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 a molecular formula of C8H15N7O2S3 and a molecular weight of 337.45 g/mol. Each famotidine tablet, USP, intended for oral administration, contains either 20 mg or 40 mg of famotidine, USP, along with inactive ingredients that include colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, pregelatinized starch, and talc. The film coating is composed of hydroxypropyl methylcellulose, polyethylene glycol, synthetic yellow iron oxide, and titanium dioxide. Famotidine, USP appears as a white to pale yellowish-white crystalline powder, which is freely soluble in dimethylformamide 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 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 doses taken in the morning and before bedtime. The medication 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 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 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 serious hypersensitivity reactions may occur.

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 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 alongside certain medications. This elevation 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

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, 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 for geriatric patients and to closely monitor their renal function throughout the course of treatment.

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 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 nursing mothers or its effects during lactation. Additionally, there is no available data on the excretion of this medication in breast milk or its potential effects on breastfed infants. Healthcare professionals should consider the absence of information 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 overdosage with famotidine tablets, the adverse reactions observed are consistent with those reported at recommended dosages see Adverse Reactions (6.1).

Management of Overdosage In the event of an overdosage, the primary approach should be symptomatic and supportive. It is essential to remove any unabsorbed material from the gastrointestinal tract. Continuous monitoring of the patient is recommended, and supportive therapy should be initiated as necessary to address any symptoms that may arise.

Elimination Considerations Famotidine exhibits low binding to plasma proteins, which facilitates its elimination through hemodialysis. However, it is important to note that there is limited clinical experience regarding the efficacy of hemodialysis as a treatment modality for famotidine overdosage. Therefore, healthcare professionals should exercise caution and consider the individual clinical scenario when determining the appropriateness of hemodialysis in these cases.

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 these studies, famotidine was administered at oral doses of up to 2,000 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, respectively. The results indicated no evidence of carcinogenic potential for famotidine in either species.

In terms of mutagenicity, famotidine was found to be negative 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. Additionally, in vivo studies conducted in mice, including a micronucleus test and a chromosomal aberration test, showed no evidence of mutagenic effects.

Fertility and reproductive performance were assessed in studies involving rats administered oral doses of up to 2,000 mg/kg/day, which is approximately 243 times the recommended human dose. The findings indicated that famotidine did not adversely affect fertility or reproductive performance in these animals.

Postmarketing Experience

Postmarketing experience has revealed reports of adverse reactions, including but not limited to confusion, delirium, hallucinations, disorientation, agitation, seizures, and lethargy. These events have been reported voluntarily or through surveillance programs. Patients are advised to report any symptoms immediately to a healthcare provider.

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 its integrity and stability. It should be stored at a temperature range of 20°C to 25°C (68°F to 77°F), in accordance with USP Controlled Room Temperature guidelines. Proper storage conditions are essential to maintain 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 Dr. Reddy's Laboratories Limited. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)