Glecaprevir/Pibrentasvir + Tacrolimus = Precautionary

Effect on Concentration

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

Pharmacologic Effects

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

Interaction History

N/A

Last Updated 22-Nov-2022

Summary

For patients receiving ABT-493/ABT-530 and tacrolimus, close monitoring of tacrolimus trough levels is warranted to minimize the possibility of tacrolimus toxicity. Dose adjustments of tacrolimus in transplant patients may be necessary.

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 tacrolimus (1 mg daily) with multiple doses of ABT-493 (300 mg daily) plus ABT-530 (120 mg daily) resulted in no significant effect on PK parameters of either ABT-493 or ABT-530.The geometric mean ratios (GMRs; ABT-493/ABT-530 + cyclosporine / ABT-493/ABT-530) [90% CIs] of ABT-493 were: 1.07 [0.94, 1.21] for Cmax, 1.00 [0.94, 1.08] for AUC24, 0.89 [0.78, 1.02] for C24The geometric mean ratios (GMRs; ABT-493/ABT-530 + cyclosporine / ABT-493/ABT-530) [90% CIs] of ABT-530 were: 0.98 [0.87, 1.11] for Cmax, 1.01 [0.93, 1.10] for AUC24, 1.00 [0.92, 1.09] for C24ABT-493/ABT-530 significantly increased PKs of tacrolimus. GMRs (ABT-493/ ABT-530 + tacrolimus / tacrolimus) [90% CIs] of AUC and Cmax for tacrolimus were 1.45 [1.24, 1.69] and 1.50 [1.24, 1.81], respectively.No clinically significant severe 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.