Famotidine

Description

Famotidine for Oral Suspension USP contains famotidine, a histamine-2 (H2) receptor antagonist, with the chemical structure N'-(aminosulfonyl)-3-[[[2-(diaminomethylene)amino-4-thiazolyl]methyl]thio] propanimidamide. The empirical formula is C8H15N7O2S3, and the molecular weight is 337.45 g/mol.

Each 5 mL dose of the suspension, when prepared as directed, provides 40 mg of famotidine along with inactive ingredients including citric acid anhydrous, microcrystalline cellulose, carboxymethylcellulose sodium, sucrose, xanthan gum, and flavoring agents (banana and cherry). Preservatives included 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 active duodenal ulcer (DU) and active gastric ulcer (GU) in adults. It is also indicated for the management of symptomatic nonerosive gastroesophageal reflux disease (GERD) and erosive esophagitis due to GERD, as diagnosed by biopsy, in adults. Additionally, this medication is indicated for the treatment of pathological hypersecretory conditions, such as Zollinger-Ellison syndrome and multiple endocrine neoplasias, in adults. Famotidine is effective in reducing the risk of DU recurrence in adults.

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

There are no teratogenic or nonteratogenic effects associated with the use of famotidine.

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 is determined by age and indication. For peptic ulcer disease in children aged 1 year to less than 17 years, 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. 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 based on the potential for severe allergic reactions in susceptible individuals.

Warnings and Precautions

Elderly patients and those with renal impairment are at an increased risk when using this medication. It is essential to reduce the dosage in these populations to mitigate potential adverse effects (2.2, 5.1, 8.5, 8.6).

Healthcare professionals should be aware that the absence of gastrointestinal symptoms does not rule out the possibility of gastric malignancy. A thorough evaluation is recommended prior to initiating therapy to ensure patient safety (5.2).

No additional general precautions or laboratory tests have been specified in the provided information.

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 guidelines.

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. This interaction can result in adverse effects such as hypotension, bradycardia, or excessive drowsiness. Therefore, it is recommended to avoid concomitant use of tizanidine with other drugs that may affect its metabolism, if possible. Monitoring of blood pressure and heart rate is advised in patients who require the use of both medications.

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 that healthcare providers use the lowest effective dose of famotidine for oral suspension in elderly patients and 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 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 limited data available on the presence of famotidine in human breast milk. Current evidence indicates that there were no effects observed on breastfed infants. However, there are no data regarding the effects of famotidine on milk production in lactating mothers.

In animal studies, famotidine has been detected in the milk of lactating rats. Notably, transient growth depression was observed in young rats suckling from mothers treated with maternotoxic doses of famotidine, which were at least 600 times the usual human dose.

When considering the use of famotidine in lactating mothers, the developmental and health benefits of breastfeeding should be weighed against the mother's clinical need for famotidine and any potential adverse effects on the breastfed child from either the medication or the underlying maternal condition.

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 populations to mitigate potential risks associated with reduced kidney function. 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 Treatment for famotidine overdosage should be primarily symptomatic and supportive. 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 to implement supportive therapy as necessary.

Elimination Considerations Due to famotidine's low binding affinity to plasma proteins, hemodialysis may facilitate its elimination from the body. However, it is important to note that there is limited clinical experience regarding the efficacy of hemodialysis in the management of famotidine overdosage. Therefore, healthcare professionals should exercise caution and consider individual patient circumstances when determining the appropriateness of this intervention.

Nonclinical Toxicology

Carcinogenic potential of famotidine was assessed 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 2000 mg/kg/day (approximately 243 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 for famotidine.

Famotidine was evaluated for mutagenicity 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. The results were negative for mutagenic effects. Additionally, in vivo studies in mice, including a micronucleus test and a chromosomal aberration test, did not reveal any evidence of mutagenicity.

In studies involving rats administered oral doses of up to 2000 mg/kg/day (approximately 243 times the recommended human dose), fertility and reproductive performance were not adversely affected.

Postmarketing Experience

Postmarketing experience has identified several adverse reactions reported voluntarily or through surveillance programs. These include confusion, delirium, hallucinations, disorientation, agitation, seizures, and lethargy. Additionally, reports of QT interval prolongation have been noted in the postmarketing experience.

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, 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, providing flexibility in its administration. They should also be made aware that Famotidine may be given concurrently with antacids, if needed.

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 integrity.

The constituted suspension should be discarded after 30 days if not used. For optimal storage conditions, the product must be dispensed in a USP tight, light-resistant container to ensure its stability and efficacy.

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

View full prescribing information (PDF)