Asunaprevir/Beclabuvir/Daclatasvir (Clinical Trial) + Methadone = Precautionary

Effect on Concentration

Asunaprevir/Beclabuvir/Daclatasvir (Clinical Trial)
No change
Applies within class?
No
Methadone
Decrease
Applies within class?
No

Pharmacologic Effects

Asunaprevir/Beclabuvir/Daclatasvir (Clinical Trial)
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

Increased monitoring in patients should be considered. The dose of Methadone in patients being treated with DCV/ASV/BCV + BCV may need to be increased due to the significant PK changes noted in the study. Monitor for signs and symptoms of pain or relapse (depending on indication of Methadone) and titrate slowly. Methadone has a very long half life (up to 59 hours) and changes in dose may not improve signs and symptoms of uncontolled pain immediately.

Sources

Asunaprevir/beclabuvir/daclatasvir vs opioid maintenance agents ^

Study Design

An open-label, 2-part study was conducted to assess the effects of a fixed dose combination of Daclatasvir/Asunaprevir/Beclabuvir (DCV/ASV/BCV) on the pharmacokinetics of Methadone, Buprenorphine (BUP), and active metabolite Norbuprenorphine (NorBUP). In part 2 of the study, participants received their once-daily dose of Buprenorphine/Naloxone (8/2mg to 24/6mg sublingual film) throughout. On days 2 through 12, participants received twice-daily doses of the fixed dose combination of DCV/ASV/BCV (30/200/75mg) + additional BCV 75mg BID to achieve the higher BCV exposures obserevd in HCV-infected patients. All study drugs were administered with food.A total of 16 participants were enrolled in part 2 of the study. One participants withdrew consent on day 6. PK blood samples were taken predose and through 24 hours post dose on day 1 and 12.

Study Results

Drug NameCmax GMR (90% CI)AUC GMR (90% CI)Methadone (R)0.65 (0.53-0.79)0.73 (0.63-0.85)Methadone (S)0.67 (0.53-0.84)0.76 (0.65-0.88)Based on the PK data, coadministration of Methadone with DCV/ASV/BCV + BCV showed a decrease in both AUC and Cmax in both enatiomers of Methadone. It was noted in the study that the PK profiles of DCV, ASV, and BCV were similar to historical data and did not indicate that Methadone had any major effects on these agents.

Study Conclusions

References

X Tao, K Sims, M Hesney. Evaluation of drug-drug interactions between the fixed-dose combination of daclatasvir/asunaprevir/beclabuvir and methadone or buprenorphine/naloxone. 50th Annual Meeting Of The European Association For The Study Of The Liver. Vienna, Austria. ; 2015.