Sofosbuvir + Methadone = Unknown or no reaction

Effect on Concentration

Sofosbuvir
No change
Applies within class?
No
Methadone
No change
Applies within class?
No

Pharmacologic Effects

Sofosbuvir
Effect
N/A
Applies within class?
No
Methadone
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 16-Jul-2018

Summary

Sources

Pharmacokinetic, pharmacodynamic, and drug-interaction profile of the hepatitis C virus NS5B polymerase inhibitor sofosbuvir. ^

Study Design

In a separate open-label, single sequence drug-drug interaction study, the effect of steady-state sofosbuvir on the steady-state PK and pharmacodynamics of R- and S-methadone was evaluated. 15 HCV-negative subjects were enrolled and were stable on methadone doses of 30-105mg daily for opiate addiction. Methadone was administered alone on day -1, followed by methadone + sofosbuvir on days 1-7. Blood sampling for PK assessment was performed on days -1 and 7. Geometric least-squares means ratios (GMR) and 90% confidence intervals (CI) of R- and S-methadone PK parameters were calculated.

Study Results

Results from the other study showed the GMR for the Cmax and AUCtau were 0.99 (0.85-1.16) and 1.01 (0.85-1.21), respectively for R-methadone, and 0.95 (0.79-1.13) and 0.95 (0.77-1.17), respectively for S-methadone. Day 7 SOF and GS-331007 PK were similar to those obtained in HCV-infected subjects (PK parameters not reported). There were no reports of subjective methadone withdrawal symptoms or indications of decreased methadone efficacy based on the Short Opiate Withdrawal Scale (SOWS), Desires for Drugs Questionnaire (DDQ) or pupil diameter measurements.

Study Conclusions

Sofosbuvir and methadone may be safely co-administered without dose adjustment.

References

Kirby BJ, Symonds WT, Kearney BP, Mathias AA. Pharmacokinetic, pharmacodynamic, and drug-interaction profile of the hepatitis c virus ns5b polymerase inhibitor sofosbuvir. Clinical Pharmacokinetics. 2015; 7: 677-690.