Amprenavir + Methadone = Unknown or no reaction

Effect on Concentration

Amprenavir
Decrease
Applies within class?
No
Methadone
No change
Applies within class?
No

Pharmacologic Effects

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

Interaction History

N/A

Last Updated 20-Jun-2018

Summary

Sources

Pharmacokinetics and pharmacodynamics of methadone enantiomers after coadministration with amprenavir in opioid-dependent subjects. ^

Study Design

On study day 1, subjects received their usual once-daily dose of methadone alone. On study days 2-11, they received the same once-daily methadone dose plus amprenavir 1200 mg twice/day. Serial blood samples were collected over 24 hours on study days 1 and 11 for measurement of plasma R- and S-methadone, and over 12 hours on day 11 for serum amprenavir concentrations.

Study Results

The concomitant use of methadone and ritonavir, nelfinavir, amprenavir, fosamprenavir, lopinavir/ritonavir, saquinavir, tipranavir (50%), and darunavir potentially decreases the plasma concentration of methadone and may require increased dosage titration. The pharmacokinetic interaction between methadone and ritonavir is significantly reduced or blunted when ritonavir is administered with lopinavir. Co-administration of methadone with amprenavir may potentially decrease amprenavir plasma concentrations causing it to be less effective; an alternative agent should be considered. Co-administration of amprenavir with methadone resulted in a 3-4 hour delay in plasma R- and S-methadone enantiomer peak concentrations at steady state (Cmax-AS). The active R-methadone enantiomer AUCt,AS, Cmax,AS, and Cmin,AS were decreased by 13%, 25%, and 21%, respectively after co-administration of methadone and amprenavir. The inactive S-enantiomer AUCt-ss, Cmax-ss, and Cmin-ss were decreased by 40%, 48%, and 52%, respectively. No clinically significant changes were noted in opioid pharmacodynamic effects, and there was no evidence of opioid withdrawal. No methadone dosage was changed in any subject.

Study Conclusions

No a priori adjustment in methadone dosage is required during coadministration with amprenavir as there is only a small effect on R-methadone exposure and no evidence of opioid withdrawal.

References

Hendrix CW, et al.. Pharmacokinetics and pharmacodynamics of methadone enantiomers after coadministration with amprenavir in opioid-dependent subjects. Pharmacotherapy. 2004; : 1110-1121.