Famotidine

INDICATIONS AND USAGE Famotidine is indicated in: 1. Short-term treatment of active duodenal ulcer. Most adult patients heal within 4 weeks; there is rarely reason to use famotidine at full dosage for longer than 6 to 8 weeks. Studies have not assessed the safety of famotidine in uncomplicated active duodenal ulcer for periods of more than eight weeks. 2. Maintenance therapy for duodenal ulcer patients at reduced dosage after healing of an active ulcer. Controlled studies in adults have not extended beyond one year. 3. Short-term treatment of active benign gastric ulcer. Most adult patients heal within 6 weeks. Studies have not assessed the safety or efficacy of famotidine in uncomplicated active benign gastric ulcer for periods of more than 8 weeks. 4. Short-term treatment of gastroesophageal reflux disease (GERD). Famotidine is indicated for short-term treatment of patients with symptoms of GERD (see CLINICAL PHARMACOLOGY IN ADULTS , Clinical Studies ). Famotidine is also indicated for the short-term treatment of esophagitis due to GERD including erosive or ulcerative disease diagnosed by endoscopy (see CLINICAL PHARMACOLOGY IN ADULTS , Clinical Studies ). 5. Treatment of pathological hypersecretory conditions (e.g., Zollinger-Ellison Syndrome, multiple endocrine adenomas) (see CLINICAL PHARMACOLOGY IN ADULTS , Clinical Studies ) .

Purpose Acid reducer

2 Dosage and Administration 2.1 Recommended Dosage Table 1 shows the recommended dosage of Famotidine 20 mg and 40 mg tablets in adults and pediatric patients weighing 40 kg or greater with normal renal function. The use of Famotidine 20 mg and 40 mg tablets is not recommended for use 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. Table 1: Recommended Dosage and Duration of Famotidine Tablets in Adults and Pediatric Patients 40kg and Greater with Normal Renal Function Indication Recommended Dosage Recommended Duration Active duodenal ulcer (DU) 40mg once daily; or 20mg twice daily a Up to 8 weeks b,c Active gastric ulcer 40mg once daily Up to 8 weeks Symptomatic non-erosive GERD 20mg twice daily Up to 6 weeks c Erosive esophagitis diagnosed by endoscopy 20mg tiwce daily; or 40mg twice daily a Up to 12 weeks Pathological hypersecretory conditions d Starting dosage: 20mg every 6 hours; adjust dosage to individual patient needs Maximum dosage 160mg every 6 hours As clinically indicated Reduction of the risk of DU recurrence d 20mg once daily 1 year c or as clinidally indicated aBoth dosages demonstrated effectiveness in clinical trials [see Clinical Studies (14)]. bIn clinical trials, the majority of patients healed within 4 weeks. For patients who do not heal after 4 weeks, consider an additional 2 to 4 weeks of treatment [see Clinical Studies (14.1)]. cLonger treatment durations have not been studied in clinical trials [see Clinical Studies (14.1, 14.2, 14.3)]. dIn pediatric patients, the safety and effectiveness of Famotidine have not been established for the reduction of the risk of duodenal ulcer recurrence or for treatment of pathological hypersecretory conditions [see Use in Specific Populations (8.4)]. 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). 2.3 Administration Instructions Take Famotidine once daily before bedtime or twice daily in the morning and before bedtime, as recommended. Famotidine may be taken with or without food [see Clinical Pharmacology (12.3)]. Famotidine may be given with antacids. Indication Recommended Dosage (2.1) Adult and Pediatric Patients 40 kg and greater Active DU 40 mg once daily; or 20 mg twice daily Active Gastric Ulcer 40 mg once daily GERD 20 mg twice daily Erosive Esophagitis 20 mg twice daily; or 40 mg twice daily Adults Pathological Hypersecretory Conditions 20 mg every 6 hours; adjust to patient needs; maximum 160 mg every 6 hours Risk Reduction of DU Recurrence 20 mg once daily See full prescribing information for complete dosing information, including dosing in renal impairment, and recommended treatment duration. (2.1, 2.2) Administration (2.3): Take once daily before bedtime or twice daily in the morning and before bedtime with or without food. 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). Table 2: Recommended Maximum Dosage of Famotidine Tablets in Adults and Pediatric Patients 40 kg and Greater w …

3 DOSAGE FORMS AND STRENGTHS Famotidine tablets, USP 20 mg: Beige colored, round shaped, film-coated, biconvex tablets, debossed with "L" on one side and "51" on other side. Famotidine tablets, USP 40 mg: Tan colored, round shaped, film-coated, biconvex tablets, debossed with "L" on one side and "52" on other side. Tablets: 20 mg, 40 mg ( 3 )

4 CONTRAINDICATIONS Famotidine tablets are contraindicated in patients with a history of serious hypersensitivity reactions (e.g., anaphylaxis) to famotidine or other histamine-2 (H 2 ) receptor antagonists. History of serious hypersensitivity reactions (e.g., anaphylaxis) to famotidine or other H 2 receptor antagonists. ( 4 )

Do not use if you have trouble or pain swallowing food, vomitiing with blood, or bloody or black stools. These may be signs of a serious condition. See your doctor. with other acid reducers

Ask a doctor before use if you have had heartburn over 3 months. This may be a sign of a more serious condition. heartburn with lightheadedness, sweating, or dizziness chest pain or shoulder pain with shortness of breath; sweating; pain spreading to arms, neck or shoulders; or lightheadedness frequent wheezing, particularly with heartburn frequent chest pain unexplained weight loss nausea or vomiting stomach pain kidney disease

Stop use and ask a doctor if your heartburn continues or worsens you need to take this product for more than 14 days

6 Adverse Reactions 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 identified during post-approval use of famotidine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably 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 The most common adverse reactions are: headache, dizziness, constipation, and diarrhea. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Valeant Pharmaceuticals North America LLC at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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

7 Drug Interactions 7.1 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 Substrate) 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. Drugs Dependent on Gastric pH for Absorption : Systemic exposure of the concomitant drug may be significantly reduced leading to loss of efficacy. See full prescribing information for a list of interacting drugs. (7.1) Tizanidine (CYP1A2) Substrate : Potential for substantial increases in blood concentrations of tizanidine resulting in hypotension, bradycardia or excessive drowsiness; avoid concomitant use, if possible. (7.2) 7.2 Tizanidine (CYP1A2 Substrate) 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.

8 Use in Specific Populations 8.1 Pregnancy Risk Summary Available data with H 2 -receptor antagonists, including famotidine, in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal reproduction studies, no adverse development effects were observed with oral administration of famotidine at doses up to approximately 243 and 122 times, respectively, the recommended human dose of 80 mg per day for the treatment of erosive esophagitis (see Data). The estimated background risk for major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, 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 2 to 4% and 15 to 20%, respectively. Data Animal Data Reproductive studies have been performed in rats and rabbits at oral doses of up to 2000 and 500 mg/kg/day, respectively, and in both species at intravenous doses of up to 200 mg/kg/day, and have revealed no significant evidence of impaired fertility or harm to the fetus due to Famotidine. While no direct fetotoxic effects have been observed, sporadic abortions occurring only in mothers displaying marked decreased food intake were seen in some rabbits at oral doses of 200 mg/kg/day (about 49 times the recommended human dose of 80 mg per day, based on body surface area) or higher. There are, however, no adequate or well-controlled studies in pregnant women. Because animal reproductive studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. 8.2 Lactation Risk Summary There are limited data available on the presence of Famotidine in human breast milk. There were no effects on the breastfed infant. There are no data on famotidine effects on milk production. Famotidine is present in the milk of lactating rats (see Data). The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Famotidine and any potential adverse effects on the breastfed child from Famotidine or from the underlying maternal condition. Data Animal Data Transient growth depression was observed in young rats suckling from mothers treated with maternotoxic doses of famotidine at least 600 times the usual human dose. 8.4 Pediatric Use The safety and effectiveness of Famotidine have been established in pediatric patients for the treatment of peptic ulcer disease (i.e., duodenal ulcer, gastric ulcer) and GERD (i.e., symptomatic nonerosive GERD, erosive esophagitis as diagnosed by endoscopy). The use of Famotidine and the recommended dosage of Famotidine in these pediatric patients is supported by evidence from adequate and well-controlled studies of Famotidine in adults and published pharmacokinetic and pharmacodynamic data in pediatric patients [see Dosage and Administration (2.1), Clinical Pharmacology (12.2, 12.3)]. In pediatric patients, the safety and effectiveness for the treatment of pathological hypersecretory conditions and reduction of risk of duodenal ulcer recurrence have not been established. Famotidine 20 and 40 mg tablets are not recommended for use in pediatric patients weighing less than 40 kg because these tablet strengths exceed the recommended dose for these patients [see Dosage and Administration (2.1)]. For pediatric patients weighing less than 40 kg, consider another famotidine formulation (e.g., oral suspension, lower dose tablet). 8.5 Geriatric Use Of the 1442 Famotidine -treated patients in clinical studies, approximately 10% were 65 and older. In these studies, no overall differences in safety or effectiveness were observed between elderly and younger patients. In postmarketing experience, CNS adverse reactions have been reported in elderly patients with and without renal impairment receiving Famotidine [see W …

12.1 Mechanism of Action Famotidine is a competitive inhibitor of histamine-2 (H 2 ) receptors. The primary clinically important pharmacologic activity of famotidine is inhibition of gastric secretion. Both the acid concentration and volume of gastric secretion are suppressed by famotidine, while changes in pepsin secretion are proportional to volume output.

11 DESCRIPTION The active ingredient in famotidine tablets, USP is a histamine-2 (H 2 ) receptor antagonist. Famotidine is N' -(aminosulfonyl)-3-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]propanimidamide. The molecular 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, USP for oral administration contains either 20 mg or 40 mg of famotidine, USP and the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, ferric oxide red, ferric oxide yellow, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, titanium dioxide, and triacetin. Famotidine, USP is a white to pale yellowish-white crystalline powder that is freely soluble in dimethyl formamide and in glacial acetic acid, slightly soluble in methanol, very slightly soluble in water, practically insoluble in acetone, in alcohol, in chloroform, in ether and in ethyl acetate. structure

Active ingredient (in each tablet) Famotidine USP, 10 mg/ 20 mg

OVERDOSAGE The adverse reactions in overdose cases are similar to the adverse reactions encountered in normal clinical experience (see ADVERSE REACTIONS ). Oral doses of up to 640 mg/day have been given to adult patients with pathological hypersecretory conditions with no serious adverse effects. In the event of overdosage, treatment should be symptomatic and supportive. Unabsorbed material should be removed from the gastrointestinal tract, the patient should be monitored, and supportive therapy should be employed. The oral LD 50 of famotidine in male and female rats and mice was greater than 3000 mg/kg and 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, but induced significant anorexia and growth depression in rabbits starting with 200 mg/kg/day orally. The intravenous LD 50 of famotidine for mice and rats ranged from 254 to 563 mg/kg and the minimum lethal single I.V. dose in dogs was approximately 300 mg/kg. Signs of acute intoxication in I.V. treated dogs were emesis, restlessness, pallor of mucous membranes or redness of mouth and ears, hypotension, tachycardia and collapse.

HOW SUPPLIED Famotidine Tablets, USP, 20 mg, are yellow colored, circular, biconvex film-coated tablets embossed with 'L113'on one side and '20' on the other side. NDC 46708-293-30 bottles of 30 tablets with child-resistant closure NDC 46708-293-31 bottles of 100 tablets with child-resistant closure NDC 46708-293-71 bottles of 500 NDC 46708-293-91 bottles of 1000 NDC 46708-293-10 Unit dose tablets of 100 (10 x 10) Famotidine Tablets, USP, 40 mg, are brown colored, circular, biconvex film-coated tablets embossed with 'L114'on one side and '40' on the other side. NDC 46708-294-30 bottles of 30 tablets with child-resistant closure NDC 46708-294-31 bottles of 100 tablets with child-resistant closure NDC 46708-294-71 bottles of 500 NDC 46708-294-91 bottles of 1000 NDC 46708-294-10 Unit dose tablets of 100 (10 x 10) Storage Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Dispense in a USP tight, light-resistant container. Call your doctor for medical advice about side effects. You may report side effects to Alembic Pharmaceuticals Limited at 1-866-210-9797 or FDA at 1-800-FDA-1088. Alembic Pharmaceuticals Limited Manufactured in India Revised: 10/2024