Famotidine

Description

The active ingredient in famotidine for oral suspension USP is a histamine-2 (H2) receptor antagonist. Famotidine is chemically defined as N'-(aminosulfonyl)-3-[[[2-(diaminomethylene)amino-4-thiazolyl]methyl]thio]propanimidamide, with a molecular formula of C8H15N7O2S3 and a molecular weight of 337.45 g/mol. Famotidine USP appears as a white to pale yellow crystalline powder. It is freely soluble in dimethyl formamide and glacial acetic acid, slightly soluble in methanol, and very slightly soluble in water. Additionally, famotidine is practically insoluble in acetone, alcohol, chloroform, ether, and ethyl acetate. Each 5 mL of famotidine for oral suspension USP contains 40 mg of famotidine USP. Inactive ingredients include citric acid monohydrate, flavors (cherry, banana, and peppermint), powdered cellulose, sucrose, sucralose, and xanthan gum. Preservatives included are methylparaben sodium, propylparaben sodium, and sodium benzoate.

Uses and Indications

Famotidine for oral suspension is indicated for the treatment of various gastrointestinal conditions. In adults, it is indicated for the management of active duodenal ulcers (DU), active gastric ulcers (GU), symptomatic nonerosive gastroesophageal reflux disease (GERD), erosive esophagitis due to GERD as diagnosed by biopsy, and pathological hypersecretory conditions, including Zollinger-Ellison syndrome and multiple endocrine neoplasias. Additionally, it is indicated for the reduction of the risk of DU recurrence.

In pediatric patients aged 1 year and older, famotidine is indicated for the treatment of peptic ulcers and GERD, with or without esophagitis and ulcerations. For pediatric patients from birth to less than 1 year of age, the drug is indicated for the treatment of GERD.

There are no teratogenic or nonteratogenic effects associated with famotidine for oral suspension.

Dosage and Administration

The recommended adult dosage for active duodenal ulcers (DU) is 40 mg once daily or 20 mg twice daily. For active gastric ulcers (GU), the dosage is 40 mg once daily. In cases of symptomatic nonerosive gastroesophageal reflux disease (GERD), the recommended dosage is 20 mg twice daily. For erosive esophagitis due to GERD, the dosage may be 20 mg twice daily or 40 mg twice daily, depending on the severity of the 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 DU recurrence, a dosage of 20 mg once daily is recommended.

For pediatric patients, the dosage for peptic ulcer disease in children aged 1 year to less than 17 years starts at 0.5 mg/kg once daily or 0.25 mg/kg twice daily, with the possibility of increasing to 1 mg/kg once daily at bedtime or 0.5 mg/kg twice daily, not exceeding a maximum of 40 mg per day. For GERD in infants from birth to less than 3 months, the starting dosage is 0.5 mg/kg once daily, which may be increased to 1 mg/kg once daily. In children aged 3 months to less than 1 year, the starting dosage is 0.5 mg/kg twice daily, with a potential increase to 1 mg/kg twice daily, also not exceeding 40 mg per day. For GERD with or without esophagitis and ulcerations in children aged 1 year to less than 17 years, the recommended dosage is 0.5 mg/kg twice daily, with a maximum of 40 mg twice daily.

Administration should occur once daily before bedtime or twice daily in the morning and before bedtime, 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 should be conducted prior to initiating 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 monitored closely, as serious hypersensitivity reactions may occur.

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, a substrate of CYP1A2, may experience significant increases in blood concentrations when administered concurrently with CYP1A2 inhibitors. 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 to mitigate these risks.

Currently, there is no information available regarding drug and laboratory test interactions.

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 for oral suspension have been established in pediatric patients aged 1 year to less than 17 years for the treatment of peptic ulcer disease and gastroesophageal reflux disease (GERD), with or without esophagitis and ulcerations. In pediatric patients from birth to less than 1 year of age, famotidine has been shown to be safe and effective for the treatment of GERD. However, the safety and effectiveness of famotidine for the treatment of peptic ulcer disease in this younger age group have not been established.

Additionally, the safety and effectiveness of famotidine for the treatment of pathological hypersecretory conditions and for the reduction of the risk of duodenal ulcer recurrence have not been established in pediatric patients. It is important to note that a safe and effective dosage has not been determined for pediatric patients with renal impairment.

Geriatric Use

In clinical studies involving 1,442 patients treated with famotidine, approximately 10% 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, 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. Given that famotidine is substantially excreted by the kidneys, the risk of adverse reactions may be heightened in this population, especially among those with compromised renal function.

It is recommended to use the lowest effective dose of famotidine for oral suspension in elderly patients and to closely monitor renal function to mitigate potential risks.

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

Management of overdosage should focus on symptomatic and supportive care. It is essential to remove any unabsorbed material from the gastrointestinal tract to mitigate the effects of the overdose. This may involve the use of activated charcoal or other appropriate measures, depending on the clinical scenario.

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

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 both studies, conducted at oral doses of up to 2000 mg/kg/day (approximately 243 times 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 associated with famotidine.

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 2000 mg/kg/day (approximately 243 times the recommended human dose). The results indicated that famotidine did not adversely affect fertility or reproductive performance.

Postmarketing Experience

No specific postmarketing experience details are available. 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 for oral suspension. 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 and their caregivers should be instructed on the proper administration of Famotidine for oral suspension. It is recommended that the medication be taken once daily before bedtime or twice daily, in the morning and before bedtime, as directed. Furthermore, patients and caregivers should be informed that Famotidine for oral suspension can be taken with or without food, and it may also be administered alongside antacids.

Storage and Handling

Famotidine for oral suspension USP is supplied as a dry powder that must be constituted prior to use. It should be stored at a temperature range of 20°C to 25°C (68°F to 77°F), with permissible excursions between 15°C to 30°C (59°F to 86°F). It is essential to protect the product from freezing to maintain its efficacy.

Once constituted, any unused suspension should be discarded after 30 days to ensure safety and effectiveness. The product should be dispensed in a USP tight, light-resistant container to safeguard against environmental factors that may compromise its quality.

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 Ajanta Pharma USA Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)