Drug interactions
Esketamine + Hydrocodone
Severity: Major
Esketamine and Hydrocodone: 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
Esketamine causes sedation and dissociation, and hydrocodone is an opioid that depresses the CNS and breathing. Used together they can produce deeper sedation and respiratory depression than either drug alone, which matters particularly because patients are observed for only a limited period after esketamine dosing.
What this interaction means in plain words
Esketamine and Hydrocodone 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; Hydrocodone belongs to Musculoskeletal.
Why it happens
Additive CNS and respiratory depression from NMDA antagonism combined with mu-opioid receptor agonism.
What to do
Monitor sedation level and respiratory status during and after esketamine dosing, and use the lowest effective opioid dose. Warn patients not to take extra opioid doses around treatment sessions.
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 Hydrocodone
- Alvimopan + Hydrocodone Contraindicated
- Bupropion-naltrexone + Hydrocodone Contraindicated
- Hydrocodone + Isocarboxazid Contraindicated
- Hydrocodone + Olanzapine / samidorphan Contraindicated
- Hydrocodone + Phenelzine Contraindicated
- Alfentanil + Hydrocodone Major
Frequently asked questions
Can I take Esketamine with Hydrocodone?
MediHelp rates the interaction as major. Esketamine and Hydrocodone 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 causes sedation and dissociation, and hydrocodone is an opioid that depresses the CNS and breathing. Used together they can produce deeper sedation and respiratory depression than either drug alone, which matters particularly because patients are observed for only a limited period after esketamine dosing.
How serious is the interaction between Esketamine and Hydrocodone?
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 level and respiratory status during and after esketamine dosing, and use the lowest effective opioid dose. Warn patients not to take extra opioid doses around treatment sessions.
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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