Asunaprevir + Methadone = 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 R-methadone were 0.97 (0.86-1.08) and 0.91 (0.82-1.01), respectively, and those for S-methadone were 1.01 (0.90-1.14) and 0.96 (0.85-1.09), respectively.Exposures were normalized to the lowest dose of methadone (40mg).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 methadone. Although coadministration of these agents was generally well tolerated, 1 subject experienced moderate opioid withdrawal symptoms (which were mild before ASV started) which was considered study drug-related. The methadone dose was not adjusted and the symptoms resloved within 5 days without treatment.

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.