Famotidine

Description

The active ingredient in famotidine tablets, USP, is a histamine-2 (H2) receptor antagonist. Famotidine is chemically designated as 3-[({2-(diaminomethylidene) amino-1, 3-thiazol-4-yl} methyl) sulfanyl]-N-sulfamoyl propanimidamide, with a molecular formula of C8H15N7O2S3 and a molecular weight of 337.45 g/mol.

Each famotidine tablet for oral administration contains either 20 mg or 40 mg of famotidine USP, along with inactive ingredients including corn starch, hypromellose, magnesium stearate, microcrystalline cellulose, sodium starch glycolate, opadry white, and opadry yellow. The opadry white component consists of hypromellose, hydroxypropyl cellulose, titanium dioxide, talc, and carnauba wax. The 20 mg tablets also contain red iron oxide and yellow iron oxide.

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. It is important to note that FDA-approved dissolution test specifications differ from those of the USP.

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, 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

For adult and pediatric patients weighing 40 kg and greater, the recommended dosages are as follows:

For active duodenal ulcer (DU), the 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 recommended. For gastroesophageal reflux disease (GERD), the dosage is 20 mg twice daily. For erosive esophagitis, the dosage may be either 20 mg twice daily or 40 mg twice daily.

In adults with 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 advised.

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.

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.

In cases of overdosage, the 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 concurrently with 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 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 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. It is important to note that 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 group. 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 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

There is no specific information available regarding the use of this medication during pregnancy, including safety concerns, dosage modifications, or special precautions that should be taken. Healthcare professionals are advised to consider the lack of data when prescribing this medication to pregnant patients and to weigh the potential benefits against any unknown risks to fetal outcomes. Women of childbearing potential should be counseled accordingly.

Lactation

There are no adequate or well-controlled studies in pregnant women regarding the use of famotidine. The potential for excretion in breast milk is not specifically addressed in the available data. Additionally, there are no specific recommendations or precautions mentioned for nursing mothers or lactation.

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 famotidine overdosage, the adverse reactions observed are consistent with those reported at recommended dosages, as detailed in the Adverse Reactions section (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 to assess their condition and provide necessary supportive therapy.

Due to famotidine's low binding affinity to plasma proteins, it is primarily eliminated through hemodialysis. However, it is important to note that there is limited clinical experience regarding the efficacy of hemodialysis in treating famotidine overdosage. Therefore, healthcare professionals should consider this when determining the appropriate management strategy for affected patients.

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, conducted at oral doses of up to 2,000 mg/kg/day (approximately 243 and 122 times the recommended human dose of 80 mg per day for the treatment of erosive esophagitis, based on body surface area), no evidence of carcinogenic potential was observed.

In terms of mutagenicity, famotidine was found to be negative 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.

Fertility and reproductive performance were assessed in studies involving rats administered oral doses of up to 2,000 mg/kg/day (approximately 243 times the recommended human dose of 80 mg per day). The results indicated that there were no adverse effects on fertility or reproductive performance.

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 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 to their healthcare provider immediately.

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, in the morning and before bedtime. 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

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 20º to 25ºC (68º to 77ºF), with permissible excursions between 15º to 30ºC (59º to 86ºF) as defined by USP Controlled Room Temperature guidelines. Proper adherence to these storage conditions is essential for maintaining 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 Rising Pharma Holdings, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)