Drug interactions
Methadone + Selegiline
Severity: Major
Methadone and Selegiline: major interaction.
Last updated Sources: Health Canada product monograph
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
Selegiline, an MAO-B inhibitor that loses selectivity at higher doses, may precipitate serotonin syndrome or severe autonomic reactions with opioids. Methadone has serotonergic activity, so the risk is meaningful, particularly with oral or higher doses of selegiline.
What this interaction means in plain words
Methadone and Selegiline 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.
Methadone belongs to Musculoskeletal; Selegiline belongs to Central Nervous System.
Why it happens
Additive serotonergic effects and MAO inhibition combined with opioid CNS effects.
What to do
Avoid concomitant use where possible and allow about 14 days after stopping selegiline before methadone if labeling demands it. If used, monitor for serotonin toxicity and hypotension.
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
Other interactions of Selegiline
- Amitriptyline + Selegiline Contraindicated
- Amoxapine + Selegiline Contraindicated
- Atomoxetine + Selegiline Contraindicated
- Benzphetamine + Selegiline Contraindicated
- Brimonidine + Selegiline Contraindicated
- Buprenorphine long-acting + Selegiline Contraindicated
Frequently asked questions
Can I take Methadone with Selegiline?
MediHelp rates the interaction as major. Methadone and Selegiline 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. Selegiline, an MAO-B inhibitor that loses selectivity at higher doses, may precipitate serotonin syndrome or severe autonomic reactions with opioids. Methadone has serotonergic activity, so the risk is meaningful, particularly with oral or higher doses of selegiline.
How serious is the interaction between Methadone and Selegiline?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Avoid concomitant use where possible and allow about 14 days after stopping selegiline before methadone if labeling demands it. If used, monitor for serotonin toxicity and hypotension.
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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