Famotidine

Description

The active ingredient in Famotidine Tablets, USP, is famotidine, a histamine-2 (H2) receptor antagonist. Famotidine is chemically designated as N′‐(aminosulfonyl)-3-[[[2-(diaminomethylene)amino-4-thiazolyl]methyl]thio] propanimidamide, with a molecular formula of C8H15N7O2S3 and a molecular weight of 337.43.

Each tablet for oral administration contains either 20 mg or 40 mg of famotidine USP, along with inactive ingredients including colloidal silicon dioxide, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, pregelatinized starch, sodium starch glycolate, talc, and titanium dioxide. The 20 mg tablets also contain ferric oxide red and ferric oxide yellow. Famotidine, USP appears as a white to pale yellowish white crystalline powder, which is freely soluble in glacial acetic acid, slightly soluble in methanol, very slightly soluble in water, and practically insoluble in ethanol. Famotidine Tablets meet the USP Dissolution Test 2.

Uses and Indications

Famotidine is indicated for the treatment of active duodenal ulcers (DU) and active gastric ulcers. It is also 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. Additionally, famotidine is indicated for the treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome and multiple endocrine neoplasias. Furthermore, it is utilized to reduce the risk of recurrence of duodenal ulcers.

There are no teratogenic or nonteratogenic effects associated with famotidine.

Dosage and Administration

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

Active Duodenal Ulcer (DU): Administer 40 mg once daily or 20 mg twice daily. Active Gastric Ulcer: Administer 40 mg once daily. Gastroesophageal Reflux Disease (GERD): Administer 20 mg twice daily. Erosive Esophagitis: Administer 20 mg twice daily or 40 mg twice daily, depending on the severity of the condition. Pathological Hypersecretory Conditions: Administer 20 mg every 6 hours, adjusting the dosage according to patient needs, with a maximum of 160 mg every 6 hours. Risk Reduction of Duodenal Ulcer Recurrence: Administer 20 mg once daily.

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

Contraindications

Use of this product is contraindicated in patients with a history of serious hypersensitivity reactions, including anaphylaxis, to famotidine or other H2 receptor antagonists.

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 and are generally considered mild to moderate in severity.

Central nervous system (CNS) adverse reactions have been noted, particularly in elderly patients and those with renal impairment, who are at an increased risk. It is recommended that the dosage be reduced in these populations to mitigate potential risks. In postmarketing experience, CNS adverse reactions have been reported in elderly patients with and without renal impairment receiving famotidine, further emphasizing the need for caution in these groups.

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

In cases of overdosage, the types of adverse reactions encountered are similar to those observed with the use of recommended dosages. Given that famotidine is substantially excreted by the kidneys, the risk of adverse reactions may be greater 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. Healthcare professionals are advised to consult the full prescribing information for a comprehensive list of interacting medications.

When considering the use of tizanidine, which is a substrate of CYP1A2, there is a potential for substantial increases in blood concentrations. This elevation may result in adverse effects such as hypotension, bradycardia, or excessive drowsiness. Therefore, it is recommended to avoid concomitant use of tizanidine with other medications that may affect its metabolism, if possible. Monitoring of blood pressure and heart rate is advised in patients who require both medications.

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 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 1,442 patients treated with famotidine, approximately 10% 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, as postmarketing experience has indicated that central nervous system (CNS) adverse reactions have been reported in this population, regardless of renal function status.

Famotidine is primarily excreted by the kidneys, which raises concerns regarding the potential for increased adverse reactions 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 renal function throughout the treatment period. This approach will help mitigate the risk of adverse effects and ensure the safe use of famotidine in this vulnerable population.

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; 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 2,000 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 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 and to avoid complications.

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 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 considered as part of standard clinical practice.

Overdosage

In cases of famotidine overdosage, the adverse reactions observed are consistent with those reported at recommended dosages (refer to Adverse Reactions (6.1) for further details).

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 as a treatment option for 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 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 2,000 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 also 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, indicating no mutagenic effect. Additionally, in vivo studies in mice, including a micronucleus test and a chromosomal aberration test, showed no evidence of mutagenicity.

In studies involving rats administered oral doses of up to 2,000 mg/kg/day (approximately 243 times the recommended human dose), fertility and reproductive performance were not adversely affected.

Postmarketing Experience

No specific postmarketing experience details are available in the extracted data. As such, there are no additional adverse events or rare case reports to summarize.

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 medication. 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, in the morning and before bedtime. 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 optimal protection and integrity. 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). 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 Contract Pharmacal Corp.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)