Famotidine

Description

The active ingredient in Famotidine Tablets USP is famotidine, a histamine-2 (H2) receptor antagonist. Famotidine, USP is chemically designated as [1-Amino-3-[[[2-(diaminomethylene)amino-4-thiazolyl]methyl]thio] propylidene] sulfamide, with a molecular formula of C8H15N7O2S3 and a molecular weight of 337.45.

Each Famotidine Tablet USP is formulated for oral administration and contains either 20 mg or 40 mg of famotidine, USP. The tablets include the following inactive ingredients: colloidal silicon dioxide, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, pregelatinized corn starch, sodium starch glycolate, talc, titanium dioxide, and yellow iron oxide. The 20 mg formulation additionally contains lactose monohydrate, red iron oxide, and triacetin, while the 40 mg formulation includes FD&C blue No. 2 aluminum lake and FD&C yellow No. 6 aluminum lake.

Famotidine, USP appears as a white to pale yellow crystalline compound. It is freely soluble in glacial acetic acid, slightly soluble in methanol, very slightly soluble in water, and practically insoluble in ethanol.

Uses and Indications

Famotidine tablets are indicated for the treatment of active duodenal ulcers (DU) and active gastric ulcers. Additionally, they are indicated for the management of symptomatic nonerosive gastroesophageal reflux disease (GERD) and for the treatment of erosive esophagitis due to GERD, as diagnosed by biopsy.

In adult patients, famotidine is also indicated for the treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome and multiple endocrine neoplasias. Furthermore, it is indicated for the reduction of the risk of recurrence of duodenal ulcers.

There are no teratogenic or nonteratogenic effects associated with the use of famotidine.

Dosage and Administration

For adult and pediatric patients weighing 40 kg and greater, the recommended dosages are as follows:

For active duodenal ulcers (DU), the 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 recommended dosage is 20 mg twice daily. Patients with erosive esophagitis may receive either 20 mg twice daily or 40 mg twice daily.

In adults with pathological hypersecretory conditions, the initial dosage is 20 mg every 6 hours, which may be adjusted based on individual patient needs, with a maximum dosage of 160 mg every 6 hours. For the risk reduction of DU recurrence, a dosage of 20 mg once daily is recommended.

Administration should occur once daily before bedtime or twice daily, 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 when using this medication; therefore, it is recommended that the dosage be reduced in these populations to mitigate potential adverse effects.

It is important to note that the absence of gastrointestinal symptoms does not rule out the possibility of gastric malignancy. A thorough evaluation should be conducted prior to initiating therapy to ensure patient safety and appropriate treatment planning.

Side Effects

Patients may experience a range of adverse reactions while undergoing treatment. Common adverse reactions reported include headache, dizziness, constipation, and diarrhea.

Particular attention should be given to central nervous system (CNS) adverse reactions, especially in elderly patients and those with renal impairment, as these populations are at an increased risk. It is recommended to reduce the dosage in these cases to mitigate potential risks.

Additionally, it is important to note that the absence of gastrointestinal (GI) symptoms does not rule out the possibility of gastric malignancy; therefore, a thorough evaluation should be conducted prior to initiating therapy.

Patients with a history of serious hypersensitivity reactions, such as anaphylaxis, to famotidine or other H2 receptor antagonists should be closely monitored, as these individuals may be at heightened risk for adverse reactions.

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. Healthcare professionals are advised 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 certain medications. This interaction can lead to adverse effects such as hypotension, bradycardia, or excessive drowsiness. It is recommended to avoid concomitant use of tizanidine with these interacting drugs whenever possible to mitigate these risks.

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 tablets have been established in pediatric patients for the treatment of peptic ulcer disease, including duodenal and gastric ulcers, as well as for gastroesophageal reflux disease (GERD), which encompasses symptomatic nonerosive GERD and erosive esophagitis diagnosed by endoscopy. The recommended dosage for pediatric patients is supported by evidence from adequate and well-controlled studies 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 tablets, approximately 10% of the 1,442 patients treated were aged 65 years 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.

Postmarketing experience has indicated that central nervous system (CNS) adverse reactions have been reported in elderly patients, both with and without renal impairment, who received famotidine tablets. Given that famotidine is substantially excreted by the kidneys, the risk of adverse reactions may be heightened in this population, especially among those with compromised renal function.

Therefore, it is recommended that healthcare providers use the lowest effective dose of famotidine tablets for elderly patients. Additionally, regular monitoring of renal function is advised to mitigate potential risks associated with the use of this medication in geriatric patients.

Pregnancy

Available data regarding the use of H2-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 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 tablets. 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 no specific statements regarding the use of this medication in lactating mothers or its effects on breastfed infants. Healthcare professionals should consider the absence of data when advising lactating mothers about the use of this medication.

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.

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 overdosage with famotidine tablets, the adverse reactions observed are consistent with those reported at recommended dosages (refer to Adverse Reactions 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, and supportive therapy should be initiated as necessary to address any symptoms that may arise.

Due to famotidine's low binding affinity to plasma proteins, it is primarily eliminated through hemodialysis. However, it is important to note that there is limited clinical experience regarding the efficacy of hemodialysis as a treatment option for famotidine overdosage. Therefore, healthcare professionals should exercise caution and consider the individual patient's condition when determining the appropriate management strategy.

Nonclinical Toxicology

Carcinogenic potential of famotidine was assessed in a 106-week oral carcinogenicity study in rats and a 92-week oral carcinogenicity study in mice. In these studies, conducted at oral doses of up to 2000 mg/kg/day (approximately 243 and 122 times the recommended human dose of 80 mg per day for the treatment of erosive esophagitis), there was no evidence of carcinogenic potential for famotidine.

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, 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 (approximately 243 times the recommended human dose), fertility and reproductive performance were not adversely affected.

Postmarketing Experience

Postmarketing experience has identified the following adverse reactions reported voluntarily or through surveillance programs: confusion, delirium, hallucinations, disorientation, agitation, seizures, and lethargy. These events have been documented in various patient populations and settings.

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

Famotidine tablets are supplied in well-closed, light-resistant containers as defined by the United States Pharmacopeia (USP), equipped with child-resistant closures as required.

For optimal storage, famotidine tablets should be maintained at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines. It is crucial to avoid exposure to temperatures exceeding 40°C (104°F) to ensure the integrity of the product.

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

View full prescribing information (PDF)