Famotidine

Description

The active ingredient in famotidine is a histamine H2-receptor antagonist. Famotidine is chemically defined as N'-(aminosulfonyl)-3-[[[2-(diamino-methylene)amino-4-thiazolyl]methyl]thio]propanimidamide, with an empirical formula of C8H15N7O2S3 and a molecular weight of 337.45. Each Famotidine tablet for oral administration contains either 20 mg or 40 mg of famotidine. The inactive ingredients in Famotidine tablets include hydroxypropyl cellulose, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, pregelatinized starch (modified corn starch), sodium starch glycolate, talc, titanium dioxide, and triacetin. 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.

Uses and Indications

Famotidine tablets are indicated for the treatment of active duodenal ulcer (DU) and active gastric ulcer (GU) in adult and pediatric patients weighing 40 kg and above. This drug is also indicated for the management of symptomatic non-erosive gastroesophageal reflux disease (GERD) and for the treatment of erosive esophagitis due to GERD, as diagnosed by biopsy. Additionally, famotidine is indicated for the treatment of pathological hypersecretory conditions, including Zollinger-Ellison Syndrome and multiple endocrine neoplasias. Furthermore, it is indicated for the reduction of the risk of duodenal ulcer recurrence in the specified patient population.

There are no teratogenic or non-teratogenic effects noted in the available data.

Dosage and Administration

Famotidine is indicated for use in adult and pediatric patients weighing 40 kg and greater with normal renal function. The recommended dosages are 20 mg and 40 mg tablets. Famotidine is not recommended for pediatric patients weighing less than 40 kg.

For patients with moderate to severe renal impairment, defined as a creatinine clearance of less than 60 mL/min, dosage adjustments are necessary. It is advised to use the lowest effective dose, and in some cases, switching to alternative formulations of famotidine, such as oral suspension or lower dose tablets, may be required.

Famotidine should be administered once daily before bedtime or twice daily, with doses taken in the morning and before bedtime, as clinically indicated. The tablets can be taken with or without food and may be administered concurrently with antacids.

Contraindications

Famotidine is contraindicated in patients with a history of serious hypersensitivity reactions, including anaphylaxis, to famotidine or other histamine-2 (H2) receptor antagonists. Due to the potential for severe allergic reactions, use in these patients is not recommended.

Warnings and Precautions

Central nervous system (CNS) adverse reactions have been observed in patients treated with Famotidine, particularly among elderly individuals and those with moderate to severe renal impairment. These reactions may include confusion, delirium, hallucinations, disorientation, agitation, seizures, and lethargy. Due to the increased blood levels of Famotidine in patients with renal impairment, it is imperative to adjust the dosage accordingly to mitigate these risks.

In adult patients, a symptomatic response to Famotidine therapy does not rule out the possibility of gastric malignancy. Therefore, healthcare professionals should consider further evaluation for gastric malignancy in adults who exhibit a suboptimal response to treatment or experience an early symptomatic relapse following the completion of Famotidine therapy.

Monitoring renal function is essential in patients receiving Famotidine, particularly in those with known renal impairment, to ensure appropriate dosage adjustments and to minimize the risk of CNS adverse effects.

Side Effects

Adverse reactions associated with famotidine have been observed in both clinical trials and postmarketing experiences.

In clinical trials, the following adverse reactions occurred in 1% or more of patients treated with famotidine: headache, dizziness, and constipation. Other adverse reactions reported in less than 1% of patients included a range of symptoms across various systems. Notably, body as a whole reactions included fever, asthenia, and fatigue. Cardiovascular reactions comprised palpitations, while gastrointestinal issues included elevated liver enzymes, vomiting, nausea, abdominal discomfort, anorexia, and dry mouth. Hematologic reactions such as thrombocytopenia were also noted. Hypersensitivity reactions included orbital edema, rash, conjunctival injection, and bronchospasm. Musculoskeletal reactions involved musculoskeletal pain and arthralgia. Central nervous system and psychiatric reactions included seizures, hallucinations, depression, anxiety, decreased libido, insomnia, and somnolence. Skin reactions reported were pruritus, dry skin, and flushing, while special senses reactions included tinnitus and taste disorder. Additionally, impotence was reported as an adverse reaction.

Postmarketing experience has revealed further adverse reactions, including serious cardiovascular events such as arrhythmia, AV block, and prolonged QT interval. Gastrointestinal adverse reactions included cholestatic jaundice and hepatitis. Hematologic reactions reported were agranulocytosis, pancytopenia, and leukopenia. Hypersensitivity reactions in the postmarketing setting included anaphylaxis, angioedema, facial edema, and urticaria. Musculoskeletal adverse reactions included rhabdomyolysis and muscle cramps. Central nervous system and psychiatric reactions such as confusion, agitation, and paresthesia were also reported. Respiratory adverse reactions included interstitial pneumonia, and skin reactions included severe conditions such as toxic epidermal necrolysis and Stevens-Johnson syndrome.

Particular attention should be given to central nervous system adverse reactions, which have been reported in elderly patients and those with moderate to severe renal impairment. These reactions may include confusion, delirium, hallucinations, disorientation, agitation, seizures, and lethargy.

In cases of overdosage, the types of adverse reactions observed are similar to those encountered with the use of recommended dosages.

Drug Interactions

Famotidine may interact with several medications, primarily through its effects on gastric acidity and its role as a weak CYP1A2 inhibitor.

Pharmacodynamic Interactions Famotidine can reduce the absorption of certain drugs by decreasing intragastric acidity. This reduction in acidity may lead to diminished efficacy of concomitantly administered medications. It is advised to avoid the concurrent use of famotidine with dasatinib, delavirdine mesylate, cefditoren, and fosamprenavir due to this interaction.

Pharmacokinetic Interactions As a weak inhibitor of the CYP1A2 enzyme, famotidine may significantly increase blood concentrations of tizanidine, which is a substrate of CYP1A2. Concomitant use of these two medications is not recommended. If the combination is deemed necessary, it is essential to monitor the patient for signs of hypotension, bradycardia, or excessive drowsiness, and to consider dosage adjustments as appropriate.

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 and gastric ulcers, as well as gastroesophageal reflux disease (GERD), which encompasses symptomatic non-erosive GERD and erosive esophagitis diagnosed by endoscopy.

The recommended dosage of Famotidine in 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.

Famotidine 20 mg and 40 mg tablets are not recommended for pediatric patients weighing less than 40 kg, as these tablet strengths exceed the recommended dose for this weight group. For pediatric patients under 40 kg, alternative formulations of Famotidine, such as oral suspension or lower dose tablets, should be considered.

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, it is important to note that in postmarketing experience, central nervous system (CNS) adverse reactions have been reported among 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 geriatric patients, particularly those with impaired renal function. Therefore, it is recommended that healthcare providers use the lowest effective dose of Famotidine for elderly patients and closely monitor their 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 the medication and any potential adverse effects on the breastfed child from famotidine or from the underlying maternal condition.

Renal Impairment

Patients with renal impairment may experience increased blood levels of famotidine compared to those with normal renal function. Consequently, dosage adjustments are recommended for this population to mitigate the risk of adverse effects.

Central nervous system (CNS) adverse reactions, such as confusion, delirium, hallucinations, disorientation, agitation, seizures, and lethargy, have been observed particularly in elderly patients and those with moderate to severe renal impairment. Healthcare professionals should closely monitor these patients for any signs of CNS effects during treatment.

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 overdosage with Famotidine, 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 symptoms typically linked to the drug's pharmacological profile.

Management of Famotidine 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. This may involve the use of activated charcoal or other appropriate measures, depending on the clinical scenario.

Additionally, due to Famotidine's low binding affinity to plasma proteins, it is noteworthy that the drug can be eliminated through hemodialysis. However, it is important to acknowledge 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 care measures.

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, respectively, based on body surface area compared to 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, indicating no mutagenic effect. In vivo studies in mice, including a micronucleus test and a chromosomal aberration test, similarly showed no 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

No specific postmarketing experience details have been reported. As such, there are no additional adverse events or rare case reports to summarize at this time.

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 acceptable for patients to take Famotidine tablets with or without food, and they may also be taken concurrently with antacids if needed.

Storage and Handling

The product is supplied in a USP tight, light-resistant container to ensure its integrity and efficacy. 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. Proper storage conditions are essential to maintain the quality of the product throughout its shelf life.

Additional Clinical Information

Elderly patients and those with moderate to severe renal impairment should be counseled on the potential risk of central nervous system (CNS) adverse reactions associated with the medication, which may include confusion, delirium, hallucinations, disorientation, agitation, seizures, and lethargy. It is important for these patients to report any such symptoms to their healthcare provider immediately. Additionally, patients with moderate to severe renal impairment should be made aware of the risk of QT interval prolongation and instructed to report any new cardiac symptoms, such as palpitations, fainting, or dizziness, to a healthcare provider without delay.

Patients should be advised on the proper administration of Famotidine tablets, which can be taken once daily before bedtime or twice daily (in the morning and before bedtime) as directed. The tablets may be taken with or without food and can be administered alongside antacids.

FDA Insert (PDF)

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

View full prescribing information (PDF)