Famotidine

Description

The active ingredient in famotidine for oral suspension, USP, is a 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 337.45.

Famotidine, USP appears as a white to pale yellowish white crystalline powder. It is freely soluble in glacial acetic acid and dimethylformamide, slightly soluble in methanol, very slightly soluble in water, and practically insoluble in acetone, alcohol, chloroform, ether, and ethyl acetate.

Each 5 mL of famotidine for oral suspension, when prepared as directed, contains 40 mg of famotidine, USP, along with inactive ingredients including citric acid monohydrate, flavors (strawberry, orange), powdered cellulose, sucrose, and xanthan gum. Preservatives included in the formulation are sodium benzoate, sodium methylparaben, and sodium propylparaben.

Uses and Indications

Famotidine for oral suspension is indicated for the treatment of various gastrointestinal conditions in both adults and pediatric patients. Specifically, it is indicated for:

• Active duodenal ulcer (DU) in adults.

• Active gastric ulcer (GU) in adults.

• Symptomatic nonerosive gastroesophageal reflux disease (GERD) in adults.

• Erosive esophagitis due to GERD, diagnosed by biopsy in adults.

• Treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome and multiple endocrine neoplasias, in adults.

• Reduction of the risk of DU recurrence in adults.

• Peptic ulcer in pediatric patients aged 1 year and older.

• GERD, with or without esophagitis and ulcerations, in pediatric patients aged 1 year and older.

• GERD in pediatric patients from birth to less than 1 year of age.

There are no teratogenic or nonteratogenic effects associated with this medication.

Dosage and Administration

The recommended adult dosage varies by indication. For active duodenal ulcers (DU), the dosage is 40 mg once daily or 20 mg twice daily. In cases of active gastric ulcers (GU), the recommended dosage is 40 mg once daily. For symptomatic nonerosive gastroesophageal reflux disease (GERD), the dosage is 20 mg twice daily. In the treatment of erosive esophagitis due to GERD, the dosage may be 20 mg twice daily or 40 mg twice daily. 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. For risk reduction of DU recurrence, the dosage is 20 mg once daily.

In pediatric patients aged 1 year to less than 17 years with peptic ulcer disease, the starting dosage is 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. For infants 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. Due to the potential for severe allergic reactions, administration in these patients may pose significant health risks.

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 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 when considering this medication.

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 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 monitor the therapeutic effects of such medications closely and consider alternative treatments if necessary.

Tizanidine, a substrate of CYP1A2, may experience substantial increases in blood concentrations when used alongside certain medications. This elevation can lead to adverse effects such as hypotension, bradycardia, or excessive drowsiness. Therefore, it is recommended to avoid concomitant use of tizanidine with these interacting drugs whenever possible. If co-administration is unavoidable, careful monitoring of tizanidine levels and patient response is essential to mitigate the risk of these adverse effects.

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

Pediatric patients aged 1 year to less than 17 years have established safety and effectiveness of famotidine for oral suspension in the treatment of peptic ulcer disease and gastroesophageal reflux disease (GERD), with or without esophagitis and ulcerations. This use is supported by evidence from adequate and well-controlled studies in adults, along with pharmacokinetic and pharmacodynamic data specific to this age group.

For pediatric patients less than 1 year of age, famotidine is also established as safe and effective for the treatment of GERD, supported by similar evidence from adult studies and additional supportive data in this younger population.

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

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 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, as postmarketing experience has indicated that central nervous system (CNS) adverse reactions have been reported in this population, regardless of renal function status.

Famotidine is primarily excreted by the kidneys, which may increase the risk of adverse reactions in elderly patients, especially those with compromised renal function. Therefore, it is recommended to use the lowest effective dose of famotidine for oral suspension in geriatric patients. Additionally, regular monitoring of renal function is advised to mitigate potential risks associated with its use in this demographic.

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/day for the treatment of erosive esophagitis.

The estimated background risk for major birth defects and miscarriage in the indicated population is unknown. 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 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/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 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 crucial, and supportive therapy should be initiated as needed to address any symptoms that may arise.

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 the treatment of famotidine overdosage. Therefore, healthcare professionals should exercise caution and consider the overall clinical context when determining the appropriateness of this intervention.

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/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 of 80 mg/day), there were no observed 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 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 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 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 dry powder is supplied in a USP tight, light-resistant container. It should be stored at a temperature of 25°C (77°F), with permissible excursions between 15° to 30°C (59° to 86°F). Proper storage conditions are essential to maintain the integrity of the product.

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 Micro Labs Limited. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)