Darunavir + Grazoprevir (Single Agent) = Precautionary

Effect on Concentration

Darunavir
No change
Applies within class?
No
Grazoprevir (Single Agent)
Increase
Applies within class?
No

Pharmacologic Effects

Darunavir
Effect
N/A
Applies within class?
No
Grazoprevir (Single Agent)
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 18-Jul-2018

Summary

Sources

Darunavir versus Grazoprevir ^

Study Design

An open-label, 3 parallel panel, 3 period study was conducted in 13 healthy adults to assess the PK effects of darunavir + ritonavir (DRV/r) when co-administered with grazoprevir (GZR). In Period 1, participants received GZR (200mg) daily for 7 days. This was followed by a 7 day washout period. In Period 2, participants received DRV/r (600mg/100mg) twice daily for 14 days. There was no washout between Period 2 and Period 3. In Period 3, participants received GZR (200mg) co-administered with DRV/r (600mg/100mg) for 7 days.

Study Results

Drug AUC GMR (90% CI) Darunavir 1.11 (0.99-1.24) Grazoprevir 7.50 (5.92-9.51) Results showed that GZR did not have any clinically significant effects on DRV concentrations. However, DRV/r increased the AUC of GZR significantly.

Study Conclusions

Concomitant use of DRV/r and GZR is not recommended until further data is available. If possible, utilize another HCV treatment regimen for patients on DRV/r or consider changing antiretroviral therapy to another agent the patient is eligible for.

References

Kiang TK. Clinical pharmacokinetics and drug–drug interactions of elbasvir/grazoprevir. European Journal Of Drug Metabolism And Pharmacokinetics. 2018; : 1-23.