Drug interactions
Methadone + Pentobarbital
Severity: Major
Methadone and Pentobarbital: 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
Pentobarbital induces CYP3A4 and other enzymes, which can lower methadone concentrations and precipitate withdrawal or reduced analgesia. At the same time, both drugs depress the CNS and breathing, so oversedation is a concern, especially if methadone is increased to compensate.
What this interaction means in plain words
Methadone and Pentobarbital 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, combined with additive CNS and respiratory depression.
What to do
Monitor for withdrawal and for sedation and respiratory depression, titrating methadone cautiously. Reassess the dose when the barbiturate is stopped.
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 Pentobarbital?
MediHelp rates the interaction as major. Methadone and Pentobarbital 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. Pentobarbital induces CYP3A4 and other enzymes, which can lower methadone concentrations and precipitate withdrawal or reduced analgesia. At the same time, both drugs depress the CNS and breathing, so oversedation is a concern, especially if methadone is increased to compensate.
How serious is the interaction between Methadone and Pentobarbital?
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 withdrawal and for sedation and respiratory depression, titrating methadone cautiously. Reassess the dose when the barbiturate is stopped.
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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