Famotidine

Description

The active ingredient in Famotidine Tablets USP is famotidine, a histamine-2 (H2) receptor antagonist. Famotidine is chemically described 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 Famotidine Tablet, USP for oral administration contains either 20 mg or 40 mg of famotidine, USP. The tablets include inactive ingredients such as hypromellose, iron oxide red, iron oxide yellow, ls-hydroxypropyl cellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, 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 tablets are a histamine-2 (H2) receptor antagonist indicated for the treatment of several gastrointestinal conditions. This drug is indicated for the management of active duodenal ulcers (DU) and active gastric ulcers. It is also indicated for the relief of symptoms associated with nonerosive gastroesophageal reflux disease (GERD) and for the treatment of erosive esophagitis due to GERD, which must be diagnosed by biopsy.

In adults, 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 as per the available data.

Dosage and Administration

For adult and pediatric patients weighing 40 kg and 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 advised. For gastroesophageal reflux disease (GERD), the recommended dosage is 20 mg twice daily. Patients with erosive esophagitis may receive either 20 mg twice daily or 40 mg twice daily, depending on clinical judgment.

In instances of pathological hypersecretory conditions, the initial dosage is 20 mg every 6 hours, with adjustments made according to the patient's needs; the maximum allowable dosage is 160 mg every 6 hours. For the risk reduction 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, 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.

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 heightened risk for similar reactions.

In cases of overdosage, the adverse reactions observed are generally consistent with those encountered at recommended dosages, underscoring the importance of adhering to prescribed guidelines.

Drug Interactions

There are currently no documented drug interactions associated with this medication. Additionally, there is no information available regarding interactions with laboratory tests. As such, no specific recommendations for dosage adjustments or monitoring are warranted at this time.

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 for gastroesophageal reflux disease (GERD), which encompasses symptomatic nonerosive GERD and erosive esophagitis diagnosed by endoscopy. The recommended dosage for pediatric patients is informed 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 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

In clinical studies involving famotidine, approximately 10% of the 1,442 treated patients 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 among elderly patients, both with and without renal impairment, who were receiving famotidine.

Given that famotidine is substantially excreted by the kidneys, the risk of adverse reactions may be heightened in geriatric patients, particularly those with compromised 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 the use of H2-receptor antagonists, including famotidine, in pregnant patients are insufficient to establish a definitive drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, oral administration of famotidine at doses up to approximately 243 and 122 times the recommended human dose of 80 mg per day for the treatment of erosive esophagitis did not reveal any adverse developmental effects.

The estimated background risk for major birth defects and miscarriage in the indicated population remains 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 shown 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.

Despite these findings, there are no adequate or well-controlled studies in pregnant women. Given that animal reproductive studies may not always predict human responses, famotidine should be used during pregnancy only if clearly needed.

Lactation

There are limited data available on the presence of famotidine in human breast milk. Studies indicate that famotidine is present in the milk of lactating rats; however, there were no observed effects on breastfed infants. Currently, there are no data regarding the effects of famotidine on milk production in lactating mothers.

When considering the use of famotidine in lactating mothers, the developmental and health benefits of breastfeeding should be weighed against the mother's clinical need for the medication and any potential adverse effects on the breastfed child from famotidine or from the underlying maternal condition. It is noteworthy that transient growth depression was observed in young rats suckling from mothers treated with maternotoxic doses of famotidine, which were at least 600 times the usual human dose.

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 famotidine overdosage, the adverse reactions observed are consistent with those associated with the use of recommended dosages. Healthcare professionals should be vigilant for these reactions, which may include symptoms such as confusion, dizziness, and gastrointestinal disturbances.

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

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 modality for famotidine overdosage. Therefore, healthcare providers should consider this option cautiously and in conjunction with other supportive measures.

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, showed no 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

No specific postmarketing experience details are available in the provided text. As such, there are no reported adverse events or case reports to summarize.

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. Patients should be encouraged to report any new cardiac symptoms, including palpitations, fainting, 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 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 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 Chartwell RX, LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)