Drug interactions
Methadone + Oxycodone
Severity: Major
Methadone and Oxycodone: 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
Using two opioids together adds to sedation, respiratory depression and hypotension. Methadone has a long and variable half-life, so accumulation can cause delayed toxicity.
What this interaction means in plain words
Methadone and Oxycodone 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; Oxycodone belongs to Musculoskeletal.
Why it happens
Additive mu-opioid receptor mediated CNS and respiratory depression.
What to do
Avoid unless clearly needed, using reduced doses of each and slow titration. Monitor for sedation and respiratory depression, especially during the first days and after dose increases.
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 Oxycodone
- Alvimopan + Oxycodone Contraindicated
- Calcium / magnesium / potassium / sodium oxybates + Oxycodone Contraindicated
- Isocarboxazid + Oxycodone Contraindicated
- Olanzapine / samidorphan + Oxycodone Contraindicated
- Oxycodone + Phenelzine Contraindicated
- Oxycodone + Sodium oxybate Contraindicated
Frequently asked questions
Can I take Methadone with Oxycodone?
MediHelp rates the interaction as major. Methadone and Oxycodone 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. Using two opioids together adds to sedation, respiratory depression and hypotension. Methadone has a long and variable half-life, so accumulation can cause delayed toxicity.
How serious is the interaction between Methadone and Oxycodone?
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 unless clearly needed, using reduced doses of each and slow titration. Monitor for sedation and respiratory depression, especially during the first days and after dose increases.
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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