Boosted Elvitegravir versus Rosuvastatin
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Study Design
In phase 1, open label, fixed-sequence study, drug interaction between cobicistat-boosted elvitegravir (EVG/co; 150/150mg) and rosuvastatin (ROS; 10mg/day) were evaluated in healthy subjects.1,212 healthy subjects received a single dose of ROS 10mg. After 3-day washout, subjects received EVG/co 150/150mg once daily for 10 days, followed by single dose coadministration of EVG/co 150/150 mg plus ROS 10mg. Samples were collected pre-dose and at specified time points for 48 hours post-dose.
Study Results
When a single dose of ROS 10mg was given with EVG/co 150/150mg, ROS AUC [90% CI] and maximum serum concentration (Cmax) [90% CI] were increased by 38% [1.14,1.67] and 89% [1.48,2.42], respectively, compared with ROS administered alone.1,2 There was no clinically important effect on EVG PKs; geometric mean ratios (GMRs; EVG/co + ROS / EVG/co) [90% CIs] of AUC, Cmax, and Cmin for EVG were 1.02 [0.91,1.14], 0.94 [0.83,1.07], and 0.98 [0.83,1.16], respectively.
Study Conclusions
The investigators concluded that ROS may be coadministered with elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) without dose adjustment as the clinical significance of PK changes in ROS is uncertain but likely to be low.1 However, it is recommend to initiate ROS with the lowest recommended dose and titrate carefully while monitoring for toxicity, including myopathy and rhabdomyolysis.3,4 Close monitoring is warranted due to very wide confidence intervals of ROS PK.
References
Custodio JM, Wang H, Hao J. Pharmacokinetics of cobicistat boosted-elvitegravir administered in combination with rosuvastatin. Journal Of Clinical Pharmacokinetics. 2014; 6: 649-656.
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