Cenicriviroc + Efavirenz = Precautionary

Effect on Concentration

Cenicriviroc
Decrease
Applies within class?
No
Efavirenz
No change
Applies within class?
No

Pharmacologic Effects

Cenicriviroc
Effect
N/A
Applies within class?
No
Efavirenz
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 22-Nov-2022

Summary

When CVC (200 mg once daily) was co-administered with EFV (600 mg once daily), CVC plasma exposure was significantly decreased when compared to CVC administered alone. If CVC and EFV are used concomitantly, consider doubling the CVC dose to 400 mg daily to offset the effect of interaction between CVC and EFV.

Sources

Efavirenz vs cenicriviroc ^

Study Design

In a phase 1, multiple-dose, open-label, fixed-sequence, crossover study, 40 healthy subjects were enrolled into 2 parallel groups (20 subjects/group).To evaluate the effect of efavirenz (EFV) on pharmacokinetic (PK) of cenicriviroc (CVC), 20 subjects received CVC 200mg once a day (period 1), followed by coadministration of CVC 200mg with EFV 600 mg once daily (period 2). After 14days of washout, CVC 200 mg qd on the first day (Day 1) of period 3 and CVC 400mg once daily on Days 2-10, coadministered with EFV 600mg everyday. To evaluate the effect of CVC on PK of EFV, 20 subjects received EFV 600mg once a day (period 1), followed by coadminsitration of EFV 600mg with CVC 400mg once a day; CVC was administered immediately after dinner and EFV at bedtime (period 2). Serial plasma CVC or EFV samples were collected 24-hour profile after the last dose of each period.

Study Results

Coadministration of efavirenz 600 mg with CVC 200 mg daily resulted in significant decrease of plasma CVC exposure; geometric mean ratios (GMRs; EFV+CVC/CVC) of AUC, Cmax, and Cmin were 0.57 [0.51, 0.63], 0.77 [0.70, 0.85], and 0.52 [0.44, 0.60], respectively. When CVC 400 mg was coadministered with EFV, GMRs (EFV+CVC/CVC) of AUC, Cmax, and Cmin were 0.98 [0.85, 1.12], 1.23 [1.12, 1.35], and 0.85 [0.71, 1.01], respectively.Efavirenz exposure was not significantly different vs PK values when administered alone; GMRs (EFV+CVC/EFV) of AUC, Cmax, and Cmin were 1.01 [0.95, 1.07] , 1.07 [0.97, 1.18], and 0.96 [0.89, 1.05], respectively.

Study Conclusions

References

E Lefebevre, J Enejosa, W Chang, et al. Pharmacokinetic interactions between cenicriviroc and efavirenz [abstract o_09b]. 14th International Workshop On Clinical Pharmacology Of Hiv Therapy. Amsterdam. ; 2013.