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 multi-dose formulation additionally contains 0.9% benzyl alcohol as a preservative.

Uses and Indications

Famotidine Injection is indicated for intravenous use in hospitalized patients with pathological hypersecretory conditions, intractable ulcers, and for short-term use in patients unable to take oral medication.

This drug is indicated for the short-term treatment of active duodenal ulcers, with most adult patients healing within 4 weeks. It is rarely used at full dosage for longer than 6 to 8 weeks, and safety has not been assessed for periods exceeding 8 weeks. Additionally, it is indicated for maintenance therapy in duodenal ulcer patients at a reduced dosage following the healing of an active ulcer; however, controlled studies in adults have not extended beyond one year.

Famotidine Injection 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 treatment 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 short-term treatment of esophagitis due to GERD, including erosive or ulcerative disease diagnosed by endoscopy.

Lastly, this drug is indicated for the treatment of pathological hypersecretory conditions, such as Zollinger-Ellison Syndrome and multiple endocrine adenomas.

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.

For pediatric patients under 1 year of age with gastroesophageal reflux disease (GERD), the starting dose is 0.5 mg/kg per dose 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.

In pediatric patients aged 1 to 16 years, the starting intravenous dose is 0.25 mg/kg, administered every 12 hours, with a maximum daily dose of 40 mg. The injection should be given 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 documented; 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, 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 as an adverse reaction.

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. Additionally, 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 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 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

Pediatric patients under 1 year of age may receive famotidine based on evidence from adequate and well-controlled studies in adults, as well as studies specifically 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 to 15 years). However, infants aged 0 to 3 months exhibited 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 patients under 1 year is similar to that observed in older pediatric patients and adults.

For the treatment of gastroesophageal reflux disease (GERD), the recommended starting dose for patients under 3 months of age is 0.5 mg/kg/dose of famotidine oral suspension once daily for up to 8 weeks. For patients aged 3 months to less than 1 year, the starting dose is 0.5 mg/kg/dose administered twice daily. The use of intravenous famotidine in this age group for GERD has not been adequately studied. Safety concerns include the observation of agitation in five patients under 1 year of age, which resolved upon discontinuation of the medication. The safety and efficacy of famotidine treatment beyond 4 weeks in patients under 1 year have not been established.

In pediatric patients aged 1 to 16 years, the use of famotidine is also supported by evidence from studies in adults and pediatric populations. Clearance of famotidine in this age group is similar to that seen 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, with a maximum of 40 mg per day. Treatment duration and dosing should be individualized based on clinical response and/or gastric pH determination and endoscopy. Uncontrolled studies have shown that gastric acid suppression can be achieved with doses up to 0.5 mg/kg intravenously every 12 hours.

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 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

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’s health.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available prescribing information. There are no dosage adjustments, special monitoring requirements, or safety considerations outlined for individuals with reduced kidney function. Healthcare professionals should exercise caution and consider the lack of data when prescribing to 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 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.

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 necessary.

Toxicity Data

Toxicological studies have established the intravenous LD50 of famotidine in mice and rats to range from 254 to 563 mg/kg, while the minimum lethal single intravenous dose in dogs is approximately 300 mg/kg. Signs of acute intoxication in dogs treated intravenously include emesis, restlessness, pallor of mucous membranes or redness of the mouth and ears, hypotension, tachycardia, and potential collapse.

The oral LD50 of famotidine has been determined to be greater than 3000 mg/kg in both male and female rats and mice, with the minimum lethal acute oral dose in dogs exceeding 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 when administered 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 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 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 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 have been reported during domestic and international clinical trials involving approximately 2,500 patients. The most common reactions included headache (4.7%), dizziness (1.3%), constipation (1.2%), and diarrhea (1.7%).

Infrequent adverse reactions have also been reported in clinical trials or since the drug's marketing. These include fever, asthenia, fatigue, arrhythmia, atrioventricular (AV) block, palpitation, prolonged QT interval, cholestatic jaundice, hepatitis, elevated liver enzymes, vomiting, nausea, abdominal discomfort, anorexia, dry mouth, agranulocytosis, pancytopenia, leukopenia, thrombocytopenia, anaphylaxis, angioedema, orbital or facial edema, urticaria, rash, conjunctival injection, bronchospasm, rhabdomyolysis, musculoskeletal pain, muscle cramps, arthralgia, seizure, hallucinations, confusion, agitation, depression, anxiety, decreased libido, paresthesia, insomnia, somnolence, interstitial pneumonia, toxic epidermal necrolysis/Stevens-Johnson syndrome, pruritus, dry skin, flushing, tinnitus, taste disorder, and 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.

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 to ensure patients understand the need for further evaluation if symptoms persist.

For patients with moderate or severe renal insufficiency, healthcare providers should discuss the necessity of adjusting the dosing regimen. These patients may require longer intervals between doses or lower doses due to the prolonged elimination half-life of famotidine.

Patients should be advised that famotidine is secreted into breast milk. Healthcare providers should guide patients in making an informed decision regarding whether to discontinue nursing or to discontinue the medication, taking into account the importance of famotidine for the mother’s health.

In pediatric patients under 1 year of age, famotidine should only be administered if conservative measures, such as thickened feedings, are implemented concurrently and if the potential benefits outweigh the risks. Caregivers of these pediatric patients should be instructed to provide conservative treatment, including thickened feedings, to support the management of their condition.

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

Additionally, patients should be made aware that the use of famotidine in pediatric patients under 1 year of age has not been adequately studied for intravenous administration, and caution should be exercised in this population.

Finally, patients should be encouraged to report any suspected adverse reactions to their healthcare provider or the FDA, fostering an open line of communication regarding their treatment and safety.

Storage and Handling

Famotidine Injection is supplied in a refrigerated state and must be stored at temperatures between 2° and 8°C (36° and 46°F). It is essential to ensure that the solution does not freeze; if freezing occurs, the solution should be brought back to room temperature and allowed sufficient time to solubilize all components before use.

Once diluted, Famotidine Injection should also be refrigerated and is recommended for use within 48 hours if not utilized immediately after preparation. Proper handling and storage conditions are critical to maintaining the integrity and efficacy of the product.

Additional Clinical Information

The recommended dosage for Famotidine Injection in adult patients is 20 mg administered intravenously every 12 hours. For pediatric patients aged 1 to 16 years, the suggested starting dose is 0.25 mg/kg intravenously, which should be injected over a period of not less than two minutes or as a 15-minute infusion, also every 12 hours, with a maximum daily limit of 40 mg.

FDA Insert (PDF)

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

View full prescribing information (PDF)