Famotidine

Description

The active ingredient in famotidine for oral suspension USP is a histamine-2 (H2) receptor antagonist. Famotidine is chemically described as N'-(aminosulfonyl)-3-[[[2-(diaminomethylene)amino-4-thiazolyl]methyl]thio]propanimidamide. Its empirical formula is C8H15N7O2S3, and it has a molecular weight of 337.45. Each 5 mL of famotidine for oral suspension USP contains 40 mg of famotidine. Inactive ingredients include monohydrate citric acid, powdered cellulose, sucrose, xanthan gum, and banana, cherry, and peppermint wash flavor. Preservatives added are methylparaben sodium, propylparaben sodium, and sodium benzoate. Famotidine 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, very slightly soluble in water, and practically insoluble in chloroform, ether, and ethyl acetate.

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, such as 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 based on 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.

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 patients 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.

Serious hypersensitivity reactions, including anaphylaxis, have been reported in patients with a history of serious hypersensitivity to famotidine or other H2 receptor antagonists.

In cases of overdose, 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

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

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. This use is supported by adequate and well-controlled studies in adults, along with pharmacokinetic and pharmacodynamic data specific to this pediatric age group.

For pediatric patients less than 1 year of age, famotidine oral suspension has demonstrated safety and effectiveness for the treatment of GERD. This indication is also supported by evidence from well-controlled studies in adults and additional data in infants from birth to less than 1 year.

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. Furthermore, a safe and effective dosage has not been determined for pediatric patients with renal impairment.

Geriatric Use

In clinical studies involving famotidine, approximately 10% of the 1,442 treated patients were aged 65 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, as postmarketing experience has indicated that central nervous system (CNS) adverse reactions have been reported in this population, regardless of renal function status.

Given that famotidine is substantially excreted by the kidneys, the risk of adverse reactions may be heightened 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 treatment in this demographic.

Pregnancy

Available data regarding the use of H2-receptor antagonists, including famotidine, in pregnant patients 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, 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 per day, based on body surface area) or higher.

It is important to emphasize that there are 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 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

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, famotidine was administered at oral doses of up to 2000 mg/kg/day, which corresponds to approximately 243 and 122 times the recommended human dose of 80 mg per day for the treatment of erosive esophagitis. The results indicated no evidence of carcinogenic potential for famotidine in either species.

In terms of mutagenicity, famotidine was assessed using the microbial mutagen test (Ames test) with Salmonella typhimurium and Escherichia coli, both with and without rat liver enzyme activation, at concentrations up to 10,000 mcg/plate. The findings were negative for mutagenic effects. Additionally, in vivo studies conducted in mice, including a micronucleus test and a chromosomal aberration test, also showed no evidence of mutagenicity.

Fertility and reproductive performance were evaluated in studies involving rats administered oral doses of up to 2000 mg/kg/day, which is approximately 243 times the recommended human dose. The results demonstrated that famotidine did not adversely affect fertility or reproductive performance in these animals.

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 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 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 made aware that Famotidine for oral suspension can be taken with or without food, providing flexibility in its administration. They should also be informed that the medication may be given alongside antacids, if necessary.

Storage and Handling

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

The constituted suspension should be discarded after 30 days if not used. For optimal preservation, it should be dispensed in a USP tight, light-resistant container to safeguard against environmental factors.

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 Lupin Pharmaceuticals, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)