Doravirine + Rifampin = Prohibited

Study Design

This was an open-label, 2-period, fixed-sequence study in healthy adult men (n=11) to evaluate the effect of single and multiple dose rifampin (RIF) 600mg on the pharmacokinetics (PK) of doravirine 100mg. In Period 1, a single dose of doravirine was administered on day 1, followed by a 7-day washout period. In Period 2, a single dose of RIF and doravirine were administered on day 1. Following a 3-day washout period, RIF was administered daily on days 4-18, and doravirine was co-administered on day 17.

Study Results

Following co-administration of single doses of doravirine and rifampin, the geometric mean ratio (90% confidence interval) of the doravirine AUC, Cmax and C24 were 0.91 (0.78-1.06), 1.40 (1.21-1.63) and 0.90 (0.80- 1.01), respectively. For single dose doravirine with multiple dose rifampin the AUC, Cmax and C24 were 0.12 (0.10-0.15), 0.03 (0.02-0.04) and 0.43 (0.35-0.52), respectively, compared to doravirine alone.While inhibition of OATP1B1 and P-gp by single dose RIF did not have a clinically meaningful effect on the PK of doravirine, its concentrations were significantly reduced due to CYP3A4 induction with multiple doses of RIF. The authors state that doravirine should not be administered with RIF and other potent CYP3A4 inducers.

Study Conclusions

References

Yee KL, Khalilieh SG, R Liu, et al. The effect of single and multiple dose rifampin on the pharmacokinetics of doravirine. Conference On Retroviruses And Opportunistic Infections. Seattle, WA. ; 2015.