Famotidine

Description

Famotidine is a histamine H2-receptor antagonist with the chemical name N'-(aminosulfonyl)-3-[[[2-(diamino-methylene)amino-4-thiazolyl]methyl]thio]propanimidamide. The empirical formula of famotidine is C8H15N7O2S3, and it has a molecular weight of 337.45. This compound appears as a white to pale yellow crystalline substance. Famotidine is freely soluble in glacial acetic acid, slightly soluble in methanol, very slightly soluble in water, and practically insoluble in ethanol.

Each tablet intended for oral administration contains either 20 mg or 40 mg of famotidine, along with the following inactive ingredients: hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycolate, sodium starch glycolate, modified corn starch (pregelatinized starch), talc, triacetin, and titanium dioxide.

Uses and Indications

Famotidine is indicated for the short-term treatment of active duodenal ulcer, with most adult patients healing within 4 weeks. It is rarely necessary to use famotidine at full dosage for longer than 6 to 8 weeks, as studies have not assessed the safety of famotidine in uncomplicated active duodenal ulcer for periods exceeding eight weeks.

Additionally, famotidine is indicated for maintenance therapy in patients with duodenal ulcers at a reduced dosage following the healing of an active ulcer; however, controlled studies in adults have not extended beyond one year.

The drug is also indicated for the short-term treatment of active benign gastric ulcer, with most adult patients healing within 6 weeks. Similar to duodenal ulcers, studies have not evaluated the safety or efficacy of famotidine in uncomplicated active benign gastric ulcer for durations longer than 8 weeks.

Famotidine is indicated for the short-term treatment of gastroesophageal reflux disease (GERD), including patients with symptoms of GERD and those with esophagitis due to GERD, such as erosive or ulcerative disease diagnosed by endoscopy.

Furthermore, famotidine is indicated for the treatment of pathological hypersecretory conditions, including Zollinger-Ellison Syndrome and multiple endocrine adenomas.

No teratogenic or nonteratogenic effects have been reported.

Dosage and Administration

For the treatment of duodenal ulcers, the recommended adult oral dosage for active duodenal ulcer is 40 mg once daily at bedtime. Most patients typically achieve healing within 4 weeks; therefore, there is rarely a need to continue famotidine at full dosage for longer than 6 to 8 weeks. An alternative regimen of 20 mg administered twice daily (b.i.d.) is also effective. For maintenance therapy, the recommended adult oral dose is 20 mg once daily at bedtime.

In the case of benign gastric ulcers, the recommended adult oral dosage for active benign gastric ulcer is 40 mg once daily at bedtime.

For gastroesophageal reflux disease (GERD), the recommended oral dosage for adult patients experiencing symptoms is 20 mg b.i.d. for a duration of up to 6 weeks. For adult patients with esophagitis, including erosions and ulcerations, and accompanying symptoms due to GERD, the recommended oral dosage is either 20 mg or 40 mg b.i.d. for up to 12 weeks.

In pediatric patients under 1 year of age with GERD, the recommended dosage is 0.5 mg/kg per dose of famotidine oral suspension. This should be 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.

For pediatric patients aged 1 to 16 years, the dosing for peptic ulcers is 0.5 mg/kg per day orally at bedtime or divided b.i.d., with a maximum of 40 mg per day. For gastroesophageal reflux disease, with or without esophagitis including erosions and ulcerations, the recommended dosage is 1.0 mg/kg per day orally, divided b.i.d., with a maximum of 40 mg b.i.d.

For pathological hypersecretory conditions, the recommended adult oral starting dose is 20 mg every 6 hours (q 6 h). In certain patients, a higher starting dose may be necessary. Doses should be tailored to individual patient needs and may continue as long as clinically indicated. Doses up to 160 mg q 6 h have been administered to some adult patients with severe Zollinger-Ellison Syndrome.

Contraindications

Use of this product is contraindicated in patients with a known hypersensitivity to any component of the formulation. Due to the potential for cross-sensitivity within this class of compounds, famotidine should not be administered to 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 the medication. Common adverse reactions, occurring in at least 1% of participants, include headache (4.7%), diarrhea (1.7%), dizziness (1.3%), and constipation (1.2%).

Serious adverse reactions have been reported, including but not limited to:

Body as a Whole: Fever, asthenia, and fatigue.

Cardiovascular: Arrhythmia, AV block, palpitation, and very rare cases of prolonged QT interval, particularly in patients with impaired renal function.

Gastrointestinal: Cholestatic jaundice, hepatitis, liver enzyme abnormalities, vomiting, nausea, abdominal discomfort, anorexia, and dry mouth.

Hematologic: Rare instances of agranulocytosis, pancytopenia, leukopenia, and thrombocytopenia.

Hypersensitivity: Anaphylaxis, angioedema, orbital or facial edema, urticaria, rash, and conjunctival injection.

Musculoskeletal: Musculoskeletal pain, including muscle cramps and arthralgia.

Nervous System/Psychiatric: Grand mal seizures, reversible psychic disturbances such as hallucinations, confusion, agitation, depression, anxiety, decreased libido, paresthesia, insomnia, somnolence, and very rare convulsions in patients with impaired renal function.

Respiratory: Bronchospasm and interstitial pneumonia.

Skin: Very rare occurrences of toxic epidermal necrolysis/Stevens-Johnson syndrome, along with alopecia, acne, pruritus, dry skin, and flushing.

Special Senses: Tinnitus and taste disorder.

Other: Rare cases of impotence and gynecomastia, with incidences not exceeding those observed with placebo.

In a clinical study involving 35 pediatric patients under 1 year of age, agitation was noted in 5 patients receiving famotidine, which resolved upon discontinuation of the medication. This highlights the importance of monitoring for adverse reactions in this population.

Drug Interactions

No significant drug interactions have been identified for the compound in question. Comprehensive studies, including those involving famotidine in humans, animal models, and in vitro assessments, indicate that there is no notable 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 a marker for hepatic drug extraction has demonstrated no significant effects, further supporting the absence of clinically relevant drug interactions.

Given the lack of identified interactions, no dosage adjustments or enhanced monitoring protocols are necessary when co-administering these compounds.

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 can be treated with famotidine, as studies support its use in this population. The clearance of famotidine in patients aged 3 months to 1 year is comparable to that of older pediatric patients and adults. 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 pediatric patients under 1 year is similar to that observed in older pediatric patients and adults. Notably, the duration of acid suppression is longer in infants less than 1 month of age compared to older pediatric patients.

For the treatment of gastroesophageal reflux disease (GERD) in pediatric patients under 1 year, the recommended dosage is 0.5 mg/kg per dose of famotidine oral suspension, administered for up to 8 weeks. For patients under 3 months of age, the medication should be given once daily, while those aged 3 months and older may receive it twice daily.

In pediatric patients aged 1 to 16 years, the use of famotidine is also supported by clinical studies. The clearance of famotidine in this age group is similar to that in adults. Suggested starting doses include 0.5 mg/kg/day orally at bedtime or divided twice daily for peptic ulcers, up to a maximum of 40 mg per day. For GERD, a starting dose of 1 mg/kg/day orally, divided twice daily, is recommended, also up to 40 mg twice daily. Treatment duration and dosing should be individualized based on clinical response, pH determination, and endoscopic findings. Published studies have utilized doses up to 1 mg/kg/day for peptic ulcers and 2 mg/kg/day for GERD, including cases with esophagitis, erosions, and ulcerations.

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 individuals.

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 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. Healthcare providers should remain vigilant in assessing renal function and adjusting the dosage accordingly to ensure the safety and efficacy of famotidine in geriatric patients.

Pregnancy

Pregnant patients should be informed that this medication is classified as Pregnancy Category B. 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 not demonstrated significant evidence of impaired fertility or harm to the fetus associated with famotidine.

While no direct fetotoxic effects have been observed, it is important to note that 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.

Due to the absence of adequate or well-controlled studies in pregnant women, and considering 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 prescribing this medication to 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, 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 severe renal insufficiency (creatinine clearance <10 mL/min), the elimination half-life of famotidine may exceed 20 hours, necessitating potential dosage adjustments. For those with moderate renal insufficiency (creatinine clearance <50 mL/min) or severe renal insufficiency, the dose of famotidine may be reduced to half the usual dose, or the dosing interval may be extended to 36-48 hours based on clinical response.

CNS adverse effects have been reported in patients with moderate and severe renal insufficiency; therefore, careful monitoring and adjustment of dosage may be required. Additionally, a prolonged QT interval has been reported very rarely in patients with impaired renal function whose dose or dosing interval of famotidine may not have been appropriately adjusted.

In elderly patients with decreased renal function, the clearance of famotidine may be reduced, which necessitates careful dose selection and monitoring of renal function. Furthermore, dosage adjustment in pediatric patients with moderate or severe renal insufficiency should be considered based on pharmacokinetic parameters.

Hepatic Impairment

Patients with hepatic impairment do not require specific dosage adjustments or precautions when receiving this medication. Additionally, no significant interference with the disposition of compounds metabolized by hepatic microsomal enzymes, including the cytochrome P450 system, has been identified.

It is important to note that liver enzyme abnormalities have been reported as an adverse reaction, which may indicate potential concerns regarding liver function. Therefore, monitoring of liver enzymes may be warranted in patients with pre-existing liver conditions or those exhibiting signs of hepatic dysfunction.

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.

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 needed.

Toxicity Data

The oral LD50 of famotidine has been determined to be greater than 3000 mg/kg in both male and female rats and mice, while the minimum lethal acute oral dose in dogs exceeds 2000 mg/kg. Notably, famotidine did not produce overt effects at high oral doses in various species, including mice, rats, cats, and dogs. However, significant anorexia and growth depression were observed in rabbits at doses starting from 200 mg/kg/day.

For intravenous administration, the LD50 for famotidine in mice and rats ranges from 254 to 563 mg/kg, with the minimum lethal single intravenous dose in dogs being approximately 300 mg/kg. Signs of acute intoxication in dogs treated intravenously may include emesis, restlessness, pallor of mucous membranes or redness of the mouth and ears, hypotension, tachycardia, and potential collapse.

Healthcare professionals should remain vigilant for these symptoms and manage the patient accordingly.

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. Additionally, in vivo studies in mice, including a micronucleus test and a chromosomal aberration test, showed no evidence of mutagenic effects.

Fertility and reproductive performance were assessed in studies involving rats administered oral doses of up to 2000 mg/kg/day or intravenous doses of up to 200 mg/kg/day. The findings indicated that famotidine did not adversely affect fertility or reproductive performance.

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%).

Infrequent adverse reactions reported either in clinical trials or post-marketing include:

Body as a Whole: Fever, asthenia, fatigue. Cardiovascular: Arrhythmia, AV block, palpitation. Prolonged QT interval has been reported very rarely in patients with impaired renal function. Gastrointestinal: Cholestatic jaundice, hepatitis, liver enzyme abnormalities, vomiting, nausea, abdominal discomfort, anorexia, dry mouth. Hematologic: Rare cases of agranulocytosis, pancytopenia, leukopenia, and thrombocytopenia. Hypersensitivity: Anaphylaxis, angioedema, orbital or facial edema, urticaria, rash, conjunctival injection. Musculoskeletal: Musculoskeletal pain, including muscle cramps and arthralgia. Nervous System/Psychiatric: Grand mal seizure; psychic disturbances, which were reversible in cases with follow-up, including hallucinations, confusion, agitation, depression, anxiety, decreased libido; paresthesia; insomnia; somnolence. Convulsions have been reported very rarely in patients with impaired renal function. Respiratory: Bronchospasm, interstitial pneumonia. Skin: Toxic epidermal necrolysis/Stevens-Johnson syndrome (very rare), alopecia, acne, pruritus, dry skin, flushing. Special Senses: Tinnitus, taste disorder. Other: Rare cases of impotence and gynecomastia have been reported; however, incidences in controlled clinical trials 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.

Patient Counseling

Patients should be informed that a symptomatic response to therapy with famotidine does not exclude the possibility of gastric malignancy. It is essential 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 to accommodate the longer elimination half-life of famotidine. This adjustment is crucial to ensure safe and effective treatment.

Patients should also be made aware that famotidine is secreted into breast milk. Healthcare providers should discuss the importance of the medication to the mother and help patients make an informed decision regarding whether to discontinue nursing or the drug itself.

In pediatric patients under 1 year of age, famotidine oral suspension is indicated for the treatment of gastroesophageal reflux disease (GERD). Healthcare providers should instruct caregivers to administer a dose of 0.5 mg/kg/dose once daily for patients under 3 months of age and 0.5 mg/kg/dose twice daily for patients aged 3 months to less than 1 year.

Caregivers should be counseled to implement conservative treatment measures, such as thickened feedings, for pediatric patients with GERD. This approach can help manage symptoms effectively.

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 the medication. Patients should be encouraged to report any unusual symptoms or side effects to their healthcare provider promptly.

Storage and Handling

The product is supplied in accordance with the National Drug Code (NDC) specifications. It should be stored at a controlled room temperature of 20° to 25°C (68° to 77°F), as defined by the United States Pharmacopeia (USP) guidelines. Proper storage conditions are essential to maintain the integrity and efficacy of the product.

Additional Clinical Information

The recommended oral dosages for adults include 40 mg once daily at bedtime for active duodenal ulcers and active benign gastric ulcers, with an alternative regimen of 20 mg twice daily also being effective. For maintenance therapy, a dosage of 20 mg once daily at bedtime is advised. In the treatment of gastroesophageal reflux disease (GERD), a dosage of 20 mg twice daily is recommended for up to 6 weeks, while patients with esophagitis, including erosions and ulcerations, may receive 20 or 40 mg twice daily for up to 12 weeks.

For pediatric patients under 1 year of age with GERD, the initial doses are 0.5 mg/kg/dose once daily for those under 3 months and 0.5 mg/kg/dose twice daily for those aged 3 months to less than 1 year. For children aged 1 to 16 years, the starting doses are 0.5 mg/kg/day orally at bedtime or divided twice daily, up to a maximum of 40 mg/day for peptic ulcers, and 1 mg/kg/day orally divided twice daily, also up to 40 mg for GERD.

FDA Insert (PDF)

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

View full prescribing information (PDF)