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, 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 multiple-dose vials, available in 4 mL and 20 mL sizes, also contain 0.9% benzyl alcohol as a preservative.

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.

For patients who have healed from an active duodenal ulcer, Famotidine Injection may be used as maintenance therapy at a reduced dosage, although controlled studies in adults have not extended beyond one year. Additionally, it is 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 treatment periods exceeding 8 weeks.

Famotidine Injection is also indicated for the short-term treatment of gastroesophageal reflux disease (GERD) in patients with symptoms, as well as 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.

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 those 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 and should continue as long as clinically indicated.

In pediatric patients aged 1 to 16 years, the starting dose 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.

It is important to note that the doses and regimen for parenteral administration in patients with gastroesophageal reflux disease (GERD) have not been established.

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 formulation. 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.

Consideration of Gastric Malignancy 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, 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 reactions reported, though less frequently, encompass fever, asthenia, and fatigue.

Serious adverse reactions may involve cardiovascular events such as arrhythmia, AV block, palpitations, and prolonged QT interval. Hematologic issues, including agranulocytosis, pancytopenia, leukopenia, and thrombocytopenia, have also been noted. Hypersensitivity reactions can manifest as anaphylaxis, angioedema, orbital or facial edema, urticaria, rash, conjunctival injection, and bronchospasm.

Gastrointestinal adverse reactions may include cholestatic jaundice, hepatitis, elevated liver enzymes, vomiting, nausea, abdominal discomfort, anorexia, and dry mouth. Additionally, musculoskeletal reactions such as rhabdomyolysis, musculoskeletal pain, muscle cramps, and arthralgia have been reported.

Nervous system and psychiatric effects may present as seizures, hallucinations, confusion, agitation, depression, anxiety, decreased libido, paresthesia, insomnia, and somnolence. Respiratory complications, including interstitial pneumonia, have also been documented.

Skin reactions can range from toxic epidermal necrolysis/Stevens-Johnson syndrome to pruritus, dry skin, and flushing. Special senses may be affected, leading to tinnitus and taste disorders. Other notable reactions include impotence.

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. Furthermore, transient irritation at the injection site has been noted with 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

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 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 after oral dosing in pediatric patients under 1 year is similar to that seen in older pediatric patients and adults. Pharmacodynamic data indicate that the duration of acid suppression in pediatric patients aged 0 to 3 months is longer compared to older pediatric patients, which aligns with the longer half-life of famotidine in this younger group.

In a double-blinded, randomized treatment-withdrawal study, 35 pediatric patients under 1 year 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. A starting dose of 0.5 mg/kg/dose may be beneficial for treating GERD in patients under 3 months of age for up to 4 weeks, while patients aged 3 months to less than 1 year may receive the medication twice daily.

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 in some older patients cannot be ruled out.

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, particularly 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 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

Studies performed in lactating rats have shown that famotidine is secreted into breast milk. Famotidine is also 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 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 this patient population.

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. While oral doses of up to 640 mg/day have been administered to adult patients suffering from pathological hypersecretory conditions without any serious adverse effects, caution is still warranted.

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 initiated as necessary.

Potential Symptoms

Acute intoxication has been documented in intravenous-treated dogs, presenting with symptoms such as emesis, restlessness, pallor of mucous membranes, redness of the mouth and ears, hypotension, tachycardia, and potential collapse. These signs indicate a need for immediate medical attention.

Toxicity Data

The intravenous LD50 of famotidine in laboratory animals, such as 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 contrast, the oral LD50 for famotidine in both male and female rats and mice exceeds 3000 mg/kg, and the minimum lethal acute oral dose in dogs is greater than 2000 mg/kg. Notably, famotidine does not produce overt effects at high oral doses in mice, rats, cats, and dogs; however, it has been observed to 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 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 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 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, yielding negative results. Additionally, in vivo studies in mice, including a micronucleus test and a chromosomal aberration test, showed no evidence of mutagenic effects.

Studies involving rats administered oral doses of up to 2000 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 marketing, with unclear relationships to famotidine therapy in many cases. 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, which has been linked to fatal ‘gasping syndrome’ in neonates. Therefore, healthcare providers should advise patients that this medication should not be used in 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 importance of famotidine for the mother’s health.

For pediatric patients under 1 year of age, famotidine should only be administered if conservative measures are concurrently employed and if the potential benefits outweigh the risks. The recommended starting dose for pediatric patients under 3 months of age is 0.5 mg/kg/dose of famotidine oral suspension once daily. For patients aged 3 months to less than 1 year, the recommended dose is 0.5 mg/kg/dose twice daily.

Healthcare providers should monitor patients for adverse reactions, particularly in pediatric patients, where agitation has been observed during clinical studies. It is important to ensure that patients and caregivers are aware of these potential side effects and the need for ongoing assessment.

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°C to 8°C (36°F 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

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 as follows: infants less than 3 months of age should receive 0.5 mg/kg of famotidine oral suspension once daily for up to 8 weeks, while those aged 3 months to less than 1 year should receive 0.5 mg/kg twice daily. For pediatric patients aged 1 to 16 years, the starting dose is 0.25 mg/kg intravenously, injected over a minimum of 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 Hikma Pharmaceuticals USA Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)