Table 2.
FDA approved directly acting antiviral drugs—telaprevir (Incivek) and boceprevir (Victrelis). Modified from Assis and Lin [9].
| Telaprevir | Boceprevir | |
|---|---|---|
| Formulation | 375 mg oral capsule | 200 mg oral capsule |
| Dosing | 750 mg/7–9 h with a fatty meal* | 800 mg every 7–9 h with food* |
| Regimen | 12 weeks of triple therapy followed by Peg-IFN/ribavirin alone for 12 or 36 weeks** | Start after 4-week lead-in of Peg-IFN and ribavirin for 24 or 44 weeks** |
| Discontinuation | If VL >1,000 IU/mL at week 4 or 12, and VL at week 24 | If VL >100 IU/mL at week 8, 12, and VL at week 24 |
| Expected SVR | Naive: 69–75% Relapser: 84–88% Partial responder: 56–61% Null responder: 31–33% |
Naive: 63–66% Relapser: 69–75% Partial responder: 40–52% Null responder: not studied |
| RGT | If negative VL at weeks 4 and 12, treat with Peg-IFN/ribavirin for 12 more weeks If not, treat for 36 more weeks** | Treatment-naive: if negative VL at week 8 and 24, complete treatment at week 28 Previously treated: if negative VL at week 8 and 24, complete treatment at week 36** |
| Barrier to resistance | Low (V3M6, R155K) | Low (V3M6, R155K) |
| Common adverse effects | Anemia (37%) Rash (56%; severe in 4–7%) Anal itching/burning (29%) |
Anemia (49%) Dysgeusia (43%) |
| Metabolism | Hepatic (CYP450)*** | Hepatic (CYP450 and aldoketoreductase)*** |
| Interactions | Strong inhibitor of CYP3A | Strong inhibitor of CYP3A4/5 and is partly metabolized by CYP3A4/5 |
| Renal/hepatic adjustment | Renal: none Hepatic: do not use if Child-Pugh score >7 |
Renal: none Hepatic: do not use if Child-Pugh score >7 |
| FDA-labeled indications | Chronic HCV genotype 1a or 1b in combination with Peg-IFN and ribavirin, in adults with compensated liver disease (Child-Pugh <7) | Chronic HCV genotype 1a or 1b, in combination with Peg-IFN and ribavirin, in adults with compensated liver disease, including cirrhosis, who are previously untreated or who failed previous Peg-IFN/ribavirin treatment |
| Contraindications | Pregnancy (due to ribavirin) Coadministration with drugs highly dependent on CYP3A for clearance |
Pregnancy (due to ribavirin) Coadministration with drugs highly dependent on CYP3A4/5 for clearance |
| Special populations | Not approved in decompensated cirrhosis, HIV-HCV or HBV-HCV coinfection, pediatrics, and posttransplant | Not approved in decompensated cirrhosis, HIV-HCV or HBV-HCV coinfection, pediatrics, and posttransplant |
FDA: US Food and Drug Administration; HBV: hepatitis B virus; HCV: hepatitis C virus; IFN: interferon; R155K: lysine to arginine substitution at position 155; RGT: response guided treatment; SVR: sustained virologic response; VL: viral load; V36M: valine to methionine substitution at position 36. *No dose reduction is allowed because of risk of engender drug resistance. **48 weeks of treatment always for patients with cirrhosis and previous null responders. In telaprevir treatment also for partial responders. In boceprevir also for previously untreated patients who respond poorly to interferon in the lead-in period (<1 log 10 decline in hepatitis C RNA from baseline). ***Special care using first-generation protease inhibitors which are hormonal contraceptives, statins, dihydropyridine calcium channel blockers, and phosphodiesterase-5 inhibitors.