Famotidine

Description

The active ingredient in Famotidine Injection is a histamine H2-receptor antagonist. Famotidine, USP is N'-(aminosulfonyl)-3-[[[2-(diaminomethylene)amino-4 thiazolyl]methyl]thio]propanimidamide. The empirical formula of famotidine is C8H15N7O2S3, and its molecular weight is 337.45. Famotidine, USP 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 supplied as a premixed, ready-to-use, sterile solution for intravenous injection. Each mL contains 4 mg of famotidine along with the following inactive ingredients: L-aspartic acid 1.6 mg, mannitol 8 mg, sodium chloride 7 mg, and Water for Injection q.s. 1 mL. The multiple-dose vials of 10 mL and 50 mL also contain benzyl alcohol 0.36% (3.6 mg per mL) as a preservative. The pH for all concentrations ranges from 5.7 to 6.4 and may have been adjusted with sodium hydroxide.

Uses and Indications

FAMOTIDINE Injection is indicated for the treatment of active duodenal ulcer (DU) in hospitalized adults, and may be used as an alternative to oral famotidine in this population. It is also indicated for the treatment of active gastric ulcer (GU) in hospitalized adults, as well as for symptomatic nonerosive gastroesophageal reflux disease (GERD) in hospitalized adults, with the option of using it as an alternative to oral famotidine.

Additionally, FAMOTIDINE Injection is indicated for the treatment of erosive esophagitis due to GERD, diagnosed by endoscopy, in hospitalized adults, and may serve as an alternative to oral famotidine. The drug is also indicated for the treatment of pathological hypersecretory conditions, such as Zollinger-Ellison syndrome and multiple endocrine neoplasias, in hospitalized adults, with the same alternative option to oral famotidine.

Furthermore, FAMOTIDINE Injection is indicated for the reduction of the risk of duodenal ulcer recurrence in hospitalized adults, or as an alternative to oral famotidine. In pediatric patients aged 1 year and older, FAMOTIDINE Injection is indicated for the treatment of peptic ulcer disease, also serving as an alternative to oral famotidine in this age group.

No teratogenic or nonteratogenic effects have been reported.

Dosage and Administration

Famotidine Injection is indicated for use in adult and pediatric hospitalized patients, serving as an alternative to oral famotidine. Treatment should be discontinued as soon as the patient is able to tolerate oral medication, at which point an appropriate oral formulation should be initiated.

For adults, the recommended dosage is 20 mg administered every 12 hours. In cases of pathological hypersecretory conditions, the dosage may be titrated according to individual patient needs.

For pediatric patients aged 1 year and older, the recommended dosage is 0.25 mg/kg administered every 12 hours, with the possibility of titration to a maximum of 0.5 mg/kg every 12 hours, not exceeding 20 mg every 12 hours. This adjustment should be based on clinical response, gastric pH determination, and endoscopic findings.

Famotidine Injection should be administered as an intravenous injection over a minimum of 2 minutes or as an intravenous infusion over a period of 15 to 30 minutes. For guidance on the recommended duration of famotidine treatment, healthcare professionals should refer to the prescribing information for oral famotidine products.

Contraindications

Use is contraindicated in patients with a history of serious hypersensitivity reactions, including anaphylaxis, to famotidine or other H2-receptor antagonists. Due to the potential for severe allergic reactions, administration in these individuals may pose significant health risks.

Warnings and Precautions

Central Nervous System (CNS) adverse reactions have been reported, particularly in elderly patients and those with moderate to severe renal impairment. It is imperative that healthcare professionals closely monitor elderly patients for any signs of CNS-related adverse effects during treatment.

The presence of gastrointestinal (GI) symptoms should not be used to rule out the possibility of concurrent GI malignancy. A thorough evaluation is recommended prior to initiating therapy to ensure that any underlying gastric malignancy is identified and addressed.

Famotidine Injection is contraindicated in neonates due to the risk of benzyl alcohol toxicity. Serious and potentially fatal adverse reactions have been documented in low-birth weight and preterm neonates who have received intravenous medications containing benzyl alcohol. The threshold amount of benzyl alcohol that may lead to these serious adverse reactions remains undetermined, underscoring the importance of avoiding its use in this vulnerable population.

Side Effects

Patients may experience a range of adverse reactions while receiving treatment. Common adverse reactions, occurring in more than 1% of patients, include headache, dizziness, constipation, and diarrhea.

Less common adverse reactions, occurring in less than 1% of patients, are categorized as follows:

Body as a Whole: Fever, asthenia, and fatigue have been reported.

Cardiovascular: Palpitations may occur.

Gastrointestinal: Patients may experience cholestatic jaundice, elevated liver enzymes, vomiting, nausea, abdominal discomfort, anorexia, and dry mouth.

Hematologic: Thrombocytopenia has been noted.

Hypersensitivity: Reactions such as orbital edema, rash, conjunctival injection, and bronchospasm have been observed.

Musculoskeletal: Musculoskeletal pain and arthralgia are possible.

Nervous System/Psychiatric: Adverse reactions in this category include seizures, hallucinations, depression, anxiety, decreased libido, insomnia, and somnolence.

Respiratory: Interstitial pneumonia has been reported.

Skin: Patients may experience pruritus, dry skin, and flushing.

Special Senses: Tinnitus and taste disorders have been noted.

Other: Impotence has also been reported.

Postmarketing experience has revealed additional adverse reactions. Cardiovascular events such as arrhythmia, AV block, and prolonged QT interval have been documented. Gastrointestinal issues, including cholestatic jaundice and hepatitis, have also been reported. Hematologic reactions such as agranulocytosis, pancytopenia, and leukopenia have been observed.

Hypersensitivity reactions in the postmarketing setting include anaphylaxis, angioedema, facial edema, and urticaria. Musculoskeletal adverse reactions such as rhabdomyolysis and muscle cramps have been noted. Nervous system and psychiatric reactions include confusion, agitation, and paresthesia. Respiratory issues, particularly interstitial pneumonia, have been reported as well. Skin reactions such as toxic epidermal necrolysis and Stevens-Johnson syndrome have been observed.

It is important to monitor elderly patients and those with moderate to severe renal impairment for central nervous system adverse reactions. Additionally, there is a risk of benzyl alcohol toxicity in neonates, with serious and potentially fatal reactions reported in low-birth weight and preterm neonates receiving benzyl-alcohol-containing drugs intravenously. A history of serious hypersensitivity reactions, such as anaphylaxis to famotidine or other H2-receptor antagonists, should be taken into consideration when treating patients.

Drug Interactions

Concomitant use of tizanidine with other medications that inhibit CYP1A2 may lead to significant increases in blood concentrations of tizanidine. This elevation can result in adverse effects such as hypotension, bradycardia, or excessive drowsiness. Therefore, it is advisable to avoid the concomitant use of tizanidine with CYP1A2 inhibitors whenever possible.

No information regarding drug and laboratory test interactions has been provided.

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

The safety and effectiveness of Famotidine Injection have been established in pediatric patients aged 1 year to less than 17 years for the treatment of peptic ulcer disease in hospitalized patients or as an alternative to oral famotidine. However, a safe and effective dosage has not been established for this age group in the presence of renal impairment.

For pediatric patients less than 1 year of age, the safety and effectiveness of Famotidine Injection for the treatment of peptic ulcer disease have not been established. Additionally, the use of Famotidine Injection for symptomatic nonerosive gastroesophageal reflux disease (GERD), erosive esophagitis due to GERD, pathological hypersecretory conditions, and the reduction of the risk of duodenal ulcer recurrence has not been established in pediatric patients.

Famotidine Injection is not approved for use in neonates. Serious adverse reactions, including new onset or worsening metabolic acidosis that progressed to neurotoxicity, and in some cases gasping syndrome, have been reported in low-birth weight and preterm neonates who received benzyl alcohol-containing drugs intravenously.

Geriatric Use

In clinical studies involving 1,442 patients treated with oral famotidine, approximately 10% were aged 65 years and older. These studies did not reveal any overall differences in safety or effectiveness between elderly patients and their younger counterparts.

Pharmacokinetic evaluations indicate that there are no clinically significant age-related changes in the pharmacokinetics of famotidine in geriatric patients. However, it is important to note that famotidine is substantially excreted by the kidneys, which may elevate the risk of adverse reactions in elderly patients, particularly those with impaired renal function.

Postmarketing experience has highlighted the occurrence of central nervous system (CNS) adverse reactions in elderly patients, both with and without renal impairment, who are receiving famotidine. Therefore, it is essential to monitor elderly patients closely for any CNS adverse reactions during treatment.

Given these considerations, healthcare providers should exercise caution and consider renal function when prescribing famotidine to geriatric patients, as dose adjustments may be necessary to mitigate the risk of adverse effects.

Pregnancy

Available data from decades of use of H2-receptor antagonists, including famotidine, in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Reproductive studies conducted in rats and rabbits at intravenous doses of up to 200 mg/kg/day and oral doses of up to 2,000 mg/kg/day in rats and 500 mg/kg/day in rabbits have shown no significant evidence of impaired fertility or harm to the fetus due to famotidine.

Famotidine Injection contains benzyl alcohol as a preservative. However, benzyl alcohol is rapidly metabolized by a pregnant female, making fetal exposure to benzyl alcohol unlikely.

It is important to note that the background risk for major birth defects and miscarriage in the indicated population is unknown. All pregnancies carry a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the background risk of major birth defects and miscarriage in clinically recognized pregnancies is estimated to be 2% to 4% and 15% to 20%, respectively. Therefore, healthcare professionals should consider these factors when prescribing famotidine to pregnant patients.

Lactation

There are limited data available on the presence of famotidine in human breast milk following oral administration. Clinical observations indicate that there were no effects on the breastfed infant. However, there are no data regarding the effects of famotidine on milk production.

Famotidine Injection contains benzyl alcohol as a preservative. Given that benzyl alcohol is rapidly metabolized by a lactating female, exposure to benzyl alcohol in the breastfed neonate is unlikely.

When considering the use of Famotidine Injection in lactating mothers, the developmental and health benefits of breastfeeding should be weighed against the mother's clinical need for the medication and any potential adverse effects on the breastfed child from famotidine or from the underlying maternal condition.

Renal Impairment

Patients with moderate and severe renal impairment may experience CNS adverse reactions and prolonged QT intervals. The clearance of famotidine is significantly reduced in these patients compared to those with normal renal function. For adults with moderate or severe renal impairment, defined as a creatinine clearance of less than 60 mL/minute, the recommended dosage is lower than that for adults with normal renal function. In contrast, adults with mild renal impairment, characterized by a creatinine clearance of 60 mL/minute or greater, may receive the same dosage as those with normal renal function. Currently, there is insufficient data to establish a safe and effective dosage for pediatric patients aged 1 year to less than 17 years with renal impairment for the treatment of peptic ulcer disease.

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 experienced at the recommended dosage levels. It is essential for healthcare professionals to recognize that the management of overdosage should be primarily symptomatic and supportive. Continuous monitoring of the patient is crucial, and supportive therapy should be initiated as necessary.

Famotidine exhibits low binding to plasma proteins, which allows for its elimination through hemodialysis. However, it is important to note that there is limited clinical experience regarding the efficacy of hemodialysis in the management of famotidine overdosage.

For further guidance on overdose management, healthcare professionals are advised to contact the Poison Help line at 1-800-222-1222 or consult a medical toxicologist. This can provide additional recommendations tailored to the specific circumstances of the overdose.

Nonclinical Toxicology

The carcinogenic potential of intravenously administered famotidine has not been established. In a 106-week study conducted in rats and a 92-week study in mice, oral doses of up to 2,000 mg/kg/day did not demonstrate any evidence of carcinogenicity associated with famotidine.

Famotidine was evaluated for mutagenic potential in the bacterial 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.

In studies involving rats administered oral doses of up to 2,000 mg/kg/day or intravenous doses of up to 200 mg/kg/day, there were no observed effects on fertility or reproductive performance.

Postmarketing Experience

During post-approval use of famotidine, various adverse reactions have been reported voluntarily from a population of uncertain size. As a result, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiovascular events include arrhythmia, AV block, and prolonged QT interval. Gastrointestinal reactions consist of cholestatic jaundice and hepatitis. Hematologic adverse events reported include agranulocytosis, pancytopenia, and leukopenia.

Hypersensitivity reactions have been noted, such as anaphylaxis, angioedema, facial edema, and urticaria. Musculoskeletal issues include rhabdomyolysis and muscle cramps. Nervous system and psychiatric events encompass confusion, agitation, and paresthesia.

Respiratory adverse reactions include interstitial pneumonia, while skin reactions reported are toxic epidermal necrolysis and Stevens-Johnson syndrome.

Patient Counseling

Healthcare providers should advise elderly patients and those with moderate to severe renal impairment about the potential risk of central nervous system (CNS) adverse reactions. These may include symptoms such as confusion, delirium, hallucinations, disorientation, agitation, seizures, and lethargy. Patients should be instructed to report any of these symptoms immediately to their healthcare provider.

Additionally, it is important to inform patients with moderate and severe renal impairment about the risk of QT interval prolongation associated with their condition. They should be encouraged to report any new cardiac symptoms, including palpitations, fainting, dizziness, or lightheadedness, to their healthcare provider without delay.

Caregivers should be made aware that serious adverse reactions, including potentially fatal reactions, have been reported in neonates who received intravenous medications containing benzyl alcohol. They should be instructed to inform the healthcare provider if any neurologic, hematologic, or cardiac adverse reactions occur in the neonate.

Storage and Handling

Famotidine Injection is supplied in a manner that ensures optimal storage and handling. It should be stored at room temperature, specifically between 20° to 25°C (68° to 77°F). Temporary excursions are permissible within the range of 15° to 30°C (59° to 86°F).

For diluted solutions of Famotidine Injection, if not used immediately, they must be stored between 2° and 8°C (36° and 46°F) for a maximum of 48 hours. It is crucial to avoid freezing the product. Additionally, the injection should be protected from light and retained in its original carton until it is time for use to maintain its integrity.

Additional Clinical Information

Postmarketing experience has revealed several adverse events associated with the use of the medication. Clinicians should be aware of potential cardiovascular issues, including arrhythmia, AV block, and prolonged QT interval. Gastrointestinal complications may manifest as cholestatic jaundice and hepatitis. Hematologic concerns include agranulocytosis, pancytopenia, and leukopenia.

Additionally, hypersensitivity reactions such as anaphylaxis, angioedema, facial edema, and urticaria have been reported. Musculoskeletal effects may involve rhabdomyolysis and muscle cramps. Neurologically, patients may experience confusion, agitation, and paresthesia. Respiratory complications, specifically interstitial pneumonia, and severe skin reactions like toxic epidermal necrolysis and Stevens-Johnson syndrome have also been documented.

FDA Insert (PDF)

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

View full prescribing information (PDF)