Limited data are available on using telaprevir (TVR)-based triple therapy to treat HCV recurrence post-liver transplantation (LTx). We report our experience on the effects of TVR on TAC pharmacokinetics (PK) and the safety of TVR-based therapy in the post-LTx setting. Methods: Patients with HCV genotype 1 recurrence on stable dose of TAC were included. TVR-based triple therapy was started with TVR 750 mg TID, ribavirin 600 mg daily, and peg-interferon Α2a 180 mcg weekly. On day 1 of treatment, TAC at half the pre-treatment daily dose was given and levels were checked at 12 and 24 hours and every other day thereafter for 2 weeks to assess TAC PK. No additional TAC was given until the level was around 4-6 ng/mL. Once the maintenance dose of TAC was established, levels were assessed weekly. Results: Ten patients (1F, 9M), mean age 59.8 ± 3.3 years, mean time from LTx 3.11 years, and mean fibrosis stage of 2.4 who completed 12 weeks of TVR therapy were included. Two were HCV treatment naÏve, 6 were prior null-responders, and 2 were partial responders. The pre-treatment TAC dose ranged from 1-7 mg BID. The TAC dose required to maintain therapeutic levels was found to be ¼- ½ the pre-treatment daily dose at a frequency of once weekly. The mean area under the concentration time curve (AUC) for TAC while on TVR was 1724.4 ± 998.9 ng.hr/mL (range 348-3232) compared to an expected AUC of 67 ng.hr/mL without TVR. The highest TAC level that we encountered in our study was 16.2 ng/mL (12-hour level after the initial dose). Rapid recovery of cytochrome P450 3A4 (CYP3A4) after TVR withdrawal was noted with all patients resuming their pre-TVR TAC dose within one week. Anemia was a common side effect with a mean baseline hemoglobin of 13.4 g/dL and a mean hemoglobin at week 12 of 9.6 g/dL. Grade 1 rash developed in only 2 patients and no grade 2/3 rashes were noted. Mean creatinine at baseline was 1.14 ± 0.23 mg/dL, at week 4 was 1.34 ± 0.24, and at week 12 was 1.24 ± 0.17. We did not encounter any infections or episodes of acute rejection. Conclusions: Although TVR has a profound effect on TAC metabolism; dose reduction of TAC based on blood levels is associated with normal TAC levels. Anemia was the most common side effect and there was a mild but not clinically significant increase in creatinine. Longer follow-up is needed to demonstrate efficacy in achieving control of HCV.

Alkhouri, N.: Speaker’s Bureau, Vertex. Zein, N.: Speaker’s Bureau, Vertex.

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