Following the coadministration of Zepatier and Stribild, the pharmacokinetics of EVG, FTC, and TFV were not significantly altered when compared to the administration of Stribild alone. Cobicistat AUC and Cmax increased 49% and 39% respectively. A five fold increase was seen in GZR AUC when comparing Zepatier monotherapy with concomitant Zepatier and Stribuild use. Similarly, a 2 fold increase in ELB AUC was shown. The authors recommend that the use of these drugs together should be avoided as cobicistat can increase concentrations of both elbasvir and grazoprevir, which may result in an increased number of adverse events.
Grazoprevir/elbasvir vs elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate
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Study Design
This study was a fixed sequence, three period study conducted in 6 healthy females and 16 healthy males. In the first period, daily doses of Stribild® (elvitegravir/cobicistat/tenofovir/emtricitabine) were given for seven days, followed by a five-day washout period. In period two, Zepatier® (grazoprevir/elbasvir) was given once daily for ten days. After no washout period, patients were then given elvitegravir/cobicistat/tenofovir/emtricitabine with grazoprevir/elbasvir daily for another ten days. Twenty-four-hour Pharmacokinetics were determined for grazoprevir (GRZ), elbasvir (ELB), elvitegravir (EVG), cobistat (COBI), emtricitabine (FTC) and tenofovir (TFV).
Study Results
Elvitegravir AUC and Cmax geometric means ratios (GMR) with 90% confidence intervals (CI) for Zepatier + Stribild versus with Stribild alone were 1.1 (1, 1.21) and 1.02 (0.93, 1.11), respectively. Similarly, for FTC, the AUC and Cmax were 1.07 (1.03, 1.1) and 0.96 (0.9, 1.02), respectively. For TFV, the AUC and Cmax were 1.18 (1.13, 1.24) and 1.25 (1.14, 1.37), respectively. For COBI, the AUC and Cmax were 1.49 (1.42, 1.57) and 1.39 (1.29, 1.50), increases of 49% and 39%, respectively. Grazoprevir (GZR) AUC and Cmax for Zepatier+Stribild versus Zepatier alone were 5.36 (4.48, 6.43) and 4.59 (3.7, 5.69) and for elbasvir, AUC and Cmax were 2.18 (2.02, 2.35) and 1.91 (1.77, 2.05), respectively.
References
Feng HP, L Caro, G Guo, D Wolford, M Iwamoto, W Yeh, et al. A clinically meaningful drug-drug interaction observed between zepatier (grazoprevir/elbasvir) and stribild hiv fixed dose combination in healthy subjects. 17th International Workshop On Clinical Pharmacology Of Hiv And Hepatitis Therapy. Washington, DC, USA. ; 2016.
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