Famotidine

Description

Famotidine Injection contains famotidine, a histamine H2-receptor antagonist, with the chemical structure N'-(aminosulfonyl)-3-[[[2-(diaminomethylene)amino-4-thiazolyl]methyl]thio]propanimidamide. The empirical formula is C8H15N7O2S3, and the molecular weight is 337.45 g/mol. Famotidine appears as a white to pale yellow crystalline compound, exhibiting solubility characteristics of being 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 solution intended for intravenous administration, packaged in plastic single-dose GALAXY containers. Each 50 mL of the premixed, iso-osmotic injection contains 20 mg of famotidine, USP, along with inactive ingredients including 6.8 mg of L-aspartic acid, 450 mg of sodium chloride, USP, and Water for Injection. The pH of the solution ranges from 5.7 to 6.4, which may be adjusted with additional L-aspartic acid and/or sodium hydroxide.

The GALAXY plastic container is constructed from a specially designed multilayer plastic, ensuring compatibility with the solution. It is noted that the solutions may come into contact with the polyethylene layer of the container, which can leach certain chemical components in minimal amounts during the expiration period. The safety and suitability of the plastic have been validated through animal testing in accordance with USP biological tests for plastic containers, as well as tissue culture toxicity studies.

Uses and Indications

Famotidine Injection is indicated for use in certain hospitalized patients with pathological hypersecretory conditions or intractable ulcers, as well as for short-term use in patients unable to take oral medication. The specific indications include:

1. Short-term treatment of active duodenal ulcer: Most adult patients heal within 4 weeks; prolonged use at full dosage beyond 6 to 8 weeks is rarely warranted. The safety of famotidine has not been evaluated for uncomplicated active duodenal ulcer treatment beyond 8 weeks.

2. Maintenance therapy for duodenal ulcer: Famotidine is indicated at a reduced dosage for patients who have healed from an active duodenal ulcer. Controlled studies in adults have not assessed efficacy beyond one year.

3. Short-term treatment of active benign gastric ulcer: Most adult patients heal within 6 weeks. The safety and efficacy of famotidine for uncomplicated active benign gastric ulcer have not been studied for periods exceeding 8 weeks.

4. Short-term treatment of gastroesophageal reflux disease (GERD): Famotidine is indicated for patients experiencing symptoms of GERD, including the short-term treatment of esophagitis due to GERD, such as erosive or ulcerative disease diagnosed via endoscopy.

5. Treatment of pathological hypersecretory conditions: This includes conditions such as Zollinger-Ellison Syndrome and multiple endocrine adenomas.

No specific teratogenic or nonteratogenic effects have been mentioned in the provided information.

Dosage and Administration

In hospitalized patients with pathological hypersecretory conditions, intractable ulcers, or 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 also be 20 mg every 12 hours, with adjustments made based on individual patient needs. Treatment should continue as long as clinically indicated, and in some cases, a higher starting dose may be necessary.

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. Uncontrolled studies have shown that doses up to 0.5 mg/kg intravenously every 12 hours can effectively suppress gastric acid in this age group.

Famotidine Injection is supplied in GALAXY containers as a 50 mL iso-osmotic solution premixed with 0.9% sodium chloride. This solution is intended for intravenous use only and should be administered using sterile equipment. The infusion should be delivered 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, administration is also contraindicated in individuals with a history of hypersensitivity to other H2-receptor antagonists.

Warnings and Precautions

Healthcare professionals should be aware that a symptomatic response to therapy with famotidine does not exclude the possibility of gastric malignancy. It is essential to consider that while famotidine may alleviate symptoms associated with gastric conditions, the underlying presence of malignancy must be ruled out through appropriate diagnostic evaluations.

Regular monitoring and assessment of patients presenting with gastrointestinal symptoms are recommended to ensure that any potential malignancies are identified and managed promptly. Healthcare providers should remain vigilant and consider further investigative procedures if symptoms persist or worsen despite treatment.

Side Effects

Patients may experience a range of adverse reactions while using this medication. Common adverse reactions, occurring in at least 1% 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 reactions may include fever, asthenia, and fatigue. Cardiovascular events such as arrhythmia, AV block, palpitations, and prolonged QT interval have also been noted. Gastrointestinal disturbances may manifest as cholestatic jaundice, hepatitis, liver enzyme abnormalities, vomiting, nausea, abdominal discomfort, anorexia, and dry mouth.

Hematologic reactions are rare but include agranulocytosis, pancytopenia, leukopenia, and thrombocytopenia. Hypersensitivity reactions can occur, including anaphylaxis, angioedema, orbital or facial edema, urticaria, rash, and conjunctival injection. Musculoskeletal pain, including muscle cramps and arthralgia, has been reported.

Nervous system and psychiatric adverse reactions may include grand mal seizures, psychic disturbances (which are reversible), such as hallucinations, confusion, agitation, depression, anxiety, decreased libido, paresthesia, insomnia, and somnolence. Convulsions have been reported in patients with impaired renal function. Respiratory issues such as bronchospasm and interstitial pneumonia have also been observed.

Skin reactions can range from toxic epidermal necrolysis/Stevens-Johnson syndrome to alopecia, acne, pruritus, dry skin, and flushing. Special senses may be affected, with reports of tinnitus and taste disorders. Additionally, rare cases of impotence and gynecomastia have been documented; however, in controlled clinical trials, the incidences were not greater than those seen with placebo.

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. Central nervous system adverse reactions have been particularly noted in elderly patients and those with moderate to severe renal insufficiency, with prolonged QT intervals also reported in this population.

Drug Interactions

Famotidine may influence the absorption and efficacy of other medications due to its ability to reduce intragastric acidity. This effect can lead to decreased absorption of drugs that rely on gastric pH for optimal bioavailability. Healthcare professionals should consult the prescribing information for specific drugs that may be affected by famotidine.

In terms of pharmacokinetic interactions, famotidine is considered a weak inhibitor of the CYP1A2 enzyme. The concomitant administration of famotidine with tizanidine, which is a substrate of CYP1A2, may result in increased plasma levels of tizanidine. This interaction could potentially lead to adverse effects such as hypotension, bradycardia, or excessive drowsiness. It is advisable to avoid the combined use of these medications. If the combination is deemed necessary for clinical reasons, healthcare providers should refer to the full prescribing information for tizanidine to determine appropriate dosage adjustments and monitoring requirements.

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 have been administered famotidine intravenously at a dosage of 0.5 mg/kg. Pharmacokinetic studies indicate that in infants aged 0-1 month (N=10), the total clearance is 0.13 ± 0.06 L/hr/kg, with a volume of distribution of 1.4 ± 0.4 L/kg and an elimination half-life of 10.5 ± 5.4 hours. For those aged 0-3 months (N=6), the area under the curve (AUC) is 2688 ± 847 ng-hr/mL, total clearance is 0.21 ± 0.06 L/hr/kg, volume of distribution is 1.8 ± 0.3 L/kg, and the elimination half-life is 8.1 ± 3.5 hours. In patients older than 3 months to 12 months (N=11), the AUC is 1160 ± 474 ng-hr/mL, total clearance is 0.49 ± 0.17 L/hr/kg, volume of distribution is 2.3 ± 0.7 L/kg, and the elimination half-life is 4.5 ± 1.1 hours.

For pediatric patients aged 1-11 years (N=20), pharmacokinetic parameters show an AUC of 1089 ± 834 ng-hr/mL, total clearance of 0.54 ± 0.34 L/hr/kg, volume of distribution of 2.07 ± 1.49 L/kg, and an elimination half-life of 3.38 ± 2.60 hours. In adolescents aged 11-15 years (N=6), the AUC is 1140 ± 320 ng-hr/mL, total clearance is 0.48 ± 0.14 L/hr/kg, volume of distribution is 1.5 ± 0.4 L/kg, and the elimination half-life is 2.3 ± 0.4 hours.

Notably, plasma clearance is reduced and the elimination half-life is prolonged in pediatric patients aged 0-3 months compared to older pediatric patients. Pharmacokinetic parameters for those aged over 3 months to 15 years are comparable to those observed in adults. Bioavailability studies in adolescents (11-15 years) indicate a mean oral bioavailability of 0.5.

Oral doses of 0.5 mg/kg resulted in AUCs of 645 ± 249 ng-hr/mL in patients under 1 year of age (N=5) and 580 ± 60 ng-hr/mL in those aged 11-15 years. The administration of a single intravenous dose of 0.5 mg/kg maintained gastric pH >4 for 19.5 hours in 11 patients aged 5-19 days. In children aged 2-7 years, a single intravenous dose of 0.3 mg/kg resulted in gastric pH >3.5 for 8.7 ± 4.7 hours. Additionally, intravenous doses of 0.4-0.8 mg/kg maintained gastric pH >4 for 6-9 hours in 18 patients aged 2-69 months.

The duration of effect of famotidine I.V. 0.5 mg/kg on gastric pH and acid suppression is longer in pediatric patients under 1 month of age compared to older 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, in post-marketing experience, central nervous system (CNS) adverse reactions have been reported among elderly patients, both with and without renal impairment, who received famotidine. Given that famotidine is substantially excreted by the kidneys, the risk of toxic reactions may be heightened in patients with impaired renal function.

Elderly patients are more likely to experience decreased renal function; therefore, it is essential to monitor renal function closely in this population. Dosage adjustments are necessary for patients with moderate or severe renal impairment 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.

Renal Impairment

In patients with moderate (creatinine clearance <50 mL/min) or severe (creatinine clearance <10 mL/min) renal insufficiency, the elimination half-life of famotidine is significantly increased, potentially exceeding 20 hours and reaching approximately 24 hours in anuric patients. To prevent excess accumulation of the drug, the dose of Famotidine Injection may be reduced to half the standard dose, or the dosing interval may be extended to 36-48 hours, depending on the patient's clinical response.

CNS adverse effects have been observed in patients with moderate and severe renal insufficiency, necessitating careful monitoring. Additionally, dosage adjustments should be considered for pediatric patients with moderate or severe renal impairment. In elderly patients, who are more likely to have decreased renal function, the clearance of famotidine may also be reduced, warranting regular monitoring of renal function.

The standard recommended dosage for Famotidine Injection in adult patients is 20 mg intravenously every 12 hours; however, adjustments may be required for those with renal impairment. Given the correlation between elimination half-life and creatinine clearance, longer intervals between doses or lower doses may be necessary for both adult and pediatric patients with moderate and severe renal insufficiency.

Hepatic Impairment

Patients with hepatic impairment do not require specific dosage adjustments or precautions when receiving treatment. Additionally, there is no information provided regarding the necessity for liver function tests in this patient population. Furthermore, the prescribing information does not indicate any specific cautions or monitoring recommendations for patients with compromised liver function.

Overdosage

In cases of overdosage, the adverse reactions observed are consistent with those encountered during normal clinical use. While oral doses of up to 640 mg/day have been administered to adult patients with pathological hypersecretory conditions without serious adverse effects, caution is warranted in the event of an overdose.

Management of Overdosage Treatment for overdosage should be symptomatic and supportive. Patients should be closely monitored, and supportive therapy should be initiated as necessary. Due to famotidine's low binding to plasma proteins, it is primarily eliminated through hemodialysis. However, there is limited experience regarding the efficacy of hemodialysis as a treatment for famotidine overdosage.

Toxicity and Symptoms The intravenous LD50 of famotidine in animal studies has been reported to range from 254 to 563 mg/kg for mice and rats, with a minimum lethal single intravenous dose in dogs estimated at approximately 300 mg/kg. Signs of acute intoxication in intravenously treated dogs included emesis, restlessness, pallor of mucous membranes or redness of the mouth and ears, hypotension, tachycardia, and collapse.

In terms of oral toxicity, the LD50 of famotidine in male and female rats and mice exceeds 3000 mg/kg, while the minimum lethal acute oral dose in dogs is greater than 2000 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 starting at doses of 200 mg/kg/day orally.

Healthcare professionals should remain vigilant for these symptoms and manage the patient accordingly in the event of an overdose.

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. The results were negative for mutagenic effects. Additionally, in vivo studies in mice, including a micronucleus test and a chromosomal aberration test, also showed no evidence of mutagenicity.

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

CNS adverse reactions have been reported in elderly patients and those with moderate to severe renal insufficiency. Prolonged QT intervals have also been noted in patients with similar renal conditions. In a clinical study involving 35 pediatric patients under 1 year of age with GERD symptoms, agitation was observed in 5 patients receiving famotidine; these symptoms resolved upon discontinuation of the medication.

Adverse reactions associated with famotidine tablets may also occur with famotidine for oral suspension, famotidine injection in Galaxy plastic containers, and famotidine injection. Transient irritation at the injection site has been documented with famotidine injection.

In controlled clinical trials, the following adverse reactions were reported in more than 1% of patients receiving famotidine: headache (4.7%), dizziness (1.3%), constipation (1.2%), and diarrhea (1.7%). Other adverse reactions reported infrequently in clinical trials or post-marketing include fever, asthenia, fatigue, arrhythmia, AV block, palpitations, prolonged QT interval, cholestatic jaundice, hepatitis, liver enzyme abnormalities, vomiting, nausea, abdominal discomfort, anorexia, dry mouth, and rare cases of agranulocytosis, pancytopenia, leukopenia, thrombocytopenia, anaphylaxis, angioedema, orbital or facial edema, urticaria, rash, conjunctival injection, musculoskeletal pain (including muscle cramps and arthralgia), grand mal seizures, and psychic disturbances (reversible), such as hallucinations, confusion, agitation, depression, anxiety, decreased libido, paresthesia, insomnia, somnolence, bronchospasm, interstitial pneumonia, toxic epidermal necrolysis/Stevens-Johnson syndrome, alopecia, acne, pruritus, dry skin, flushing, tinnitus, taste disorder, and rare cases of impotence and gynecomastia.

In cases of overdose, the adverse reactions observed are similar to those encountered in normal clinical experience.

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. This adjustment is crucial to ensure patient safety and efficacy of treatment.

Patients should also be made aware that famotidine can reduce the absorption of other medications that rely on gastric pH for their effectiveness. This interaction may lead to a loss of efficacy of those drugs, and healthcare providers should discuss this potential issue with patients.

In cases where patients are taking tizanidine, a CYP1A2 substrate, it is essential to advise them to avoid concomitant use with famotidine unless clinically necessary. This combination may result in increased exposure to tizanidine and a higher risk of adverse reactions.

Healthcare providers should inform patients that famotidine is secreted into breast milk. A careful decision should be made regarding whether to discontinue nursing or to discontinue the medication, taking into account the importance of famotidine to the mother’s health.

For pediatric patients under one year of age, famotidine should only be administered if conservative measures are concurrently employed and if the potential benefits outweigh the risks. This consideration is vital for the safety of young patients.

Patients should be instructed to inspect the container for minute leaks prior to use by squeezing the bag firmly. If any leaks are detected, the solution should be discarded, as sterility may be compromised. Additionally, patients should not use the solution unless it is clear and the seal is intact.

Antacids may be administered concomitantly if needed, and healthcare providers should reassure patients about this option. Furthermore, patients should be advised to avoid excessive heat exposure to the premixed product, although brief exposure to temperatures up to 35°C (95°F) does not adversely affect the product.

Storage and Handling

Famotidine Injection is supplied in GALAXY containers. It should be stored at room temperature, specifically at 25°C (77°F). Care should be taken to avoid exposure of the premixed product to excessive heat. However, brief exposure to temperatures up to 35°C (95°F) is acceptable and does not adversely affect the product.

Additional Clinical Information

Famotidine Injection is provided as a premixed solution in GALAXY plastic containers, specifically for intravenous administration. For adult patients, the recommended dosage is 20 mg administered intravenously every 12 hours. In pediatric patients aged 1 to 16 years, the starting dose is 0.25 mg/kg intravenously, which can be injected over a minimum of two minutes or delivered as a 15-minute infusion, also every 12 hours, with a maximum daily limit of 40 mg. The safety and efficacy of intravenous famotidine in pediatric patients under 1 year of age with gastroesophageal reflux disease (GERD) have not been adequately studied.

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 Baxter Healthcare Corporation. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)