Famotidine

Description

The active ingredient in Famotidine Tablets, USP is famotidine, a histamine-2 (H2) receptor antagonist. Famotidine is chemically designated as 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 appears as a white to pale yellowish white crystalline powder, which is freely soluble in glacial acetic acid, slightly soluble in methanol, very slightly soluble in water, and practically insoluble in ethanol. Each tablet for oral administration contains either 20 mg or 40 mg of famotidine USP, along with inactive ingredients including colloidal silicon dioxide, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, pregelatinized starch, sodium starch glycolate, talc, and titanium dioxide. The 20 mg tablets also contain ferric oxide red and ferric oxide yellow. Famotidine Tablets, USP meet the requirements of USP Dissolution Test 2.

Uses and Indications

Famotidine is indicated for the treatment of active duodenal ulcers (DU) and active gastric ulcers. It is also indicated for the management of symptomatic nonerosive gastroesophageal reflux disease (GERD) and for the treatment of erosive esophagitis due to GERD, as diagnosed by biopsy.

In adult patients, famotidine is indicated for the treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome and multiple endocrine neoplasias. Additionally, it is indicated for the reduction of the risk of recurrence of duodenal ulcers.

There are no teratogenic or nonteratogenic effects associated with famotidine.

Dosage and Administration

For adult and pediatric patients weighing 40 kg and greater, the recommended dosage for the treatment of active duodenal ulcers (DU) is 40 mg administered once daily, or alternatively, 20 mg given twice daily. For the management of active gastric ulcers, a dosage of 40 mg once daily is advised. In cases of gastroesophageal reflux disease (GERD), the recommended dosage is 20 mg twice daily. For erosive esophagitis, healthcare professionals may prescribe either 20 mg twice daily or 40 mg twice daily, depending on the severity of the condition.

In adult patients with pathological hypersecretory conditions, the initial dosage is 20 mg every 6 hours, with adjustments made according to individual patient needs. The maximum allowable dosage in this scenario is 160 mg every 6 hours. For the risk reduction of duodenal ulcer recurrence, a dosage of 20 mg once daily is recommended.

Administration of the medication should occur once daily before bedtime or twice daily, with doses taken in the morning and before bedtime. The medication may be taken with or without food, allowing for flexibility in patient adherence.

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 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 exclude any underlying conditions that may not present with overt symptoms.

No additional general precautions or laboratory tests have been specified in the provided information. Healthcare professionals are advised to remain vigilant and consider individual patient factors when prescribing this therapy.

Side Effects

Patients may experience a range of adverse reactions while receiving treatment. Common adverse reactions, occurring in 1% or more of participants in clinical trials, include headache, dizziness, and constipation.

In addition to these common reactions, other adverse reactions have been reported in less than 1% of patients. These include:

• Body as a Whole: Fever, asthenia, fatigue

• Cardiovascular: Palpitations

• Gastrointestinal: Elevated liver enzymes, vomiting, nausea, abdominal discomfort, anorexia, dry mouth

• Hematologic: Thrombocytopenia

• Hypersensitivity: Orbital edema, rash, conjunctival injection, bronchospasm

• Musculoskeletal: Musculoskeletal pain, arthralgia

• Nervous System/Psychiatric: Seizure, hallucinations, depression, anxiety, decreased libido, insomnia, somnolence

• Skin: Pruritus, dry skin, flushing

• Special Senses: Tinnitus, taste disorder

• Other: Impotence

Postmarketing experience has revealed additional serious adverse reactions. Cardiovascular events such as arrhythmia, AV block, and prolonged QT interval have been reported. Gastrointestinal issues including cholestatic jaundice and hepatitis, as well as hematologic conditions such as agranulocytosis, pancytopenia, and leukopenia, have also been noted. Hypersensitivity reactions can be severe, with cases of anaphylaxis, angioedema, facial edema, and urticaria documented. Musculoskeletal adverse reactions include rhabdomyolysis and muscle cramps. Neurological effects such as confusion, agitation, and paresthesia have been observed, along with respiratory complications like interstitial pneumonia. Skin reactions can be serious, including toxic epidermal necrolysis and Stevens-Johnson syndrome.

It is important to note that elderly patients and those with renal impairment may be at an increased risk for central nervous system adverse reactions, necessitating dosage adjustments. Additionally, the absence of gastrointestinal symptoms does not rule out the possibility of gastric malignancy, and evaluation is recommended prior to initiating therapy. A history of serious hypersensitivity reactions, such as anaphylaxis to famotidine or other H2 receptor antagonists, should be considered when prescribing this treatment.

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 alongside other medications 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 such drugs whenever possible. 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

The safety and effectiveness of famotidine have been established in pediatric patients for the treatment of peptic ulcer disease, including duodenal ulcers and gastric ulcers, as well as for gastroesophageal reflux disease (GERD), which encompasses symptomatic nonerosive GERD and erosive esophagitis diagnosed by endoscopy. The recommended dosage of famotidine in these pediatric patients is supported by evidence from adequate and well-controlled studies conducted in adults, along with published pharmacokinetic and pharmacodynamic data specific to pediatric populations.

However, the safety and effectiveness of famotidine for the treatment of pathological hypersecretory conditions and for the reduction of the risk of duodenal ulcer recurrence in pediatric patients have not been established. Additionally, famotidine 20 mg and 40 mg tablets are not recommended for use in pediatric patients weighing less than 40 kg, as these tablet strengths exceed the recommended dose for this weight group. For pediatric patients weighing less than 40 kg, alternative formulations of famotidine, such as oral suspension or lower dose tablets, should be considered.

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, 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 in geriatric patients and to closely monitor renal function throughout the treatment period. This approach will help mitigate potential risks and ensure the safe use of famotidine in the elderly population.

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 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 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 that 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 the medication and any potential adverse effects on the breastfed child from famotidine or from the underlying maternal condition.

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 patients with mild renal impairment, defined as a creatinine clearance of greater than or equal to 60 mL/minute, no dosage adjustment is necessary. However, for adult and pediatric patients weighing 40 kg or more with moderate or severe renal impairment (creatinine clearance less than 60 mL/minute), a dosage reduction is recommended. Monitoring for adverse effects is advised in this population due to the potential for increased sensitivity to the medication.

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 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 promptly. This may involve the use of activated charcoal or other appropriate measures, depending on the timing of the overdose and the clinical scenario. Continuous monitoring of the patient is crucial to assess for any evolving symptoms and to provide necessary supportive therapy.

Due to famotidine's low binding affinity to plasma proteins, it is noteworthy that the drug can be eliminated through hemodialysis. However, 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 weigh the potential benefits against the available evidence.

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 2,000 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 also 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 2,000 mg/kg/day (approximately 243 times the recommended human dose), fertility and reproductive performance were not adversely affected.

Postmarketing Experience

During post-approval use of famotidine, various adverse reactions have been reported voluntarily from a population of uncertain size. Due to the nature of these reports, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiovascular events include arrhythmia, atrioventricular (AV) block, and prolonged QT interval. Gastrointestinal reactions consist of cholestatic jaundice and hepatitis. Hematologic adverse events reported include agranulocytosis, pancytopenia, and leukopenia.

Hypersensitivity reactions have been noted, such as anaphylaxis, angioedema, facial edema, and urticaria. Musculoskeletal issues include rhabdomyolysis and muscle cramps. Nervous system and psychiatric effects reported are confusion, agitation, and paresthesia. Additionally, respiratory events such as interstitial pneumonia have been documented.

Skin reactions include severe conditions such as toxic epidermal necrolysis and Stevens-Johnson syndrome.

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 use of famotidine. 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 should be instructed on the proper administration of famotidine tablets, which may be taken once daily before bedtime or twice daily, as recommended by their healthcare provider. It is also important to inform patients that famotidine tablets can be taken with or without food and may be administered alongside antacids if needed.

Storage and Handling

The product is supplied in a USP tight, light-resistant container to ensure its integrity and stability. It should be stored at a temperature of 25°C (77°F), with permissible excursions between 15° to 30°C (59° to 86°F) in accordance with USP Controlled Room Temperature guidelines. Proper storage conditions are essential to maintain the quality and efficacy of the product.

Additional Clinical Information

Postmarketing experience has revealed several adverse events associated with the use of the medication. Clinicians should be aware of potential cardiovascular issues, including arrhythmia, AV block, and prolonged QT interval. Gastrointestinal complications may manifest as cholestatic jaundice and hepatitis. Hematologic concerns include agranulocytosis, pancytopenia, and leukopenia.

Additionally, hypersensitivity reactions such as anaphylaxis, angioedema, facial edema, and urticaria have been reported. Musculoskeletal effects may involve rhabdomyolysis and muscle cramps. Neurologically, patients may experience confusion, agitation, and paresthesia. Respiratory complications, specifically interstitial pneumonia, and severe skin reactions like toxic epidermal necrolysis and Stevens-Johnson syndrome have also been documented.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Famotidine as submitted by Westminster Pharmaceuticals, LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)