What is the recommended dosing adjustment for HNB‑B in patients with severe renal impairment (eGFR ≤15 mL/min/1.73 m²) or end‑stage renal disease?

HNB-B Dosing in Severe Renal Impairment

Direct Answer

No dosing recommendation can be provided for HNB-B (sofosbuvir-based regimens) in patients with severe renal impairment (eGFR ≤15 mL/min/1.73 m²) or end-stage renal disease, and sofosbuvir-free regimens should be strongly preferred in this population. 1

Evidence-Based Rationale

Why Sofosbuvir Cannot Be Recommended

• Sofosbuvir is eliminated primarily by the renal route, with approximately 80% recovered in urine, making it problematic in severe renal dysfunction 1
• In patients with eGFR <30 mL/min/1.73 m², sofosbuvir and its metabolite GS-331007 accumulate dramatically, with increases of +171% and +451% in drug exposure respectively compared to patients with normal renal function 1
• In ESRD patients on hemodialysis, GS-331007 concentrations were 10-fold higher pre-dialysis and 20-fold higher post-dialysis than in patients with normal renal function 1
• Progressive deterioration of renal function and renal symptoms have been reported in patients with severe renal impairment receiving sofosbuvir-based regimens 1

Licensing and Safety Concerns

• Sofosbuvir use in CKD stage 4 or 5 or in hemodialysis patients is outside license recommendations 1
• The appropriate therapeutic dose of sofosbuvir in patients with advanced renal disease or ESRD is not established 1
• Data on safety and efficacy of sofosbuvir-based regimens are lacking in this population 1

Recommended Alternative Regimens

For Severe Renal Impairment (eGFR <30 mL/min/1.73 m²)

Sofosbuvir-free regimens are strongly preferred whenever possible 1, 2:

• Grazoprevir/elbasvir for genotype 1 and 4 patients (no dose adjustment required) 1, 2
• Glecaprevir/pibrentasvir for genotypes 1-6 patients (no dose adjustment required) 1, 2
• Ritonavir-boosted paritaprevir, ombitasvir and dasabuvir for genotype 1 patients (no dose adjustment required) 1, 2

Specific Genotype Recommendations

• For genotype 1 patients with eGFR <30 mL/min: Elbasvir/grazoprevir for 12 weeks resulted in 99% SVR without dose modification 1
• For genotype 1a patients: Ombitasvir/paritaprevir/ritonavir plus dasabuvir with ribavirin 200 mg/day can be considered 1
• For genotype 1b patients: Daclatasvir plus asunaprevir for 24 weeks achieved 100% SVR in dialysis patients without dose modification 1

Critical Clinical Considerations

When Sofosbuvir Might Be Considered (With Extreme Caution)

If treatment is urgent and no sofosbuvir-free regimen is available (particularly for genotypes 2 and 3), the risks versus benefits must be carefully weighed 1:

• Further deterioration in renal function may occur 1
• Close monitoring for adverse events is mandatory 1
• Treatment should occur in expert centers with multidisciplinary team involvement 2

Monitoring Requirements

• Patients with severe renal impairment should be treated in expert centers with close monitoring by a multidisciplinary team 2
• Regular assessment of renal function is essential, especially when starting new medications 2
• Consider nephrology consultation for specialized management 2

Common Pitfalls to Avoid

• Do not use standard sofosbuvir dosing in severe renal impairment without understanding the significant accumulation risk 1
• Do not assume that dose reduction of sofosbuvir is safe – the appropriate dose is not established 1
• Do not overlook sofosbuvir-free alternatives that have proven efficacy and safety in this population 1, 2
• Do not forget that many medications require dose adjustment in severe renal impairment beyond just hepatitis C treatments 2, 3