Drug interactions
Esketamine + Methadone
Severity: Major
Esketamine and Methadone: major interaction.
Last updated Sources: EMA SmPC
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
Methadone is a long-acting opioid that causes sedation and respiratory depression, and esketamine adds to the CNS depression. Because methadone has a long half-life, the additive effect may persist well beyond the esketamine observation period.
What this interaction means in plain words
Esketamine 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.
Esketamine belongs to Central Nervous System; Methadone belongs to Musculoskeletal.
Why it happens
Additive CNS and respiratory depression from NMDA antagonism combined with mu-opioid agonism.
What to do
Monitor sedation and respiratory function closely during and after dosing. Do not adjust methadone abruptly, but coordinate with the prescriber and warn the patient about delayed sedation.
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 Esketamine
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 Esketamine with Methadone?
MediHelp rates the interaction as major. Esketamine 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. Methadone is a long-acting opioid that causes sedation and respiratory depression, and esketamine adds to the CNS depression. Because methadone has a long half-life, the additive effect may persist well beyond the esketamine observation period.
How serious is the interaction between Esketamine 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: Monitor sedation and respiratory function closely during and after dosing. Do not adjust methadone abruptly, but coordinate with the prescriber and warn the patient about delayed sedation.
What other medicines interact with Esketamine?
MediHelp also lists interactions of Esketamine with, for example, Alfentanil, Amobarbital, Belladonna and opium. The full list is on the Esketamine page.
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