Famotidine

Famotidine tablets are indicated in adult and pediatric patients 40 kg and greater 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. 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. Famotidine is a histamine-2 (H2) receptor antagonist indicated : In adult and pediatric patients 40 kg and greater for the treatment of: active duodenal ulcer (DU). active gastric ulcer. symptomatic nonerosive gastroesophageal reflux disease (GERD). erosive esophagitis due to GERD, diagnosed by biopsy.

In adults for the: treatment of pathological hypersecretory conditions (e.g., Zollinger-Ellison syndrome, multiple endocrine neoplasias). reduction of the risk of DU recurrence.

Indication Recommended Dosage 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: Take once daily before bedtime or twice daily in the morning and before bedtime with or without food.

2.1Recommended 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. Table 1: Recommended Dosage and Duration of Famotidine Tablets in Adult and Pediatric Patients 40 kg and Greater with Normal Renal Function Indication Recommended Dosage Recommended Duration Active duodenal ulcer (DU) 40 mg once daily; or 20 mg twice daily a Up to 8 weeks b,c Active gastric ulcer 40 mg once daily Up to 8 weeks c Symptomatic nonerosive GERD 20 mg twice daily Up to 6 weeks c Erosive esophagitis diagnosed by endoscopy 20 mg twice daily; or 40 mg twice daily a Up to 12 weeks Pathological hypersecretory conditions d 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 d 20 mg once daily 1 year c or as clinically indicated a Both dosages demonstrated effectiveness in clinical trials . 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 . C Longer treatment durations have not been studied in clinical trials . d In pediatric patients, the safety and effectiveness of famotidine tablets have not been established for the reduction of the risk of duodenal ulcer recurrence or for treatment of pathological hypersecretory conditions .

2.2Dosage in Renal Impairment Dosage

adjustments of famotidine tablets are recommended for patients with moderate to severe renal impairment (creatinine clearance less than 60 mL/min) . 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 Adult and Pediatric Patients 40 kg and Greater with Moderate and Severe Renal Impairment Indication Recommended Maximum Dosages Creatinine clearance 30 to 60 mL/minute Creatinine clearance less than 30 mL/minute Active duodenal ulcer (DU) 20 mg once daily; or 40 mg every other day 20 mg every other day a Active gastric ulcer 20 mg once daily; or 40 mg every other day 20 mg every other day a Symptomatic nonerosive GERD 20 mg once daily 20 mg every other day a Erosive esophagitis diagnosed by endoscopy b 20 mg once daily; or 40 mg every other day b 20 mg every other day a,b 40 mg once daily b 20 mg once daily b Pathological hypersecretory conditions c Avoid use d Reduction of the risk of DU recurrence c 20 mg every other day a e a An alternate dosage regimen is 10 mg once daily. Since 20 mg or 40 mg tablet strength cannot be used for this dosage regimen, use an alternate famotidine formulation. b 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 . c In pediatric patients, the safety and effectiveness of famotidine tablets have not been established for the reduction of the risk of duodenal ulcer recurrence or for treatment of pathological hypersecretory conditions . d Doses required to treat pathological hypersecretory conditions may exceed the maximum doses evaluated in patients with impaired renal function. The risk for increased adverse reactions in renally impaired patients treated with famotidine tablets for pathological hypersecretory conditions is unknown. e Recommended dosage regimen is 10 mg every other day.

Since 20 mg or 40 mg tablet strength cannot be used for this dosage regimen, use an alternate famotidine formulation.

2.3Administration Instructions Take

famotidine tablets once daily before bedtime or twice daily in the morning and before bedtime, as recommended. Famotidine tablets may be taken with or without food . Famotidine tablets may be given with antacids.

Central Nervous System (CNS) Adverse Reactions: Elderly patients and patients with renal impairment at increased risk; reduce the dosage. ( 2.2 , 5.1 , 8.5 , 8.6 ) GI Malignancy: Absence of GI symptoms does not preclude the presence of gastric malignancy; evaluate prior to initiating therapy.

5.1Central Nervous System Adverse Reactions

Central nervous system (CNS) adverse reactions, including confusion, delirium, hallucinations, disorientation, agitation, seizures, and lethargy, have been reported in elderly patients and patients with moderate and severe renal impairment treated with famotidine. Since famotidine blood levels are higher in patients with renal impairment than in patients with normal renal function, dosage adjustments are recommended in patients with renal impairment .

5.2Concurrent Gastric Malignancy In

adults, symptomatic response to therapy with famotidine does not preclude the presence of gastric malignancy. Consider evaluation for gastric malignancy in adult patients who have a suboptimal response or an early symptomatic relapse after completing treatment with famotidine.

Famotidine tablets are contraindicated in patients with a history of serious hypersensitivity reactions (e.g., anaphylaxis) to famotidine or other histamine-2 (H2) receptor antagonists. History of serious hypersensitivity reactions (e.g., anaphylaxis) to famotidine or other H 2 receptor antagonists.

8.1Pregnancy Risk Summary Available

data with H2-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 . 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.

The most common adverse reactions are: headache, dizziness, constipation, and diarrhea. To report SUSPECTED ADVERSE REACTIONS, contact Ascend Laboratories, LLC at 1-877-272-7901 or F DA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical 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 . 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

6.2Postmarketing 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