Successful treatment of hepatitis C virus infection in patients on anti-epileptics or mood stabilizers using pharmacokinetic enhancers.

Co-administration of hepatitis C virus (HCV) direct-acting antivirals (DAAs) with anti-epileptics or mood stabilizers with cytochrome P450 (CYP) and/or drug transport-inducing properties is contraindicated due to concerns of subtherapeutic DAA levels that can lead to treatment failure and viral resistance. The recommended strategy is to change the interacting medication to a different agent that does not have inducing properties, but this is not always possible depending on the clinical scenario. We report on three patients who received DAAs for their HCV infection while remaining on the contraindicated anti-epileptic or mood stabilizer by utilizing CYP and drug transport inhibitors as pharmacokinetic enhancers to attempt to overcome the induction effects and maximize chances of achieving sustained virologic response (SVR). All patients achieved SVR despite the drug-drug interactions and there were no safety concerns. In patients facing this unique clinical quandary, the use of CYP and drug transport inhibitors appears to be a safe and possible strategy.

Safety and effectiveness of direct acting antivirals for treatment of hepatitis C virus in patients with solid organ transplantation.

BACKGROUND: The direct acting antivirals (DAAs) for treatment of hepatitis C virus (HCV) infection have sustained virologic response (SVR) rates of greater than 90% in most patients. However, data evaluating DAA use in transplant patients are limited. The goal of this study was to evaluate the effectiveness and safety of HCV treatment in this high-risk population. METHODOLOGY: This single-center retrospective study included liver, kidney, lung, and/or heart transplant patients who were treated for HCV infection with DAAs. The primary objective was to identify drug-drug interactions between DAAs and immunosuppressants by comparing immunosuppression dosages and levels at baseline and week 4 of HCV treatment. As secondary objectives, we described the percentage of patients with new or worsening rejection and/or graft dysfunction during HCV treatment, and the percentage of study patients who achieved SVR. RESULTS: Of the 108 patients included, the majority had liver (76%) or kidney (13%) transplants. Simeprevir plus sofosbuvir was the most commonly prescribed HCV treatment (33.9%) and tacrolimus was the most common immunosuppressant (91%). We did not detect a statistically significant difference in immunosuppression dosages or levels during HCV treatment. Furthermore, only one patient (<1%) experienced rejection and five patients (4.6%) had six episodes of graft dysfunction while on DAAs. Efficacy was high with 98% of patients achieving SVR. CONCLUSION: DAAs appear to be safe and effective for HCV treatment in patients with a history of liver and/or kidney transplantation. More data are needed to evaluate DAAs in lung and/or heart transplant patients.