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 an empirical formula of C8H15N7O2S3 and a molecular weight of 337.43. Each tablet for oral administration contains either 20 mg or 40 mg of famotidine, along with inactive ingredients that include hydroxypropyl cellulose, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, pregelatinized starch (modified corn starch), sodium starch glycolate, talc, titanium dioxide, and triacetin. Famotidine appears as a white to pale yellow crystalline compound, which is freely soluble in glacial acetic acid, very slightly soluble in methanol, very slightly soluble in water, and practically insoluble in ethanol.

Uses and Indications

Famotidine 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 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, both 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

Adult and pediatric patients weighing 40 kg and greater may be prescribed the following dosages based on their specific condition:

For active duodenal ulcers (DU), the recommended dosage is 40 mg once daily or 20 mg twice daily. In the case of active gastric ulcers, a dosage of 40 mg once daily is advised. For gastroesophageal reflux disease (GERD), the dosage is 20 mg twice daily. Patients with erosive esophagitis may receive either 20 mg twice daily or 40 mg twice daily, depending on the severity of their condition. For pathological hypersecretory conditions, the initial dosage is 20 mg every 6 hours, with adjustments made according to 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 of the medication should occur once daily before bedtime or twice daily, in the morning and before bedtime. It 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 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 necessary prior to initiating therapy to ensure patient safety (5.2).

No additional general precautions or laboratory tests have been specified in the provided information.

Side Effects

Patients may experience a range of adverse reactions while undergoing treatment. Common adverse reactions include headache, dizziness, constipation, and diarrhea.

Serious central nervous system (CNS) adverse reactions have been reported, including confusion, delirium, hallucinations, disorientation, agitation, seizures, and lethargy. Elderly patients and those with renal impairment are at an increased risk for these CNS effects; therefore, dosage reduction is recommended in these populations.

There is also a risk of QT interval prolongation, particularly in patients with moderate to severe renal impairment. Patients should be advised to report any new cardiac symptoms, such as palpitations, fainting, or dizziness/lightheadedness, to their healthcare provider immediately.

It is important to note that the absence of gastrointestinal (GI) symptoms does not rule out the possibility of gastric malignancy; therefore, evaluation is necessary prior to initiating therapy. Additionally, patients with a history of serious hypersensitivity reactions, such as anaphylaxis, to famotidine or other H2 receptor antagonists should be closely monitored.

In cases of overdosage, the types of adverse reactions observed are similar to those encountered with the use of recommended dosages.

Drug Interactions

Concomitant use of drugs that are dependent 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 interacting medications.

When considering the use of tizanidine, which is a substrate of CYP1A2, there is a potential for substantial increases in blood concentrations. This elevation may lead to adverse effects such as hypotension, bradycardia, or excessive drowsiness. Therefore, it is recommended to avoid concomitant use of tizanidine with other medications that may affect its metabolism, if possible. Monitoring of blood pressure and heart rate is advised in patients receiving tizanidine alongside other interacting agents.

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 and gastric ulcers, as well as gastroesophageal reflux disease (GERD), which encompasses symptomatic non-erosive GERD and erosive esophagitis diagnosed by endoscopy.

The recommended dosage of Famotidine in 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.

Famotidine 20 mg and 40 mg tablets are not recommended for pediatric patients weighing less than 40 kg, as these tablet strengths exceed the recommended dose 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 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.

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 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, 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. 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 nursing mothers or lactation in the provided text. Therefore, the effects of this medication on lactating mothers and breastfed infants remain undefined. Healthcare professionals should consider the absence of data when advising lactating mothers on 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 this population to mitigate potential risks associated with reduced kidney function. Monitoring of renal function is advised to ensure appropriate dosing adjustments are made.

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, the adverse reactions observed are consistent with those reported at recommended dosages, as detailed in the Adverse Reactions section (6.1).

Management of Famotidine overdosage should be primarily symptomatic and supportive. It is essential to remove any unabsorbed material from the gastrointestinal tract promptly. Continuous monitoring of the patient is recommended to assess their condition and to implement supportive therapy as necessary.

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 in the treatment of 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 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), there was no evidence of carcinogenic potential for famotidine.

Famotidine was negative in the microbial mutagen test (Ames test) using Salmonella typhimurium and Escherichia coli with or without rat liver enzyme activation at concentrations up to 10,000 mcg/plate. Additionally, in in vivo studies in mice, including a micronucleus test and a chromosomal aberration test, no evidence of a mutagenic effect was observed.

In studies with rats administered oral doses of up to 2000 mg/kg/day (approximately 243 times the recommended human dose of 80 mg per day), fertility and reproductive performance were not affected.

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 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. They should take the medication once daily before bedtime or, if recommended, twice daily—once in the morning and once before bedtime. Famotidine tablets can be taken with or without food, and patients should be informed that these tablets 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 efficacy. 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. Proper storage conditions are essential to maintain the quality of the product throughout its shelf life.

Additional Clinical Information

Elderly patients and those with moderate to severe renal impairment should be counseled about the potential risk of central nervous system (CNS) adverse reactions, which may include confusion, delirium, hallucinations, disorientation, agitation, seizures, and lethargy. It is important for these patients to report any such symptoms to a healthcare provider immediately. Additionally, patients with moderate and severe renal impairment should be made aware of the risk of QT interval prolongation and should report any new cardiac symptoms, such as palpitations, fainting, or dizziness, to their healthcare provider without delay.

Patients are advised to take Famotidine once daily before bedtime or twice daily as directed, in the morning and before bedtime. The tablets can be taken with or without food and may be administered alongside antacids.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Famotidine as submitted by Cardinal Health 107, LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)