Interaction Checker
Potential Interaction
Ritonavir (RTV)
Methadone
Quality of Evidence: Moderate
Summary:
Moderate to weak decreases in methadone AUC have been observed with ritonavir used at 100-200 mg daily to boost other protease inhibitors. No a priori adjustment of methadone dosage is required but patients should be monitored for opiate withdrawal symptoms and managed appropriately.
Description:
Based on parallel group comparison, coadministration of methadone (5mg single dose) and ritonavir (500 mg twice daily) decreased methadone AUC by 36% and Cmin by 38%. Increased methadone dose may be necessary when concomitantly administered with ritonavir dosed as an antiretroviral agent or as a pharmacokinetic enhancer due to induction of glucuronidation. Dose adjustment should be considered based on the patient's clinical response to methadone therapy.
Norvir Summary of Product Characteristics, AbbVie Ltd, September 2016.
The coadministration of ritonavir (500 mg every 12 hours for 15 days) with methadone (5 mg single dose) was investigated in 11 subjects. Effects were assessed on a dose-normalised comparison to a methadone 20 mg single dose. Methadone AUC and Cmax were reduced by 36% and 38%, respectively. Dosage increase in methadone may be considered.
Norvir Prescribing Information, AbbVie Inc, December 2016.
The effect of ritonavir 400 mg/saquinavir 400 mg twice daily on the stereoselective pharmacokinetics of methadone was examined in 12 HIV-infected, methadone-using study subjects Ritonavir/saquinavir administration was associated with 40% decrease in the AUC0-24h for total S-methadone and 32% decrease in R-methadone: 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 AUC0–24h 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.
Effect of ritonavir/saquinavir on stereoselective pharmacokinetics of methadone: results of AIDS Clinical Trials Group (ACTG) 401. Gerber JG, Rosenkranz S, Segal Y, et al. J Acquir Immune Defic Syndr, 2001, 27:153-160.
Coadministration of ritonavir (500 mg 12 hourly) and a single dose of methadone (5 mg single dose) was studied in 11 healthy volunteers. There was a 36% decrease in methadone AUC and a 38% decrease in methadone Cmax when normalised and compared with 20 mg single dose. Methadone had no appreciable effect on ritonavir pharmacokinetics.
Ritonavir does not increase methadone exposure in healthy volunteers. Hsu A, Granneman GR, Carothers L, et al. 5th Conference on Retroviruses and Opportunistic Infections, 1998, abstract 342.
There is a case report where the addition of ritonavir reduced the concentration of methadone from 365 ng/ml to 161 ng/ml in a single patient who was previously stable on a methadone daily dose of 55 mg. An increased methadone dose may be necessary when concomitantly administered with ritonavir, depending on the patient's response.
Therapeutic drug monitoring of methadone in HIV-infected patients receiving protease inhibitors. Beauverie P, Taburet A-M, Dessalles M-C, et al. AIDS, 1998, 12:2510–1.
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