Telaprevir therapy required tacrolimus dose reduction in liver transplant recipients with HCV

Telaprevir therapy required tacrolimus dose reduction in liver transplant recipients with HCV

 October 26, 2012

LAS VEGAS — Telaprevir affected the metabolism of tacrolimus in liver transplant recipients with HCV, but may be an effective treatment for this population, according to data presented at the 2012 American College of Gastroenterology Annual Scientific Meeting.

Researchers assigned telaprevir-based triple therapy to four patients who experienced HCV genotype 1 recurrence following a liver transplant. The dosage included 750 mg telaprevir three times daily, 600 mg ribavirin daily, and 180 mcg pegylated interferon alfa-2a once a week, for a mean duration of 10.75 weeks (range 8-16 weeks).

All four patients had been on tacrolimus for 6 months or longer, with a dosage ranging from 1 mg to 3 mg twice daily, prior to treatment initiation. Upon initiating triple therapy, half the pre-treatment tacrolimus dose was administered each day, with levels checked twice daily for two weeks and additional tacrolimus administered when levels reached 4 ng/mL to 6 ng/mL. Upon establishing a maintenance dose, investigators subsequently monitored tacrolimus levels weekly.

Tacrolimus levels peaked at 16.2 ng/mL, at 12 hours after initiation of telaprevir. The necessary dosage dropped to between one-fourth and one-half the initial daily dose after initiating triple therapy. AUC analysis indicated a value of 1,353.46 ng.hr/mL for tacrolimus during telaprevir treatment (range 685.25-2,040.05), which researchers compared with an expected AUC of 67 ng.hr/mL without telaprevir.

No incidence of acute rejection, infection or neurologic toxicity was observed. Anemia (Hb levels below 10 g/dL) occurred in two patients and required a 200-mg ribavirin dose reduction, as well as treatment with epoietin. Researchers also noted that mean creatinine levels increased from 1.12 mg/dL to 1.35 mg/dL during the study.

“There isn’t FDA approval yet for telaprevir in post liver-transplant patients, so it’s an off-label use, but when you do use it, you have to be very careful of the tacrolimus levels because they will skyrocket due to the inhibition of the CYP3A4 cytochrome system,” researcher Gurshawn Singh, MD, resident at Cleveland Clinic told Healio.com, adding that six additional patients have been added to the study since the preliminary results. “Because of that drug interaction … you want to dose-reduce tacrolimus and monitor tacrolimus levels when you initiate treatment.” The researchers also wrote that additional study should be performed to assess the treatment’s efficacy and impact on renal function.

For more information:
Alkhouri N. P1329: Effect of Telaprevir on the Pharmacokinetics of Tacrolimus in the Treatment of Hepatitis C After Liver Transplantation. Presented at: the 2012 American College of Gastroenterology Annual Scientific Meeting; Oct. 19-24, Las Vegas.

Source- http://www.healio.com/hepatology/chronic-hepatitis/news/online/%7BEFF98932-AFE1-478B-9757-0CBE22DDA2E1%7D/Telaprevir-therapy-required-tacrolimus-dose-reduction-in-liver-transplant-recipients-with-HCV