Drug interactions
Methadone + Tramadol
Severity: Major
Methadone and Tramadol: 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
Tramadol is an opioid agonist with serotonin and norepinephrine reuptake inhibition, and combining it with methadone adds opioid and serotonergic effects. This raises the risks of respiratory depression, sedation, serotonin syndrome and seizures, and tramadol may complicate stable opioid maintenance.
What this interaction means in plain words
Methadone and Tramadol 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; Tramadol belongs to Musculoskeletal.
Why it happens
Additive opioid CNS and respiratory depression plus additive serotonergic activity and lowered seizure threshold.
What to do
Avoid concurrent use where possible and select a non-serotonergic analgesic. If both are required, use the lowest doses and monitor for sedation, respiratory depression and serotonin toxicity.
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?
Pro+ members
Unlock the full page
Create an account and start a Pro+ trial to unlock the full management advice for Methadone and Tramadol, the additional notes, the evidence detail and the whole-prescription interaction checker.
- Full clinical management advice
- Additional notes
- Evidence detail
- Interaction checker for a whole prescription
Try Pro+ free for 7 days on the web. No card needed.
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 Tramadol
- Isocarboxazid + Tramadol Contraindicated
- Olanzapine / samidorphan + Tramadol Contraindicated
- Phenelzine + Tramadol Contraindicated
- Procarbazine + Tramadol Contraindicated
- Rasagiline + Tramadol Contraindicated
- Safinamide + Tramadol Contraindicated
Frequently asked questions
Can I take Methadone with Tramadol?
MediHelp rates the interaction as major. Methadone and Tramadol 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. Tramadol is an opioid agonist with serotonin and norepinephrine reuptake inhibition, and combining it with methadone adds opioid and serotonergic effects. This raises the risks of respiratory depression, sedation, serotonin syndrome and seizures, and tramadol may complicate stable opioid maintenance.
How serious is the interaction between Methadone and Tramadol?
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 concurrent use where possible and select a non-serotonergic analgesic. If both are required, use the lowest doses and monitor for sedation, respiratory depression and serotonin toxicity.
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.
Full monographs, dosing and an interaction checker in the MediHelp app
Open the complete reference, check multi-drug interactions and use dosing tools in the MediHelp app.
