Famotidine

Description

Famotidine for Oral Suspension contains the active ingredient famotidine, a histamine H2-receptor antagonist. The chemical structure of famotidine is represented by the name N-(aminosulfonyl)-3-[[[2-(diaminomethylene)amino-4-thiazolyl]methyl]thio]propanimidamide. Its empirical formula is C8H15N7O2S3, with a molecular weight of 337.43 g/mol.

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. Each 5 mL of the prepared oral suspension contains 40 mg of famotidine along with several inactive ingredients, including anhydrous citric acid, flavors (cherry, banana, and mint), microcrystalline cellulose, carboxymethylcellulose sodium, confectioner's sugar, corn starch, colloidal silicon dioxide, and xanthan gum. Preservatives included in the formulation are sodium benzoate and sodium methylparaben.

Uses and Indications

Famotidine for Oral Suspension is indicated for the short-term treatment of active duodenal ulcer. Most adult patients typically achieve healing within 4 weeks; however, there is rarely justification for the use of Famotidine at full dosage for longer than 6 to 8 weeks. The safety of Famotidine has not been evaluated in uncomplicated active duodenal ulcer cases for durations exceeding eight weeks.

This drug is also indicated for maintenance therapy in patients with duodenal ulcers at a reduced dosage following the healing of an active ulcer. Controlled studies in adults have not extended beyond one year for this indication.

Additionally, Famotidine is indicated for the short-term treatment of active benign gastric ulcer, with most adult patients healing within 6 weeks. The safety and efficacy of Famotidine in uncomplicated active benign gastric ulcer have not been assessed for periods longer than 8 weeks.

Famotidine is further indicated for the short-term treatment of gastroesophageal reflux disease (GERD), including the management of symptoms associated with GERD. It is also indicated for the short-term treatment of esophagitis due to GERD, including erosive or ulcerative disease as diagnosed by endoscopy.

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

Dosage and Administration

For the treatment of duodenal ulcers, the recommended acute therapy is 40 mg administered once daily at bedtime. Most patients typically achieve healing within 4 weeks; however, treatment should not exceed 6 to 8 weeks unless clinically warranted. An alternative regimen of 20 mg taken twice daily (b.i.d.) is also effective. For maintenance therapy, a dose of 20 mg once daily at bedtime is advised.

In the case of benign gastric ulcers, the acute therapy consists of 40 mg once daily at bedtime.

For gastroesophageal reflux disease (GERD), the treatment of symptoms is initiated with 20 mg taken twice daily for a duration of up to 6 weeks. When treating esophagitis, including erosions and ulcerations, a dosage of either 20 mg or 40 mg b.i.d. is recommended for up to 12 weeks.

In pediatric patients under 1 year of age with GERD, the dosage 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 old. For those aged 3 months to less than 1 year, the dosage is 0.5 mg/kg per dose given twice daily.

For pediatric patients aged 1 to 16 years, the dosage for peptic ulcers is 0.5 mg/kg per day, administered orally at bedtime or divided into two doses, not exceeding 40 mg per day. For gastroesophageal reflux disease, with or without esophagitis, the recommended dosage is 1.0 mg/kg per day, given orally and divided into two doses, with a maximum of 40 mg b.i.d.

In cases of pathological hypersecretory conditions, such as Zollinger-Ellison syndrome, the recommended starting dose for adults is 20 mg every 6 hours (q 6 h). Dosing may be adjusted based on individual patient needs, with some patients requiring doses up to 160 mg q 6 h.

For the preparation of the oral suspension, it is essential to prepare the suspension at the time of dispensing by slowly adding 46 mL of purified water. The mixture should be shaken vigorously for 5 to 10 seconds immediately after adding the water and just before use.

For patients with moderate or severe renal insufficiency, defined as a creatinine clearance of less than 50 mL/min or less than 10 mL/min respectively, it is recommended to reduce the dose to half or to prolong the dosing interval to 36 to 48 hours, as indicated by the clinical response.

Contraindications

Use of this product is contraindicated in patients with hypersensitivity to any component of the formulation. Cross-sensitivity among H2-receptor antagonists has been observed; therefore, Famotidine should not be administered to individuals with a history of hypersensitivity to other H2-receptor antagonists.

Warnings and Precautions

Symptomatic response to therapy with Famotidine does not preclude the presence of gastric malignancy. Healthcare professionals should remain vigilant for the possibility of underlying malignancies in patients presenting with symptoms that may be alleviated by Famotidine.

Patients with moderate or severe renal insufficiency require special consideration. Adverse central nervous system effects have been reported in this population. Therefore, it may be necessary to adjust the dosing regimen by extending the intervals between doses or reducing the dose itself. Specifically, patients with moderate renal insufficiency (creatinine clearance <50 mL/min) or severe renal insufficiency (creatinine clearance <10 mL/min) should be monitored closely to account for the prolonged elimination half-life of Famotidine.

No specific laboratory tests are recommended for monitoring during the use of Famotidine. However, healthcare providers should exercise clinical judgment and consider individual patient factors when determining the need for any additional assessments.

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%), dizziness (1.3%), diarrhea (1.7%), and constipation (1.2%).

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

Body as a Whole: Patients may experience fever, asthenia, and fatigue.

Cardiovascular: Arrhythmia, AV block, and palpitations have been noted.

Gastrointestinal: Adverse reactions in this category include cholestatic jaundice, liver enzyme abnormalities, vomiting, nausea, abdominal discomfort, anorexia, and dry mouth.

Hematologic: Rare cases of agranulocytosis, pancytopenia, leukopenia, and thrombocytopenia have been documented.

Hypersensitivity: Serious hypersensitivity reactions such as anaphylaxis, angioedema, orbital or facial edema, urticaria, rash, and conjunctival injection have been reported.

Musculoskeletal: Patients may experience musculoskeletal pain, including muscle cramps and arthralgia.

Nervous System/Psychiatric: Serious neurological events include grand mal seizures and psychic disturbances, which are reversible in cases where follow-up was obtained. These disturbances may manifest as hallucinations, confusion, agitation, depression, anxiety, decreased libido, paresthesia, insomnia, and somnolence. Convulsions have been reported very rarely in patients with impaired renal function.

Respiratory: Bronchospasm and interstitial pneumonia have been observed.

Skin: Very rare cases of toxic epidermal necrolysis/Stevens-Johnson syndrome, alopecia, acne, pruritus, dry skin, and flushing have been reported.

Special Senses: Tinnitus and taste disorders have been noted.

Other: Rare cases of impotence and gynecomastia have been reported; 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.

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 settings 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 have demonstrated clearance of famotidine similar to older pediatric patients (1 to 15 years) and adults, with the exception of those aged 0 to 3 months, who exhibit clearance values that are 2- to 4-fold lower. The mean bioavailability of famotidine in this age group after oral dosing is comparable to that of older pediatric patients and adults. For the treatment of gastroesophageal reflux disease (GERD), the recommended starting doses are 0.5 mg/kg/dose once daily for patients under 3 months of age and 0.5 mg/kg/dose twice daily for those aged 3 months to less than 1 year. It is important to note that the safety and efficacy of famotidine treatment beyond 4 weeks have not been established, and famotidine should only be considered for GERD treatment in conjunction with conservative measures, such as thickened feedings.

In pediatric patients aged 1 to 16 years, famotidine use is also supported by clinical studies. The clearance of famotidine in this population is similar to that observed in adults. Suggested starting doses include 0.5 mg/kg/day orally at bedtime or divided twice daily for peptic ulcer treatment, up to a maximum of 40 mg/day, and 1.0 mg/kg/day orally divided twice daily for GERD with or without esophagitis, 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 ulcer and 2 mg/kg/day for GERD with or without esophagitis.

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, which cannot be ruled out.

No dosage adjustment is required based solely on age. Nevertheless, famotidine is substantially excreted by the kidneys, and the risk of toxic reactions may be heightened 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. It is advisable to monitor renal function in this population. In cases of moderate or severe renal impairment, dosage adjustments are necessary to mitigate the risk of adverse effects.

Pregnancy

Pregnant patients should be aware that Famotidine 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. 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.

Despite these findings, there are no adequate or well-controlled studies in pregnant women. Therefore, due to the limitations of animal reproductive studies in predicting human outcomes, 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 severe renal insufficiency (creatinine clearance <10 mL/min), the elimination half-life of Famotidine may exceed 20 hours, which necessitates dose adjustments or extended dosing intervals. For those with moderate renal insufficiency (creatinine clearance <50 mL/min) or severe renal insufficiency, longer intervals between doses or lower doses may be required to accommodate the prolonged elimination half-life of Famotidine. Specifically, the dose may be reduced to half the standard dose, or the dosing interval may be extended to 36 to 48 hours, depending on the patient's clinical response.

Elderly patients with decreased renal function may experience reduced clearance of Famotidine, warranting careful consideration in dose selection. Additionally, dosage adjustments should be considered for pediatric patients with moderate or severe renal insufficiency. It is important to note that the elimination of Famotidine is primarily renal (65 to 70%), and its pharmacokinetics are closely related to creatinine clearance values, underscoring the need for vigilant monitoring and appropriate dose modifications in this patient population.

Hepatic Impairment

Patients with hepatic impairment do not require specific dosage adjustments or precautions when receiving treatment. The available data indicate that there is no significant interference with the disposition of compounds metabolized by hepatic microsomal enzymes, suggesting that hepatic metabolism is not a concern for famotidine. Additionally, there are no warnings or special monitoring instructions for patients with compromised liver function, and liver function tests are not specifically mentioned as necessary for monitoring in this population. Therefore, standard dosing can be applied without modification for patients with hepatic impairment.

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.

Toxicological 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 of 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 them accordingly in cases of suspected overdosage.

Nonclinical Toxicology

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 in both species, have shown no significant evidence of impaired fertility or teratogenic effects associated with Famotidine. Although no direct fetotoxic effects were observed, sporadic abortions were noted in some rabbits that exhibited marked decreased food intake when administered oral doses of 200 mg/kg/day or higher, which is approximately 250 times the usual human dose.

In studies involving rats receiving oral doses of up to 2000 mg/kg/day or intravenous doses of up to 200 mg/kg/day, fertility and reproductive performance remained unaffected, indicating a lack of non-teratogenic effects.

Long-term carcinogenicity studies, including a 106-week study in rats and a 92-week study in mice, administered oral doses of up to 2000 mg/kg/day (approximately 2500 times the recommended human dose for active duodenal ulcer), revealed no evidence of carcinogenic potential for Famotidine. Additionally, Famotidine was found to be negative 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. In vivo studies in mice, including a micronucleus test and a chromosomal aberration test, also showed no evidence of mutagenic effects.

The oral LD50 of Famotidine in male and female rats and mice was determined to be greater than 3000 mg/kg, while the minimum lethal acute oral dose in dogs exceeded 2000 mg/kg. 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 an oral dose of 200 mg/kg/day. The intravenous LD50 for mice and rats ranged from 254 to 563 mg/kg, and the minimum lethal single intravenous dose in dogs was approximately 300 mg/kg. Signs of acute intoxication observed in dogs treated intravenously included emesis, restlessness, pallor of mucous membranes or redness of the mouth and ears, hypotension, tachycardia, and collapse.

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, with the relationship to Famotidine therapy remaining unclear in many instances. These reactions are categorized as follows:

Body as a Whole: Fever, asthenia, fatigue. Cardiovascular: Arrhythmia, AV block, palpitation. Gastrointestinal: Cholestatic jaundice, liver enzyme abnormalities, vomiting, nausea, abdominal discomfort, anorexia, dry mouth. Hematologic: Rare cases of agranulocytosis, pancytopenia, leukopenia, 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

Healthcare providers should instruct patients to shake the oral suspension vigorously for 5 to 10 seconds prior to each use to ensure proper mixing of the medication. It is also important to inform patients that any unused constituted oral suspension should be discarded after 30 days to maintain safety and efficacy.

Storage and Handling

Famotidine for Oral Suspension is supplied in well-closed, light-resistant containers to ensure product integrity. The dry powder and suspension should be stored at a controlled room temperature of 25°C (77°F), with permissible excursions between 15-30°C (59-86°F). It is essential to protect the suspension from freezing to maintain its efficacy. Any unused suspension must be discarded after 30 days to ensure safety and effectiveness.

Additional Clinical Information

Patients should be instructed to shake the oral suspension vigorously for 5 to 10 seconds prior to each use. It is important to note that any unused constituted oral suspension should be discarded after 30 days to ensure safety and efficacy.

FDA Insert (PDF)

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

View full prescribing information (PDF)