Glecaprevir/Pibrentasvir + Cyclosporine = Precautionary

Effect on Concentration

Glecaprevir/Pibrentasvir
Increase
Applies within class?
No
Cyclosporine
No change
Applies within class?
No

Pharmacologic Effects

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

Interaction History

N/A

Last Updated 22-Nov-2022

Summary

Investigators concluded that no dose adjustment is required for ABT-493, ABT-530, and cyclosporine when coadministered. However, the authors state that additionalevaluations of the drug-drug interaction between cyclosporine 400 mg and ABT-493/ABT-530 are currently underway for clinical dosing guidance.

Sources

Glecaprevir/Pibrentasvir vs cyclosporine or tacrolimus ^

Study Design

In a 2-period, single-center, open-label, phase I study, the pharmacokinetic (PK) drug interaction potential was assessed between ABT-493 + ABT-530 and cyclosporine. Healthy adult subjects received cyclosporine 100mg (n=12) once daily on Day 1 in Period 1. Following a 6-day washout period on Days 2-7 in Period 2, subjects received ABT-493 (300 mg daily) + ABT-530 (120 mg daily) for 14 days, with co-administration of single-dose cyclosporine on Days 1 and 8.For assessment of pharmacokinetics (PK) of cyclosporine, serial blood samples were collected on Day 1 of Period 1 and Days 1 and 8 of Period 2. For assessment of PK of ABT-493 and ABT-530, serial blood samples were collected on Days 7 and 8 of Period 2.

Study Results

Coadministration of a single dose of cyclosporine (100 mg daily) with multiple doses of ABT-493 (300 mg daily) plus ABT-530 (120 mg daily) resulted in significantly increased PK parameters of both ABT-493 and ABT-530.The geometric mean ratios (GMRs; ABT-493/ABT-530 + cyclosporine / ABT-493/ABT-530) [90% CIs] of ABT-493 were: 1.30 [0.95, 1.78] for Cmax, 1.37 [1.13, 1.66] for AUC24, 1.34 [1.12, 1.60] for C24GMRs (ABT-493/ABT-530 + cyclosporine / ABT-493/ABT-530) [90% CIs] of ABT-530 were: 1.11 [0.92, 1.33] for Cmax, 1.22 [1.10, 1.36] for AUC24, 1.26 [1.15, 1.37] for C24ABT-493/ ABT-530 minimally affected PKs of cyclosporine. GMRs (ABT-493/ ABT-530 + cyclosporine / cyclosporine) [90% CIs] of Cmax and AUC for multiple-dosecyclosporine were 1.11 [0.88, 1.40] and 1.14 [1.02, 1.27], respectively.No clinically significant adverse events or new safety signals were observed in this study.

Study Conclusions

References

Kosloski MP, S Dutta, W Zhao, et al. Drug-drug interactions between next generation direct acting antivirals abt-493 and abt-530 with cyclosporine or tacrolimus in healthy subjects. 66th Annual Meeting Of The American Association For The Study Of Liver Diseases (aasld). San Francisco, CA. ; 2015.