Management of patients with hepatitis C infection and renal disease

Table 1 Dosage modification for patients with renal impairment

Creatinine clearance	Pegylated-interferon alfa-2a	Pegylated-interferon alfa-2b	Ribavirin
30-50 mL/min	180 μg/wk	1.125 μg/kg per week (25% reduction)	Alternating doses; 200 mg and 400 mg every other day
< 30 mL/min	135 μg/wk (25%-45% reduction)	0.75 μg/kg per week (50% reduction)	200 mg/d
Hemodialysis	135 μg/wk (25%-45% reduction)	0.75 μg/kg per week (50% reduction)	200 mg/d

Table 2 Pharmacokinetic and metabolic parameters of selected direct acting antivirals

Drugs	Metabolism/excretion route	Interaction with CYP3A	Comments
NS3/4A protease inhibitors
Boceprevir	Hepatic (CYP3A, aldoketoreductase)	Moderate CYP3A inhibitor	Significant DDI with other CYP3A substrate drugs
Telaprevir	Hepatic (CYP3A)	Strong CYP3A inhibitor	Significant DDI with other CYP3A and P-gp substrate drugs
Simeprevir	Hepatic (CYP3A)	Mild CYP1A2 and CYP3A inhibitor	Unconjugated hyperbilirubinemia commonly seen
Faldaprevir	Hepatic (CYP3A)	Moderate CYP3A inhibitor; weak CYP2C9 inhibitor	Inhibition of UGTA1 results in unconjugated hyperbilirubinemia
ABT-450/ ritonavir	Hepatic (CYP3A)	Strong CYP3A inhibitor (by ritonavir)	Unconjugated hyperbilirubinemia
NS5A replication complex inhibitors
Daclatasvir	Hepatic (CYP3A)	No/minimal
Ledipasvir	Feces (major); hepatic and renal (minor)	No/minimal
NS5B nucleos(t)ide polymerase inhibitors
Sofosbuvir	Renal	No/minimal	Dose reduction if moderate to severe renal impairment
NS5B non-nucleoside polymerase inhibitors
ABT-333	Hepatic (CYP2C8 60%, CYP3A4 30% and CYP2D6 10%)	No/minimal

Adapted from Tischer et al[55]. CYP3A4: Cytochrome P450 3A4.