Incivek

2.1 INCIVEK/Peginterferon Alfa/Ribavirin Combination Treatment

The recommended dose of INCIVEK tablets is 1125 mg (three 375-mg tablets) taken orally twice daily (10-14 hours apart) with food (not low fat) [see Clinical Pharmacology (12.3)].

For specific dosage instructions for peginterferon alfa and ribavirin, refer to their respective prescribing information.

Duration of Treatment

The recommended duration of treatment with INCIVEK is 12 weeks in combination with peginterferon alfa and ribavirin. HCV RNA levels should be monitored at weeks 4 and 12 to determine combination treatment duration and assess for treatment futility (Tables 1 and 2).

Table 1: Recommended Treatment Duration (See also Table 2 for Treatment Futility Rules) * In clinical trials, HCV RNA in plasma was measured using a COBAS ® TaqMan ® assay with a lower limit of quantification of 25 IU/mL and a limit of detection of 10 IU/mL. See Laboratory Tests (5.5) for a description of HCV RNA assay recommendations. Treatment-Naïve and Prior Relapse Patients Triple Therapy Dual Therapy Total Treatment Duration HCV RNA* INCIVEK,
peginterferon alfa and ribavirin peginterferon alfa and ribavirin Undetectable (Target Not Detected) at Weeks 4 and 12 First 12 weeks Additional 12 weeks 24 weeks Detectable (1000 IU/mL or less) at Weeks 4 and/or 12 First 12 weeks Additional 36 weeks 48 weeks Prior Partial and Null Responder Patients Triple Therapy Dual Therapy Total Treatment Duration INCIVEK,
peginterferon alfa and ribavirin peginterferon alfa and ribavirin All Patients First 12 weeks Additional 36 weeks 48 weeks

For the purpose of assessing response-guided therapy eligibility at weeks 4 and 12 (see Table 1), an "undetectable" HCV RNA (Target Not Detected) result is required; a confirmed "detectable but below limit of quantification" HCV RNA result should not be considered equivalent to an "undetectable" HCV RNA (Target Not Detected) result [see Laboratory Tests (5.5)].

Treatment-naïve patients with cirrhosis who have undetectable HCV RNA (Target Not Detected) at weeks 4 and 12 of INCIVEK combination treatment may benefit from an additional 36 weeks of peginterferon alfa and ribavirin (48 weeks total) [see Clinical Studies (14.2)].

2.2 Dose Reduction

To prevent treatment failure, the dose of INCIVEK must not be reduced or interrupted. Refer to the respective prescribing information for dose modification of peginterferon alfa and ribavirin [see Warnings and Precautions (5.6)].

2.3 Discontinuation of Dosing

Patients with inadequate viral response are unlikely to achieve SVR, and may develop treatment-emergent resistance substitutions [see Microbiology (12.4)]. Discontinuation of therapy is recommended in all patients with (1) HCV RNA levels of greater than 1000 IU/mL at Treatment Week 4 or 12; or (2) confirmed detectable HCV RNA levels at Treatment Week 24 (see Table 2).

Table 2: Treatment Futility Rules: All Patients HCV RNA Action Week 4 or Week 12: Greater than 1000 IU/mL Discontinue INCIVEK and peginterferon alfa and ribavirin (INCIVEK treatment complete at 12 weeks) Week 24: Detectable Discontinue peginterferon alfa and ribavirin

If peginterferon alfa or ribavirin is discontinued for any reason, INCIVEK must also be discontinued.