Drug interactions
Codeine + Methadone
Severity: Major
Codeine and Methadone: 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
Two opioids together add to CNS and respiratory depression, sedation and constipation. Methadone's long and variable half-life makes accumulation possible when other opioids are added, and codeine may add little extra analgesia.
What this interaction means in plain words
Codeine and Methadone 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.
Codeine belongs to Musculoskeletal; Methadone belongs to Musculoskeletal.
Why it happens
Additive mu-opioid receptor agonism causing CNS and respiratory depression.
What to do
Avoid routine concurrent use of the two opioids. If it is unavoidable, use the lowest doses and monitor 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?
Pro+ members
Unlock the full page
Create an account and start a Pro+ trial to unlock the full management advice for Codeine and Methadone, 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 Codeine
- Alvimopan + Codeine Contraindicated
- Codeine + Isocarboxazid Contraindicated
- Codeine + Olanzapine / samidorphan Contraindicated
- Codeine + Phenelzine Contraindicated
- Codeine + Tranylcypromine Contraindicated
- Alfentanil + Codeine Major
Frequently asked questions
Can I take Codeine with Methadone?
MediHelp rates the interaction as major. Codeine and Methadone 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. Two opioids together add to CNS and respiratory depression, sedation and constipation. Methadone's long and variable half-life makes accumulation possible when other opioids are added, and codeine may add little extra analgesia.
How serious is the interaction between Codeine and Methadone?
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 routine concurrent use of the two opioids. If it is unavoidable, use the lowest doses and monitor 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.
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.
