FAMOTIDINE

The active ingredient in famotidine, is a histamine H 2 -receptor antagonist. Famotidine is N' -(aminosulfonyl)-3-[[[2-[(diamino-methylene)amino]-4- thiazolyl]methyl]thio]propanimidamide. The empirical formula of famotidine is C 8 H 15 N 7 O 2 S 3 and its molecular weight is 337.45. Its structural formula is: Each Famotidine tablet for oral administration contains either 20 mg or 40 mg of famotidine and the following inactive ingredients: hydroxypropyl cellulose, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, pregelatinized starch (modified corn starch), sodium starch glycolate, talc, titanium dioxide and triacetin. Famotidine is a white to pale yellow crystalline compound that is freely soluble in glacial acetic acid, slightly soluble in methanol, very slightly soluble in water, and practically insoluble in ethanol. structural formula

Famotidine tablets are indicated in adult and pediatric patients 40 kg and above for the treatment of: active duodenal ulcer (DU). active gastric ulcer(GU). symptomatic non-erosive gastroesophageal reflux disease (GERD). erosive esophagitis due to GERD, diagnosed by biopsy. Famotidine tablets are indicated in adults for the: treatment of pathological hypersecretory conditions (e.g., Zollinger-Ellison Syndrome, multiple endocrine neoplasias). reduction of the risk of duodenal ulcer recurrence.

2.1 Recommended Dosage Table 1 shows the recommended dosage of Famotidine 20 mg and 40 mg tablets in adult and pediatric patients weighing 40 kg and greater with normal renal function. The use of Famotidine 20 mg and 40 mg tablets is not recommended in pediatric patients weighing less than 40 kg because the lowest available strength (20 mg) exceeds the recommended dose for these patients. Use another famotidine formulation for pediatric patients weighing less than 40 kg. 1 2.2 Dosage in Renal Impairment Dosage adjustments of Famotidine are recommended for patients with moderate to severe renal impairment (creatinine clearance less than 60 mL/min) [see Use in Specific Populations ( 8.6)]. Table 2 shows the recommended maximum dosage of Famotidine 20 mg or 40 mg tablets for patients with renal impairment, by indication. Use the lowest effective dose. Some dosage adjustments may require switching to other formulations of famotidine (e.g., oral suspension, lower dose tablet). 2 2.3 Administration Instructions Take Famotidine once daily before bedtime or twice daily in the morning and before bedtime, as recommended. Famotidine tablets may be taken with or without food [see Clinical Pharmacology ( 12.3)]. Famotidine tablets may be given with antacids.

Famotidine is contraindicated in patients with a history of serious hypersensitivity reactions (e.g., anaphylaxis) to famotidine or other histamine-2 (H 2) receptor antagonists.

6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Famotidine was studied in 7 US and international placebo- and active-controlled trials in approximately 2500 patients [see Clinical Studies ( 14)]. A total of 1442 patients were treated with Famotidine, including 302 treated with 40 mg twice daily, 456 treated with 20 mg twice daily, 461 treated with 40 mg once daily, and 396 treated with 20 mg once daily. The population was 17-91 years old, fairly well distributed between gender and race; however, the predominant race treated was Caucasian. The following adverse reactions occurred in greater than or equal to 1% of Famotidine treated patients: headache, dizziness and constipation. The following other adverse reactions were reported in less than 1% of patients in clinical trials: Body as a Whole: fever, asthenia, fatigue Cardiovascular: palpitations Gastrointestinal: elevated liver enzymes, vomiting, nausea, abdominal discomfort, anorexia, dry mouth Hematologic: thrombocytopenia Hypersensitivity: orbital edema, rash, conjunctival injection, bronchospasm Musculoskeletal: musculoskeletal pain, arthralgia Nervous System/Psychiatric: seizure, hallucinations, depression, anxiety, decreased libido, insomnia, somnolence Skin: pruritus, dry skin, flushing Special Senses: tinnitus, taste disorder Other: impotence 6.2 Postmarketing Experience The following adverse reactions have been reported during post-approval use of famotidine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or establish a causal relationship to drug exposure. Cardiovascular: arrhythmia, AV block, prolonged QT interval Gastrointestinal: cholestatic jaundice, hepatitis Hematologic: agranulocytosis, pancytopenia, leukopenia Hypersensitivity: anaphylaxis, angioedema, facial edema, urticaria Musculoskeletal: rhabdomyolysis, muscle cramps Nervous System/Psychiatric: confusion, agitation, paresthesia Respiratory: interstitial pneumonia Skin: toxic epidermal necrolysis/Stevens-Johnson syndrome To report SUSPECTED ADVERSE REACTIONS, contact AvKARE at 1-855-361-3993; email [email protected] or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

1 Drugs Dependent on Gastric pH for Absorption Famotidine can reduce the absorption of other drugs, due to its effect on reducing intragastric acidity, leading to loss of efficacy of the concomitant drug. Concomitant administration of Famotidine with dasatinib, delavirdine mesylate, cefditoren, and fosamprenavir is not recommended. See the prescribing information for other drugs dependent on gastric pH for absorption for administration instructions, including atazanavir, erlotinib, ketoconazole, itraconazole, ledipasvir/sofosbuvir, nilotinib, and rilpivirine. 7.2 Tizanidine (CYP1A2 Subtrate) Although not studied clinically, famotidine is considered a weak CYP1A2 inhibitor and may lead to substantial increases in blood concentrations of tizanidine, a CYP1A2 substrate. Avoid concomitant use with Famotidine. If concomitant use is necessary, monitor for hypotension, bradycardia or excessive drowsiness. Refer to the full prescribing information for tizanidine.