Methadone NNRTIs

METHADONE NNRTIs Methadone levels may be significantly 1 by efavirenz and nevirapine t CYP3A4- and 2B6-mediated metabolism of methadone Monitor closely for opioid withdrawal t dose as necessaiy. Likely to need dose titration of methadone (mean 22% but up to 186% t)... 

Nevirapine NNRTI 200 mg bid Rash, hepatitis, nausea, headache Dose-escalate from 200 mg qd over 14 days to decrease frequency of rash. Avoid concurrent use with ketoconazole, methadone, and... 

Of 80 injecting drug users who took two NRTIs + nevirapine (NNRTI), 20 discontinued treatment and 20 had treatment failures (5). Adverse events led to withdrawal of therapy in 10 patients eight had a rash (in one case Stevens-Johnson syndrome) one had liver failure thought to be unrelated to the drugs and one had general intolerance. Two patients taking methadone had opioid withdrawal symptoms, presumably due to induction of methadone metabolism by nevirapine. 

Treatment with the NNRTIs efavirenz and nevirapine was noted to cause methadone withdrawal symptoms in patients with HIV [66, 52], Subsequently, both NNRTIs were shown to induce drug-metabolizing enzymes in cultured hepatocytes due to activation of CAR and weak activation of PXR [37]. 

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