Glecaprevir/Pibrentasvir + Atazanavir = Prohibited

Effect on Concentration

Glecaprevir/Pibrentasvir
Increase
Applies within class?
No
Atazanavir
Unknown
Applies within class?
No

Pharmacologic Effects

Glecaprevir/Pibrentasvir
Effect
N/A
Applies within class?
No
Atazanavir
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 01-Mar-2022

Summary

Atazanvir is contraindicated with GLE/PIB due to safety concerns of increased GLE and PIB.

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

The first dose of Atazanavir increase glecaprevir (Cmax increased to 4.1- fold, AUC24 increased to 6.5-fold, and C24 increased to 14-fold) and Pibrenatasvir (Cmax increased 29, AUC24 increased 64, and C24 increased to 2.3-fold) exposures. The cohort was prematurely discontinued on day 13 of period 2 due to safety concerns.

Study Conclusions

Atazanvir is contraindicated with GLE/PIB.

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.