Glecaprevir/Pibrentasvir + Methadone = Unknown or no reaction

Effect on Concentration

Glecaprevir/Pibrentasvir
Unknown
Applies within class?
No
Methadone
No change
Applies within class?
No

Pharmacologic Effects

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

Interaction History

N/A

Last Updated 22-Nov-2022

Summary

Investigators concluded that no dose adjustments are required for coadministration of ABT-493 and ABT-530 with methadone.

Sources

Glecaprevir/pibrentasvir vs opioid maintenance agents ^

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 methadone. Healthy adults subjects received individualized regimens of methadone (n=11) once daily on Days 1-9 in Period 1. In Period 2, subjects received ABT-493 (300 mg daily) + ABT-530 (120 mg daily) together with methadone for 7 days, followed by methadone alone on Days 8-10.The maintenance therapy dose for methadone ranged from 22 to 120 mg.For assessment of pharmacokinetics (PK) of R- and S- methadone, serial blood samples were collected on Day 9 of Period 1 and Day 7 of Period 2. For assessment of PK of ABT-493 and ABT-530, serial blood samples were collected on Day 7 of Period 2.

Study Results

Coadministration of methadone 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 R- or S- methadone.The geometric mean ratios (GMRs; ABT-493/ABT-530 + methadone / methadone) [90% CIs] of R-methadone were: 0.96 [0.91, 1.02] for Cmax, 1.02 [0.98, 1.06] for AUC24, 0.98 [0.93, 1.04] for C24GMRs (ABT-493/ABT-530 + methadone / methadone) [90% CIs] of S-methadone were: 0.98 [0.93, 1.03] for Cmax, 1.05 [1.01, 1.09] for AUC24, 1.02 [0.96, 1.08] for C24Although the effect of methadone on ABT-493 and ABT-530 was not evaluated in this study, the investigators reported that their exposures were similar to those reported in other studies in healthy subjects.Subjects experienced mild adverse events. Common adverse events were abdominal pain, constipation, and headache. However, no changes in pupillary response, SOWS and DDQ were observed when ABT-493 and ABT-530 were added to methadone therapy.

Study Conclusions

References

Kosloski MP, S Dutta, W Zhao, et al. Absence of significant drug-drug interactions between next generation direct acting antivirals abt-493 and abt-530 and methadone or buprenorphine/naloxone in subjects on opioid maintenance therapy. 66th Annual Meeting Of The American Association For The Study Of Liver Diseases (aasld). San Francisco, CA. ; 2015.