Asunaprevir + Buprenorphine = Precautionary

Study Design

This was an open-label study to assess the effect of asunaprevir (ASV) on the pharmacokinetics (PK) of methadone in non-HCV infected participants stable on methadone therapy. 15 subjects received study drug.Methadone was administered as 40-120mg QD throughout the study on days 1-12, and ASV was given as 100mg BID on days 2-12. Blood samples for R-methadone (isomer with therapeutic effect) and S-methadone PK analysis were collected predose and for 24 hours postdose on days 1 (methadone alone) and 12 (methadone + ASV).

Study Results

Using geometric mean ratios (GMR) and 90% confidence intervals (CI), the Cmax and AUCtau for BUP were 0.85 (0.71-1.01) and 0.97 (0.73-1.30), respectively, and those for norbuprenorphine were 1.17 (0.96-1.42) and 1.10 (0.72-1.68), respectively.Exposures were normalized to the lowest dose of BUP (8mg).The authors state that mean steady-state Cmax and AUCtau for ASV were similar compared to historical control subjects, and that no dose adjustments should be required when ASV is coadministered with BUP/NLX.Although coadministration of these agents was generally well tolerated, 1 subject experienced mild opioid withdrawal symptoms which was considered not study drug-related.Based on the wide confidence intervals reported in this study, monitor patients for not only opioid withdrawal, but also increased sedation and cognitive effects.

Study Conclusions

References

T Garimella, T Eley, B He, et al. Evaluation of drug-drug interaction between asunaprevir and methadone or buprenorphine/naloxone. Open Forum Infect Dis. 2014; 1(suppl 1):822. Presented At: Id Week 2014. Philadelphia, PA. ; 2014.