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.

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.

Each famotidine tablet, USP, for oral administration contains either 20 mg or 40 mg of famotidine, USP, along with the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, ferric oxide red, ferric oxide yellow, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, titanium dioxide, and triacetin.

Uses and Indications

Famotidine tablets are histamine-2 (H2) receptor antagonists indicated for the treatment of various gastrointestinal conditions. This drug 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 treatment of active gastric ulcer in the same patient population. Additionally, famotidine is indicated for the treatment of symptomatic nonerosive gastroesophageal reflux disease (GERD) and for the treatment of erosive esophagitis due to GERD, which must be diagnosed by biopsy, in adult and pediatric patients weighing 40 kg and greater.

Furthermore, famotidine is indicated for the treatment of pathological hypersecretory conditions, such as Zollinger-Ellison syndrome and multiple endocrine neoplasias, in adults. The drug is also indicated for the reduction of the risk of duodenal ulcer recurrence in adults.

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:

For the treatment of active duodenal ulcers (DU), a dosage of 40 mg is to be administered once daily, or alternatively, 20 mg may be given twice daily. In cases of active gastric ulcer, the recommended dosage is 40 mg once daily. For gastroesophageal reflux disease (GERD), the dosage is 20 mg twice daily. In the treatment of erosive esophagitis, the patient may receive either 20 mg or 40 mg, both administered twice daily.

For adults with pathological hypersecretory conditions, the initial dosage is 20 mg every 6 hours, with adjustments made according to the patient's 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 recommended.

Administration of the medication can be performed either 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, as per the patient's preference.

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.

Clinicians 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 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 they may be at risk for similar 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 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. 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 alongside 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 tablets have been established in pediatric patients for the treatment of peptic ulcer disease, including duodenal ulcers, gastric ulcers, and gastroesophageal reflux disease (GERD), which encompasses symptomatic nonerosive GERD and erosive esophagitis as 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 tablets for the treatment of pathological hypersecretory conditions and the reduction of the risk of duodenal ulcer recurrence in pediatric patients have not been established. Additionally, famotidine tablets in strengths of 20 mg and 40 mg are not recommended for pediatric patients weighing less than 40 kg, as these dosages exceed the recommended limits 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 tablets 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 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 geriatric patients, particularly those with impaired renal function. Therefore, it is recommended that healthcare providers use the lowest effective dose of famotidine tablets for elderly patients and closely monitor their renal function to mitigate potential risks.

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, 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 adequate or well-controlled studies in breastfeeding women regarding the use of famotidine. The potential for excretion of famotidine in breast milk is unknown. Therefore, caution should be exercised when administering famotidine to nursing mothers.

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 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, 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 the treatment of famotidine overdosage. Therefore, healthcare professionals should exercise caution and consider individual patient circumstances when determining the appropriate management strategy.

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 2000 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. The results indicated no evidence of carcinogenic potential for famotidine in either species.

In terms of mutagenicity, 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. The findings were negative, indicating no mutagenic effects. Additionally, in vivo studies conducted in mice, including a micronucleus test and a chromosomal aberration test, also showed no evidence of mutagenic effects.

Fertility and reproductive performance were evaluated in studies involving rats administered oral doses of up to 2000 mg/kg/day, which is approximately 243 times the recommended human dose. The results demonstrated that famotidine did not adversely affect fertility or reproductive performance in these animals.

Postmarketing Experience

No specific postmarketing experience details have been reported. As such, there are no additional adverse events or rare case reports to summarize at this time.

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. They should be advised 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°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 quality and efficacy 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 Lifestar Pharma LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)