Famotidine

Description

Famotidine Injection, USP contains famotidine, a histamine H2-receptor antagonist. The chemical structure of famotidine is N′-(aminosulfonyl)-3-[[[2-(diaminomethylene)amino-4-thiazolyl]methyl]thio] propanimidamide, with an empirical formula of C₈H₁₅N₇O₂S₃ and a molecular weight of 337.43 g/mol. Famotidine appears as a white to pale yellowish white crystalline powder that is freely soluble in dimethylformamide and glacial acetic acid, slightly soluble in methanol, very slightly soluble in water, and practically insoluble in acetone, alcohol, chloroform, ether, and ethyl acetate.

Famotidine Injection, USP 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 multidose formulation additionally contains 0.9% benzyl alcohol as a preservative.

Uses and Indications

Famotidine Injection is indicated for intravenous use only in hospitalized patients with pathological hypersecretory conditions or intractable ulcers, or as an alternative to oral dosage forms for short-term use in patients unable to take oral medication.

This drug is indicated for the following conditions:

1. Active Duodenal Ulcer: Famotidine is indicated for the short-term treatment of active duodenal ulcer, with most adult patients healing within 4 weeks. There is rarely a reason to use famotidine at full dosage for longer than 6 to 8 weeks, and studies have not assessed the safety of famotidine in uncomplicated active duodenal ulcer for periods exceeding eight weeks.

2. Maintenance Therapy for Duodenal Ulcer: Famotidine is indicated for maintenance therapy in duodenal ulcer patients at a reduced dosage following the healing of an active ulcer. Controlled studies in adults have not extended beyond one year.

3. Active Benign Gastric Ulcer: Famotidine is indicated for the short-term treatment of active benign gastric ulcer, with most adult patients healing within 6 weeks. The safety and efficacy of famotidine in uncomplicated active benign gastric ulcer have not been assessed for periods longer than 8 weeks.

4. Gastroesophageal Reflux Disease (GERD): Famotidine is indicated for the short-term treatment of patients with symptoms of GERD. It is also indicated for the short-term treatment of esophagitis due to GERD, including erosive or ulcerative disease diagnosed by endoscopy.

5. Pathological Hypersecretory Conditions: Famotidine is indicated for the treatment of pathological hypersecretory conditions, such as Zollinger-Ellison Syndrome and multiple endocrine adenomas.

No teratogenic or nonteratogenic effects have been mentioned in the available data.

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 patients with pathological hypersecretory conditions, the intravenous dose may also be 20 mg every 12 hours, with adjustments made based on individual patient needs.

In pediatric patients under 1 year of age diagnosed with gastroesophageal reflux disease (GERD), the starting dose is as follows: for those less than 3 months of age, 0.5 mg/kg of Famotidine oral suspension should be given once daily; for patients aged 3 months to less than 1 year, the dose is 0.5 mg/kg administered twice daily. For pediatric patients aged 1 to 16 years, the starting intravenous dose is 0.25 mg/kg, injected over a period of not less than two minutes or as a 15-minute infusion, administered 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 5% Dextrose or another compatible solution, and infused over a period of 15 to 30 minutes.

Contraindications

Use of Famotidine Injection is contraindicated in patients with a known hypersensitivity to any component of the product. Due to the potential for cross-sensitivity among H2-receptor antagonists, administration is also contraindicated in individuals with a history of hypersensitivity to other H2-receptor antagonists.

Warnings and Precautions

Famotidine Injection in multiple dose vials (4 mL and 20 mL) contains the preservative benzyl alcohol, which poses significant risks, particularly in vulnerable populations. Reports indicate that the administration of intravenous solutions containing benzyl alcohol has been associated with fatal 'gasping syndrome' in neonates (children less than one month of age). This syndrome is characterized by a sudden onset of gasping respiration, hypotension, bradycardia, and cardiovascular collapse. Due to its small molecular size, benzyl alcohol is capable of crossing the placental barrier and entering immature fetal tissues, as well as the blood-brain barrier. Consequently, Famotidine Injection from multiple dose vials containing benzyl alcohol is contraindicated in neonates and pregnant women.

In addition to the warnings regarding benzyl alcohol, healthcare professionals should be aware that a symptomatic response to famotidine therapy does not exclude the possibility of gastric malignancy. Therefore, appropriate diagnostic evaluations should be considered in patients presenting with symptoms suggestive of gastric pathology.

Furthermore, caution is advised when administering famotidine to patients with renal insufficiency. Central nervous system (CNS) adverse effects have been reported in individuals with moderate to severe renal impairment. For patients with moderate renal insufficiency (creatinine clearance <50 mL/min) or severe renal insufficiency (creatinine clearance <10 mL/min), it may be necessary to extend the intervals between doses or reduce the dosage to accommodate the prolonged elimination half-life of famotidine.

No specific laboratory tests are recommended for monitoring during the use of famotidine. However, healthcare providers should remain vigilant for any adverse effects, particularly in at-risk populations.

Side Effects

Patients receiving famotidine may experience a range of adverse reactions. Common adverse reactions, occurring in more than 1% of patients, include headache (4.7%), diarrhea (1.7%), dizziness (1.3%), and constipation (1.2%).

Infrequent adverse reactions reported in clinical trials or postmarketing experiences encompass a variety of systems:

Body as a Whole: Patients have reported fever, asthenia, and fatigue.

Cardiovascular: Adverse reactions may include arrhythmia, AV block, palpitation, 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 conditions such as agranulocytosis, pancytopenia, leukopenia, and thrombocytopenia have been reported.

Hypersensitivity: Reactions can include anaphylaxis, angioedema, orbital or facial edema, urticaria, rash, conjunctival injection, and bronchospasm.

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

Nervous System/Psychiatric: Adverse reactions in this category include seizures, hallucinations, confusion, agitation, depression, anxiety, decreased libido, paresthesia, insomnia, and somnolence.

Respiratory: Interstitial pneumonia has been reported.

Skin: Serious skin reactions such as toxic epidermal necrolysis/Stevens-Johnson syndrome, pruritus, dry skin, and flushing have been observed.

Special Senses: Tinnitus and taste disorders have been reported.

Other: Impotence has also been noted.

In pediatric patients, agitation was observed in five individuals receiving famotidine, which resolved upon discontinuation of the medication.

It is important to note that famotidine injection formulations (4 mL and 20 mL multiple dose vials) contain 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 and affect immature fetal tissues, famotidine injection from multiple dose vials containing benzyl alcohol should not be used in neonates or pregnant women.

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

Drug Interactions

No drug interactions have been identified for the compound in question. Comprehensive studies, including those conducted in humans, animal models, and in vitro assessments, have demonstrated that the compound does not significantly interfere with the metabolism of drugs processed by hepatic microsomal enzymes, specifically the cytochrome P450 system.

The following compounds have been evaluated in clinical studies without evidence of interaction: warfarin, theophylline, phenytoin, diazepam, aminopyrine, and antipyrine. Additionally, the use of indocyanine green as a marker for hepatic drug extraction has shown no significant effects, further supporting the absence of clinically relevant drug interactions.

As a result, no dosage adjustments or enhanced monitoring are necessary when co-administering these compounds with the drug in question.

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 use of famotidine in pediatric patients under 1 year of age is supported by evidence from adequate and well-controlled studies in adults, as well as studies specifically involving pediatric patients in this age group. Two pharmacokinetic studies involving 48 pediatric patients under 1 year of age demonstrated that the clearance of famotidine in patients aged 3 months to 1 year is comparable to that observed in older pediatric patients (1 to 15 years) and adults. However, pediatric patients aged 0 to 3 months exhibited famotidine clearance values that were 2- to 4-fold lower than those in older pediatric patients and adults.

The mean bioavailability of famotidine following oral dosing in pediatric patients under 1 year of age is similar to that of older pediatric patients and adults. Pharmacodynamic data indicate that the duration of acid suppression in pediatric patients aged 0 to 3 months is longer than in older pediatric patients, which aligns with the extended half-life of famotidine in this younger cohort.

In a double-blind, randomized, treatment-withdrawal study, 35 pediatric patients under 1 year of age diagnosed with gastroesophageal reflux disease (GERD) were treated with famotidine oral suspension at doses of 0.5 mg/kg/dose or 1 mg/kg/dose for up to 4 weeks. The recommended dosing regimen is once daily for patients under 3 months of age and twice daily for those aged 3 months to less than 1 year. These studies suggest that a starting dose of 0.5 mg/kg/dose of famotidine oral suspension may be beneficial for treating GERD for up to 4 weeks in patients under 3 months of age, and twice daily in patients aged 3 months to less than 1 year.

The safety and efficacy of famotidine treatment beyond 4 weeks have not been established. Famotidine should be considered for the treatment of GERD only when conservative measures, such as thickened feedings, are implemented concurrently, and when the potential benefits outweigh the risks.

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 2000 mg/kg/day and 500 mg/kg/day, respectively, as well as intravenous doses of up to 200 mg/kg/day, 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

Famotidine is secreted into breast milk, as demonstrated in studies conducted with lactating rats. In these studies, transient growth depression was noted in young rats suckling from mothers treated with maternotoxic doses of at least 600 times the usual human dose. Additionally, famotidine is detectable in human milk.

Due to the potential for serious adverse reactions in breastfed infants, healthcare professionals should consider the risks and benefits when advising lactating mothers. A decision should be made whether to discontinue nursing or to discontinue famotidine, taking into account the importance of the medication to the mother.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available data regarding dosage adjustments, special monitoring, or safety considerations. Therefore, healthcare professionals should exercise caution when prescribing this medication to patients with reduced kidney function, as the lack of information necessitates careful clinical judgment and monitoring.

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, the adverse reactions observed are consistent with those typically encountered during normal clinical use. Notably, adult patients with pathological hypersecretory conditions have tolerated oral doses of up to 640 mg/day without experiencing serious adverse effects.

Management of Overdosage

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 recommended, alongside the implementation of supportive therapy as needed.

Toxicity Data

The intravenous LD50 of famotidine has been reported for mice and rats, ranging from 254 to 563 mg/kg. In canine subjects, the minimum lethal single intravenous dose was approximately 300 mg/kg. Signs of acute intoxication in dogs treated intravenously included emesis, restlessness, pallor of mucous membranes or redness of the mouth and ears, hypotension, tachycardia, and potential collapse.

For oral administration, the LD50 of famotidine in both male and female rats and mice exceeds 3000 mg/kg, while the minimum lethal acute oral dose in dogs is noted to exceed 2000 mg/kg. It is important to highlight that famotidine did not produce overt effects at high oral doses in mice, rats, cats, and dogs. However, significant anorexia and growth depression were observed in rabbits starting at an oral dose of 200 mg/kg/day.

Healthcare professionals should remain vigilant for these symptoms and manage the patient accordingly in cases of suspected overdosage.

Nonclinical Toxicology

In a 106-week study conducted in rats and a 92-week study in mice, oral administration of famotidine at doses up to 2000 mg/kg/day, which is approximately 2500 times the recommended human dose for active duodenal ulcer, did not demonstrate any evidence of carcinogenic potential.

Famotidine was evaluated for mutagenicity using the microbial mutagen test (Ames test) with 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 activity. Additionally, in vivo studies in mice, including a micronucleus test and a chromosomal aberration test, showed no evidence of mutagenic effects.

Fertility and reproductive performance were assessed in studies involving rats administered oral doses of up to 2000 mg/kg/day or intravenous doses of up to 200 mg/kg/day. The findings indicated that famotidine did not adversely affect fertility or reproductive performance.

Postmarketing Experience

Adverse reactions reported in postmarketing experience include those occurring in more than 1% of patients receiving famotidine in controlled clinical trials, which may be causally related to the drug. These reactions include headache (4.7%), dizziness (1.3%), constipation (1.2%), and diarrhea (1.7%).

Additionally, other adverse reactions have been reported infrequently in clinical trials or since the drug's marketing, with the relationship to famotidine therapy remaining unclear in many instances. These reactions are categorized as follows:

Body as a Whole: Fever, asthenia, fatigue. Cardiovascular: Arrhythmia, AV block, palpitation, prolonged QT interval. Gastrointestinal: Cholestatic jaundice, hepatitis, elevated liver enzymes, 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.

It is noted that the adverse reactions reported for Famotidine Tablets may also occur with Famotidine for Oral Suspension or Famotidine Injection. Furthermore, 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 GERD symptoms, agitation was observed in 5 patients receiving famotidine, which resolved upon discontinuation of the medication.

Patient Counseling

Patients should be informed that a symptomatic response to therapy with famotidine does not exclude the possibility of gastric malignancy. Healthcare providers should emphasize the importance of further evaluation if symptoms persist despite treatment.

For patients with moderate or severe renal insufficiency, it is crucial to discuss the need for longer intervals between doses or lower doses of famotidine, as the drug has a longer elimination half-life in these individuals.

Healthcare providers should also inform patients that famotidine Injection contains benzyl alcohol, which poses a risk of fatal ‘gasping syndrome’ and should not be used in neonates and pregnant women.

Nursing mothers should be advised that famotidine is secreted into breast milk. A careful decision should be made regarding whether to discontinue nursing or the medication, taking into account the importance of famotidine for the mother’s health.

For pediatric patients under 1 year of age, famotidine should only be administered if conservative measures, such as thickened feedings, are used concurrently, and if the potential benefits outweigh the risks. The recommended starting dose for this age group with gastroesophageal reflux disease (GERD) is 0.5 mg/kg/dose of famotidine oral suspension for up to 8 weeks, with specific dosing frequency determined by the patient's age.

For pediatric patients aged 1 to 16 years, the initial dose may be 0.25 mg/kg intravenously, administered over a period of not less than two minutes or as a 15-minute infusion, with a maximum daily dose of 40 mg.

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

Storage and Handling

Famotidine Injection, USP is supplied in a manner that ensures optimal storage and handling conditions. It should be stored at a temperature range of 2º to 8ºC (36º to 46ºF). In the event that the solution freezes, it must be brought back to room temperature, allowing sufficient time for all components to solubilize completely.

To maintain the integrity of the product, it is essential to protect Famotidine Injection from light and to retain it in its original carton until it is ready for use. While diluted Famotidine Injection has demonstrated physical and chemical stability for up to 7 days at room temperature, it is advisable that any diluted solutions not used immediately after preparation be refrigerated and utilized within 48 hours to ensure safety and efficacy.

Additional Clinical Information

The recommended dosage for Famotidine Injection in adult patients is 20 mg administered intravenously every 12 hours. For pediatric patients under 1 year of age, the starting doses for the treatment of Gastroesophageal Reflux Disease (GERD) are 0.5 mg/kg/dose of famotidine oral suspension, given once daily for up to 8 weeks in patients under 3 months of age, and 0.5 mg/kg/dose twice daily for those aged 3 months to less than 1 year. In pediatric patients aged 1 to 16 years, the suggested starting dose is 0.25 mg/kg intravenously, injected over a period of no less than two minutes or as a 15-minute infusion, administered every 12 hours, with a maximum daily dose of 40 mg.

FDA Insert (PDF)

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

View full prescribing information (PDF)