Famotidine

Description

The active ingredient in Famotidine Tablets USP is famotidine, a histamine-2 (H2) receptor antagonist. Famotidine, USP is chemically designated as [1-Amino-3-[[[2-(diaminomethylene)amino-4-thiazolyl]methyl]thio] propylidene] sulfamide, with a structural formula that reflects its molecular composition. Each Famotidine Tablet USP is available in two strengths: 20 mg and 40 mg of famotidine, USP.

The tablets contain a variety of inactive ingredients, including colloidal silicon dioxide, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, pregelatinized corn starch, sodium starch glycolate, talc, titanium dioxide, and yellow iron oxide. The 20 mg formulation additionally includes lactose monohydrate, red iron oxide, and triacetin, while the 40 mg formulation contains FD&C blue No. 2 aluminum lake and FD&C yellow No. 6 aluminum lake.

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 tablets are indicated for the treatment of active duodenal ulcer (DU) in adult and pediatric patients weighing 40 kg and greater. This medication is also indicated for the management 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 erosive esophagitis due to GERD, as diagnosed by biopsy, in adult and pediatric patients weighing 40 kg and greater.

In adults, famotidine is further indicated for the treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome and multiple endocrine neoplasias. It is also indicated for the reduction of the risk of duodenal ulcer recurrence.

There are no teratogenic or nonteratogenic effects associated with famotidine.

Dosage and Administration

The recommended dosage for the treatment of various conditions is as follows:

For Active Duodenal Ulcer (DU), the recommended dosage is 40 mg once daily or 20 mg twice daily. In the case of Active Gastric Ulcer, a dosage of 40 mg once daily is advised. For Gastroesophageal Reflux Disease (GERD), the recommended dosage is 20 mg twice daily. Patients with Erosive Esophagitis may be prescribed either 20 mg twice daily or 40 mg twice daily, depending on the severity of the condition. For those with a Pathological Hypersecretory Condition, the initial dosage is 20 mg every 6 hours, with adjustments made according to individual patient needs, not exceeding a maximum of 160 mg every 6 hours. To reduce the risk of duodenal ulcer recurrence, a dosage of 20 mg once daily is recommended.

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, allowing for flexibility in patient adherence.

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 when using this medication. It is recommended that the dosage be reduced in these populations to mitigate potential adverse effects (2.2, 5.1, 8.5, 8.6).

Healthcare professionals should be aware that the absence of gastrointestinal symptoms does not rule out the possibility of gastric malignancy. A thorough evaluation is advised prior to initiating therapy to ensure patient safety and appropriate treatment planning (5.2).

No specific laboratory tests are required for monitoring during the use of this medication; however, clinicians should remain vigilant and consider individual patient factors when determining the need for any additional assessments.

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, as these reactions may recur.

In cases of overdosage, the types of adverse reactions observed are similar to those encountered with the use of recommended dosages, indicating a consistent profile of adverse effects regardless of dosage levels.

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 monitor the therapeutic effects of such drugs closely when used in conjunction with agents that alter gastric pH.

Tizanidine, a substrate of CYP1A2, may experience substantial increases in blood concentrations when used with inhibitors of this enzyme. 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 CYP1A2 inhibitors whenever possible. If co-administration is necessary, careful monitoring of blood pressure and sedation levels is advised, and dosage adjustments may be required based on clinical response.

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 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 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 category. 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 tablets in clinical studies 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.

In postmarketing experience, central nervous system (CNS) adverse reactions have been reported among elderly patients receiving famotidine tablets, regardless of their renal function status. Given that famotidine is primarily excreted by the kidneys, the risk of adverse reactions may be heightened in elderly patients, especially those with compromised renal function.

It is recommended to use the lowest effective dose of famotidine tablets for elderly patients and to closely monitor their renal function throughout the treatment period. This approach will help mitigate potential risks and ensure the safe use of famotidine in this 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 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 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 populations to mitigate potential risks associated with reduced kidney function. 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 option for famotidine tablet overdosage. Therefore, healthcare professionals should exercise caution and consider the individual clinical scenario when determining the 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 for mutagenic effects. Additionally, in vivo studies conducted in mice, including a micronucleus test and a chromosomal aberration test, also showed no evidence of mutagenicity.

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 are available in the extracted data. 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 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 if needed.

Storage and Handling

Famotidine tablets are supplied in well-closed, light-resistant containers as defined by the United States Pharmacopeia (USP), equipped with child-resistant closures as required.

For optimal storage, famotidine tablets should be maintained at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines. It is critical to avoid exposure to temperatures exceeding 40°C (104°F) to ensure the integrity of the product.

Healthcare professionals are reminded to keep this medication, along with all other medications, out of the reach of children.

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 Legacy Pharmaceutical Packaging, LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)