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Furosemide (Lasix): Drug Monograph

    Brand Names
    • Lasix
    Drug Class
    • Diuretic
    Indications
    • Treatment of edema associated with congestive heart failure, cirrhosis of the liver, and renal disease, including the nephrotic syndrome in adults and pediatric patients
    • Treatment of hypertension alone or in combination with other antihypertensive agents in adults
    • Injection: Adjunctive therapy for acute pulmonary edema
    Dosing

    (Adult):

    • Edema (Heart Failure)
      • Oral: 20 to 80 mg given as a single dose
        • The dose may be raised by 20 to 40 mg and given not sooner than 6 to 8 hours after the previous dose until the desired diuretic effect has been obtained. 
        • Severe edematous states: May carefully titrate dose up to 600 mg/day
        • Consider giving on 2-4 consecutive days each week
        • Closely monitor of kidney function and electrolytes when exceeding 80 mg/day for prolonged periods
      • Injection: 20-40 mg as a single dose IV/IM; give IV dose slowly (1-2- minutes)
        • May repeat the same dose if needed or increase by 20 mg no sooner than 2 hours after the previous injection; give individually determined single dose every day or twice daily
    • Hypertension
      • 40 mg twice a day.
    • Pulmonary edema, acute
      • 40 mg IV slowly (over 1-2 minutes)
      • May increase to 80 mg IV slowly (over 1-2 minutes), if satisfactory response does not occur within 1 hour
      • Additional therapy (e.g., digitalis, oxygen) may be administered concomitantly if necessary

    (Pediatrics):

    • Edema
      • Oral: 2 mg/kg body weight given as a single dose.
        • If the diuretic response is not satisfactory after the initial dose, dosage may be increased by 1 or 2 mg/kg no sooner than 6 to 8 hours after the previous dose.
        • Doses greater than 6 mg/kg body weight are not recommended.
      • Injection: 1 mg/kg IV/IM.  May increase by 1 mg/kg no sooner than 2 hours after the previous dose, if response is not satisfactory.  Maximum: 6 mg/kg
      • Premature Infants: 1 mg/kg/day
    Renal Dosing
    • None
    Hepatic Dosing
    • None
    Dosage Forms
    • Tablets:  20 mg, 40 mg, 80 mg
    • Injection: 10 mg/mL (in 2 mL, 4 mL, 10 mL vials)
    • Oral Solution: 8 mg/mL (in 5 mL, 500 mL) and 10 mg/mL (in 60 mL, 120 mL)
    Black Box Warnings
    • Furosemide is a potent diuretic, which, if given in excessive amounts, can lead to a profound diuresis with water and electrolyte depletion.
    • Dose and dose schedule must be adjusted to the individual patient's needs.
    Contraindications
    • Patients with anuria
    • Known history of hypersensitivity to furosemide
    Warnings
    • In patients with hepatic cirrhosis and ascites, 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.  Strict observation necessary during the period of diuresis.
    • If increasing azotemia and oliguria occur during treatment of severe progressive renal disease, discontinue furosemide. 
    • Cases of tinnitus and reversible or irreversible hearing impairment and deafness possible.  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.  Controlled intravenous infusion is advisable.
    • Electrolyte depletion
    • Hypokalemia
    • Urinary retention
    • Deterioration in renal function - in patients at high risk for radiocontrast nephropathy
    • Asymptomatic hyperuricemia
    • Gout
    • Exacerbation or activation of systemic lupus erythematosus - in patients allergic to furosemide
    Adverse Reactions
    • Gastrointestinal system reactions:  hepatic encephalopathy in patients with hepatocellular insufficiency, pancreatitis, jaundice, increased liver enzymes, anorexia, oral and gastric irritation, cramping, diarrhea, constipation, nausea, and vomiting
    • Systemic hypersensitivity reactions:  severe anaphylactic or anaphylactoid reactions, systemic vasculitis, interstitial nephritis, necrotizing angiitis
    • CNS 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 eosinophilia and systemic symptoms, acute generalized Exanthematous Pustulosis, exfoliative dermatitis, bullous pemphigoid, purpura, photosensitivity, rash, pruritis, urticaria
    • Cardiovascular reaction:  orthostatic hypotension (may 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, fever
    Overdose
    • Signs and symptoms include dehydration, blood volume reduction, hypotension, electrolyte imbalance, hypokalemia and hypochloremic alkalosis, and any extensions of its diuretic action. 
    • Concentration of furosemide in biological fluids associated with toxicity or death is not known.
    • Treatment consists of replacement of excessive fluid and electrolyte losses.  Serum electrolytes, carbon dioxide level and blood pressure should be determined frequently. 
    • Adequate drainage must be assured in patients with urinary bladder outlet obstruction (such as prostatic hypertrophy).
    • Hemodialysis does not accelerate elimination.
    Antidote
    • None
    Drug Interactions
    • Aminoglycoside antibiotics - furosemide may increase the ototoxic potential of these, especially in the presence of impaired renal function.  Avoid combination if possible.
    • Ethacrynic acid - possibility of ototoxicity
    • High doses of salicylates - may experience salicylate toxicity at lower doses because of competitive renal excretory sites
    • Cisplatin - risk of ototoxic effects
    • Tubocurarine - may antagonize the skeletal muscle relaxing effect of this drug
    • Succinylcholine - may potentiate the action of this drug
    • Lithium - reduces lithium's renal clearance and adds a high risk of lithium toxicity
    • Angiotensin converting enzyme inhibitors or angiotensin II receptor blockers - may lead to severe hypotension and deterioration in renal function, including renal failure
    • Ganglioic or peripheral adrenergic blocking drugs - potentiation occurs
    • Sucralfate - may reduce the natriuretic and antihypertensive effects of furosemide.  Observe patients closely.  Separate intake of each by at least two hours.
    • Chloral hydrate - may lead to flushing, sweating attacks, restlessness, nausea, increase in blood pressure, and tachycardia.  Do not use.
    • Phenytoin - interferes directly with renal action of furosemide
    • Methotrexate and other drugs that undergo significant renal tubular secretion - may reduce the effect of furosemide and furosemide may decrease renal elimination of those drugs
    • Cyclosporine - increased risk of gouty arthritis secondary to furosemide-induced hyperurecemia and cyclosporine impairment or renal urate excretion
    • Acetylsalicylic acid - temporarily reduces creatinine clearance in patients with chronic renal insufficiency
    • Indomethacin - may reduce the natriuretic and antihypertensive effects of furosemide.  Observe patients
    Special Populations
    • Pregnancy: Pregnancy Category C
    • Labor and Delivery: None
    • Nursing Mothers: Caution should be exercised when administered to a nursing mother since it appears in breast milk.  It may inhibit lactation. 
    • Renal Impairment: None
    • Hepatic Impairment: None
    • Pediatric Patients: In premature infants, may precipitate nephrocalcinosis/nephrolithiasis.  Monitor renal function, and renal ultrasonography should be considered, in pediatric patients receiving furosemide. If administered to premature infants during the first weeks of life, may increase the risk of persistence of patent ductus arteriosus.
    • Geriatric Patients: In general, dose selection for the elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and it may be useful to monitor renal function.
    Pregnancy Rating
    • Category C
    Breastfeeding
    • Caution should be exercised when administered to a nursing mother since it appears in breast milk.  It may inhibit lactation.
    Chemical Structure

      • Scientific Name:  4-chloro-N-furfuryl-5-sulfamoylanthranilic acid
      Mechanism of Action
      • Inhibits primarily the absorption of sodium and chloride not only in the proximal and distal tubules but also in the loop of Henle.
      Pharmacodynamics
      • The onset of diuresis following oral administration is within 1 hour
      Pharmacokinetics
      • Absorption: The mean bioavailability of the tablets and oral solution is 64% and 60%, respectively, of that from an intravenous injection of the drug.
      • Distribution: Furosemide is extensively bound to plasma proteins, mainly to albumin at 91 to 99% bound in healthy individuals. The unbound fraction averages 2.3 to 4.1% at therapeutic concentrations.
      • Onset of Action: The onset of diuresis following oral administration is within 1 hour. The peak effect occurs within the first or second hour.
      • Duration of Action: The duration of diuretic effect is 6 to 8 hours.
      • Elimination: Significantly more furosemide is excreted in urine following the IV injection than after the tablet or oral solution.
      • Geriatric Population: Furosemide binding to albumin may be reduced in elderly patients. Furosemide is predominantly excreted unchanged in the urine. The renal clearance of furosemide after intravenous administration in older healthy male subjects (60-70 years of age) is statistically significantly smaller than in younger healthy male subjects (20-35 years of age). The initial diuretic effect of furosemide in older subjects is decreased relative to younger subjects.
      Pharmacogenetics
      • None
      Counseling Points
      • Advise patients that they may experience symptoms from excessive fluid and/or electrolyte losses.  The postural hypotension that sometimes occurs can usually be managed by getting up slowly.  Potassium supplements and/or dietary measures may be needed to control or avoid hypokalemia. 
      • Patients with diabetes mellitus should be told that furosemide may increase blood glucose levels and thereby affect urine glucose tests.  The skin of some patients may be more sensitive to the effects of sunlight while taking furosemide.
      • Hypertensive patients should avoid medications that may increase blood pressure, including over-the-counter products for appetite suppression and cold symptoms.
      References
      • Furosemide (Lasix).  Product information.  sanofi-aventis U.S. LLC.  Bridgewater, NJ.  2012.

    MESH Terms & Keywords

    • Furosemide, Lasix, Diuretic