Famotidine

Description

The active ingredient in famotidine tablets, USP, is a histamine-2 (H2) receptor antagonist. Famotidine is chemically designated as N'-(aminosulfonyl)-3-[[[2-(diaminomethylene)amino-4-thiazolyl]methyl] thio]propanimidamide, with an empirical formula of C8H15N7O2S3 and a molecular weight of 337.45.

Each famotidine tablet, USP, intended for oral administration, contains either 20 mg or 40 mg of famotidine. The formulation includes inactive ingredients such as corn starch, hypromellose, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. The film coating comprises carnauba wax, hydroxypropyl cellulose, hypromellose, talc, and titanium dioxide, with the 20 mg tablets additionally containing iron oxide red and iron oxide yellow.

Famotidine, USP, appears as a white to pale yellowish white crystalline powder. It is freely soluble in dimethyl formamide and glacial acetic acid, slightly soluble in methanol, very slightly soluble in water, and practically insoluble in acetone, alcohol, chloroform, ether, and ethyl acetate.

Uses and Indications

Famotidine tablets are indicated for the treatment of active duodenal ulcer (DU) in adult and pediatric patients weighing 40 kg and greater. This medication is also indicated for the management of active gastric ulcer in the same patient population. Additionally, famotidine is indicated for the treatment of symptomatic nonerosive gastroesophageal reflux disease (GERD) and erosive esophagitis due to GERD, both diagnosed by biopsy, in adult and pediatric patients weighing 40 kg and greater.

In adults, famotidine is further indicated for the treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome and multiple endocrine neoplasias. It is also indicated for the reduction of the risk of duodenal ulcer recurrence.

There are no teratogenic or nonteratogenic effects associated with famotidine.

Dosage and Administration

Adult and pediatric patients weighing 40 kg and greater may receive the following dosages based on their specific conditions:

For active duodenal ulcers (DU), the recommended dosage is 40 mg once daily or 20 mg twice daily. In the case of active gastric ulcers, a dosage of 40 mg once daily is advised. For gastroesophageal reflux disease (GERD), the dosage is 20 mg twice daily. Patients with erosive esophagitis may be prescribed either 20 mg twice daily or 40 mg twice daily, depending on the severity of the condition. For pathological hypersecretory conditions, the initial dosage is 20 mg every 6 hours, with adjustments made according to patient needs; the maximum dosage should not exceed 160 mg every 6 hours. To reduce the risk of duodenal ulcer recurrence, a dosage of 20 mg once daily is recommended.

Administration should occur once daily before bedtime or twice daily, with doses taken in the morning and before bedtime. The medication may be taken with or without food.

Contraindications

Use is contraindicated in patients with a history of serious hypersensitivity reactions, including anaphylaxis, to famotidine or other H2 receptor antagonists. This contraindication is due to the potential for severe allergic reactions in susceptible individuals.

Warnings and Precautions

Elderly patients and those with renal impairment are at an increased risk for Central Nervous System (CNS) adverse reactions. It is recommended that the dosage be reduced in these populations to mitigate potential risks.

Healthcare professionals should be aware that the absence of gastrointestinal (GI) symptoms does not rule out the possibility of gastric malignancy. A thorough evaluation for GI malignancy is advised prior to the initiation of therapy to ensure patient safety and appropriate treatment planning.

Side Effects

Adverse reactions associated with famotidine include both common and serious events.

Common adverse reactions reported in clinical trials include headache, dizziness, constipation, and diarrhea. These reactions were observed among participants receiving the medication and are generally considered manageable.

Serious adverse reactions may occur, particularly in patients with a history of serious hypersensitivity reactions, such as anaphylaxis, to famotidine or other H2 receptor antagonists. It is crucial for healthcare providers to monitor these patients closely.

Central nervous system (CNS) adverse reactions have been noted, especially in elderly patients and those with renal impairment, who are at an increased risk. In such populations, a dosage reduction may be warranted to mitigate these risks. Postmarketing experience has further indicated that CNS adverse reactions have been reported in elderly patients, both with and without renal impairment, who are receiving famotidine.

In cases of overdosage, the types of adverse reactions observed are similar to those encountered with the use of recommended dosages. Given that famotidine is substantially excreted by the kidneys, the risk of adverse reactions may be heightened in elderly patients, particularly those with impaired renal function. Therefore, careful consideration of patient history and renal status is essential when prescribing famotidine.

Drug Interactions

Concomitant use of drugs that depend on gastric pH for absorption may lead to a significant reduction in systemic exposure of the affected drug, potentially resulting in a loss of efficacy. It is advisable to consult the full prescribing information for a comprehensive list of these interacting drugs.

Tizanidine, a substrate of CYP1A2, may experience substantial increases in blood concentrations when used with other medications that affect this enzyme. This interaction can lead to adverse effects such as hypotension, bradycardia, or excessive drowsiness. Therefore, it is recommended to avoid concomitant use of tizanidine with such drugs whenever possible. Monitoring of blood pressure and heart rate is advised if co-administration cannot be avoided.

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

The safety and effectiveness of famotidine have been established in pediatric patients for the treatment of peptic ulcer disease, including duodenal ulcers and gastric ulcers, as well as for gastroesophageal reflux disease (GERD), which encompasses symptomatic nonerosive GERD and erosive esophagitis as diagnosed by endoscopy. The recommended dosage of famotidine in these pediatric patients is supported by evidence from adequate and well-controlled studies conducted in adults, along with published pharmacokinetic and pharmacodynamic data specific to pediatric populations.

However, the safety and effectiveness of famotidine for the treatment of pathological hypersecretory conditions and for the reduction of the risk of duodenal ulcer recurrence in pediatric patients have not been established. Additionally, famotidine 20 mg and 40 mg tablets are not recommended for use in pediatric patients weighing less than 40 kg, as these tablet strengths exceed the recommended dose for this weight group. For pediatric patients weighing less than 40 kg, alternative formulations of famotidine, such as oral suspension or lower dose tablets, should be considered.

Geriatric Use

In clinical studies involving famotidine, approximately 10% of the 1,442 treated patients were aged 65 and older. These studies did not reveal any overall differences in safety or effectiveness between elderly patients and their younger counterparts. However, caution is warranted when prescribing famotidine to geriatric patients, particularly those with renal impairment, as postmarketing experience has indicated that central nervous system (CNS) adverse reactions have been reported in this population, regardless of renal function status.

Given that famotidine is substantially excreted by the kidneys, the risk of adverse reactions may be heightened in elderly patients, especially those with compromised renal function. Therefore, it is recommended to use the lowest effective dose of famotidine in geriatric patients and to closely monitor their renal function throughout the treatment period. This approach will help mitigate potential risks and ensure the safe use of famotidine in the elderly population.

Pregnancy

Available data regarding the use of H2-receptor antagonists, including famotidine, in pregnant patients 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 developmental effects were observed with oral administration of famotidine at doses up to approximately 243 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 in the indicated population is unknown. It is important to note that all pregnancies carry a background risk of birth defects, 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 estimated to be 2 to 4% and 15 to 20%, respectively.

Reproductive studies conducted in rats and rabbits at oral doses of up to 2000 and 500 mg/kg/day, respectively, as well as intravenous doses of up to 200 mg/kg/day, 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 were noted in some rabbits that exhibited marked decreased food intake at oral doses of 200 mg/kg/day (approximately 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. Given that animal reproductive studies are not always predictive of human response, famotidine should be used during pregnancy only if clearly needed.

Lactation

There are limited data available on the presence of famotidine in human breast milk. Current evidence indicates that there were no effects observed on breastfed infants. However, there are no data regarding the effects of famotidine on milk production in lactating mothers.

In animal studies, famotidine has been detected in the milk of lactating rats. Notably, transient growth depression was observed in young rats suckling from mothers treated with maternotoxic doses of famotidine, which were at least 600 times the usual human dose.

When considering the use of famotidine in lactating mothers, the developmental and health benefits of breastfeeding should be weighed against the mother's clinical need for the medication and any potential adverse effects on the breastfed child from famotidine or from the underlying maternal condition.

Renal Impairment

Patients with renal impairment, particularly elderly individuals, are at an increased risk for adverse effects. It is recommended that the dosage be reduced in these patients to mitigate potential risks associated with reduced kidney function. Careful monitoring of renal function is advised to ensure appropriate dosing adjustments are made based on individual patient needs.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to the use of this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions outlined for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the available information.

Overdosage

In cases of famotidine overdosage, the adverse reactions observed are consistent with those reported at recommended dosages, as detailed in the Adverse Reactions section (6.1).

Management of overdosage should focus on symptomatic and supportive care. It is essential to remove any unabsorbed material from the gastrointestinal tract promptly. Continuous monitoring of the patient is recommended to assess their condition and provide necessary supportive therapy.

Due to famotidine's low binding affinity to plasma proteins, hemodialysis may facilitate its elimination from the body. However, it is important to note that there is limited clinical experience regarding the efficacy of hemodialysis in treating famotidine overdosage. Therefore, healthcare professionals should consider this option cautiously and in conjunction with other supportive measures.

Nonclinical Toxicology

The carcinogenic potential of famotidine was evaluated in a 106-week oral carcinogenicity study in rats and a 92-week oral carcinogenicity study in mice. In these studies, famotidine was administered at oral doses of up to 2000 mg/kg/day, which corresponds to approximately 243 and 122 times the recommended human dose of 80 mg per day for the treatment of erosive esophagitis. No evidence of carcinogenic potential was observed in either study.

Famotidine was also assessed for mutagenicity in the microbial mutagen test (Ames test) using Salmonella typhimurium and Escherichia coli, both with and without rat liver enzyme activation, at concentrations up to 10,000 mcg/plate. The results were negative for mutagenic effects. Additionally, in vivo studies in mice, including a micronucleus test and a chromosomal aberration test, did not reveal any evidence of mutagenicity.

In studies involving rats administered oral doses of up to 2000 mg/kg/day, which is approximately 243 times the recommended human dose, there were no observed effects on fertility or reproductive performance.

Postmarketing Experience

Postmarketing experience has identified several adverse reactions reported voluntarily or through surveillance programs. These include confusion, delirium, hallucinations, disorientation, agitation, seizures, and lethargy. Additionally, reports of QT interval prolongation have been noted in the postmarketing data.

Patient Counseling

Healthcare providers should advise elderly patients and those with moderate to severe renal impairment about the potential risk of central nervous system (CNS) adverse reactions associated with the use of famotidine. These reactions may include confusion, delirium, hallucinations, disorientation, agitation, seizures, and lethargy. Patients should be instructed to report any of these symptoms immediately to their healthcare provider.

Additionally, it is important to inform patients with moderate and severe renal impairment about the risk of QT interval prolongation. They should be advised to report any new cardiac symptoms, such as palpitations, fainting, or feelings of dizziness or lightheadedness, to their healthcare provider without delay.

Patients should be instructed on the proper administration of famotidine tablets, which may be taken once daily before bedtime or twice daily, as recommended by their healthcare provider. It is acceptable for famotidine tablets to be taken with or without food, and they may also be administered alongside antacids if needed.

Storage and Handling

The product is supplied in a USP tight, light-resistant container to ensure its integrity and stability. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), with permissible excursions between 15° to 30°C (59° to 86°F) as defined by USP Controlled Room Temperature guidelines. Proper adherence to these storage conditions is essential for maintaining the product's efficacy and safety.

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 Camber Pharmaceuticals, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)