Can a patient with severe renal impairment and dialysis dependence take Remdesivir (remdesivir) or other medications to treat COVID-19?

Remdesivir Use in Severe Renal Impairment and Dialysis

Remdesivir can be safely administered to patients with severe renal impairment and those on dialysis, despite manufacturer labeling concerns, as recent evidence demonstrates no clinically significant increase in adverse events and potential mortality benefit in this population. 1, 2, 3, 4

Key Contraindication Update

• The FDA label states remdesivir is contraindicated in patients with eGFR <30 mL/min, primarily due to theoretical concerns about accumulation of the vehicle excipient SBECD (sulfobutylether-β-cyclodextrin) 5, 1
• However, this contraindication is increasingly recognized as overly cautious based on accumulating real-world evidence showing safety in this population 2, 3, 4

Evidence Supporting Use in Severe Renal Impairment

Pharmacokinetic Data

• Remdesivir exposures are NOT significantly affected by renal function, even in patients with eGFR <15 mL/min or on dialysis 1
• While metabolite exposures (GS-441524, GS-704277, and SBECD) increase up to 7.9-fold, 2.8-fold, and 21-fold respectively in severe renal impairment, these changes are not considered clinically significant 1
• Remdesivir is not efficiently removed by hemodialysis, so timing around dialysis sessions is not critical 1

Safety Profile in Renal Impairment

• A systematic review of 22 studies found mortality rates of 7.3-50% in renally impaired patients receiving remdesivir, with NO increase in adverse effects attributed to the drug 2
• In a retrospective study of 135 patients, only 30% of those with severe renal impairment experienced possible adverse events versus 11% without renal impairment (p=0.06), which was not statistically significant 3
• A 2024 study of 101 renally-impaired COVID-19 patients (eGFR <30) found remdesivir-treated patients had LOWER rates of acute kidney injury (18.4% vs 51.7%) compared to those not receiving antivirals 4
• There were no cases of remdesivir discontinuation due to adverse reactions in renally-impaired patients 4

Clinical Decision Algorithm

Step 1: Assess Baseline Renal Function

• Calculate eGFR and determine if patient has:
  • Severe renal impairment (eGFR 15-29 mL/min/1.73m²)
  • Kidney failure (eGFR <15 mL/min/1.73m²)
  • Active dialysis dependence (hemodialysis or peritoneal dialysis) 1

Step 2: Check Additional Contraindications

• Absolute contraindications that override renal considerations:
  • ALT >5 times upper limit of normal at baseline 5, 6
  • History of clinically significant hypersensitivity to remdesivir 1
• If these are present, do NOT use remdesivir regardless of renal function 5

Step 3: Assess COVID-19 Severity and Timing

• For hospitalized patients requiring mechanical ventilation/ECMO: Use 10-day course (200 mg loading dose day 1, then 100 mg daily) 6, 1
• For hospitalized patients NOT requiring mechanical ventilation/ECMO: Use 5-day course 6, 1
• For non-hospitalized high-risk patients: Use 3-day course if within 7 days of symptom onset 6, 1

Step 4: Monitoring Protocol for Renally-Impaired Patients

• Before starting remdesivir:

  • Obtain baseline hepatic function tests (ALT, AST, bilirubin) 6, 1
  • Check prothrombin time 6, 1
  • Document baseline creatinine (even though dosing doesn't change) 1

• During treatment:

  • Monitor for hypersensitivity reactions during infusion 1
  • Observe patients for at least 1 hour after infusion completion 1
  • Discontinue if ALT increases to >10 times upper limit of normal OR if ALT elevation is accompanied by signs/symptoms of liver inflammation 6, 1
  • Monitor renal function as clinically appropriate, though worsening is more likely due to COVID-19 itself than remdesivir 4

Important Caveats

Dialysis Timing

• No dosage adjustment is needed for patients on dialysis 1
• Administration timing relative to dialysis sessions does not matter, as remdesivir is not efficiently removed by hemodialysis 1
• Metabolites ARE partially cleared by dialysis (average clearance of GS-441524: 149 mL/min; GS-704277: 92.6 mL/min), but this does not require dose modification 1

Acute Kidney Injury Considerations

• Remdesivir may actually be beneficial in COVID-19-induced acute kidney injury, as the virus itself causes renal damage through direct invasion 2
• In the comparative study, remdesivir-treated patients with renal impairment had significantly LOWER rates of new AKI (18.4%) compared to controls (51.7%) 4

Alternative Therapies

If remdesivir is truly contraindicated or unavailable:

• Paxlovid (nirmatrelvir/ritonavir) is also contraindicated in eGFR <30 mL/min 7
• Molnupiravir may be used but is less effective 7
• High-titer convalescent plasma is an option, particularly for immunocompromised patients 7

Common Pitfalls to Avoid

1. Do not automatically exclude patients with eGFR <30 from remdesivir based solely on manufacturer labeling - the evidence supports safety in this population 2, 3, 4

2. Do not confuse pre-existing renal impairment with remdesivir-induced nephrotoxicity - most creatinine elevations in these patients are due to COVID-19 progression, not the drug 3, 4

3. Do not delay or avoid dialysis in patients receiving remdesivir - the drug is not significantly removed by dialysis and timing is not critical 1

4. Do not assume metabolite accumulation equals toxicity - while SBECD and other metabolites do accumulate up to 21-fold in severe renal impairment, this has not translated to clinical harm in real-world studies 1, 2

5. Do monitor liver function more closely than renal function during treatment - hepatotoxicity (ALT >10x ULN) is the primary reason to discontinue remdesivir, not worsening renal function 6, 1