What are the risks associated with using furosemide (Lasix)?

Risks of Furosemide

Furosemide carries significant risks of electrolyte depletion, volume depletion with circulatory collapse, ototoxicity, and nephrocalcinosis (particularly in premature infants), requiring vigilant monitoring of fluid status, electrolytes, and renal function throughout therapy. 1

Electrolyte and Metabolic Disturbances

The most common adverse effects of furosemide relate to its potent diuretic action:

• Hypokalemia occurs in approximately 3.6% of patients and represents one of the most frequent complications, particularly with brisk diuresis, inadequate oral electrolyte intake, cirrhosis, or concurrent use of corticosteroids, ACTH, or laxatives 2, 3
• Hypomagnesemia and hypocalcemia can develop, with rare cases of tetany reported; periodic monitoring of these electrolytes is essential 1
• Metabolic alkalosis frequently accompanies electrolyte depletion and can exacerbate CO2 retention in patients with chronic lung disease 2
• Hyperglycemia and alterations in glucose tolerance tests have been observed, with rare precipitation of diabetes mellitus 1
• Hyperuricemia can occur asymptomatically, and gout may rarely be precipitated 1

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, a process potentiated by renin-angiotensin-aldosterone system activation 2. 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 2.

Volume Depletion and Hemodynamic Effects

• Excessive diuresis causes dehydration and blood volume reduction with circulatory collapse in approximately 4.6% of patients, particularly in elderly patients 1, 3
• Vascular thrombosis and embolism may occur secondary to volume depletion, especially in elderly patients 1
• Hypotension and azotemia can result from excessive diuretic use, impairing renal function and exercise tolerance 2
• Initial hemodynamic worsening may occur with IV administration, including orthostatic hypotension, transient decrease in stroke volume, and increased systemic vascular resistance 4

When hypotension and azotemia occur without signs of fluid retention, they likely reflect volume depletion and may resolve with diuretic dose reduction; however, when these occur with persistent fluid retention, they reflect worsening heart failure and declining peripheral perfusion—an ominous scenario requiring advanced management 2.

Ototoxicity

• Transient or permanent hearing loss can occur, particularly with rapid IV administration of high doses (>6 mg/kg/day) or when used concomitantly with other ototoxic drugs 2
• 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 2
• Avoid combination with aminoglycosides except in life-threatening situations due to increased ototoxic potential, especially with impaired renal function 1
• Do not use concomitantly with ethacrynic acid because of the possibility of ototoxicity 1
• Cisplatin combination carries risk of ototoxic effects 1

Renal Complications

• Nephrocalcinosis and nephrolithiasis occur with long-term use, particularly in premature infants, requiring monitoring of renal function and renal ultrasonography 2, 4, 1
• Hypercalciuria leads to nephrocalcinosis risk 2
• Acute urinary retention can occur in patients with severe urinary retention symptoms (bladder emptying disorders, prostatic hyperplasia, urethral narrowing) due to increased urine production; these patients require careful monitoring, especially during initial treatment 1
• Radiocontrast nephropathy occurs at higher incidence in high-risk patients receiving furosemide compared to those receiving only IV hydration prior to radiocontrast 1
• Azotemia with reversible BUN elevations may occur and are associated with dehydration 1

Drug Interactions

Critical interactions that increase risk:

• Lithium toxicity: Diuretics reduce lithium's renal clearance; lithium generally should not be given with diuretics 1
• ACE inhibitors or ARBs: Combined use may lead to severe hypotension and deterioration in renal function, including renal failure; dose interruption or reduction may be necessary 1
• NSAIDs (including COX-2 inhibitors): Block diuretic effects and can cause increased BUN, serum creatinine, potassium levels, and weight gain 2, 1
• Salicylates: High-dose concurrent use may cause salicylate toxicity at lower doses due to competitive renal excretory sites 1
• Cephalosporins: Furosemide increases risk of cephalosporin-induced nephrotoxicity even with minor or transient renal impairment 1
• Cyclosporine: Concomitant use increases risk of gouty arthritis secondary to furosemide-induced hyperuricemia and cyclosporine impairment of renal urate excretion 1
• Sucralfate: Reduces natriuretic and antihypertensive effects; separate administration by at least 2 hours 1

Special Population Risks

Premature infants and neonates:

• Nephrocalcinosis/nephrolithiasis risk necessitates renal function monitoring and renal ultrasonography 1
• Cholelithiasis in premature infants receiving total parenteral nutrition concomitantly 5
• Secondary hyperparathyroidism and bone disease with long-term treatment 5

Patients with hypoproteinemia:

• The effect of furosemide may be weakened and ototoxicity potentiated in patients with nephrotic syndrome 1

Diabetic patients:

• Furosemide may increase blood glucose levels and affect urine glucose tests; periodic monitoring required 1

Monitoring Requirements

To mitigate risks, the FDA label mandates specific monitoring:

• Serum electrolytes (particularly potassium), CO2, creatinine, and BUN should be determined frequently during the first few months of therapy and periodically thereafter 1
• Serum calcium and magnesium levels should be determined periodically 1
• Urine and blood glucose should be checked periodically in diabetics 1
• Fluid status assessment for signs of volume depletion: dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, arrhythmia, or gastrointestinal disturbances 1

Overall Safety Profile

Despite these risks, furosemide is relatively safe across a wide range of clinical situations when used appropriately. In a large surveillance study of 2,367 hospitalized patients receiving furosemide, adverse reactions occurred in 10.1% of patients, but only 14 instances (0.6%) were considered life-threatening 3. Serious adverse reactions are uncommon and occur primarily in the seriously ill 3. The overall frequency of adverse reactions increases progressively with higher daily doses but is not correlated with total cumulative dose 3.