Program

PO3-9-7

Calcium-channel blockers exacerbate edema induced by ombitasvir/paritaprevir/ritonavir (VIEKIRAX®)

[Speaker] Akiyo Hori:1
[Co-author] Akiko Kwaji:1, Yuna Sadaka:4, Yuka Asama:4, Midori Soda:4, Takashi Mizui:1, Yoichi Nishigaki:2, Eiichi Tomita:3, Kiyoyuki Kitaichi:4, Chitoshi Goto:1
1:Department of Pharmacy, Gifu Municipal Hospital, Japan, 2:Department of Hepatology, Gifu Municipal Hospital, Japan, 3:Department of Gastroenterology, Gifu Municipal Hospital, Japan, 4:Laboratory of Pharmaceutics, Department of Biomedical Pharmaceutics, Gifu Pharmaceutical University, Japan

Background
Ombitasvir/paritaprevir/ritonavir (VIEKIRAX®, VIE) is a new treatment option for hepatitis C apart from conventional treatments such as interferon therapy. Given the use of VIE in elderly patients, edema, an adverse effect of VIE, may be exacerbated in elderly patients with hypertension who are administered calcium-channel blockers (Ca-Bs) because VIE contains a CYP3A inhibitor, ritonavir, and Ca-Bs also cause edema. Hence, we prospectively monitored the status of edema in patients taking VIE. Plasma concentrations of Ca-Bs were also measured in patients receiving amlodipine.

Methods
We enrolled 52 patients treated with VIE between December 2015 and December 2016 (25 males and 27 females; average age, 69.6 years). Patients' background data, including laboratory data and history of Ca-B use, were obtained. Edema (in the limbs) was evaluated according to the CTCAE v4.0. Plasma samples collected from patients were applied to LC-MS/MS to measure plasma concentrations of the Ca-B amlodipine administered to the Ca-B group. All patients provided written informed consent, and the study was approved by the ethics committees of Gifu Pharmaceutical University (27-19) and Gifu Municipal Hospital (301).

Results
Ca-Bs was administered to 20 patients, and edema began to develop at approximately 1 week after initiating VIE treatment. The use of Ca-Bs worsened the edema, i.e., the median duration of edema occurrence was 17 days in the Ca-B group and 28 days in the non-Ca-B group. Kaplan-Meier analysis revealed a significantly higher occurrence of edema over G2 in the Ca-B group than in the non-Ca-B group. Moreover, the plasma concentrations of amlodipine were significantly increased and reached approximately 200% at 1 week after initiating VIE treatment. However, it should be noted that the occurrence of edema was not a contraindication for VIE treatment.

Discussion
Although this study has a small sample size, our results suggest that the inhibition of CYP3A by ritonavir could increase the plasma concentration of Ca-Bs, subsequently leading to the exacerbation of edema. Hence, appropriate precautions for preventing edema, particularly in elderly patients taking Ca-Bs, are required for the successful treatment of hepatitis C using VIE.

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