-receptor antagonists has been documented; therefore, famotidine should not be administered to individuals with a history of hypersensitivity to other H2-receptor antagonists.

Warnings and Precautions

Symptomatic response to therapy with famotidine does not exclude the possibility of gastric malignancy. Healthcare professionals should remain vigilant for signs of malignancy in patients receiving this treatment, as symptom relief may mask underlying conditions.

Patients with moderate or severe renal insufficiency require special consideration when prescribing famotidine. Adverse central nervous system effects have been reported in this population. Therefore, it is advisable to extend the intervals between doses or to reduce the dosage for patients with moderate renal insufficiency (creatinine clearance <50 mL/min) or severe renal insufficiency (creatinine clearance <10 mL/min). This adjustment is necessary to account for the prolonged elimination half-life of famotidine. Additionally, there have been rare reports of prolonged QT interval in patients with impaired renal function, particularly when the dosing regimen has not been appropriately modified.

No specific laboratory tests are recommended for monitoring during the use of famotidine. However, healthcare providers should remain attentive to the renal function of patients, especially those with known renal impairments, to ensure safe and effective use of the medication.

Side Effects

Patients may experience a range of adverse reactions while receiving treatment. Common adverse reactions observed in clinical trials include headache (4.7%), dizziness (1.3%), constipation (1.2%), and diarrhea (1.7%).

Serious adverse reactions can occur, including hypersensitivity reactions such as anaphylaxis, angioedema, and urticaria. Rare but serious hematologic reactions include agranulocytosis, pancytopenia, leukopenia, and thrombocytopenia. Additionally, there have been reports of grand mal seizures and psychic disturbances, which are reversible in cases where follow-up was obtained. These disturbances may manifest as hallucinations, confusion, agitation, depression, anxiety, and decreased libido. Convulsions have been reported very rarely, particularly in patients with impaired renal function.

Gastrointestinal adverse reactions may include cholestatic jaundice, hepatitis, liver enzyme abnormalities, vomiting, nausea, abdominal discomfort, anorexia, and dry mouth. Cardiovascular effects can include arrhythmia, AV block, palpitations, and a prolonged QT interval, particularly in patients with impaired renal function.

Other adverse reactions reported include musculoskeletal pain, including muscle cramps and arthralgia, as well as respiratory issues such as bronchospasm and interstitial pneumonia. Skin reactions may range from alopecia, acne, and pruritus to very rare cases of toxic epidermal necrolysis or Stevens-Johnson syndrome.

In pediatric patients, agitation was observed in five subjects receiving famotidine in a clinical study involving 35 patients under one year of age with gastroesophageal reflux disease (GERD) symptoms; this agitation resolved upon discontinuation of the medication.

Patients should be monitored for these adverse reactions, and any serious or unexpected reactions should be reported to healthcare providers.

Drug Interactions

There are currently no documented drug interactions associated with this medication. Additionally, there is no information available regarding interactions with laboratory tests. As such, no specific recommendations for dosage adjustments or monitoring are warranted at this time.

Packaging & NDC

The table below lists all NDC Code configurations of Famotidine, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

Pediatric patients under 1 year of age can be treated with famotidine, as studies support its use in this population. For gastroesophageal reflux disease (GERD), the recommended starting dose is 0.5 mg/kg/dose once daily for patients less than 3 months of age, and twice daily for those 3 months and older. The safety and efficacy of famotidine beyond 4 weeks in this age group have not been established, and it is advised that conservative measures, such as thickened feedings, be implemented concurrently.

For pediatric patients aged 1 to 16 years, the starting dose for peptic ulcers is 0.5 mg/kg/day administered orally at bedtime or divided into two doses, with a maximum of 40 mg/day. For GERD, with or without esophagitis, the starting dose is 1 mg/kg/day orally, divided into two doses, also up to 40 mg b.i.d. Treatment duration and dosing should be tailored to the individual based on clinical response, pH determination, and endoscopic findings. Published studies indicate that doses may be increased to 1 mg/kg/day for peptic ulcers and 2 mg/kg/day for GERD.

Pharmacokinetic data reveal that famotidine clearance in patients aged over 3 months to 1 year is comparable to that of older pediatric patients and adults. However, infants aged 0 to 3 months exhibit clearance values that are 2- to 4-fold lower than those in older pediatric patients and adults. The mean oral bioavailability in patients under 1 year is similar to that of older pediatric patients and adults. Additionally, pharmacodynamic studies indicate that the duration of acid suppression is longer in pediatric patients under 1 month of age compared to older children.

Adverse reactions have been noted in a study involving 35 pediatric patients under 1 year of age with GERD symptoms, where agitation was observed in 5 patients receiving famotidine; these symptoms resolved upon discontinuation of the medication.

Geriatric Use

In clinical studies involving 4,966 subjects treated with famotidine, 488 subjects (9.8%) were aged 65 years and older, while 88 subjects (1.7%) were over 75 years of age. No overall differences in safety or effectiveness were observed between these elderly patients and their younger counterparts. However, it is important to note that greater sensitivity to the drug may be present in some older individuals, which cannot be ruled out.

No dosage adjustment based solely on age is required for elderly patients. Nonetheless, famotidine is substantially excreted by the kidneys, and the risk of toxic reactions may be heightened in patients with impaired renal function. Given that elderly patients are more likely to experience decreased renal function, careful consideration should be given during dose selection. It is advisable to monitor renal function in this population. In cases of moderate or severe renal impairment, dosage adjustments are necessary to mitigate the risk of adverse effects.

Pregnancy

Pregnancy Category B indicates that reproductive studies conducted in rats and rabbits at oral doses of up to 2000 mg/kg/day and 500 mg/kg/day, respectively, as well as intravenous doses of up to 200 mg/kg/day, have not demonstrated significant evidence of impaired fertility or harm to the fetus due to famotidine. While no direct fetotoxic effects have been observed, it is important to note that sporadic abortions were reported in some rabbits that exhibited marked decreased food intake when administered oral doses of 200 mg/kg/day (approximately 250 times the usual human dose) or higher.

Despite these findings, there are no adequate or well-controlled studies in pregnant women. Therefore, due to the limitations of animal reproductive studies in predicting human response, famotidine should be used during pregnancy only if clearly needed. Healthcare professionals are advised to weigh the potential benefits against the risks when considering the use of this medication in pregnant patients.

Lactation

Famotidine is secreted into breast milk, as demonstrated in studies conducted with lactating rats. In these studies, transient growth depression was noted in young rats suckling from mothers treated with maternotoxic doses of at least 600 times the usual human dose. Additionally, famotidine is detectable in human milk.

Due to the potential for serious adverse reactions in breastfed infants, healthcare professionals should consider the risks and benefits when advising lactating mothers. A decision should be made whether to discontinue nursing or to discontinue famotidine, taking into account the importance of the medication to the mother.

Renal Impairment

In patients with severe renal insufficiency (creatinine clearance <10 mL/min), the elimination half-life of famotidine may exceed 20 hours, which necessitates adjustment of the dose or dosing intervals. For those with moderate renal insufficiency (creatinine clearance <50 mL/min) or severe renal insufficiency, longer intervals between doses or lower doses may be required to account for the prolonged elimination half-life of famotidine.

CNS adverse effects have been reported in patients with moderate and severe renal insufficiency. To mitigate the risk of excess drug accumulation, the dose of famotidine may be reduced to half the standard dose, or the dosing interval may be extended to 36 to 48 hours, depending on the patient's clinical response.

Additionally, a prolonged QT interval has been reported very rarely in patients with impaired renal function when the dose or dosing interval of famotidine has not been appropriately adjusted. In elderly patients with decreased renal function, the clearance of famotidine may be further reduced; therefore, careful consideration in dose selection is essential, along with recommended monitoring of renal function.

For pediatric patients with moderate or severe renal insufficiency, dosage adjustment should be considered based on pharmacokinetic parameters.

Hepatic Impairment

Patients with hepatic impairment do not require specific dosage adjustments, as no alterations in dosing have been indicated for this population. The drug has shown no significant interference with the disposition of compounds that are metabolized by hepatic microsomal enzymes, including the cytochrome P450 system.

Hepatic metabolism of the drug is minimal, and there have been no significant effects reported on hepatic drug extraction. While adverse reactions such as hepatitis and liver enzyme abnormalities have been infrequently reported in clinical trials and post-marketing experience, routine monitoring of liver function tests may be considered to ensure patient safety.

Overdosage

In cases of overdosage, it has been observed that oral doses of up to 640 mg/day have been administered to adult patients with pathological hypersecretory conditions without resulting in serious adverse effects. However, in the event of an overdosage, treatment should be primarily symptomatic and supportive.

Management of Overdosage The management of overdosage involves the removal of unabsorbed material from the gastrointestinal tract, and continuous monitoring of the patient is essential. Healthcare professionals should be vigilant in assessing the patient's condition and providing appropriate supportive care.

Toxicity Data Toxicological studies indicate that the oral LD50 of famotidine in male and female rats and mice exceeds 3000 mg/kg, while the minimum lethal acute oral dose in dogs is reported to be greater than 2000 mg/kg. Notably, famotidine did not produce overt effects at high oral doses in various species, including mice, rats, cats, and dogs. However, significant anorexia and growth depression were observed in rabbits at doses starting from 200 mg/kg/day orally.

For intravenous administration, the LD50 of famotidine for mice and rats ranges from 254 to 563 mg/kg, with the minimum lethal single intravenous dose in dogs being approximately 300 mg/kg. Signs of acute intoxication in dogs treated intravenously may include emesis, restlessness, pallor of mucous membranes or redness of the mouth and ears, hypotension, tachycardia, and collapse.

Healthcare professionals should remain alert to these potential symptoms and manage them accordingly to ensure patient safety and recovery.

Nonclinical Toxicology

In a 106-week study conducted in rats and a 92-week study in mice, oral doses of famotidine up to 2000 mg/kg/day, which is approximately 2500 times the recommended human dose for active duodenal ulcer, did not demonstrate any evidence of carcinogenic potential.

Famotidine was evaluated for mutagenicity in the microbial mutagen test (Ames test) using Salmonella typhimurium and Escherichia coli, both with and without rat liver enzyme activation. The results were negative at concentrations up to 10,000 mcg/plate. Additionally, in vivo studies in mice, including a micronucleus test and a chromosomal aberration test, showed no evidence of mutagenic effects.

Furthermore, studies involving rats administered oral doses of up to 2000 mg/kg/day or intravenous doses of up to 200 mg/kg/day indicated that fertility and reproductive performance were not adversely affected.

Postmarketing Experience

Adverse reactions reported in postmarketing experience include those observed in clinical trials and voluntary reports. In controlled clinical trials, the following adverse reactions occurred in more than 1% of patients receiving famotidine: headache (4.7%), diarrhea (1.7%), dizziness (1.3%), and constipation (1.2%).

Other adverse reactions have been reported infrequently in clinical trials or since the drug's marketing, with unclear relationships to famotidine therapy in many cases. These reactions are categorized as follows:

Body as a Whole: Fever, asthenia, fatigue. Cardiovascular: Arrhythmia, AV block, palpitation. Prolonged QT interval has been reported very rarely in patients with impaired renal function. Gastrointestinal: Cholestatic jaundice, hepatitis, liver enzyme abnormalities, vomiting, nausea, abdominal discomfort, anorexia, dry mouth. Hematologic: Rare cases of agranulocytosis, pancytopenia, leukopenia, thrombocytopenia. Hypersensitivity: Anaphylaxis, angioedema, orbital or facial edema, urticaria, rash, conjunctival injection. Musculoskeletal: Musculoskeletal pain, including muscle cramps and arthralgia. Nervous System/Psychiatric: Grand mal seizure; psychic disturbances, which were reversible in cases with follow-up, including hallucinations, confusion, agitation, depression, anxiety, decreased libido; paresthesia; insomnia; somnolence. Convulsions have been reported very rarely in patients with impaired renal function. Respiratory: Bronchospasm, interstitial pneumonia. Skin: Toxic epidermal necrolysis/Stevens-Johnson syndrome (very rare), alopecia, acne, pruritus, dry skin, flushing. Special Senses: Tinnitus, taste disorder. Other: Rare cases of impotence and gynecomastia have been reported; however, incidences in controlled clinical trials were not greater than those seen with placebo.

In a clinical study involving 35 pediatric patients under 1 year of age with GERD symptoms, agitation was observed in 5 patients receiving famotidine, which resolved upon discontinuation of the medication.

Patient Counseling

Patients should be informed that a symptomatic response to therapy with famotidine does not exclude the possibility of gastric malignancy. It is essential for healthcare providers to emphasize this point during discussions with patients.

For patients with moderate or severe renal insufficiency, healthcare providers should advise that longer intervals between doses or lower doses may be necessary to accommodate the longer elimination half-life of famotidine. This adjustment is crucial for ensuring patient safety and efficacy of treatment.

Patients should also be made aware that famotidine is secreted into breast milk. Healthcare providers should discuss the importance of the medication to the mother and help her make an informed decision regarding whether to discontinue nursing or the drug itself.

In pediatric patients under 1 year of age, famotidine oral suspension may be prescribed for the treatment of gastroesophageal reflux disease (GERD) for a duration of up to 8 weeks. The recommended starting dose is 0.5 mg/kg/dose once daily for patients under 3 months of age, and twice daily for those aged 3 months to less than 1 year. Caregivers should be instructed to implement conservative treatment measures, such as thickened feedings, for pediatric patients with GERD.

Healthcare providers should communicate that the safety and benefit of famotidine treatment beyond 4 weeks in pediatric patients have not been established, and this should be taken into consideration when discussing treatment plans.

Finally, patients should be advised to contact their healthcare provider for medical advice regarding any side effects they may experience. They may also report side effects to Alembic Pharmaceuticals Limited or the FDA, ensuring that they are aware of the channels available for reporting adverse events.

Storage and Handling

The product is supplied in a USP tight, light-resistant container to ensure its integrity and efficacy. It should be stored at a controlled room temperature of 25°C (77°F), with permissible excursions between 15°C to 30°C (59°F to 86°F) as defined by USP guidelines. Proper storage conditions are essential to maintain the quality of the product throughout its shelf life.

Additional Clinical Information

No further data are available.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Famotidine as submitted by Alembic Pharmaceuticals Limited. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)