Dolutegravir + Elbasvir/Grazoprevir = Precautionary

Study Design

This was an open label, 2-period, fixed sequence study in 12 healthy adults. In Period 1, a single dose of dolutegravir (DTG) 50mg was administered followed by a 3-day washout. In Period 2, grazoprevir 200mg + elbasvir 50mg were co-administered daily on days 1-11, with a single dose of DTG on day 9.Pharmacokinetic (PK) assessments of DTG were performed on day 1 of Period 1 and day 9 of Period 2, and for grazoprevir and elbasvir on days 8 and 9 of Period 2.

Study Results

Co-administration of grazoprevir + elbasvir had no clinically meaningful effect on the PK of DTG. Using geometric mean ratios and 90% confidence intervals the AUC and C24 were 1.16 (1.00-1.34) and 1.14 (0.95-1.36), respectively. Similarly, elbasvir PK were unaffected by co-administration with DTG; the AUC, Cmax and C24 were 0.98 (0.93-1.04), 0.97 (0.89-1.05) and 0.98 (0.93-1.03), respectively. Co-administration with DTG did cause a decrease in grazoprevir PK; the AUC, Cmax and C24 were 0.81 (0.67-0.97), 0.64 (0.44-0.93) and 0.86 (0.79-0.93), respectively. However, the decrease was within the therapeutic window currently defined for grazoprevir.The authors state that grazoprevir + elbasvir and DTG may be co-administered in co-infected patients without the need for dose adjustments.

Study Conclusions

References

WW Yeh, T Marenco, HP Feng, et al. Drug-drug interaction between hcv inhibitors grazoprevir/elbasvir with dolutegravir. Conference On Retroviruses And Opportunistic Infections. Seattle, WA. ; 2015.