Drug interactions
Methadone + Rifampin
Severity: Major
Methadone and Rifampin: 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
Rifampin markedly lowers methadone concentrations and can precipitate opioid withdrawal in dependent patients, or cause loss of analgesia. The effect begins within days of starting rifampin and persists for a time after it is stopped, when methadone levels can rise and cause toxicity.
What this interaction means in plain words
Methadone and Rifampin 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
Rifampin induces CYP3A4 and CYP2B6 (and P-glycoprotein), accelerating methadone metabolism.
What to do
Monitor for withdrawal symptoms and titrate methadone upward as needed during rifampin therapy. When rifampin is discontinued, reduce methadone gradually and watch for sedation and respiratory depression.
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 Rifampin?
MediHelp rates the interaction as major. Methadone and Rifampin 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. Rifampin markedly lowers methadone concentrations and can precipitate opioid withdrawal in dependent patients, or cause loss of analgesia. The effect begins within days of starting rifampin and persists for a time after it is stopped, when methadone levels can rise and cause toxicity.
How serious is the interaction between Methadone and Rifampin?
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 symptoms and titrate methadone upward as needed during rifampin therapy. When rifampin is discontinued, reduce methadone gradually and watch for sedation and respiratory depression.
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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