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 337.43. The structural formula is provided in the accompanying documentation.

Each famotidine tablet for oral administration contains either 20 mg or 40 mg of famotidine USP, along with the following inactive ingredients: microcrystalline cellulose, pregelatinized starch, silicon dioxide, povidone, magnesium stearate, hypromellose, polyethylene glycol, titanium dioxide, and talc. Famotidine 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 is indicated for the treatment of active duodenal ulcer (DU) in adult and pediatric patients weighing 40 kg and greater. It 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, as 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 DU recurrence.

There are no teratogenic or nonteratogenic effects associated with Famotidine.

Dosage and Administration

The recommended dosage for Active Duodenal Ulcer (DU) is 40 mg administered once daily or 20 mg administered twice daily. For the treatment of Active Gastric Ulcer, the dosage is 40 mg once daily. In cases of Gastroesophageal Reflux Disease (GERD), the recommended dosage is 20 mg taken twice daily. For Erosive Esophagitis, the dosage may be 20 mg taken twice daily or 40 mg taken twice daily, depending on the severity of the condition.

For patients with Pathological Hypersecretory Conditions, the initial dosage is 20 mg every 6 hours, with adjustments made according to individual patient needs; the maximum dosage should not exceed 160 mg every 6 hours. To reduce the risk of recurrence of DU, a dosage of 20 mg once daily is recommended.

The medication should be taken once daily before bedtime or twice daily, in the morning and before bedtime, 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 (2.2, 5.1, 8.5, 8.6).

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 (5.2).

No additional general precautions or laboratory tests have been specified in the provided information.

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 patients 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.

In cases of overdosage, the types of adverse reactions observed are similar to those encountered with the use of recommended dosages, underscoring the importance of adhering to prescribed guidelines.

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 concurrently with other medications that affect its metabolism. 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 and gastric ulcers, as well as gastroesophageal reflux disease (GERD), which encompasses symptomatic nonerosive GERD and erosive esophagitis diagnosed by endoscopy. The recommended dosage for pediatric patients is informed 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.

Famotidine 20 mg and 40 mg tablets are not recommended for pediatric patients weighing less than 40 kg, as these tablet strengths exceed the recommended dose for this weight group. For pediatric patients under 40 kg, alternative formulations of famotidine, such as oral suspension or lower dose tablets, should be considered.

Geriatric Use

Approximately 10% of the 1,442 patients treated with famotidine in clinical studies 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, it is important to note that in postmarketing experience, central nervous system (CNS) adverse reactions have been reported in geriatric patients, both with and without renal impairment, who were receiving famotidine.

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, it is recommended to use the lowest effective dose of famotidine in this population. Additionally, careful monitoring of renal function is advised to mitigate potential risks associated with treatment in geriatric patients.

Pregnancy

Available data regarding the use of H-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; however, 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.

It is important to note that there are 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 nursing mothers or lactation in the provided text. Therefore, the effects of the drug on breastfed infants and the excretion of the drug in human milk are not addressed. Healthcare professionals should consider the absence of data when advising lactating mothers on 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 this population to mitigate potential risks associated with reduced kidney function. 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 this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions 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, it is primarily eliminated through hemodialysis. 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 when determining the most appropriate management strategy for affected patients.

Nonclinical Toxicology

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 both 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 associated with famotidine.

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

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

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. These may include symptoms such as 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 associated with famotidine. Patients should be encouraged to report any new cardiac symptoms, including 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 also important to inform patients that famotidine tablets can be taken with or without food and may 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 XLCare Pharmaceuticals, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)