Do Lithium and Furosemide (Lasix) interact?

Lithium and Furosemide (Lasix) Interaction

Yes, lithium and furosemide (Lasix) interact significantly—furosemide reduces lithium's renal clearance and substantially increases the risk of lithium toxicity, which can be life-threatening. 1, 2

Mechanism of Interaction

• Furosemide decreases lithium's renal clearance by reducing glomerular filtration rate and increasing proximal tubular reabsorption of lithium, leading to elevated serum lithium levels. 3
• The FDA drug label for lithium explicitly states: "Lithium generally should not be given with diuretics because they reduce lithium's renal clearance and add a high risk of lithium toxicity." 2
• The FDA drug label for furosemide confirms: "Lithium generally should not be given with diuretics because they reduce lithium's renal clearance and add a high risk of lithium toxicity." 1

Clinical Significance and Risk

• Loop diuretics like furosemide have variable but significant effects on lithium levels, with the potential to cause serious toxicity. 3
• A multicentre case-control study found that use of diuretics was associated with elevated lithium serum levels, with an odds ratio of 3.83 (95% CI 1.28-11.48) for potentially interacting co-medication including diuretics. 4
• Female sex, older age, and use of certain diuretics significantly predict the severity of lithium intoxication. 5
• The risk is particularly elevated in patients with preexisting decreased renal function or decreased intravascular volume. 6

Management Recommendations

If this combination must be used:

• Decrease the lithium dosage preemptively when initiating furosemide. 2
• Monitor serum lithium levels more frequently—initially every 3-5 days after starting furosemide, then weekly until stable. 2, 5
• Monitor for clinical signs of lithium toxicity: diarrhea, vomiting, tremor, mild ataxia, drowsiness, muscular weakness, confusion, or lethargy. 2
• Monitor renal function (serum creatinine, BUN) and electrolytes (particularly sodium) closely, as both medications affect renal function. 1, 2
• Ensure the patient maintains adequate sodium intake and hydration (2500-3000 mL daily), as sodium depletion from furosemide further increases lithium retention. 2

Alternative Considerations

• Consider alternative diuretics with lower interaction potential if possible, though all diuretics carry some risk. 3
• Thiazide diuretics demonstrate the greatest potential to increase lithium concentrations (25-40% increase), while loop diuretics like furosemide have more variable effects. 3
• Potassium-sparing diuretics have minor variable effects and may be safer alternatives when diuresis is necessary. 3

Common Pitfalls

• Failing to reduce lithium dose prophylactically when starting furosemide—waiting for toxicity to develop before adjusting is dangerous. 2
• Inadequate monitoring frequency—lithium levels can rise rapidly within days of starting furosemide. 4
• Ignoring early signs of toxicity (tremor, mild confusion) as "minor" symptoms—these can progress rapidly to severe neurotoxicity. 2
• Not counseling patients about maintaining adequate salt and fluid intake, which is critical when both medications are used together. 2