Drug interactions
Methadone + Phenobarbital
Severity: Major
Methadone and Phenobarbital: major interaction.
Last updated Sources: US FDA label
For healthcare professionals — reference only. This page is a brief summary, not medical advice and not a substitute for official labeling or clinical judgement. Always verify before prescribing or dispensing.
Summary
Phenobarbital induces hepatic enzymes including CYP3A4 and CYP2B6, lowering methadone levels and potentially causing withdrawal or reduced analgesia. Both drugs also depress the CNS, so sedation and respiratory depression are a risk, particularly if methadone is raised or the inducer is withdrawn.
What this interaction means in plain words
Methadone and Phenobarbital can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for.
Why it happens
Enzyme induction increases methadone clearance, plus additive CNS and respiratory depression.
What to do
Monitor for opioid withdrawal and oversedation, and titrate methadone to response. Reduce methadone dose as needed after phenobarbital is discontinued.
What to ask your pharmacist
- Does the benefit of taking both outweigh the risk in my case?
- Do I need any blood test, ECG or other check while on both?
- What early warning signs should I watch for, and what should I do if they appear?
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References
Other interactions of Methadone
- Alvimopan + Methadone Contraindicated
- Calcium / magnesium / potassium / sodium oxybates + Methadone Contraindicated
- Droperidol + Methadone Contraindicated
- Ibutilide + Methadone Contraindicated
- Isocarboxazid + Methadone Contraindicated
- Lefamulin + Methadone Contraindicated
Frequently asked questions
Can I take Methadone with Phenobarbital?
MediHelp rates the interaction as major. Methadone and Phenobarbital can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for. Phenobarbital induces hepatic enzymes including CYP3A4 and CYP2B6, lowering methadone levels and potentially causing withdrawal or reduced analgesia. Both drugs also depress the CNS, so sedation and respiratory depression are a risk, particularly if methadone is raised or the inducer is withdrawn.
How serious is the interaction between Methadone and Phenobarbital?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Monitor for opioid withdrawal and oversedation, and titrate methadone to response. Reduce methadone dose as needed after phenobarbital is discontinued.
What other medicines interact with Methadone?
MediHelp also lists interactions of Methadone with, for example, Alvimopan, Calcium / magnesium / potassium / sodium oxybates, Droperidol. The full list is on the Methadone page.
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