Famotidine

Description

The active ingredient in famotidine tablets is 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 337.45. The structural formula is provided in the accompanying documentation.

Each famotidine tablet for oral administration contains either 20 mg or 40 mg of famotidine, along with the following inactive ingredients: colloidal silicon dioxide, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, pregelatinized starch (source: maize), sodium starch glycolate, talc, and titanium dioxide. 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, and very slightly soluble in water. It is practically insoluble in acetone, alcohol, chloroform, ether, and ethyl acetate. The FDA-approved dissolution test specifications for famotidine differ from those established by the USP.

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.

In adult patients, famotidine is indicated for the treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome and multiple endocrine neoplasias. Additionally, it is indicated for the reduction of 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 or greater, the recommended dosages are as follows:

For active duodenal ulcers (DU), the dosage is 40 mg administered once daily or 20 mg administered twice daily. In the case of active gastric ulcers, a dosage of 40 mg once daily is recommended. For gastroesophageal reflux disease (GERD), the dosage is 20 mg twice daily. For erosive esophagitis, the dosage may be 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, with adjustments made according to individual patient needs. The maximum dosage should not exceed 160 mg every 6 hours. For the risk reduction of duodenal ulcer recurrence, a dosage of 20 mg once daily is advised.

Administration should occur once daily before bedtime or twice daily, with the first dose in the morning and the second dose 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

Patients may experience a range of adverse reactions while using the medication. 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, patients with a history of serious hypersensitivity reactions, such as anaphylaxis, to famotidine or other H2 receptor antagonists should exercise caution when considering this medication.

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 amounts.

Drug Interactions

Concomitant use of drugs that depend on gastric pH for absorption may lead to a significant reduction in systemic exposure of these medications, potentially resulting in a loss of efficacy. Healthcare professionals are advised to consult the full prescribing information for a comprehensive list of interacting drugs.

Tizanidine, a substrate of CYP1A2, may experience substantial increases in blood concentrations when used alongside certain medications. This elevation in tizanidine levels 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 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, 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.

Given that famotidine is substantially excreted by the kidneys, the risk of adverse reactions may be heightened in geriatric patients, particularly those with impaired renal function. Therefore, it is recommended that healthcare providers use the lowest effective dose of famotidine for elderly patients and closely monitor their renal function to mitigate potential risks.

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 times 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, 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 2,000 mg/kg/day 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 emphasize 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 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 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 crucial, and supportive therapy should be initiated as needed to address any symptoms that may arise.

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

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 times 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 in vivo studies in mice, including a micronucleus test and a chromosomal aberration test, no evidence of mutagenicity was observed.

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

Reports of side effects have been received through voluntary submissions and surveillance programs. Patients are encouraged to contact their healthcare provider for medical advice regarding any adverse events. Additionally, side effects can be reported to the FDA at 1-800-FDA-1088.

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, patients with moderate and severe renal impairment should be informed about the risk of QT interval prolongation associated with famotidine. They 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. It is important to inform patients that famotidine tablets can be taken with or without food and may be administered alongside antacids.

Healthcare providers should remind patients to seek medical advice regarding any side effects they may experience. Patients can report side effects to the FDA at 1-800-FDA-1088. For further information, patients may contact Medical Affairs at Zydus USA via email at MedicalAffairs@zydususa.com or by telephone at 1-877-993-8779.

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 temperature range of 20°C to 25°C (68°F to 77°F), with permissible excursions between 15°C to 30°C (59°F to 86°F) as defined by USP Controlled Room Temperature guidelines. Proper adherence to these storage conditions is essential for maintaining the quality 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 Zydus Pharmaceuticals USA Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)