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 inactive ingredients that include 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 following conditions:

Short-term Treatment of Active Duodenal Ulcer This drug is indicated for the short-term treatment of active duodenal ulcer. Most adult patients 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 assessed in uncomplicated active duodenal ulcer for periods exceeding eight weeks.

Maintenance Therapy for Duodenal Ulcer Famotidine is 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 evaluated the efficacy of maintenance therapy beyond one year.

Short-term Treatment of Active Benign Gastric Ulcer This drug 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 studied for durations longer than 8 weeks.

Short-term Treatment of Gastroesophageal Reflux Disease (GERD) Famotidine is indicated for the short-term treatment of patients experiencing symptoms of gastroesophageal reflux disease (GERD). It is also indicated for the short-term treatment of esophagitis due to GERD, including erosive or ulcerative disease as diagnosed by endoscopy.

Treatment of Pathological Hypersecretory Conditions This drug is indicated for the treatment of pathological hypersecretory conditions, such as Zollinger-Ellison Syndrome and multiple endocrine adenomas.

Limitations of Use The safety and efficacy of Famotidine have not been established for use beyond the specified durations for each indication.

Dosage and Administration

The recommended adult oral dosage for the treatment of active duodenal ulcer is 40 mg once daily at bedtime. Most patients typically achieve healing within 4 weeks; however, there is generally no justification for extending the use of famotidine oral suspension at full dosage beyond 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.

For the treatment of active benign gastric ulcer, the recommended adult oral dosage is 40 mg once daily at bedtime.

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

For 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 of age. For patients aged 3 months to less than 1 year, the dosage is 0.5 mg/kg per dose, administered twice daily.

In pediatric patients aged 1 to 16 years, the dosage for peptic ulcer treatment is 0.5 mg/kg per day, given 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 dosage is 1.0 mg/kg per day, administered orally and divided b.i.d., with a maximum of 40 mg b.i.d.

For pathological hypersecretory conditions, such as Zollinger-Ellison Syndrome and Multiple Endocrine Adenomas, the recommended starting oral dose for adults is 20 mg every 6 hours (q 6 h). In some cases, doses up to 160 mg q 6 h have been administered to adult patients with severe Zollinger-Ellison Syndrome.

Each five mL of the oral suspension contains 40 mg of famotidine after the powder is constituted with 46 mL of Purified Water as directed.

For patients with moderate or severe renal insufficiency, dosage adjustments are necessary. In cases of severe renal insufficiency, the dose of famotidine 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.

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 among H2-receptor antagonists, Famotidine should not be administered to individuals with a history of hypersensitivity to other agents within this class.

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 is advisable to adjust the dosing regimen for patients with moderate renal insufficiency (creatinine clearance <50 mL/min) or severe renal insufficiency (creatinine clearance <10 mL/min). This may involve extending the intervals between doses or reducing the dosage to account for the prolonged elimination half-life of Famotidine.

No specific laboratory tests are recommended for monitoring the use of Famotidine; however, healthcare providers should assess renal function periodically in patients with known renal impairment to ensure safe and effective use of the medication.

Side Effects

Patients receiving treatment have reported a range of adverse reactions, categorized by frequency and seriousness.

Common adverse reactions observed in clinical trials include headache (4.7%), dizziness (1.3%), constipation (1.2%), and diarrhea (1.7%). These reactions were noted to occur with varying degrees of severity among participants.

Infrequent adverse reactions encompass a broader spectrum of effects. Systemic reactions such as fever, asthenia, and fatigue have been reported. Cardiovascular events include arrhythmia, AV block, and palpitations. Gastrointestinal disturbances may manifest as cholestatic jaundice, liver enzyme abnormalities, vomiting, nausea, abdominal discomfort, anorexia, and dry mouth.

Hematologic reactions, although rare, include agranulocytosis, pancytopenia, leukopenia, and thrombocytopenia. Hypersensitivity reactions can be serious, with reports of anaphylaxis, angioedema, orbital or facial edema, urticaria, rash, and conjunctival injection. Musculoskeletal complaints such as muscle cramps and arthralgia have also been noted.

Nervous system and psychiatric effects 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 very rarely in patients with impaired renal function.

Respiratory adverse reactions include bronchospasm and interstitial pneumonia. Skin reactions, although very rare, may involve toxic epidermal necrolysis or Stevens-Johnson syndrome, as well as alopecia, acne, pruritus, dry skin, and flushing. Special senses may be affected, with reports of tinnitus and taste disorders. Other rare adverse reactions include impotence and gynecomastia, with incidences not exceeding those observed in placebo groups.

In pediatric patients, agitation was observed in five patients under one year of age with gastroesophageal reflux disease (GERD) symptoms, which resolved upon discontinuation of famotidine.

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 compounds evaluated in these studies include warfarin, theophylline, phenytoin, diazepam, aminopyrine, and antipyrine, all of which showed no notable interactions. Additionally, the use of indocyanine green as a marker for hepatic drug extraction has also indicated no significant effects.

Given the absence 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 indicate that the clearance of famotidine in patients aged 3 months to 1 year is comparable to that in older pediatric patients and adults. However, infants aged 0 to 3 months exhibit clearance values that are 2- to 4-fold lower than those in older groups. For the treatment of gastroesophageal reflux disease (GERD), the recommended starting dose is 0.5 mg/kg per dose of famotidine oral suspension for a maximum of 8 weeks. Infants under 3 months should receive this dose once daily, while those aged 3 months to less than 1 year should be dosed twice daily. The safety and efficacy of famotidine beyond 4 weeks have not been established, and its use should be considered only if conservative measures, such as thickened feedings, are implemented concurrently, and if the potential benefits outweigh the risks.

In pediatric patients aged 1 to 16 years, famotidine use is supported by studies demonstrating that its clearance is similar to that of adults. The starting doses for this age group are as follows: for peptic ulcer, 0.5 mg/kg per day orally at bedtime or divided twice daily, not exceeding 40 mg per day; for GERD with or without esophagitis, 1.0 mg/kg per day orally divided twice daily, also not exceeding 40 mg twice daily. Treatment duration and dosing should be tailored to the individual based on clinical response, pH determination, and endoscopic findings. Uncontrolled studies have reported doses up to 1 mg/kg per day for peptic ulcer and 2 mg/kg per day for GERD, including cases with 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. It may be beneficial 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 fetal harm. While no direct fetotoxic effects have been observed, there were instances of sporadic abortions in rabbits that exhibited marked decreased food intake at oral doses of 200 mg/kg/day, which is approximately 250 times the usual human dose.

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 performed in lactating rats. It has been detected in human milk as well. In animal 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. Due to the potential for serious adverse reactions in breastfed infants, healthcare professionals should consider whether to discontinue nursing or discontinue famotidine, weighing the importance of the medication to the mother against the risks to the nursing infant.

Renal Impairment

In patients with moderate renal insufficiency (creatinine clearance <50 mL/min), it may be necessary to extend dosing intervals or reduce the dose of famotidine due to its longer elimination half-life. For those with severe renal insufficiency (creatinine clearance <10 mL/min), the elimination half-life of famotidine can exceed 20 hours, potentially reaching approximately 24 hours in anuric patients. To prevent excessive accumulation of the drug in individuals with moderate or severe renal insufficiency, the famotidine dose may be reduced to half or the dosing interval may be extended to 36 to 48 hours, depending on the patient's clinical response.

In pediatric patients with moderate or severe renal insufficiency, dosage adjustments should be considered based on pharmacokinetic parameters. The pharmacokinetics of famotidine demonstrate a significant correlation between creatinine clearance values and the drug's elimination half-life. Therefore, in patients with severe renal insufficiency, careful adjustment of the dose or dosing intervals is warranted. Additionally, caution should be exercised in dose selection for elderly patients, who are more likely to exhibit decreased renal function, and monitoring of renal function may be beneficial.

Hepatic Impairment

Patients with hepatic impairment do not require specific dosage adjustments, as no alterations in dosing are indicated in the prescribing information. Furthermore, there are no special monitoring requirements or precautions outlined for this patient population. The insert indicates that there is no significant interference with the disposition of compounds metabolized by hepatic microsomal enzymes, suggesting that the impact on hepatic metabolism is minimal. While liver enzyme abnormalities have been reported as an adverse reaction, the prescribing information does not provide specific guidance for managing patients with hepatic impairment.

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.

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 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 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, have shown no significant evidence of impaired fertility or fetal harm associated with Famotidine. Although no direct fetotoxic effects were noted, sporadic abortions were observed in some rabbits at oral doses of 200 mg/kg/day (250 times the usual human dose) or higher, occurring only in mothers that exhibited marked decreased food intake.

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.

In a 106-week study in rats and a 92-week study in mice receiving oral doses of up to 2000 mg/kg/day (approximately 2500 times the recommended human dose for active duodenal ulcer), no evidence of carcinogenic potential was found for Famotidine. The drug was also 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, did not reveal any 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.

No specific details regarding animal pharmacology and toxicology beyond the studies mentioned in the nonclinical toxicology section are provided.

Postmarketing Experience

Adverse reactions reported in postmarketing experience with Famotidine include both common and infrequent events. In controlled clinical trials, the following adverse reactions occurred in more than 1% of patients: 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. 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.

It is noted that the adverse reactions associated with Famotidine Tablets may also occur with Famotidine for Oral Suspension. 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

Famotidine for Oral Suspension can be substituted for Famotidine Tablets in applicable indications. Each 5 mL of the suspension contains 40 mg of famotidine, prepared by constituting the powder with 46 mL of Purified Water. Clinicians should instruct patients to prepare the suspension at the time of dispensing by slowly adding the water and shaking vigorously for 5 to 10 seconds immediately after mixing and before each use. It is important to note that any unused constituted oral suspension should be discarded after 30 days.

Patients should be counseled to shake the oral suspension vigorously prior to each use and to adhere to the 30-day discard guideline for any unused product. No additional information is available regarding laboratory tests, abuse potential, or postmarketing experience.

FDA Insert (PDF)

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

View full prescribing information (PDF)