What are the contraindications for Remdesivir?

Contraindications for Remdesivir

Remdesivir is contraindicated in patients with a history of clinically significant hypersensitivity reactions to remdesivir or any components of the product, as well as in patients with liver dysfunction (ALT >5 times normal at baseline) or renal dysfunction (eGFR <30 mL/min). 1, 2

Primary Contraindications

1. Hypersensitivity reactions:

   • History of clinically significant hypersensitivity to remdesivir or any components
   • Previous infusion-related or anaphylactic reactions to the medication 2

2. Liver dysfunction:

   • ALT levels greater than 5 times the upper limit of normal at baseline
   • Signs or symptoms of liver inflammation with elevated ALT 1, 2

3. Renal dysfunction:

   • Historical contraindication for eGFR <30 mL/min 1

   Important update: Recent evidence from a 2025 phase I study has led to an extension of indication for remdesivir in the USA and Europe for use in patients with all stages of renal impairment, including those on dialysis, with no dose adjustment 3. However, clinicians should still exercise caution and monitor these patients closely.

Monitoring Requirements

When administering remdesivir, the following monitoring is essential:

• Hepatic function:

  • Perform baseline hepatic laboratory testing before starting treatment
  • Continue monitoring during treatment as clinically appropriate
  • Consider discontinuing if ALT increases to >10 times the upper limit of normal
  • Discontinue immediately if ALT elevation is accompanied by signs or symptoms of liver inflammation 2

• Renal function:

  • Assess baseline renal function
  • Monitor during treatment as clinically appropriate 1

• Hypersensitivity monitoring:

  • Monitor patients during infusion
  • Observe for at least one hour after infusion completion
  • If signs of hypersensitivity occur, immediately discontinue and initiate appropriate treatment 2

Drug Interactions

• Not recommended for coadministration with:

  • Chloroquine phosphate
  • Hydroxychloroquine sulfate

  These medications may have an antagonistic effect on the intracellular metabolic activation and antiviral activity of remdesivir 2, 4

• Drug interaction monitoring:

  • Remdesivir is not a significant inducer or inhibitor of CYP enzymes
  • However, monitoring is recommended when co-administered with strong inducers or inhibitors of CYP enzymes 1

Special Considerations

1. Pregnancy: Limited data available as pregnant women were excluded from many clinical trials 1

2. Administration route: Only available as intravenous infusion, which may limit use in some settings 1

3. Cost and availability: Relatively costly with potentially limited availability in some regions 1

4. Adverse events: Common adverse reactions include:

   • Nausea
   • Increased ALT
   • Increased AST 2, 5

Clinical Decision Algorithm

1. Assess contraindications:

   • Check for history of hypersensitivity to remdesivir
   • Evaluate baseline liver function (ALT/AST)
   • Assess renal function (eGFR)

2. Review concomitant medications:

   • Check for chloroquine or hydroxychloroquine use
   • Evaluate potential interactions with CYP inducers/inhibitors

3. If no contraindications exist:

   • Proceed with appropriate dosing based on:
     • Patient weight
     • Hospitalization status
     • Severity of COVID-19
     • Time since symptom onset

4. During treatment:

   • Monitor for hypersensitivity reactions during and after infusion
   • Regularly assess liver and renal function
   • Watch for adverse events, particularly hepatotoxicity

Remember that while remdesivir may be beneficial in the clinical course for both hospitalized and non-hospitalized COVID-19 patients, the evidence for mortality benefit remains limited 6, and treatment decisions should prioritize patient safety by strictly adhering to contraindication guidelines.