FAMOTIDINE

The active ingredient in Famotidine for Oral Suspension, USP is a H 2 -receptor antagonist. Famotidine is N' -(aminosulfonyl)-3-[[[2-[(diaminomethylene)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 337.43. Its structural formula is: Each 5 mL of Famotidine for Oral Suspension when prepared as directed contains 40 mg of famotidine and the following inactive ingredients: edetate disodium dihydrate, microcrystalline cellulose, sucrose, xanthan gum, flavors (banana and peppermint). Added as preservatives are sodium benzoate, methylparaben sodium and propylparaben sodium. 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 for Oral Suspension is indicated in adults for the treatment of: active duodenal ulcer (DU). active gastric ulcer (GU). symptomatic nonerosive gastroesophageal reflux disease (GERD). erosive esophagitis due to GERD, diagnosed by biopsy. treatment of pathological hypersecretory conditions (e.g., Zollinger-Ellison syndrome, multiple endocrine neoplasias). reduction of the risk of DU recurrence. Famotidine for Oral Suspension is indicated in pediatric patients 1 year of age and older for the treatment of: peptic ulcer disease. GERD with or without esophagitis and ulcerations. Famotidine for Oral Suspension is indicated in pediatric patients from birth to less than 1 year of age for the treatment of: GERD. Famotidine for Oral Suspension is a histamine-2 (H 2 ) receptor antagonist indicated ( 1 ): In adults for the treatment of: active duodenal ulcer (DU). active gastric ulcer (GU). symptomatic nonerosive gastroesophageal reflux disease (GERD). erosive esophagitis due to GERD, diagnosed by biopsy. treatment of pathological hypersecretory conditions (e.g., Zollinger-Ellison syndrome, multiple endocrine neoplasias). reduction of the risk of DU recurrence. In pediatric patients 1 year of age and older for the treatment of: peptic ulcer. GERD with or without esophagitis and ulcerations. In pediatric patients from birth to less than 1 year of age for the treatment of: GERD.

Recommended adult dosage by indication ( 2.1 ): Active DU 40 mg once daily; or 20 mg twice daily Active GU 40 mg once daily Symptomatic Nonerosive GERD 20 mg twice daily Erosive Esophagitis due to GERD 20 mg twice daily; or 40 mg twice daily 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 Recommended pediatric dosage by indication ( 2.2 ): Peptic Ulcer Disease 1 year to less than 17 years Starting dosage 0.5 mg/kg once daily; or 0.25 mg/kg twice daily; may increase to 1 mg/kg once daily at bedtime or 0.5 mg/kg twice daily; Maximum of 40 mg per day GERD Birth to less than 3 months Starting dosage 0.5 mg/kg once daily; may increase to 1 mg/kg once daily 3 months to less than 1 year Starting dosage 0.5 mg/kg twice daily; may increase to 1 mg/kg twice daily; Maximum of 40 mg per day GERD with or without esophagitis and ulcerations 1 year to less than 17 years 0.5 mg/kg twice daily Maximum of 40 mg twice daily See full prescribing information for complete dosing information in adults and pediatrics, recommended treatment duration by indication, and dosage adjustment for adult patients with renal impairment. ( 2.1 , 2.2 , 2.3 ) Administration ( 2.4 ) : Take once daily before bedtime or twice daily in the morning and before bedtime with or without food. 2.1 Recommended Dosage in Adults The recommended dosage and duration of Famotidine for Oral Suspension in adults with normal renal function is shown in Table 1 . • After preparation, the concentration of Famotidine for Oral Suspension is 8 mg/mL [see Dosage and Administration ( 2.3 )] . Table 1: Recommended Dosage and Duration of Famotidine for Oral Suspension in Adults with Normal Renal Function a Both dosages demonstrated effectiveness in clinical trials [s ee Clinical Studies ( 14 ) ] . b In 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 [s ee Clinical Studies ( 14.1 ) ]. c Longer treatment durations have not been studied in clinical trials [s ee Clinical Studies ( 14.1 , 14.2 , 14.3 ) ] . Indication Recommended Dosage Rec ommended Duration Active DU 40 mg once daily; or 20 mg twice daily a Up to 8 weeks b,c Active GU 40 mg once daily Up to 8 weeks c Symptomatic nonerosive GERD 20 mg twice daily Up to 6 weeks c Erosive esophagitis due to GERD, diagnosed by endoscopy 20 mg twice daily; or 40 mg twice daily a Up to 12 weeks Pathological hypersecretory conditions Starting dosage: 20 mg every 6 hours; adjust dosage to individual patient needs Maximum dosage 160 mg every 6 hours As clinically indicated Reduction of the risk of DU recurrence 20 mg once daily 1 year b,c or as clinically indicated 2.2 Recommended Dosage in Pediatric Patients The recommended dosage and duration of Famotidine for Oral Suspension in pediatric patients with normal renal function is shown in Table 2 . • After preparation, the concentration of Famotidine for Oral Suspension is 8 mg/mL [see Dosage and Administration ( 2.3 )] . Table 2: Recommended Dosage and Duration of Famotidine for Oral Suspension in Pediatric Patients with Normal Renal Function a Treatment duration based on adult recommendations (see Table 1 ). Individualize the dose and duration based upon clinical response and/or pH determinations (gastric or esophageal) and endoscopy. b Use conservative measures (e.g., thickened feedings) concurrently [s ee Use in Specific Populations ( 8.4 ) ] . c After 4 weeks of treatment re-evaluate the patient. Consider an additional 4 weeks of treatment if treatment benefit outweighs potential risks. Indication Pediatric Age Range Recommended Dosage Duration Peptic Ulcer Disease 1 year to less than 17 years Starting dosage 0.5 mg/kg once daily; or 0.25 mg/kg twice daily May increase to 1 mg/kg once daily at bedtime or 0.5 mg/kg twice daily Maximum of 40 mg per day 8 weeks a GERD Birth to less than 3 months Starting dosage 0.5 mg/kg once daily. May increase to 1 mg/kg once daily a Up to 8 weeks a,b,c 3 months to less than 1 year Starting dosage 0.5 mg/kg twice daily. May increase to 1 mg/kg twice daily b Maximum of 40 mg per day GERD with or without esophagitis and ulcerations 1 year to less than 17 years 0.5 mg/kg twice daily Maximum of 40 mg twice daily 6 to 12 weeks a 2.3 Recommended Dosage in Adults with Renal Impairment Recommended dosage adjustments for adults with moderate to severe renal impairment (creatinine clearance less than 60 mL/min) by indication are shown in Table 3 . Use the lowest effective dosage [s ee Use in Specific Populations ( 8.6 ) ] . A safe and effective dosage has not been established in pediatric patients with renal impairment. Table 3: Recommended Maximum Dosage of Famotidine for Oral Suspension in Adults with Moderate and Severe Renal Impairment a Dosage adjustments for renal impairment are provided for both dosing regimens (20 mg twice daily and 40 mg twice daily) which showed effectiveness for the treatment of erosive esophagitis in clinical trials [s ee Clinical Studies ( 14.4 ) ] . b The dosage required to treat pathological hypersecretory conditions may exceed the maximum dosage evaluated in patients with impaired renal function. The risk for increased adverse reactions in renally impaired patients treated with Famotidine for Oral Suspension for pathological hypersecretory conditions is unknown. Indication Rec o m mended Maximum Dosage Creatinine Clearance 30 to 60 mL/minute Creatinine Clearance Less Than 30 mL/minute Active DU 20 mg once daily; or 40 mg every other day 10 mg once daily; or 20 mg every other day Active GU 20 mg once daily; or 40 mg every other day 10 mg once daily; or 20 mg every other day Symptomatic nonerosive GERD 20 mg once daily 10 mg once daily; or 20 mg every other day Erosive esophagitis due to GERD, diagnosed by endoscopy a 20 mg once daily; or 40 mg every other day b 10 mg once daily; or 20 mg every other day b 40 mg once daily b 20 mg once daily b Pathological hypersecretory conditions Avoid use b Reduction of the risk of DU recurrence 10 mg once daily; or 20 mg every other day 10 mg every other day 2.4 Preparation and Administration Instructions Preparation of Reconstituted Suspension by a Healthcare Provider Prior to Dispensing Prior to dispensing, constitute Famotidine for Oral Suspension by slowly adding 46 mL of purified water to the bottle. Shake vigorously for 5 to 10 seconds immediately after adding the water. The bottle of constituted suspension contains 55 mL (40 mg of famotidine per 5 mL), and should be an off-white, homogeneous suspension. Administration and Storage of Constituted Suspension Shake the bottle of constituted Famotidine for Oral Suspension vigorously for 5 to 10 seconds prior to each use. Take Famotidine for Oral Suspension once daily before bedtime or twice daily in the morning and before bedtime, as recommended. Famotidine for Oral Suspension may be taken with or without food [s ee Clinical Pharmacology ( 12.3 ) ] . Famotidine for Oral Suspension may be given with antacids. Store the constituted suspension at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Protect from freezing. Discard unused constituted suspension after 30 days.

Famotidine for Oral Suspension is contraindicated in patients with a history of serious hypersensitivity reactions (e.g., anaphylaxis) to famotidine or other H 2 -receptor antagonists. History of serious hypersensitivity reactions (e.g., anaphylaxis) to famotidine or other H 2 -receptor antagonists. ( 4 )

The most common adverse reactions are: headache, dizziness, constipation, and diarrhea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Lannett Company, Inc. at 1-844-834-0530 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 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. The safety of Famotidine for Oral Suspension has been established based on adequate and well-controlled studies of another oral famotidine product [s ee Clinical Studies ( 14 ) ] . The following is a summary of the adverse reactions reported in those studies. Oral famotidine was studied in 7 U.S. 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 to 91 years old, fairly well distributed between sex and race; however, the predominant race was White. 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 Pediatric Patients Less Than 1 Year of Age In a clinical study in 35 pediatric patients less than 1 year of age with GERD symptoms, two patients discontinued due to adverse reactions. Agitation observed in 5 patients resolved when famotidine was discontinued [s ee Use in Specific Populations ( 8.4 ) ] . 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

Drugs Dependent on Gastric pH for Absorpti on : Systemic exposure of the concomitant drug may be significantly reduced leading to loss of efficacy. ( 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 ) 7.1 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 for Oral Suspension 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 for Oral Suspension. If concomitant use is necessary, monitor for hypotension, bradycardia or excessive drowsiness. Refer to the full prescribing information for tizanidine.