Famotidine

Description

The active ingredient in famotidine for oral suspension, USP is a H2-receptor antagonist. Famotidine is N'-(aminosulfonyl)-3-[[[2-(diaminomethylene)amino-4-thiazolyl]methyl]thio]propanimidamide, with a molecular formula of C8H15N7O2S3 and a molecular weight of 337.43 g/mol. 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. 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 and 2 mg of sodium. Inactive ingredients include banana flavor (which contains propylene glycol), cherry flavor (which contains acetic acid, propylene glycol, and triethyl citrate), citric acid monohydrate, peppermint flavor (which contains ethyl alcohol and water), powdered cellulose, sucrose, and xanthan gum. Preservatives included are methylparaben sodium 0.1%, propylparaben sodium 0.02%, and sodium benzoate 0.1%.

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 duodenal ulcer 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 dosage is 40 mg once daily. For symptomatic nonerosive gastroesophageal reflux disease (GERD), the recommended 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. 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 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 risk for similar reactions.

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

Concomitant use of tizanidine, a substrate of CYP1A2, with other medications that affect CYP1A2 may lead to significant increases in blood concentrations of tizanidine. This elevation can result in adverse effects such as hypotension, bradycardia, or excessive drowsiness. Therefore, it is advisable to avoid the concomitant use of tizanidine with such drugs whenever possible.

No additional drug interactions or laboratory test interactions have been identified.

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 for famotidine oral suspension in the treatment of peptic ulcer disease and gastroesophageal reflux disease (GERD), with or without esophagitis and ulcerations. In contrast, the safety and effectiveness of famotidine for oral suspension in treating peptic ulcer disease in pediatric patients less than 1 year of age have not been established.

For pediatric patients from birth to less than 1 year of age, famotidine oral suspension has demonstrated safety and effectiveness specifically for the treatment of GERD. 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 any pediatric population.

Additionally, a safe and effective dosage for famotidine has not been established in pediatric patients with renal impairment.

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 significant differences in safety or effectiveness between elderly patients and their younger counterparts. However, postmarketing experience has indicated that central nervous system (CNS) adverse reactions may occur in geriatric patients, both with and without renal impairment, who are receiving famotidine.

Given that famotidine is primarily excreted by the kidneys, elderly patients, particularly those with compromised renal function, may be at an increased risk for adverse reactions. Therefore, it is recommended that healthcare providers prescribe the lowest effective dose of famotidine for oral suspension in this population. Additionally, careful monitoring of renal function is advised to mitigate potential risks associated with treatment in geriatric patients.

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; 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/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 are no known data on excretion in breast milk or effects on breastfed infants. Healthcare professionals should consider the absence 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.

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 associated with the administration of recommended dosages. Healthcare professionals should be vigilant for these reactions, which may include a range of gastrointestinal and central nervous system symptoms.

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 timely intervention should symptoms arise.

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/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 are available in the extracted data. As such, there are no additional adverse events or rare 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 the medication. They should be advised to report any new cardiac symptoms, including palpitations, fainting, or feelings of dizziness or lightheadedness, to their healthcare provider without delay.

Patients should also be instructed on the proper administration of famotidine for oral suspension. They should use an oral dosing syringe to accurately measure the prescribed amount of medication. Healthcare providers can inform patients that oral dosing syringes are available at the pharmacy.

Finally, patients should be advised to shake the bottle of reconstituted famotidine for oral suspension vigorously for 5 seconds before each use to ensure proper mixing of the medication.

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 range of 20° to 25°C (68° to 77°F), with permissible excursions between 15° to 30°C (59° to 86°F) as defined by USP Controlled Room Temperature guidelines.

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 Aurobindo Pharma Limited. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)