Dolutegravir + Telaprevir = Unknown or no reaction

Effect on Concentration

Dolutegravir
No change
Applies within class?
No
Telaprevir
No change
Applies within class?
No

Pharmacologic Effects

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

Interaction History

N/A

Last Updated 11-Jul-2018

Summary

Sources

Effects of boceprevir and telaprevir on the pharmacokinetics of dolutegravir. ^

Study Design

Thirty two healthy adult subjects were enrolled in a single center, randomized, open-label, two cohort, two period, one way study with no wash-out period between treatment periods. In this trial all treatments were administered with a moderate fat meal. In the first cohort, sixteen subjects received dolutegravir 50 mg daily for five days, followed immediately by Boceprevir 800 mg q8h plus dolutegravir 50 mg daily for ten days. In the second cohort, sixteen subjects received dolutegravir 50 mg daily for five days, followed immediately by Telaprevir 750 mg q8h plus 50 mg of dolutegravir for ten days.

Study Results

Cohort DTG 50 mg daily x 5 days DTG 50 mg daily + BOC 800 mg q8h x 10 days AUC (mcg*h/ml) 68.9 (25) 84.2 (21) Cmax (mcg/ml) 4.99 (23) 5.81 (15) Cmin (mcg/ml) 1.59 (35) 2.09 (28) T ½ (h) 14.5 (19) 16.7 (18) Tmax (h) 3.00 (1, 4) 4.00 (1.1, 4.0) DTG Parameter Ratio of GLS Means (90% CI) DTG + BCV vs DTG AUC 1.07 (0.948, 1.2) Cmax 1.05 (0.96, 1.15) Cmin 1.08 (0.911, 1.28) T ½ 1.05 (0.959, 1.14) Results Cohort DTG 50 mg daily x 5 days DTG 50 mg daily + TPV 750 mg q8h x 10 days AUC (mcg*h/ml) 61.5 (27) 65.3 (22) Cmax (mcg/ml) 4.62 (21) 4.82 (17) Cmin (mcg/ml) 1.31 (38) 1.4 (36) T ½ (h) 13.2 (18) 13.8 (19) Tmax (h) 2.5 (1, 4) 3 (1, 4) DTG Parameter Ratio of GLS Means (90% CI) DTG + TPV vs DTG AUC 1.25 (1.2, 1.31) Cmax 1.19 (1.11, 1.26) Cmin 1.37 (1.29, 1.45) T ½ 1.18 (1.08, 1.28) Results Cohort DTG 50 mg daily x 5 days DTG 50 mg daily + TPV 750 mg q8h x 10 days AUC (mcg*h/ml) 61.5 (27) 65.3 (22) Cmax (mcg/ml) 4.62 (21) 4.82 (17) Cmin (mcg/ml) 1.31 (38) 1.4 (36) T ½ (h) 13.2 (18) 13.8 (19) Tmax (h) 2.5 (1, 4) 3 (1, 4) DTG Parameter Ratio of GLS Means (90% CI) DTG + TPV vs DTG AUC 1.25 (1.2, 1.31) Cmax 1.19 (1.11, 1.26) Cmin 1.37 (1.29, 1.45) T ½ 1.18 (1.08, 1.28)

Study Conclusions

Boceprevir does not appear to have a clinically significant effect on plasma Dolutegravir exposure. Boceprevir has minimal impact on the pharmacokinetics of dolutegravir (8% increase in Cmin). The combination of dolutegravir with boceprevir is generally safe and well tolerated. It appears that dolutegravir can be administered with boceprevir without dose adjustment with either of these treatments for HCV. Telaprevir did not appear to have a clinically significant effect on plasma Dolutegravir exposure. Telaprevir led to a small impact on dolutegravir pharmacokinetics, causing modest (18-25%) increases in AUC, Cmax, and T ½ , respectively, and a moderate (37%) increase in Cmin. The combination of dolutegravir with telaprevir is generally safe and well tolerated. It appears that dolutegravir can be administered with telaprevir without dose adjustment with either of these treatments for HCV.

References

Johnson M, Borland J, Chen S, Savina P, Wynne B, Piscitelli S. Effects of boceprevir and telaprevir on the pharmacokinetics of dolutegravir. British Journal Of Clinical Pharmacology. 2014; 5: 1043-1049.