Famotidine

Description

Famotidine Injection, USP contains famotidine as the active ingredient, which is 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. 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; 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.

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; safety or efficacy has not been assessed for durations longer than 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 mentioned in the available data.

Dosage and Administration

Famotidine Injection is indicated for use in adult and pediatric patients with specific conditions requiring gastric acid suppression.

For adult patients, the recommended dosage is 20 mg administered intravenously every 12 hours (q 12 h). In cases of pathological hypersecretory conditions, the same dosage of 20 mg every 12 hours is recommended, with adjustments made based on individual patient needs. For severe cases such as Zollinger-Ellison Syndrome, oral doses may be increased to 160 mg every 6 hours (q 6 h) as clinically indicated.

In pediatric patients under 1 year of age with gastroesophageal reflux disease (GERD), the dosing varies by age. For those less than 3 months old, the recommended dosage is 0.5 mg/kg of famotidine oral suspension once daily for up to 8 weeks. For patients aged 3 months to less than 1 year, the dosage 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, which should be injected over a period of not less than two minutes or as a 15-minute infusion, administered every 12 hours (q 12 h), with a maximum daily dose of 40 mg. Doses up to 0.5 mg/kg intravenously every 12 hours have been shown to effectively suppress gastric acid.

In patients with moderate or severe renal insufficiency, defined as creatinine clearance of less than 50 mL/min or less than 10 mL/min respectively, dosage adjustments are necessary. The dose may be reduced to half, or the dosing interval may be extended to 36 to 48 hours, depending on the clinical response.

For intravenous administration, it is essential to prepare the solution aseptically. To prepare intravenous solutions, 2 mL of Famotidine Injection (10 mg/mL) should be diluted with Sodium Chloride Injection 0.9% or another compatible intravenous solution to achieve a total volume of either 5 mL or 10 mL, which should then 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 agents within this class.

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 malignancy in symptomatic patients.

Side Effects

Patients receiving treatment may experience a range of adverse reactions. Common adverse reactions observed in clinical trials include headache (4.7%), dizziness (1.3%), diarrhea (1.7%), and constipation (1.2%).

Serious adverse reactions have been reported across various systems. In the body as a whole, patients may experience fever, asthenia, and fatigue. Cardiovascular events such as arrhythmia, AV block, palpitations, and prolonged QT interval have also been noted. Gastrointestinal reactions can include cholestatic jaundice, hepatitis, elevated liver enzymes, vomiting, nausea, abdominal discomfort, anorexia, and dry mouth.

Hematologic adverse reactions include agranulocytosis, pancytopenia, leukopenia, and thrombocytopenia. Hypersensitivity reactions may manifest as anaphylaxis, angioedema, orbital or facial edema, urticaria, rash, conjunctival injection, and bronchospasm. Musculoskeletal issues such as rhabdomyolysis, musculoskeletal pain, muscle cramps, and arthralgia have been reported as well.

Nervous system and psychiatric adverse reactions include seizures, hallucinations, confusion, agitation, depression, anxiety, decreased libido, paresthesia, insomnia, and somnolence. Respiratory adverse reactions may involve interstitial pneumonia. Skin reactions can range from toxic epidermal necrolysis/Stevens-Johnson syndrome to pruritus, dry skin, and flushing. Additionally, some patients may experience tinnitus and taste disorders, as well as impotence.

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, which resolved upon discontinuation of the medication.

It is important to note that Famotidine Injection in multiple dose vials (4 mL and 20 mL) contains the preservative benzyl alcohol. There have been reports of fatal 'gasping syndrome' in neonates (children less than one month of age) following the administration of intravenous solutions containing benzyl alcohol. Symptoms of this syndrome include a striking onset of gasping respiration, hypotension, bradycardia, and cardiovascular collapse. Given its ability to cross the placental barrier and the blood-brain barrier, Famotidine Injection from multiple dose vials containing benzyl alcohol should not be used in neonates and pregnant women.

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.

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

Pediatric patients under 1 year of age may be treated with famotidine based on evidence from adequate and well-controlled studies in adults, as well as studies specifically involving this age group. Pharmacokinetic studies indicate that famotidine clearance in patients aged 3 months to 1 year is comparable to that in older pediatric patients (1-15 years). However, infants aged 0-3 months exhibit clearance values that are 2- to 4-fold lower than those in older pediatric patients and adults. The mean bioavailability of famotidine after oral dosing in patients under 1 year is similar to that observed in older pediatric patients and adults. Notably, pharmacodynamic data suggest that the duration of acid suppression is prolonged in infants 0-3 months due to a longer half-life of famotidine in this age group.

For the treatment of gastroesophageal reflux disease (GERD), the recommended starting dose is 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 only be considered for GERD treatment if conservative measures, such as thickened feedings, are implemented concurrently, and if 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. For patients aged 11 to 15 years, oral doses of 0.5 mg/kg have shown a mean area under the curve (AUC) similar to that of adults receiving 40 mg orally. The starting intravenous dose for this age group 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 of 40 mg per day. Treatment duration and dosing should be tailored to the individual based on clinical response and/or gastric pH determination and endoscopy findings. Uncontrolled studies have demonstrated effective gastric acid suppression with doses up to 0.5 mg/kg intravenously every 12 hours in pediatric patients.

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 the potential 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.

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

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 from famotidine, healthcare professionals should consider the risks and benefits when advising lactating mothers. A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of famotidine to the mother’s health.

Renal Impairment

Patients with renal impairment have no specific information regarding dosage adjustments, special monitoring, or safety considerations provided in the text. Therefore, healthcare professionals should exercise caution and consider individual patient factors when prescribing to this population. Regular monitoring of renal function may be warranted to ensure patient safety and therapeutic 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 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.

Toxicological data indicate 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. In dogs treated with intravenous famotidine, signs of acute intoxication 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, 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.

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, 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

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 these patients may experience a prolonged elimination half-life of the medication.

Famotidine Injection contains benzyl alcohol, and healthcare providers should advise patients that it should not be used in neonates and pregnant women due to the associated 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 famotidine for the mother's health.

For pediatric patients under 1 year of age, famotidine oral suspension is recommended for the treatment of gastroesophageal reflux disease (GERD) for a duration of up to 8 weeks, with conservative measures such as thickened feedings employed concurrently.

The starting dose for pediatric patients aged 1 to 16 years is 0.25 mg/kg administered intravenously, either injected 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.

Healthcare providers should monitor patients for adverse reactions, particularly in pediatric patients, where agitation has been reported. It is important to note that this agitation resolved upon discontinuation of famotidine.

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 and utilized within 48 hours to ensure optimal quality and effectiveness.

Additional Clinical Information

Famotidine Injection may be administered until oral therapy can be instituted. The recommended dosage for adult patients is 20 mg intravenously every 12 hours. 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)