Glecaprevir/Pibrentasvir + Darunavir/Ritonavir = Prohibited

Effect on Concentration

Glecaprevir/Pibrentasvir
Increase
Applies within class?
Yes, see medications
Darunavir/Ritonavir
Increase
Applies within class?
No

Pharmacologic Effects

Glecaprevir/Pibrentasvir
Effect
N/A
Applies within class?
Yes, see medications
Darunavir/Ritonavir
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 01-Mar-2022

Summary

The use of DRV/r with GLE/PIB is not recommended.

Sources

Drug-Drug Interactions of Glecaprevir and Pibrentasvir Coadministered With Human Immunodeficiency Virus Antiretrovirals. ^

Study Design

In a parallel 2-periods, open-label, single-center, phase I study, the pharmacokinetic (PK) drug interaction potential was assessed betweeen GLE/PIB and ATV/r. Healthy adults age between 18 and 55 recevied GLE 300mg/PIB 120mg (n7) once daily in period 1(Days 1-7). In period 2 (days 1-14), subjects recevied GLE/PIB with ATV 300mg/r 100mg once daily (n13). For assessment of the GLE/PIB plasma concentration, samples were collected on period 1 day 7 and period 2 days 1 and 14 prior dosing. For ATV/r, samples were collected on period 2 days 1 and 14.

Study Results

Exposures were higher for DRV (Cmax increased 30 and AUC increased 29) and ritonavir (Cmax increased 103 and AUC increased 87) when coadministered with GLE/PIB than for DRV/r alone. GLE exposure increased (Cmax increased to 3.1 fold, AUC increased to 5.0 fold, and C24 increased to 8.2 fold) and PIB Cmax and AUC were similar (&8804;16 difference) but C24 was higher (increased 66).

Study Conclusions

The use of DRV/r with GLE/PIB is not recommended.

References

Koloski MP, et al.. Drug-drug interactions of glecaprevir and pibrentasvir coadministered with human immunodeficiency virus antiretrovirals. Journal Of Infectious Diseases. 2020; 2: 223-31.