Famotidine

5 WARNINGS AND PRECAUTIONS Central Nervous System (CNS) Adverse Reactions : Reported in elderly patients and patients with moderate and severe renal impairment; monitor elderly patients for CNS adverse reactions. ( 5.1 , 8.5 , 8.6 ) Concurrent GI Malignancy : Absence of GI symptoms does not preclude the presence of gastric malignancy; evaluate prior to initiating therapy. ( 5.2 ) Risk of Benzyl Alcohol Toxicity in Neonates : Famotidine Injection is not approved in neonates. Serious and fatal adverse reactions have been reported in low-birth weight and preterm neonates who received benzyl-alcohol-containing drugs intravenously. The minimum amount of benzyl alcohol at which these serious adverse reactions may occur is not known. ( 5.3 ) 5.1 Central 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. Monitor elderly patients for CNS adverse reactions [see Use in Specific Populations ( 8.5 )] . Dosage adjustments are recommended in adult patients with moderate and severe renal impairment due to higher famotidine systemic exposure compared to patients with normal renal function [see Dosage and Administration ( 2.3 ), Use in Specific Populations ( 8.6 ), and Clinical Pharmacology ( 12.3 )]. 5.2 Concurrent Gastric Malignancy In adults, symptomatic response to therapy with Famotidine Injection 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 Injection. 5.3 Risk of Benzyl Alcohol Toxicity in Neonates Famotidine Injection is not approved in neonates. Serious adverse reactions, including fatal reactions, of new onset or worsening metabolic acidosis that progressed to neurotoxicity, and in some cases gasping syndrome, have been reported in low-birth weight neonates (less than 2,500 grams) and preterm neonates (gestational age less than 34 weeks) who received benzyl alcohol (BA)-containing drugs intravenously. Gasping syndrome is a life-threatening condition in neonates caused by BA toxicity and is primarily characterized by multiorgan dysfunction secondary to metabolic acidosis, which leads to gasping respirations and death. The minimum amount of BA at which these serious adverse reactions, including fatal reactions, may occur is not known (Famotidine Injection contains 3.6 mg of BA per mL) [see Use in Specific Populations ( 8.4 )] .

6 ADVERSE REACTIONS Most common adverse reactions (>1%) are: headache, dizziness, constipation, and diarrhea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sagent Pharmaceuticals at 1-866-625-1618 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials 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 Injection has been established based on adequate and well-controlled studies of an oral famotidine product. 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 2,500 patients. A total of 1,442 patients were treated with oral 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. Adverse reactions reported in ≥1% of patients treated with oral famotidine in clinical trials were: headache, dizziness, constipation, and diarrhea. The following other adverse reactions were reported in less than 1% of patients treated with oral famotidine in clinical trials: Body as a Whole : fever, asthenia, fatigue Cardiovascular : palpitations Gastrointestinal : cholestatic jaundice, 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 Respiratory : interstitial pneumonia Skin : pruritus, dry skin, flushing Special Senses : tinnitus, taste disorder Other : impotence Adverse reactions reported with oral famotidine may also occur with Famotidine Injection. In addition, transient irritation at the injection site was reported with intravenous famotidine. 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