Drug interactions
Methadone + Morphine
Severity: Major
Methadone and Morphine: 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
Combining two full opioid agonists increases the risk of excessive sedation and respiratory depression. Methadone has a long and variable half-life, so effects may accumulate over days. Incomplete cross-tolerance can cause unexpected toxicity when switching between the two.
What this interaction means in plain words
Methadone and Morphine 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; Morphine belongs to Musculoskeletal.
Why it happens
Additive mu-opioid receptor agonism.
What to do
Avoid unplanned co-prescription; if both are needed, use conservative doses, titrate slowly and monitor respiratory rate and sedation. Reduce the dose substantially when rotating between them.
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 Morphine
- Alvimopan + Morphine Contraindicated
- Isocarboxazid + Morphine Contraindicated
- Morphine + Olanzapine / samidorphan Contraindicated
- Morphine + Phenelzine Contraindicated
- Morphine + Tranylcypromine Contraindicated
- Alfentanil + Morphine Major
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 Morphine?
MediHelp rates the interaction as major. Methadone and Morphine 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. Combining two full opioid agonists increases the risk of excessive sedation and respiratory depression. Methadone has a long and variable half-life, so effects may accumulate over days. Incomplete cross-tolerance can cause unexpected toxicity when switching between the two.
How serious is the interaction between Methadone and Morphine?
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 unplanned co-prescription; if both are needed, use conservative doses, titrate slowly and monitor respiratory rate and sedation. Reduce the dose substantially when rotating between them.
What other medicines interact with Morphine?
MediHelp also lists interactions of Morphine with, for example, Alvimopan, Isocarboxazid, Olanzapine / samidorphan. The full list is on the Morphine page.
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