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 active ingredient appears as a white to pale yellow crystalline compound. Famotidine 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 L-aspartic acid (4 mg), mannitol (20 mg), Water for Injection (q.s. 1 mL), and benzyl alcohol (0.9% as a preservative).

Uses and Indications

Famotidine Injection is indicated for intravenous use in hospitalized patients with various gastrointestinal conditions. This drug is indicated for the treatment of pathological hypersecretory conditions, including Zollinger-Ellison Syndrome and multiple endocrine adenomas. It is also indicated for the short-term treatment of active duodenal ulcers, with most adult patients healing within 4 weeks; however, it is rarely used at full dosage for longer than 6 to 8 weeks, as safety has not been assessed for periods exceeding 8 weeks.

Additionally, Famotidine Injection is indicated for maintenance therapy in patients with duodenal ulcers at a reduced dosage following the healing of an active ulcer, although controlled studies in adults have not extended beyond one year. The drug 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 durations 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 treatment of esophagitis due to GERD, including erosive or ulcerative disease diagnosed by endoscopy.

There are no teratogenic or nonteratogenic effects associated with Famotidine Injection.

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 dosage may be adjusted based on individual patient needs, but the standard is also 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 of famotidine oral suspension once daily for up to 8 weeks in patients less than 3 months of age, and 0.5 mg/kg twice daily in patients aged 3 months to less than 1 year. For pediatric patients aged 1 to 16 years, the starting dose is 0.25 mg/kg administered intravenously every 12 hours, with a maximum daily dose of 40 mg. The intravenous injection should be administered over a period of not less than two minutes or as a 15-minute infusion.

To prepare intravenous solutions, healthcare professionals should aseptically dilute 2 mL of Famotidine Injection (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. 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 treatment may experience a range of adverse reactions. The most common adverse reactions, occurring in 1% or more of participants, include headache (4.7%), dizziness (1.3%), diarrhea (1.7%), and constipation (1.2%).

Infrequent adverse reactions have been reported across various systems:

Body as a Whole: Patients may experience 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 as a potential adverse reaction.

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

Special Senses: Patients may report tinnitus and taste disorders.

Other: Impotence has also been noted as an adverse reaction.

Warnings associated with Famotidine Injection include the presence of benzyl alcohol, which has been linked to fatal ‘gasping syndrome’ in neonates. Symptoms of this syndrome include gasping respiration, hypotension, bradycardia, and cardiovascular collapse. Therefore, Famotidine Injection should not be used in neonates or pregnant women.

In a clinical study involving 35 pediatric patients under 1 year of age, agitation was observed in 5 patients receiving famotidine; this agitation resolved upon discontinuation of the medication.

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 following compounds have been tested in human studies without revealing any notable interactions: warfarin, theophylline, phenytoin, diazepam, aminopyrine, and antipyrine. Additionally, the use of indocyanine green as an index 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

Use of famotidine in pediatric patients under 1 year of age is supported by studies specifically conducted in this population. For the treatment of gastroesophageal reflux disease (GERD), the recommended starting doses are 0.5 mg/kg/dose once daily for patients less than 3 months of age and 0.5 mg/kg/dose twice daily for those aged 3 months to less than 1 year. However, the safety and efficacy of famotidine treatment beyond 4 weeks have not been established. Additionally, the use of intravenous famotidine in this age group for GERD has not been adequately studied.

In pediatric patients aged 1 to 16 years, the starting dose is 0.25 mg/kg administered intravenously (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. The clearance of famotidine in this age group is comparable to that observed in adults. Limited studies indicate that the relationship between serum concentration and acid suppression in pediatric patients aged 1 to 15 years is similar to that in adults. Treatment duration and dosing should be individualized based on clinical response and/or gastric pH determination and endoscopy.

Safety concerns in pediatric patients under 1 year of age include the observation of agitation in 5 patients during a clinical study, which 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. The data indicated no overall differences in safety or effectiveness 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 potential for 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 noted 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

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 oral doses of up to 640 mg/day have been administered to adult patients suffering from pathological hypersecretory conditions without any 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 advised, along with the implementation of supportive therapy as necessary.

Potential Symptoms

Animal studies have provided insight into the potential symptoms of acute intoxication. In intravenous-treated dogs, signs of overdose included emesis, restlessness, pallor of mucous membranes or redness of the mouth and ears, hypotension, tachycardia, and collapse. The intravenous LD50 for 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.

Conversely, the oral LD50 of famotidine in 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 did not produce overt effects at high oral doses in mice, rats, cats, and dogs; however, it did induce 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 the patient accordingly, ensuring that appropriate supportive measures are in place.

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, revealed 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. 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 must advise that famotidine Injection contains benzyl alcohol, which has been linked to fatal ‘gasping syndrome’ in neonates. Therefore, it should not be administered to neonates or pregnant women.

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 significance of the drug for the mother’s health.

For pediatric patients under 1 year of age, famotidine should only be used if conservative measures, such as thickened feedings, are implemented concurrently and if the potential benefits outweigh the risks. Caregivers should be instructed to provide these conservative treatments.

Patients, particularly pediatric patients, should be closely monitored for adverse reactions. It is important to note that agitation has been observed in some pediatric cases, which resolved upon discontinuation of the medication. Healthcare providers should ensure that caregivers are aware of this potential side effect and the need for monitoring.

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 adequate time for all components to fully solubilize before use.

Once diluted, Famotidine Injection should be refrigerated and is recommended for use within 48 hours if not utilized immediately after preparation. Proper adherence to these storage conditions is essential to ensure the integrity and effectiveness of the product.

Additional Clinical Information

Famotidine Injection may be administered until oral therapy can be initiated. For adult patients, the recommended dosage is 20 mg intravenously every 12 hours. In pediatric patients aged 1 to 16 years, the suggested starting dose is 0.25 mg/kg intravenously, administered over a period of not less than two minutes or as a 15-minute infusion, also every 12 hours, with a maximum daily dose of 40 mg.

No additional 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)