FUROSEMIDE

Furosemide is a diuretic which is an anthranilic acid derivative. Chemically it is 4-chloro-N-furfuryl-5-sulfamoylanthranilic acid. Furosemide is a white to slightly-yellow crystalline powder. It is practically insoluble in water, sparingly soluble in alcohol, freely soluble in dilute alkali solutions and insoluble in dilute acids. It has the following structural formula: Molecular formula: C12H11CI N2O5S Molecular weight: 330.75 Furosemide Injection, USP is a sterile solution intended for intramuscular or intravenous administration. Each mL contains furosemide 10 mg and sodium chloride sufficient to render solution isotonic in water for injection. Contains sodium hydroxide and may contain hydrochloric acid for pH adjustment. pH is 8.0 to 9.3. The plastic syringe is molded from a specially formulated polypropylene. Water permeates from inside the container at an extremely slow rate which will have an insignificant effect on solution concentration over the expected shelf life. Solutions in contact with the plastic container may leach out certain chemical components from the plastic in very small amounts; however, biological testing was supportive of the safety of the syringe material. Contains no preservative. STRUCTURE

INDICATIONS & USAGE Parenteral therapy should be reserved for patients unable to take oral medication or for patients in emergency clinical situations. Edema Furosemide is indicated in adults and pediatric patients for the treatment of edema associated with congestive heart failure, cirrhosis of the liver and renal disease, including the nephrotic syndrome. Furosemide is particularly useful when an agent with greater diuretic potential is desired. Furosemide is indicated as adjunctive therapy in acute pulmonary edema. The intravenous administration of furosemide is indicated when a rapid onset of diuresis is desired, e.g., in acute pulmonary edema. If gastrointestinal absorption is impaired or oral medication is not practical for any reason, furosemide is indicated by the intravenous or intramuscular route. Parenteral use should be replaced with oral furosemide as soon as practical.

DOSAGE & ADMINISTRATION Adults Parenteral therapy with Furosemide Injection, USP should be used only in patients unable to take oral medication or in emergency situations and should be replaced with oral therapy as soon as practical. Edema The usual initial dose of furosemide is 20 to 40 mg given as a single dose, injected intramuscularly or intravenously. The intravenous dose should be given slowly (1 to 2 minutes). Ordinarily a prompt diuresis ensues. If needed, another dose may be administered in the same manner 2 hours later or the dose may be increased. The dose may be raised by 20 mg and given not sooner than 2 hours after the previous dose until the desired diuretic effect has been obtained. This individually determined single dose should then be given once or twice daily. Therapy should be individualized according to patient response to gain maximal therapeutic response and to determine the minimal dose needed to maintain that response. Close medical supervision is necessary. When furosemide is given for prolonged periods, careful clinical observation and laboratory monitoring are particularly advisable (see PRECAUTIONS : Laboratory Tests). If the physician elects to use high dose parenteral therapy, add the furosemide to either Sodium Chloride Injection, USP, Lactated Ringer's Injection, USP, or Dextrose Injection 5%, USP, after pH has been adjusted to above 5.5, and administer as a controlled intravenous infusion at a rate not greater than 4 mg/min. Furosemide Injection is a buffered alkaline solution with a pH of about 9 and the drug may precipitate at pH values below 7. Care must be taken to ensure that the pH of the prepared infusion solution is in the weakly alkaline to neutral range. Acid solutions, including other parenteral medications (e.g., labetalol, ciprofloxacin, amrinone, milrinone) must not be administered concurrently in the same infusion because they may cause precipitation of the furosemide. In addition, furosemide injection should not be added to a running intravenous line containing any of these acidic products. Acute Pulmonary Edema The usual initial dose of furosemide is 40 mg injected slowly intravenously (over 1 to 2 minutes). If a satisfactory response does not occur within 1 hour, the dose may be increased to 80 mg injected slowly intravenously (over 1 to 2 minutes). If necessary, additional therapy (e.g., digitalis, oxygen) may be administered concomitantly. Geriatric patients In general, dose selection for the elderly patient should be cautious, usually starting at the low end of the dosing range (see PRECAUTIONS , Geriatric Use). Pediatric Patients Parenteral therapy should be used only in patients unable to take oral medication or in emergency situations and should be replaced with oral therapy as soon as practical. The usual initial dose of furosemide injection (intravenously or intramuscularly) in pediatric patients is 1 mg/kg body weight and should be given slowly under close medical supervision. If the diuretic response to the initial dose is not satisfactory, dosage may be increased by 1 mg/kg not sooner than 2 hours after the previous dose, until the desired diuretic effect has been obtained. Doses greater than 6 mg/kg body weight are not recommended. Literature reports suggest that the maximum dose for premature infants should not exceed 1 mg/kg/day (see WARNINGS , Pediatric Use). Furosemide Injection should be inspected visually for particulate matter and discoloration before administration. Do not use if solution is discolored. To prevent needle-stick injuries, needles should not be recapped, purposely bent, or broken by hand.

Furosemide is contraindicated in patients with anuria and in patients with a history of hypersensitivity to furosemide.

Adverse reactions are categorized below by organ system and listed by decreasing severity. Gastrointestinal System Reactions (1) Hepatic encephalopathy in patients with hepatocellular insufficiency (2) Pancreatitis (3) Jaundice (intrahepatic cholestatic jaundice) (4) Increased liver enzymes (5) Anorexia (6) Oral and gastric irritation (7) Cramping (8) Diarrhea (9) Constipation (10) Nausea (11) Vomiting Systemic Hypersensitivity Reactions (1) Severe anaphylactic or anaphylactoid reactions (e.g., with shock) (2) Systemic vasculitis (3) Interstitial nephritis (4) Necrotizing angiitis Central Nervous System Reactions (1) Tinnitus and hearing loss (2) Paresthesias (3) Vertigo (4) Dizziness (5) Headache (6) Blurred vision (7) Xanthopsia Hematologic Reactions (1) Aplastic anemia (2)Thrombocytopenia (3) Agranulocytosis (4) Hemolytic anemia (5) Leukopenia (6) Anemia (7) Eosinophilia. Dermatologic-Hypersensitivity Reactions (1) Toxic epidermal necrolysis (2) Stevens-Johnson Syndrome (3) Erythema multiforme (4) Drug rash with eosinophila and systemic symptoms (5) Acute generalized exanthematous pustulosis (6) Exfoliative dermatitis (7) Bullous pemphigoid (8) Purpura (9) Photosensitivity (10) Rash (11) Pruritus (12) Urticaria Cardiovascular Reactions (1) Orthostatic hypotension may occur and be aggravated by alcohol, barbiturates or narcotics (2) Increase in cholesterol and triglyceride serum levels Other Reactions (1) Hyperglycemia (2) Glycosuria (3) Hyperuricemia (4) Muscle spasm (5) Weakness (6) Restlessness (7) Urinary bladder spasm (8) Thrombophlebitis (9) Transient injection site pain following intramuscular injection (10) Fever. Whenever adverse reactions are moderate or severe, furosemide dosage should be reduced or therapy withdrawn.