Famotidine

Description

Famotidine Injection, USP contains famotidine, a histamine H2-receptor antagonist. The chemical structure of famotidine is described as [1-Amino-3-[[[2-(diaminomethylene)amino-4-thiazolyl] methyl]thio]propylidene] sulfamide. This compound appears as a white to pale yellow crystalline substance. It is freely soluble in glacial acetic acid, slightly soluble in methanol, very slightly soluble in water, and practically insoluble in ethanol.

Famotidine Injection, USP is provided as a sterile concentrated solution intended for intravenous administration. Each milliliter of the 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.

Uses and Indications

Famotidine Injection is indicated for intravenous use in hospitalized patients with pathological hypersecretory conditions or intractable ulcers. It is also indicated for the short-term treatment of active duodenal ulcers, with most adult patients healing within 4 weeks. The use of Famotidine Injection at full dosage for longer than 6 to 8 weeks is rarely recommended, as safety has not been assessed for periods exceeding 8 weeks.

For patients who have healed from an active duodenal ulcer, Famotidine Injection may be used as maintenance therapy at a reduced dosage. Controlled studies in adults have not extended beyond one year for this indication. Additionally, it is indicated for the short-term treatment of active benign gastric ulcers, with most adult patients healing within 6 weeks; however, safety or efficacy has not been assessed for treatment durations over 8 weeks.

Famotidine Injection is also 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. Furthermore, it 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 reported.

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, this dosage may be adjusted based on individual patient needs. It is important to note that the doses and regimen for parenteral administration in patients with gastroesophageal reflux disease (GERD) have not been established.

In pediatric patients under 1 year of age with GERD, the starting dose is 0.5 mg/kg 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 (solution containing 10 mg/mL) with Sodium Chloride Injection 0.9% 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.

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 both 4 mL and 20 mL multiple dose vials contains the preservative benzyl alcohol. It is critical to note that there have been reports of fatal ‘gasping syndrome’ in neonates (children less than one month of age) following the administration of intravenous solutions containing this preservative. Symptoms of this syndrome include 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 into immature fetal tissues as easily as it crosses the blood-brain barrier. Consequently, Famotidine Injection from multiple dose vials containing benzyl alcohol is contraindicated in neonates and pregnant women.

Healthcare professionals should be aware that a symptomatic response to therapy with famotidine does not exclude the possibility of gastric malignancy. Therefore, appropriate diagnostic evaluations should be considered to rule out such conditions, even in patients who exhibit improvement in symptoms.

No specific laboratory tests have been recommended for monitoring during the use of famotidine; however, clinicians should remain vigilant for any signs of adverse reactions, particularly in vulnerable populations.

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.

Warnings associated with Famotidine Injection indicate that the 4 mL and 20 mL multiple dose vials contain the preservative benzyl alcohol, which has been linked to fatal ‘gasping syndrome’ in neonates following intravenous administration. 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 these vials should not be used in neonates or pregnant women.

Additionally, it is important to note that adverse reactions reported for Famotidine Tablets may also occur with Famotidine for Oral Suspension or Famotidine Injection. Transient irritation at the injection site has been observed with Famotidine Injection. In a clinical study involving 35 pediatric patients under one year of age with GERD symptoms, agitation was noted in five patients receiving famotidine, which resolved upon discontinuation of the medication.

Drug Interactions

No significant 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 notable interference with the metabolism of compounds 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.

Given the lack of identified interactions, no dosage adjustments or enhanced monitoring protocols are necessary when co-administering these compounds.

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 based on evidence from both adult studies and specific studies involving this age group. Two pharmacokinetic studies involving 48 pediatric patients demonstrated that famotidine clearance in those aged 3 months to 1 year is comparable to that in older pediatric patients (1-15 years). However, patients aged 0-3 months exhibited clearance values that were 2- to 4-fold lower than those in older pediatric patients and adults. The mean bioavailability following oral dosing in patients under 1 year is similar to that observed in older pediatric patients and adults. Notably, pharmacodynamic data indicate that the duration of acid suppression in patients aged 0-3 months is longer than in older pediatric patients.

For the treatment of gastroesophageal reflux disease (GERD), the recommended starting doses are 0.5 mg/kg/dose of famotidine oral suspension 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. Famotidine should be considered for GERD treatment only when conservative measures, such as thickened feedings, are implemented concurrently, and when the potential benefits outweigh the risks.

In pediatric patients aged 1 to 16 years, the use of famotidine is also supported by adequate and well-controlled studies in adults and pediatric populations. Clearance of famotidine in this age group is similar to that in adults. The recommended starting dose for patients aged 1 to 16 years is 0.25 mg/kg intravenously, administered over a period of not less than two minutes or as a 15-minute infusion, every 12 hours, with a maximum of 40 mg per day. Treatment duration and dosing should be tailored based on clinical response and/or gastric pH determination and endoscopy findings. Uncontrolled studies have shown that gastric acid suppression can be achieved with doses up to 0.5 mg/kg intravenously every 12 hours in this population.

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 solely based 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 to dose selection in this population. Monitoring of renal function may be beneficial to ensure safety.

In cases of moderate or severe renal impairment, dosage adjustments are necessary to mitigate the risk of adverse effects.

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, there were instances of sporadic abortions 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 performed in lactating rats. In these studies, transient growth depression was observed 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 discontinue the drug, taking into account the importance of famotidine to the mother’s health.

Renal Impairment

There is no specific information available 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 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 reported during normal clinical use (refer to the ADVERSE REACTIONS section for further details). Clinical experience indicates that 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, along with the implementation of supportive therapy as needed.

Toxicity Data

Toxicological studies have established the intravenous LD50 of famotidine in mice and rats to range from 254 to 563 mg/kg. In dogs, the minimum lethal single intravenous dose is approximately 300 mg/kg. Signs of acute intoxication in dogs treated intravenously may include 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 male and female rats and mice exceeds 3,000 mg/kg, while 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, significant anorexia and growth depression were observed in rabbits at doses starting from 200 mg/kg/day administered orally.

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 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, at concentrations up to 10,000 mcg/plate. The results were negative, indicating no mutagenic activity. Additionally, in vivo studies in mice, including a micronucleus test and a chromosomal aberration test, also 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 reported in postmarketing experience include those observed in clinical trials and voluntary reports. In controlled clinical trials, the following adverse reactions occurred in more than 1% of patients receiving famotidine: headache (4.7%), diarrhea (1.7%), dizziness (1.3%), and constipation (1.2%).

Other adverse reactions have been reported infrequently in clinical trials or since the drug's market introduction, 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 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

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 been noted 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

Patients should be informed that a symptomatic response to therapy with famotidine does not exclude the possibility of gastric malignancy. It is important for healthcare providers to emphasize this point during discussions with patients.

For patients with moderate or severe renal insufficiency, healthcare providers should advise that longer intervals between doses or lower doses may be necessary due to the longer elimination half-life of famotidine.

Healthcare providers should also inform patients that Famotidine Injection contains the preservative benzyl alcohol, which is contraindicated in neonates and pregnant women due to the risk of fatal ‘gasping syndrome’.

Nursing mothers should be counseled 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 the drug to 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 these patients 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.

Healthcare providers should monitor patients for adverse reactions, particularly in pediatric patients, where agitation has been reported but resolved upon discontinuation of famotidine. Patients should be advised to report any suspected adverse reactions to their healthcare provider or the FDA to ensure proper management and safety.

Storage and Handling

Famotidine Injection is supplied in a form that requires careful storage and handling to maintain its efficacy. It should be stored at a temperature range of 2° to 8°C (36° to 46°F). In the event that the solution freezes, it must be brought back to room temperature, allowing sufficient time for all components to solubilize completely.

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. These diluted solutions should be utilized within 48 hours to ensure optimal effectiveness.

Additional Clinical Information

The recommended dosage for Famotidine Injection in adult patients is 20 mg administered intravenously every 12 hours. No further information is available regarding laboratory tests, abuse potential, patient counseling, or postmarketing experience.

FDA Insert (PDF)

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

View full prescribing information (PDF)