Dolutegravir + Doravirine = Unknown or no reaction

Effect on Concentration

Dolutegravir
Increase
Applies within class?
No
Doravirine
No change
Applies within class?
No

Pharmacologic Effects

Dolutegravir
Effect
N/A
Applies within class?
No
Doravirine
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 22-Nov-2022

Summary

*** The anticipated clinical dose of doravirine is 100mg, and not the dose (200mg) investigated in this study.

Sources

Dolutegravir vs doravirine ^

Study Design

In an open-label, fixed-sequence study, healthy subjects (n=12) received dolutegravir (DTG) 50 mg once daily for 7 days (period 1). Following a 7-day washout, subjects received doravirine (formerly known as MK-1439) 200 mg once daily for 7 days (Period 2), followed by coadministration of DTG 50 mg once daily plus doravirine 200 mg once daily for 7 days (Period 3).

Study Results

Coadministration of DTG 50 mg once daily and doravirine 200 mg once daily for 7 days resulted in increased pharmacokinetic (PK) parameters of DTG and no change in PK parameters of doravirine. The geometric mean ratios (GMRs; DTG + doravirine / DTG) [90% CIs] of DTG were:1.43 [1.20, 1.71] for Cmax, 1.36 [1.15, 1.62] for AUC, and 1.27 [1.06, 1.53] for C24h.GMRs (DTG + doravirine / doravirine) [90% CIs] of doravirine were:1.06 [0.88,1.28] for Cmax, 1.00 [0.89,1.12] for AUC, and 0.98 [0.88, 1.09] for C24h.Doravirine 200 mg significantly increased PK parameters of DTG. Investigators concluded that the magnitude of these chages were not clinically meaningful. DTG 50 mg at steady state did not affect the PK of co-administered doravirine 200 mg.All reported adverse effects (n=4) were mild in intensity, none of which led to study discontinuation.

Study Conclusions

References

M S Anderson, S Khalilieh, K L Yee, et al. A 2-way steady state pk ineraction study of doravirine (mk-1439) and dolutegravir. 16th International Workshop On Clinical Pharmacology Of Hiv ; Hepatitis Therapy. Washington, DC. ; 2015.