Concomitant administration of RBT and doravirine is not recommended due to the significant reduction in doravirine exposures observed and the subesquent potential for insufficient antiviral activity.
Rifabutin vs doravirine
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Study Design
This was an open-label, 2-period, 2-treatment, fixed-sequence pharmacokinetic (PK) drug interaction study in healthy adults (n=18) to evaluate the effect of rifabutin co-administration on the PK of doravirine. In Period 1, a single dose of doravirine 100mg was administered on Day 1. Following a 7-day washout period, rifabutin (RBT) 300mg was administered once daily for 16 days in Period 2, with co-administration of doravirine 100mg on Day 14.
Study Results
12 participants completed the study.Following co-administration with multiple dose RBT, doravirine peak exposure was not affected, however, total and trough exposures of doravirine were significantly reduced by approximately 50% and 68%, respectively.Using geometric mean ratios and 90% confidence intervals, the AUC, Cmax and C24 for doravirine (RBT+doravirine / doravirine) were 0.50 [0.45, 0.55], 0.99 [0.85, 1.15] and 0.32 [0.28, 0.35], respectively. This reduction in doravirine exposure is consistent with the inductive effect of RBT on CYP3A4.The effect of doravirine on the PK of RBT was not reported.Co-administration of doravirine and RBT was generally well tolerated and there were serious adverse events.
References
Khalilieh SG, Yee KL, Sanchez RI, et al. Mutliple-dose treatment with rifabutin reduces the exposure of doravirine. Conference On Retroviruses And Opportunistic Infections. Boston, MA. ; 2016.
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