What are the risks of adding Lasix (furosemide) to a patient on Paxlovid (nirmatrelvir/ritonavir)?

Risks of Adding Furosemide to a Patient on Paxlovid

Adding furosemide (Lasix) to a patient on Paxlovid (nirmatrelvir/ritonavir) should be avoided due to potential drug interactions that could lead to significant toxicity, unless absolutely necessary for volume management.

Drug Interaction Mechanism

Ritonavir, a component of Paxlovid, is a potent inhibitor of the CYP3A4 enzyme system, which affects the metabolism of many medications. While furosemide itself is not primarily metabolized through CYP3A4, several important considerations exist:

• Ritonavir can affect multiple metabolic pathways and drug transporters that may influence furosemide pharmacokinetics
• The combination may increase risk of electrolyte abnormalities and acute kidney injury
• Patients with COVID-19 often have altered fluid status and kidney function, making them more vulnerable to adverse effects

Specific Risks

1. Electrolyte Disturbances

• Furosemide causes sodium, potassium, magnesium, and calcium excretion
• COVID-19 itself can cause electrolyte abnormalities
• Combined effects may lead to severe electrolyte imbalances

2. Acute Kidney Injury

• Paxlovid may alter renal blood flow through drug interactions
• Furosemide can cause volume depletion and pre-renal injury
• The combination increases risk of acute kidney injury, especially in patients with:
  • Pre-existing kidney disease
  • Heart failure
  • Volume depletion

3. Hemodynamic Effects

• Furosemide can cause hypotension through volume depletion
• COVID-19 patients may have hemodynamic instability
• Combined effects may worsen perfusion and organ function

Evidence-Based Recommendations

1. Avoid concurrent use if possible

   • The KDOQI guidelines specifically mention that ritonavir/nirmatrelvir (Paxlovid) should not be used concomitantly with medications that may increase risk of toxicity 1

2. If furosemide is absolutely necessary:

   • Use the lowest effective dose
   • Monitor renal function closely
   • Check electrolytes daily
   • Assess volume status frequently
   • Consider alternative diuretics with fewer interactions

3. Monitor for signs of toxicity:

   • Acute kidney injury
   • Electrolyte abnormalities (especially hypokalemia)
   • Hypotension
   • Dehydration

Alternative Approaches

If diuresis is necessary in a patient on Paxlovid:

1. Consider thiazide diuretics if appropriate for the clinical situation
2. Use careful fluid balance monitoring rather than aggressive diuresis
3. Evaluate if Paxlovid can be temporarily held if diuresis is urgently needed
4. Consider alternative COVID-19 treatments if diuresis cannot be delayed

Clinical Pearls

• Furosemide should not be used unless hypervolemia, hyperkalemia, and/or renal acidosis are present 1
• The Liverpool COVID-19 drug interaction tool is a valuable resource for checking specific drug interactions with Paxlovid 1
• Patients with kidney disease require special attention as both drugs may affect renal function
• Document careful risk-benefit assessment if concurrent use is unavoidable

Remember that drug interactions with Paxlovid have led to significant toxicity with other medications, as demonstrated in multiple case reports of tacrolimus toxicity 2, 3, and similar mechanisms could apply to other medications including diuretics.