What are the side effects of Lasix (furosemide)?

Side Effects of Lasix (Furosemide)

Furosemide causes a wide range of adverse effects, with electrolyte disturbances being the most common (occurring in approximately 10% of patients), followed by volume depletion, ototoxicity with high doses, and various organ-specific reactions. 1, 2

Most Common Side Effects

Electrolyte and Metabolic Disturbances

• Hypokalemia occurs in approximately 3.6% of patients, particularly with aggressive diuresis, inadequate oral intake, cirrhosis, or concurrent corticosteroid/ACTH/laxative use 3, 2
• Metabolic alkalosis frequently accompanies electrolyte depletion and can worsen CO2 retention in chronic lung disease patients 3
• Hyponatremia, hypochloremic alkalosis, hypomagnesemia, and hypocalcemia can all occur, presenting as dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle cramps, or arrhythmias 1
• Hyperglycemia and altered glucose tolerance may occur, with rare precipitation of diabetes mellitus 1
• Hyperuricemia is common and gout may rarely be precipitated 1

Volume Depletion and Cardiovascular Effects

• Intravascular volume depletion occurs in 4.6% of patients, potentially causing dehydration, circulatory collapse, vascular thrombosis, and embolism, particularly in elderly patients 1, 2
• Orthostatic hypotension may occur and be aggravated by alcohol, barbiturates, or narcotics 1
• Initial IV administration can cause hemodynamic worsening including transient decrease in stroke volume and increased systemic vascular resistance 3
• Hypotension and azotemia from excessive use can impair renal function and exercise tolerance 3

Serious Adverse Effects

Ototoxicity

• Transient or permanent hearing loss can occur, particularly with rapid IV administration of high doses (>6 mg/kg/day) or concurrent use of other ototoxic drugs 3
• High-dose furosemide (>6 mg/kg/day) should not be given for periods longer than 1 week, and infusions should be administered over 5-30 minutes to avoid hearing loss 3
• Tinnitus and hearing loss are listed as central nervous system reactions 1

Renal Complications

• Nephrocalcinosis and nephrolithiasis occur with long-term use, particularly in premature infants, requiring monitoring with renal ultrasonography 3, 1
• Hypercalciuria contributes to nephrocalcinosis risk 3
• Azotemia and worsening renal function can occur with excessive diuresis 3, 1
• Acute urinary retention may occur in patients with bladder emptying disorders, prostatic hyperplasia, or urethral narrowing 1

Severe Hypersensitivity and Systemic Reactions

• Severe anaphylactic or anaphylactoid reactions with shock 1
• Systemic vasculitis, interstitial nephritis, and necrotizing angiitis 1
• Stevens-Johnson Syndrome, toxic epidermal necrolysis, and erythema multiforme 1
• Drug rash with eosinophilia and systemic symptoms (DRESS) 1

Hematologic Reactions

• Aplastic anemia, thrombocytopenia, agranulocytosis, hemolytic anemia, leukopenia, anemia, and eosinophilia 1

Gastrointestinal Effects

• Hepatic encephalopathy in patients with hepatocellular insufficiency 1
• Pancreatitis and jaundice (intrahepatic cholestatic) 1
• Increased liver enzymes, anorexia, oral and gastric irritation, cramping, diarrhea, constipation, nausea, and vomiting 1

Dermatologic Reactions

• Photosensitivity, rash, pruritus, urticaria, exfoliative dermatitis, bullous pemphigoid, and purpura 1
• Patients should be warned that skin may be more sensitive to sunlight 1

Neurologic Effects

• Paresthesias, vertigo, dizziness, headache, blurred vision, and xanthopsia 1

Other Effects

• Muscle spasm, weakness, restlessness, urinary bladder spasm, thrombophlebitis, and fever 1
• Increased cholesterol and triglyceride levels 1

Important Clinical Caveats

Risk Factors for Enhanced Toxicity

• The risk of electrolyte depletion is markedly enhanced when two diuretics are used in combination, as enhanced sodium delivery to distal tubules increases cation exchange 3
• Patients with hypoproteinemia (e.g., nephrotic syndrome) may have weakened diuretic effects and potentiated ototoxicity 1
• Patients allergic to sulfonamides may also be allergic to furosemide 1

Drug Interactions Increasing Side Effects

• NSAIDs (including COX-2 inhibitors) can block diuretic effects and cause increased BUN, creatinine, potassium, and weight gain 3
• Aminoglycoside antibiotics increase ototoxicity risk, especially with impaired renal function—avoid this combination except in life-threatening situations 1
• Cisplatin increases both ototoxicity and nephrotoxicity risk 1
• Salicylates may cause toxicity at lower doses due to competitive renal excretion 1
• ACE inhibitors or angiotensin II receptor blockers may cause severe hypotension and renal deterioration 1

Protective Measures

• Concomitant administration of ACE inhibitors or potassium-sparing agents like spironolactone can prevent electrolyte depletion and often eliminates the need for long-term oral potassium supplementation 3
• Among patients receiving potassium supplements or potassium-sparing diuretics, hypokalemia was less frequent, less severe, and of slower onset 2

Monitoring Requirements

• Serum electrolytes (particularly potassium), CO2, creatinine, and BUN should be determined frequently during the first few months and periodically thereafter 1
• Serum calcium and magnesium levels should be monitored periodically (rare cases of tetany have been reported) 1
• Urine and blood glucose should be checked periodically in diabetics 1
• In premature infants, renal function and renal ultrasonography must be performed 1

Overall Safety Profile

• In a large surveillance study of 2,367 hospitalized patients receiving furosemide, adverse reactions occurred in 10.1%, but only 14 instances (0.6%) were considered life-threatening 2
• Serious adverse reactions are uncommon and occur primarily in the seriously ill 2
• When dosage is increased or therapy causes moderate to severe adverse reactions, furosemide dosage should be reduced or therapy withdrawn 1