Famotidine

Description

The active ingredient in famotidine tablets, USP, is a histamine-2 (H2) receptor antagonist. Famotidine is chemically defined as N’-(aminosulfonyl)-3-[[[2(diaminomethylene)amino-4-thiazolyl]methyl]thio]propanimidamide. Its empirical formula is C8H15N7O2S3, and it has a molecular weight of 337.43. Each famotidine tablet, USP, for oral administration contains either 20 mg or 40 mg of famotidine. The inactive ingredients in famotidine tablets include colloidal silicon dioxide, yellow iron oxide, red iron oxide, lecithin, macrogel/PEG 3350, magnesium stearate, microcrystalline cellulose, polyvinyl alcohol, pregelatinized starch, talc, and titanium dioxide. Famotidine, USP, 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 tablet is indicated for the treatment of active duodenal ulcer (DU) and active gastric ulcer. 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 DU recurrence.

There are no teratogenic or nonteratogenic effects associated with the use of famotidine.

Dosage and Administration

For adult and pediatric patients weighing 40 kg and greater, the following dosing regimens are recommended:

• For active duodenal ulcer (DU), the recommended dosage is 40 mg administered once daily or 20 mg administered twice daily.

• In the case of active gastric ulcer, a dosage of 40 mg once daily is advised.

• For gastroesophageal reflux disease (GERD), the dosage is 20 mg twice daily.

• For erosive esophagitis, the patient may receive either 20 mg twice daily or 40 mg twice daily.

In adults specifically, for the management of 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 recommended.

The medication should be taken once daily before bedtime or twice daily, in the morning and before bedtime. It may be administered 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 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 cases 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 guidelines.

Drug Interactions

Tizanidine is primarily metabolized by the CYP1A2 enzyme. When administered concurrently with CYP1A2 inhibitors, there may be significant increases in blood concentrations of tizanidine. This interaction can result in adverse effects such as hypotension, bradycardia, or excessive drowsiness. Therefore, it is advisable to avoid concomitant use of tizanidine with CYP1A2 inhibitors whenever possible.

No information regarding drug and laboratory test interactions has been provided.

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 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 tablets 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 tablets in 20 mg and 40 mg strengths 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

In clinical studies involving famotidine tablets, approximately 10% of the 1,442 patients treated were aged 65 years and older. These studies did not reveal any significant 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.

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 tablets. Given that famotidine is primarily excreted by the kidneys, the risk of adverse reactions may be heightened in this population, especially among those with compromised renal function.

Therefore, it is recommended that healthcare providers use the lowest effective dose of famotidine tablets for elderly patients. Additionally, regular monitoring of renal function is advised to mitigate potential risks associated with treatment in this demographic.

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 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 specific statements regarding the use of this medication in nursing mothers or during lactation. Additionally, there is no available data on the excretion of this medication in breast milk or its effects on breastfed infants. Healthcare professionals should consider the lack 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 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 associated with the use of recommended dosages. Healthcare professionals should be vigilant for these reactions, as they may manifest similarly regardless of the dosage.

Management of overdosage should be primarily symptomatic and supportive. It is essential to remove any unabsorbed material from the gastrointestinal tract to mitigate potential effects. Continuous monitoring of the patient is recommended to ensure their safety and to address any emerging symptoms promptly.

Due to famotidine's low binding affinity to plasma proteins, it is 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 providers should consider this factor when determining the most appropriate management strategy for affected patients.

Nonclinical Toxicology

The 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), no evidence of carcinogenic potential was observed.

Famotidine demonstrated a negative result 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 in mice, including a micronucleus test and a chromosomal aberration test, did not reveal any evidence of mutagenic effects.

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

Postmarketing Experience

Reports of side effects have been received through voluntary submissions and surveillance programs. Patients are encouraged to consult their healthcare provider for medical advice regarding any adverse effects experienced. 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 associated with the use of famotidine. 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 by their healthcare provider. It is acceptable for famotidine tablets to be taken with or without food, and they may also be administered alongside antacids.

Healthcare providers should encourage 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 Alembic Pharmaceuticals Limited at 1-866-210-9797.

Storage and Handling

The product is supplied in a USP tight, light-resistant container to ensure optimal protection. It should be stored at a temperature of 25°C (77°F), with permissible excursions between 15°C to 30°C (59°F to 86°F) in accordance with USP Controlled Room Temperature guidelines.

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 Alembic Pharmaceuticals Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)