FUROSEMIDE

WARNINGS In patients with hepatic cirrhosis and ascites, furosemide therapy is best initiated in the hospital. In hepatic coma and in states of electrolyte depletion, therapy should not be instituted until the basic condition is improved. Sudden alterations of fluid and electrolyte balance in patients with cirrhosis may precipitate hepatic coma; therefore, strict observation is necessary during the period of diuresis. Supplemental potassium chloride and, if required, an aldosterone antagonist are helpful in preventing hypokalemia and metabolic alkalosis. If increasing azotemia and oliguria occur during treatment of severe progressive renal disease, furosemide should be discontinued. Cases of tinnitus and reversible or irreversible hearing impairment and deafness have been reported. Reports usually indicate that furosemide ototoxicity is associated with rapid injection, severe renal impairment, the use of higher than recommended doses, hypoproteinemia or concomitant therapy with aminoglycoside antibiotics, ethacrynic acid, or other ototoxic drugs. If the physician elects to use high dose parenteral therapy, controlled intravenous infusion is advisable (for adults, an infusion rate not exceeding 4 mg furosemide per minute has been used) (see PRECAUTIONS, DRUG INTERACTIONS ). Pediatric Use In premature neonates with respiratory distress syndrome, diuretic treatment with furosemide in the first few weeks of life may increase the risk of persistent patent ductus arteriosus (PDA), possibly through a prostaglandin-E-mediated process. Literature reports indicate that premature infants with post conceptual age (gestational plus postnatal) less than 31 weeks receiving doses exceeding 1 mg/kg/24 hours may develop plasma levels which could be associated with potential toxic effects including ototoxicity. Hearing loss in neonates has been associated with the use of furosemide injection (see WARNINGS , above).

ADVERSE REACTIONS Adverse reactions are categorized below by organ system and listed by decreasing severity. Gastrointestinal System Reactions Hepatic encephalopathy in patients with hepatocellular insufficiency Pancreatitis Jaundice (intrahepatic cholestatic jaundice) Increased liver enzymes Anorexia Oral and gastric irritation Cramping Diarrhea Constipation Nausea Vomiting Systemic Hypersensitivity Reactions Severe anaphylactic or anaphylactoid reactions (e.g., with shock) Systemic vasculitis Interstitial nephritis Necrotizing angiitis Central Nervous System Reactions Tinnitus and hearing loss Paresthesias Vertigo Dizziness Headache Blurred vision Xanthopsia Hematologic Reactions Aplastic anemia Thrombocytopenia Agranulocytosis Hemolytic anemia Leukopenia Anemia Eosinophilia Dermatologic-Hypersensitivity Reactions Toxic epidermal necrolysis Stevens-Johnson Syndrome Erythema multiforme Drug rash with eosinophila and systemic symptoms Acute generalized exanthematous pustulosis Exfoliative dermatitis Bullous pemphigoid Purpura Photosensitivity Rash Pruritus Urticaria Cardiovascular Reactions Orthostatic hypotension may occur and be aggravated by alcohol, barbiturates or narcotics Increase in cholesterol and triglyceride serum levels Other Reactions Hyperglycemia Glycosuria Hyperuricemia Muscle spasm Weakness Restlessness Urinary bladder spasm Thrombophlebitis Transient injection site pain following intramuscular injection Fever Whenever adverse reactions are moderate or severe, furosemide dosage should be reduced or therapy withdrawn.