Saquinavir + Methadone = Precautionary

Effect on Concentration

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

Pharmacologic Effects

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

Interaction History

N/A

Last Updated 30-Jul-2018

Summary

Sources

Saquinavir versus Methadone ^

Study Design

A 24-hour methadone pharmacokinetic study was performed before antiretroviral therapy was begun and after 15 days of therapy. Methadone concentration was measured by a chiral plasma assay because the drug is administered as a racemic mixture of R- and S-methadone, but only the R-isomer is active. Both changes in plasma protein binding and changes in objective and subjective opioid effect were monitored.

Study Results

Ritonavir/saquinavir administration was associated with 40% decrease in total S-methadone AUC0-24hr and 32% decrease in R-methadone area under the curve (AUC)0-24hr, and both changes were statistically significant (p =.001 for both). When AUC was corrected for the changes in protein binding induced by ritonavir/saquinavir, R-methadone free AUC0-24hr decreased 19.6% whereas the S-methadone decreased 24.6%, neither of these changes was statistically significant (p =.129 and p =.0537, respectively). This change in methadone exposure was not associated with any evidence of withdrawal from narcotics and no modification of methadone dose was required.

Study Conclusions

References

Gerber JG, Rosenkranz S, Segal Y, Aberg J, D'Amico R, Mildvan D, Hsu A. Effect of ritonavir/saquinavir on stereoselective pharmacokinetics of methadone: results of aids clinical trials group (actg) 401. Journal Of Acquired Immune Deficiency Syndromes . 2001; 2: 153-160.