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.
To cite this abstract in AMA style:Alkhouri N, Bollinger J, Singh G, Issa D, Carey W, Fung J, Zein N, Eghtesad B. Safety of Telaprevir and Its Effect on the Pharmacokinetics of Tacrolimus in the Treatment of Hepatitis C after Liver Transplantation, The [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/safety-of-telaprevir-and-its-effect-on-the-pharmacokinetics-of-tacrolimus-in-the-treatment-of-hepatitis-c-after-liver-transplantation-the/. Accessed May 17, 2021.
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