Famotidine

Description

Famotidine Injection, USP contains famotidine, a histamine H2-receptor antagonist. The chemical structure of famotidine is designated as [1-Amino-3-[[[2-(diaminomethylene)amino-4-thiazolyl]methyl]thio] propylidene] sulfamide, with a molecular formula of C8H15N7O2S3 and a molecular weight of 337.45.

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. Famotidine Injection is provided as a sterile concentrated solution intended for intravenous administration. Each milliliter of the single-dose solution contains 10 mg of famotidine, along with inactive ingredients including 4 mg of L-aspartic acid, 20 mg of mannitol, and Water for Injection to a total volume of 1 mL. The multi-dose formulation additionally contains 0.9% benzyl alcohol as a preservative.

Uses and Indications

Famotidine Injection is indicated for intravenous use in hospitalized patients with pathological hypersecretory conditions, intractable ulcers, and for short-term use in patients unable to take oral medication.

This drug is indicated for the short-term treatment of active duodenal ulcers, with most adult patients healing within 4 weeks. It is rarely used at full dosage for longer than 6 to 8 weeks, and safety has not been assessed for periods exceeding 8 weeks. Additionally, it is indicated for maintenance therapy in duodenal ulcer patients at a reduced dosage following the healing of an active ulcer; however, controlled studies in adults have not extended beyond one year.

Famotidine Injection is also indicated for the short-term treatment of active benign gastric ulcers, with most adult patients healing within 6 weeks. Safety and efficacy have not been assessed for periods longer than 8 weeks. Furthermore, it is indicated for the short-term treatment of gastroesophageal reflux disease (GERD), specifically for patients exhibiting symptoms of GERD and for the short-term treatment of esophagitis due to GERD, including erosive or ulcerative disease diagnosed by endoscopy.

Lastly, this drug is indicated for the treatment of pathological hypersecretory conditions, such as Zollinger-Ellison Syndrome and multiple endocrine adenomas.

Dosage and Administration

In hospitalized patients with pathological hypersecretory conditions or intractable ulcers, or in patients unable to take oral medication, Famotidine Injection may be administered until oral therapy can be initiated.

For adult patients, the recommended dosage of Famotidine Injection is 20 mg administered intravenously every 12 hours. In cases of pathological hypersecretory conditions, the intravenous dose may be adjusted based on individual patient needs, but the standard recommendation remains at 20 mg every 12 hours.

In pediatric patients under 1 year of age with gastroesophageal reflux disease (GERD), the starting dose is 0.5 mg/kg per dose of famotidine oral suspension, administered once daily for up to 8 weeks in patients less than 3 months of age, and twice daily in patients aged 3 months to less than 1 year. For pediatric patients aged 1 to 16 years, the starting intravenous dose is 0.25 mg/kg, administered over a period of not less than two minutes or as a 15-minute infusion, every 12 hours, with a maximum daily dose of 40 mg.

To prepare intravenous solutions, healthcare professionals should aseptically dilute 2 mL of Famotidine Injection (10 mg/mL) with 0.9% Sodium Chloride Injection or another compatible intravenous solution to achieve a total volume of either 5 mL or 10 mL. This solution should be injected over a period of not less than 2 minutes. For intravenous infusion solutions, 2 mL of Famotidine Injection should be aseptically diluted with 100 mL of Dextrose 5% or another compatible solution, and infused over a period of 15 to 30 minutes.

The dosing regimen for parenteral administration in patients with GERD has not been established.

Contraindications

Use of Famotidine Injection is contraindicated in patients with a known hypersensitivity to any component of the product. Cross-sensitivity among H2-receptor antagonists has been observed; therefore, administration is also contraindicated in individuals with a history of hypersensitivity to other H2-receptor antagonists.

Warnings and Precautions

Famotidine Injection is associated with specific warnings and precautions that healthcare professionals must consider to ensure patient safety.

Use in Neonates and Pregnant Women Famotidine Injection in both 4 mL and 20 mL multiple dose vials contains the preservative benzyl alcohol. The use of benzyl alcohol in intravenous solutions has been linked to fatal ‘gasping syndrome’ in neonates, defined as children less than one month of age. Clinicians should be vigilant for symptoms such as gasping respiration, hypotension, bradycardia, and cardiovascular collapse in this population. Given that benzyl alcohol can cross the placental barrier and the blood-brain barrier, it is imperative that Famotidine Injection from multiple dose vials containing this preservative is contraindicated in neonates and pregnant women.

Gastric Malignancy Consideration It is important to note that a symptomatic response to famotidine therapy does not exclude the possibility of gastric malignancy. Healthcare professionals should remain cautious and consider further diagnostic evaluation in patients presenting with symptoms suggestive of gastric conditions, even if they exhibit improvement with famotidine treatment. Regular monitoring and appropriate laboratory tests may be warranted to rule out serious underlying conditions.

Side Effects

Patients receiving Famotidine may experience a range of adverse reactions, which can be categorized by frequency and seriousness.

Common adverse reactions observed in clinical trials include headache (4.7%), dizziness (1.3%), diarrhea (1.7%), and constipation (1.2%).

Other adverse reactions, though less common, have been reported across various systems:

Body as a Whole: Patients may experience fever, asthenia, and fatigue.

Cardiovascular: Adverse reactions in this category include arrhythmia, AV block, palpitations, and prolonged QT interval.

Gastrointestinal: Reactions such as cholestatic jaundice, hepatitis, elevated liver enzymes, vomiting, nausea, abdominal discomfort, anorexia, and dry mouth have been noted.

Hematologic: Serious hematologic reactions include agranulocytosis, pancytopenia, leukopenia, and thrombocytopenia.

Hypersensitivity: Severe hypersensitivity reactions can occur, including anaphylaxis, angioedema, orbital or facial edema, urticaria, rash, conjunctival injection, and bronchospasm.

Musculoskeletal: Patients may report rhabdomyolysis, musculoskeletal pain, muscle cramps, and arthralgia.

Nervous System/Psychiatric: Adverse reactions affecting the nervous system and psychiatric health include seizures, hallucinations, confusion, agitation, depression, anxiety, decreased libido, paresthesia, insomnia, and somnolence.

Respiratory: Interstitial pneumonia has been reported as a potential adverse reaction.

Skin: Skin reactions may include toxic epidermal necrolysis/Stevens-Johnson syndrome, pruritus, dry skin, and flushing.

Special Senses: Patients may experience tinnitus and taste disorders.

Other: Impotence has also been reported.

In a clinical study involving 35 pediatric patients under one year of age with gastroesophageal reflux disease (GERD) symptoms, agitation was observed in five patients receiving famotidine; this agitation resolved upon discontinuation of the medication.

It is important to note that Famotidine Injection in multiple dose vials contains the preservative benzyl alcohol, which has been associated with fatal 'gasping syndrome' in neonates. Symptoms of this syndrome include gasping respiration, hypotension, bradycardia, and cardiovascular collapse. Due to the potential for benzyl alcohol to cross the placental barrier, Famotidine Injection from multiple dose vials should not be used in neonates or pregnant women.

Transient irritation at the injection site has also been observed with Famotidine Injection. The adverse reactions reported for Famotidine Tablets may similarly occur with Famotidine for Oral Suspension or Famotidine Injection.

Drug Interactions

No drug interactions have been identified for the compound in question. Comprehensive studies, including those involving famotidine in humans, animal models, and in vitro assessments, have demonstrated that there is no significant interference with the metabolism of compounds processed by hepatic microsomal enzymes, specifically the cytochrome P450 system.

The compounds evaluated in these studies include warfarin, theophylline, phenytoin, diazepam, aminopyrine, and antipyrine, all of which showed no notable interactions. Additionally, the use of indocyanine green as an index for hepatic drug extraction has also indicated no significant effects. Therefore, no dosage adjustments or enhanced monitoring are necessary when co-administering these agents.

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 under 1 year of age may receive famotidine for gastroesophageal reflux disease (GERD) with specific dosing recommendations. For infants less than 3 months of age, the starting dose is 0.5 mg/kg of famotidine oral suspension once daily for up to 8 weeks. For those aged 3 months to less than 1 year, the recommended dose is 0.5 mg/kg twice daily. It is important to note that the use of intravenous famotidine in this age group has not been adequately studied. Clearance of famotidine in patients aged 3 months to 1 year is comparable to that in older pediatric patients (1 to 15 years), while infants 0 to 3 months exhibit clearance values that are 2- to 4-fold lower than those in older children and adults. Pharmacodynamic data indicate that the duration of acid suppression may be longer in this younger cohort.

For pediatric patients aged 1 to 16 years, the recommended starting dose of famotidine is 0.25 mg/kg administered intravenously every 12 hours, with a maximum daily dose of 40 mg. Clearance in this age group is similar to that observed in adults, and limited studies suggest that the relationship between serum concentration and acid suppression is comparable to that in adults. Treatment duration and dosing should be tailored to the individual based on clinical response, gastric pH, and endoscopic findings. Uncontrolled studies have shown effective gastric acid suppression with doses up to 0.5 mg/kg intravenously every 12 hours.

Safety concerns have been noted in pediatric patients under 1 year of age, with agitation reported in five patients during a clinical study. This agitation resolved upon discontinuation of the medication.

Geriatric Use

In clinical studies involving 4,966 subjects treated with famotidine, 488 subjects (9.8%) were aged 65 years and older, while 88 subjects (1.7%) were over 75 years of age. No overall differences in safety or effectiveness were observed between these elderly patients and their younger counterparts. However, it is important to note that greater sensitivity to the drug may be present in some older patients.

No dosage adjustment is required based solely on age. Nevertheless, famotidine is substantially excreted by the kidneys, which raises concerns regarding the risk of toxic reactions in patients with impaired renal function. Given that elderly patients are more likely to experience decreased renal function, careful consideration should be given during dose selection. Monitoring of renal function may be beneficial in this population.

In cases of moderate or severe renal impairment, dosage adjustments are necessary to mitigate the risk of adverse effects. Healthcare providers should remain vigilant in assessing renal function and adjusting the dosage accordingly to ensure the safety and efficacy of famotidine in geriatric patients.

Pregnancy

Reproductive studies conducted in rats and rabbits at oral doses of up to 2,000 mg/kg/day and 500 mg/kg/day, respectively, as well as intravenous doses of up to 200 mg/kg/day in both species, have shown no significant evidence of impaired fertility or harm to the fetus associated with famotidine. Although no direct fetotoxic effects have been observed, sporadic abortions were reported in some rabbits that exhibited marked decreased food intake when administered oral doses of 200 mg/kg/day (approximately 250 times the usual human dose) or higher.

It is important to note that there are no adequate or well-controlled studies in pregnant women. Given that animal reproductive studies may not always predict human responses, famotidine should be used during pregnancy only if clearly needed. Healthcare professionals are advised to weigh the potential benefits against the risks when considering the use of this medication in pregnant patients.

Lactation

Studies performed in lactating rats have shown that famotidine is secreted into breast milk. Additionally, famotidine is detectable in human milk. Transient growth depression was observed in young rats suckling from mothers treated with maternotoxic doses of at least 600 times the usual human dose.

Due to the potential for serious adverse reactions in nursing infants from famotidine, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Renal Impairment

There is no specific information regarding dosage adjustments, special monitoring, or safety considerations for patients with renal impairment. Healthcare professionals should exercise caution when prescribing to patients with reduced kidney function, as the absence of detailed guidance necessitates careful clinical judgment. Regular monitoring of renal function may be advisable in these patients to ensure safety and efficacy.

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 overdosage, the adverse reactions observed are consistent with those typically encountered during normal clinical use. Clinical experience indicates that oral doses of up to 640 mg/day have been administered to adult patients suffering from pathological hypersecretory conditions without resulting in serious adverse effects.

Recommended Actions

In the event of an overdosage, treatment should be primarily symptomatic and supportive. It is essential to remove any unabsorbed material from the gastrointestinal tract. Continuous monitoring of the patient is crucial, and supportive therapy should be implemented as necessary.

Potential Symptoms

Acute intoxication, particularly in dogs treated intravenously, may present with a range of symptoms including emesis, restlessness, pallor of mucous membranes, or redness of the mouth and ears. Additional signs may include hypotension, tachycardia, and potential collapse.

Toxicity Data

Toxicity studies have established that the intravenous LD50 of famotidine in mice and rats ranges from 254 to 563 mg/kg, while the minimum lethal single intravenous dose in dogs is approximately 300 mg/kg. Furthermore, the oral LD50 for famotidine in both male and female rats and mice exceeds 3,000 mg/kg, and the minimum lethal acute oral dose in dogs is greater than 2,000 mg/kg. Notably, famotidine has not demonstrated overt effects at high oral doses in mice, rats, cats, and dogs; however, it has been associated with significant anorexia and growth depression in rabbits at doses starting from 200 mg/kg/day orally.

Healthcare professionals should remain vigilant for these symptoms and manage overdosage cases with appropriate interventions.

Nonclinical Toxicology

In a 106-week study conducted in rats and a 92-week study in mice, oral doses of famotidine up to 2,000 mg/kg/day, which is approximately 2,500 times the recommended human dose for active duodenal ulcer, did not demonstrate any evidence of carcinogenic potential.

Famotidine was evaluated in the microbial mutagen test (Ames test) using Salmonella typhimurium and Escherichia coli, both with and without rat liver enzyme activation, and was found to be negative at concentrations up to 10,000 mcg/plate. Additionally, in vivo studies in mice, including a micronucleus test and a chromosomal aberration test, showed no evidence of mutagenic effects.

Furthermore, studies involving rats administered oral doses of up to 2,000 mg/kg/day or intravenous doses of up to 200 mg/kg/day indicated that fertility and reproductive performance were not adversely affected.

Postmarketing Experience

Adverse reactions have been reported during domestic and international clinical trials involving approximately 2,500 patients. In controlled clinical trials comparing famotidine tablets to placebo, the incidence of adverse experiences in the group receiving famotidine tablets (40 mg at bedtime) was similar to that in the placebo group.

In these trials, the following adverse reactions were reported in more than 1% of patients receiving famotidine and may be causally related to the drug: headache (4.7%), dizziness (1.3%), constipation (1.2%), and diarrhea (1.7%).

Other adverse reactions have been reported infrequently in clinical trials or since the drug was marketed, with the relationship to famotidine therapy remaining unclear in many cases. These reactions are categorized as follows, listed in order of decreasing severity:

Body as a Whole: fever, asthenia, fatigue Cardiovascular: arrhythmia, AV block, palpitation, prolonged QT interval Gastrointestinal: cholestatic jaundice, hepatitis, elevated liver enzyme, vomiting, nausea, abdominal discomfort, anorexia, dry mouth Hematologic: agranulocytosis, pancytopenia, leukopenia, thrombocytopenia Hypersensitivity: anaphylaxis, angioedema, orbital or facial edema, urticaria, rash, conjunctival injection, bronchospasm Musculoskeletal: rhabdomyolysis, musculoskeletal pain, muscle cramps, arthralgia Nervous System/Psychiatric: seizure, hallucinations, confusion, agitation, depression, anxiety, decreased libido, paresthesia, insomnia, somnolence Respiratory: interstitial pneumonia Skin: toxic epidermal necrolysis/Stevens-Johnson syndrome, pruritus, dry skin, flushing Special Senses: tinnitus, taste disorder Other: impotence

Adverse reactions reported for famotidine tablets may also occur with famotidine for oral suspension or famotidine injection. Additionally, transient irritation at the injection site has been observed with famotidine injection.

In a clinical study involving 35 pediatric patients under 1 year of age with gastroesophageal reflux disease (GERD) symptoms, agitation was observed in 5 patients receiving famotidine, which resolved upon discontinuation of the medication.

Patient Counseling

Healthcare providers should advise patients that Famotidine Injection is contraindicated in individuals with a history of hypersensitivity to other H2-receptor antagonists. It is crucial to inform patients that this medication contains benzyl alcohol, which poses a risk of fatal ‘gasping syndrome’ in neonates. Symptoms of this syndrome include gasping respiration, hypotension, bradycardia, and cardiovascular collapse; therefore, Famotidine Injection should not be administered to neonates or pregnant women.

Patients must be made aware that a symptomatic response to therapy with famotidine does not rule out the possibility of gastric malignancy. For patients with moderate or severe renal insufficiency, healthcare providers should consider adjusting the dosing regimen, as these patients may require longer intervals between doses or lower doses due to the prolonged elimination half-life of famotidine.

It is important to discuss with patients that famotidine is secreted into breast milk. A careful decision should be made regarding whether to discontinue nursing or to discontinue the medication, taking into account the significance of the drug for the mother’s health.

For pediatric patients under 1 year of age, healthcare providers should recommend the use of famotidine oral suspension for the treatment of gastroesophageal reflux disease (GERD) for a duration of up to 8 weeks, while also implementing conservative measures such as thickened feedings. Providers should inform caregivers that the safety and efficacy of famotidine treatment beyond 4 weeks in pediatric patients have not been established, and they should be instructed to continue conservative treatment alongside medication.

Finally, healthcare providers should monitor patients for adverse reactions, particularly in pediatric patients, where agitation has been reported. This agitation typically resolves upon discontinuation of famotidine.

Storage and Handling

The product is supplied in a refrigerated state and must be stored at temperatures between 2° and 8°C (36° and 46°F). It is essential to ensure that the solution does not freeze; if freezing occurs, the solution should be brought to room temperature and allowed sufficient time to solubilize all components before use.

Once diluted, Famotidine Injection should also be refrigerated and is recommended for use within 48 hours if not utilized immediately after preparation. Proper handling and storage conditions are critical to maintaining the integrity and efficacy of the product.

Additional Clinical Information

Famotidine Injection may be administered until oral therapy can be instituted, with a recommended dosage of 20 mg intravenously every 12 hours for adult patients. When using famotidine for gastroesophageal reflux disease (GERD), it is important for patients to also receive conservative measures, such as thickened feedings, to enhance treatment efficacy.

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 Famotidine as submitted by Sagent Pharmaceuticals. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)