Famotidine

Description

Famotidine for oral suspension contains the active ingredient famotidine, a histamine-2 (H2) receptor antagonist. The chemical structure of famotidine is represented by the name N'-(aminosulfonyl)-3-[[[2-(diaminomethylene)amino-4-thiazolyl]methyl]thio]propanimidamide. Its empirical formula is C8H15N7O2S3, with a molecular weight of 337.43 g/mol.

Famotidine appears as a white to pale yellow crystalline compound. It is freely soluble in glacial acetic acid, slightly soluble in methanol, very slightly soluble in water, and practically insoluble in ethanol. Each 5 mL of the prepared oral suspension contains 40 mg of famotidine along with inactive ingredients, which include citric acid NF, confectioner's sugar NF, natural and artificial cherry flavor, natural and artificial peppermint flavor, natural banana flavor, sodium hydroxide NF, and xanthan gum NF. Preservatives included in the formulation are methylparaben, propylparaben, and sodium hydroxide.

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 the following:

• 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 receiving treatment. Common adverse reactions include headache, dizziness, constipation, and diarrhea.

Serious adverse reactions may occur, particularly in elderly patients and those with renal impairment, who 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. In the context of CNS effects, postmarketing experience has indicated that such reactions have been reported in elderly patients, both with and without renal impairment, who are receiving famotidine.

It is important to note that the absence of gastrointestinal (GI) symptoms does not rule out the possibility of gastric malignancy; therefore, evaluation for GI malignancy should be conducted prior to initiating therapy. Additionally, patients with a history of serious hypersensitivity reactions, such as anaphylaxis, to famotidine or other H2 receptor antagonists should be closely monitored.

In cases of overdosage, the types of adverse reactions observed are similar to those encountered with the use of recommended dosages. Given that famotidine is substantially excreted by the kidneys, the risk of adverse reactions may be heightened in elderly patients, particularly those with impaired renal function.

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. Healthcare professionals are advised 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 that affect its metabolism. This interaction can lead to adverse effects such as hypotension, bradycardia, or excessive drowsiness. It is recommended to avoid concomitant use of tizanidine with such drugs whenever possible to mitigate these risks. Monitoring of blood pressure and heart rate is advised if co-administration cannot be avoided.

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 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. 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.

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. Studies indicate that famotidine is present in the milk of lactating rats; however, there were no observed effects on breastfed infants. Currently, there are no data regarding the effects of famotidine on milk production in lactating mothers.

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. It is important to note that 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.

Renal Impairment

Patients with moderate and severe renal impairment may experience CNS adverse reactions and prolonged QT intervals. The clearance of famotidine is significantly reduced in these patients compared to those with normal renal function. For adults with mild renal impairment, defined as a creatinine clearance of greater than or equal to 60 mL/minute, no dosage adjustment is necessary. However, a dosage reduction is recommended for adults with moderate or severe renal impairment, where creatinine clearance is less than 60 mL/minute. Currently, data are insufficient to establish a safe and effective dosage for pediatric patients with renal impairment.

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 (refer to the Adverse Reactions section for further details).

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 advised, and supportive therapy should be initiated as necessary 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 as a treatment modality for famotidine overdosage. Therefore, healthcare professionals should consider this when determining the appropriate management strategy for affected patients.

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 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 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 show 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 of 80 mg per day), fertility and reproductive performance were not adversely affected.

Postmarketing Experience

Postmarketing experience has revealed reports of various adverse reactions, including confusion, delirium, hallucinations, disorientation, agitation, seizures, and lethargy. Additionally, there have been reports of QT interval prolongation. These events were reported voluntarily or identified through surveillance programs.

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, which should be taken once daily before bedtime or twice daily, in the morning and before bedtime, as recommended. It is also essential to inform them that famotidine can be taken with or without food, providing flexibility in its administration.

Furthermore, patients and caregivers should be made aware that famotidine may be given concurrently with antacids, allowing for effective management of their condition.

Storage and Handling

Famotidine for oral suspension is supplied as a dry powder that must be constituted prior to use. It should be stored at a controlled room temperature of 25°C (77°F), with permissible excursions between 15° to 30°C (59° to 86°F) as defined by USP guidelines. It is essential to protect the product from freezing to maintain its efficacy.

Once constituted, the suspension must be discarded after 30 days if not used. For optimal preservation, famotidine should be dispensed in a USP tight, light-resistant container to safeguard against environmental factors that may compromise the product's integrity.

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 Akorn. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)