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Drug Interactions

methadone and efavirenz

MajorAvoid this combination where possible.

Mechanism
Efavirenz induces hepatic CYP3A4 and CYP2B6 enzymes, which are involved in methadone metabolism. This induction increases the rate of methadone clearance, lowering plasma concentrations.
What it means clinically
Methadone plasma levels can fall significantly, leading to opioid withdrawal symptoms in patients maintained on methadone. This may include craving, agitation, abdominal cramps, diarrhoea, and tachycardia. In some cases, the reduction in methadone effect can undermine addiction treatment and cause patients to discontinue therapy.
What to do
Monitor patients closely for signs of opioid withdrawal when starting efavirenz. An increase in the methadone dose may be necessary; dose should be titrated based on clinical response. Reassess after stopping efavirenz, as methadone levels may rise.
Evidence
Well established in clinical studies and case reports. The interaction is consistent and clinically relevant.
The two drugs
methadoneOpioid receptor agonistRead the monographefavirenzHIV non-nucleoside reverse transcriptase inhibitorRead the monograph

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Other interactions involving methadone or efavirenz

Educational reference for students and clinicians in training. It does not replace professional judgement, local protocols or current prescribing information.