Pepcid

Description

The active ingredient in PEPCID 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 an empirical formula of C8H15N7O2S3 and a molecular weight of 337.43.

Each PEPCID tablet for oral administration contains either 20 mg or 40 mg of famotidine, along with inactive ingredients that 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

PEPCID is indicated for the treatment of active duodenal ulcer (DU) and active gastric ulcer in adult and pediatric patients weighing 40 kg and greater. 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 the same patient population.

In adults, PEPCID is additionally 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 DU recurrence.

There are no teratogenic or nonteratogenic effects associated with PEPCID.

Dosage and Administration

For adult and pediatric patients weighing 40 kg or 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 recommended. For gastroesophageal reflux disease (GERD), the dosage is 20 mg twice daily. For erosive esophagitis, the patient may receive either 20 mg twice daily or 40 mg twice daily.

In adults with pathological hypersecretory conditions, the initial dosage is 20 mg every 6 hours, with adjustments made according to the patient's 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 advised.

Administration should occur once daily before bedtime or twice daily, with the first dose in the morning and the second dose before bedtime. The medication may be taken 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.

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.

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.

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, 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. Healthcare professionals are advised to consult the full prescribing information for a comprehensive list of these interacting drugs.

When considering the use of tizanidine, which is a substrate of CYP1A2, there is a potential for substantial increases in blood concentrations. This elevation may result in adverse effects such as hypotension, bradycardia, or excessive drowsiness. Therefore, it is recommended to avoid concomitant use of tizanidine with other medications that may affect its metabolism, if possible. Monitoring of blood pressure and heart rate is advised in patients who require both medications.

Packaging & NDC

The table below lists all NDC Code configurations of Pepcid (famotidine), the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

The safety and effectiveness of PEPCID 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 nonerosive GERD and erosive esophagitis diagnosed by endoscopy. The recommended dosage of PEPCID 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 PEPCID 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, PEPCID 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 PEPCID, 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, postmarketing experience has indicated that central nervous system (CNS) adverse reactions have been reported in elderly patients, both with and without renal impairment, who received PEPCID.

Given that famotidine is primarily excreted by the kidneys, the risk of adverse reactions may be heightened in geriatric patients, particularly those with compromised renal function. Therefore, it is recommended that healthcare providers utilize the lowest effective dose of PEPCID 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 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 famotidine and any potential adverse effects on the breastfed child from famotidine or from 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 and to avoid complications.

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 PEPCID, the adverse reactions observed are consistent with those reported at recommended dosages, as detailed in the Adverse Reactions section (6.1).

Management of Overdosage In the event of an overdosage, the primary approach should be symptomatic and supportive. It is essential to remove any unabsorbed material from the gastrointestinal tract promptly. Continuous monitoring of the patient is crucial, and supportive therapy should be initiated as needed to address any symptoms that may arise.

Considerations for Hemodialysis Due to famotidine's low binding affinity to plasma proteins, it is eliminated through hemodialysis. However, there is limited clinical experience regarding the efficacy of hemodialysis as a treatment modality for PEPCID overdosage. Therefore, healthcare professionals should exercise caution and consider the individual patient's circumstances when determining the appropriateness of this intervention.

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 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 associated with famotidine.

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.

Fertility and reproductive performance were assessed 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). The results indicated that famotidine did not adversely affect fertility or reproductive performance in these animals.

Postmarketing Experience

Postmarketing experience has identified several adverse reactions reported voluntarily or through surveillance programs. These include confusion, delirium, hallucinations, disorientation, agitation, seizures, and lethargy. Additionally, reports of QT interval prolongation have been noted in the postmarketing experience.

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 PEPCID. 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 PEPCID, which can be taken once daily before bedtime or twice daily, as recommended, in the morning and before bedtime. It is also important to inform patients that PEPCID may be taken with or without food and that it 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° 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

PEPCID can be administered once daily before bedtime or twice daily in the morning and before bedtime, as recommended. The suggested dosage regimen is 10 mg every other day. Patients may take PEPCID with or without food, and it can be co-administered with antacids.

No additional information is available regarding laboratory tests, abuse potential, or postmarketing experience.

FDA Insert (PDF)

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

View full prescribing information (PDF)