Famotidine

Description

Famotidine for oral suspension, USP is an H2-receptor antagonist. The active ingredient, famotidine, is chemically designated as 3-[2-(Diaminomethyleneamino)thiazol-4-ylmethylthio]-N'-Sulfamoylpropanimidamide, with a molecular formula of C8H15N7O2S3 and a molecular weight of 337.45. Famotidine appears as a white to yellowish-white crystalline powder or crystals, which is freely soluble in glacial acetic acid and dimethyl formamide, very slightly soluble in methanol, and practically insoluble in ethanol and ethyl acetate.

When prepared as directed, each 5 mL of famotidine for oral suspension, USP contains 40 mg of famotidine, USP, along with inactive ingredients including citric acid monohydrate, flavors (cherry, banana, and peppermint), microcrystalline cellulose, sucrose, and xanthan gum. Preservatives included in the formulation are sodium benzoate (0.38%), sodium methylparaben (0.38%), and sodium propylparaben (0.08%).

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.

No teratogenic or nonteratogenic effects have been reported.

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. For risk reduction of DU recurrence, the dosage is 20 mg once daily.

In pediatric patients, the recommended dosage for peptic ulcer disease in children aged 1 year to less than 17 years is a starting dosage of 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 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 of adverse effects; therefore, it is recommended that the dosage be reduced in these populations to ensure safety and efficacy.

It is important to note that the absence of gastrointestinal symptoms does not rule out the possibility of gastric malignancy. A thorough evaluation should be conducted prior to initiating therapy to rule out any underlying conditions that may not present with overt symptoms.

Healthcare professionals are advised to remain vigilant and consider these factors when prescribing treatment to ensure optimal patient outcomes.

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 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 outcomes of such medications closely when used in conjunction.

Tizanidine, a substrate of CYP1A2, may experience substantial increases in blood concentrations when co-administered with other agents that affect its metabolism. This interaction can lead to adverse effects such as hypotension, bradycardia, or excessive drowsiness. Therefore, it is recommended to avoid concomitant use of tizanidine with these agents whenever possible. If co-administration is necessary, careful monitoring of the patient’s response and potential side effects is warranted.

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

For pediatric patients less than 1 year of age, famotidine oral suspension has been shown to be safe and effective for the treatment of GERD. This indication is also supported by data from adequate and well-controlled studies in adults and additional supportive data in infants from birth to less than 1 year of age.

However, the safety and effectiveness of famotidine for the treatment of peptic ulcer disease in patients less than 1 year of age have not been established. Furthermore, 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. It is important to note that 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 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.

Famotidine is primarily excreted by the kidneys, which raises concerns regarding the potential for increased 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 the risk of adverse effects and ensure safe 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; 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 2,000 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.

It is important to note 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 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 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 recommended to assess their condition and to implement supportive therapy as needed.

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 consider this when determining the appropriate management strategy for affected patients.

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, conducted at oral doses of up to 2,000 mg/kg/day (approximately 243 and 122 times the recommended human dose of 80 mg/day for the treatment of erosive esophagitis, based on body surface area), no evidence of carcinogenic potential was observed.

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.

Regarding reproductive toxicity, studies involving rats administered oral doses of up to 2,000 mg/kg/day (approximately 243 times the recommended human dose of 80 mg/day, based on body surface area) indicated that fertility and reproductive performance were not adversely affected.

Postmarketing Experience

Postmarketing experience has revealed reports of various adverse reactions associated with the use of the product. These reactions include, but are not limited to, confusion, delirium, hallucinations, disorientation, agitation, seizures, and lethargy.

Patients are advised to report any symptoms of these adverse reactions immediately to a healthcare provider.

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 should be instructed on the proper administration of famotidione for oral suspension. They should use an oral dosing syringe to accurately measure the prescribed amount of medication, which can be obtained from the pharmacy. Prior to each use, patients or caregivers should shake the bottle of reconstituted famotidione vigorously for 5 to 10 seconds.

Patients should take the medication once daily before bedtime or twice daily, as recommended, either with or without food. It is also acceptable to administer famotidione with antacids.

Storage and Handling

Famotidine for oral suspension 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°C to 30°C (59°F 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 Novadoz Pharmaceuticals LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)