Famotidine

Uses and Indications

Famotidine is indicated for the treatment of active duodenal ulcer (DU) in adult and pediatric patients weighing 40 kg and greater. It is also indicated for the management of active gastric ulcer in the same patient population. Additionally, Famotidine is used for the treatment of symptomatic nonerosive gastroesophageal reflux disease (GERD) and erosive esophagitis due to GERD, both diagnosed by biopsy, in adult and pediatric patients weighing 40 kg and greater.

In adults, Famotidine is further indicated for the treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome and multiple endocrine neoplasias. It is also indicated for the reduction of the risk of duodenal ulcer recurrence.

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 dosages are as follows:

For active duodenal ulcers (DU), the dosage is 40 mg administered once daily or 20 mg administered twice daily. In the case of active gastric ulcers, a dosage of 40 mg once daily is advised. For gastroesophageal reflux disease (GERD), the recommended dosage is 20 mg twice daily. Patients with erosive esophagitis may receive either 20 mg twice daily or 40 mg twice daily, depending on clinical judgment. For pathological hypersecretory conditions, the initial dosage is 20 mg every 6 hours, with adjustments made according to patient needs; the maximum dosage should not exceed 160 mg every 6 hours. For the risk reduction of duodenal ulcer recurrence, a dosage of 20 mg once daily is recommended.

Administration 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, as per the patient's preference.

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 should be conducted 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 using the medication. Common adverse reactions reported include headache, dizziness, constipation, and diarrhea.

Serious central nervous system (CNS) adverse reactions have also been observed. These include confusion, delirium, hallucinations, disorientation, agitation, seizures, and lethargy. It is important to note that elderly patients and those with renal impairment are at an increased risk for these CNS adverse reactions. Additionally, there is a risk of QT interval prolongation in patients with moderate and severe renal impairment.

A history of serious hypersensitivity reactions, including anaphylaxis to famotidine or other H2 receptor antagonists, has been documented. Monitoring for these adverse reactions is recommended, particularly in susceptible populations.

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 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 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 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 in geriatric patients and to 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. 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. 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 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 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 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 similar to those seen at therapeutic levels.

Management of Famotidine overdosage should be primarily symptomatic and supportive. It is essential to remove any unabsorbed material from the gastrointestinal tract promptly. This may involve measures such as gastric lavage or the administration of activated charcoal, depending on the timing and circumstances of the overdose.

Continuous monitoring of the patient is crucial to assess for any potential complications and to provide appropriate supportive therapy as needed. Given 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 specifically for the treatment of Famotidine overdosage. Therefore, healthcare providers should consider this option cautiously and in conjunction with other supportive 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. Additionally, in in vivo studies in mice, including a micronucleus test and a chromosomal aberration test, no evidence of a mutagenic effect was observed.

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 postmarketing experience details are available in the provided data.

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 to their healthcare provider immediately.

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, in the morning and before bedtime. It is acceptable for patients to take Famotidine tablets with or without food. Furthermore, patients should be informed that Famotidine tablets can 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°C to 30°C (59°F to 86°F) in accordance with USP controlled room temperature guidelines. Proper storage conditions are essential to maintain the product's efficacy and safety.

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, which may include confusion, delirium, hallucinations, disorientation, agitation, seizures, and lethargy. It is important for these patients to report any such symptoms to a healthcare provider immediately. Additionally, patients with moderate and severe renal impairment should be made aware of the risk of QT interval prolongation and should report any new cardiac symptoms, such as palpitations, fainting, or dizziness, to their healthcare provider without delay.

Patients are advised to take Famotidine tablets once daily before bedtime or twice daily as directed, in the morning and before bedtime. The tablets can be taken with or without food and may be administered alongside antacids.

FDA Insert (PDF)

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

View full prescribing information (PDF)