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Author: Admin | 2025-04-28
Lead to opiate withdrawal symptoms; however, there seems to be a discordance between the degree of decrease in methadone concentrations and the risk of opioid withdrawal.45,46,51,52 It has been hypothesized that this discordance may be due to an increase in the metabolism of the inactive S-isomer of methadone or to alterations in methadone protein binding.45 Of the PIs, this drug-drug interaction with methadone is more pronounced with lopinavir/ritonavir and nelfinavir, with decreases in methadone AUCs of 53% and 47%, respectively.53,54 Efavirenz and nevirapine, both NNRTIs and known inducers of CYP3A4, have also been shown to cause significant decreases in methadone concentrations when coadministered.55 Concentrations of methadone were reduced up to 60% when taken with efavirenz and by 46% with nevirapine.19,46,56,57 Managing these drug interactions can be challenging due to the unpredictable changes in serum methadone concentrations and correspondence to patient response; however, changes in methadone doses should be guided by patient opioid response and signs and symptoms of opioid withdrawal. If methadone doses need to be increased, it is recommended that the doses be augmented 10 mg at a time and all changes be accompanied by careful monitoring.51 If opioid withdrawal symptoms are present, a dose increase of 20 mg may also be acceptable.51 The NNRTI delavirdine is a CYP3A4 inhibitor, and coadministration of this medication results in increased methadone concentrations. Based on a pharmacokinetic study, the AUC was increased by 19%.58 When methadone therapy is needed in conjunction to a delavirdine-containing HAART regimen, patient response to methadone should be
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