Drug interactions
Esketamine + Midazolam intranasal
Severity: Major
Esketamine and Midazolam intranasal: major interaction.
Last updated Sources: UK 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
Midazolam and esketamine are both CNS depressants, and the combination can cause deep sedation, hypoventilation, airway obstruction or apnea. Effects may be profound and prolonged, particularly if other sedatives are also present.
What this interaction means in plain words
Esketamine and Midazolam intranasal 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.
Why it happens
Additive CNS and respiratory depression from GABA-A potentiation and NMDA antagonism.
What to do
Avoid unmonitored co-use. If both are needed, reduce the midazolam dose and provide continuous pulse oximetry with airway and resuscitation equipment available.
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
- Esketamine 25 mg/ml solution for injection/infusion - SmPC sections 4.3/4.5 (class statement: benzodiazepines; "In combination with hypnotics, benzodiazepines or antipsychotics, there is a reduction in adverse effects but also a prolongation of the duration of effect of e") — electronic medicines compendium (UK SmPC)
Other interactions of Esketamine
Frequently asked questions
Can I take Esketamine with Midazolam intranasal?
MediHelp rates the interaction as major. Esketamine and Midazolam intranasal 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. Midazolam and esketamine are both CNS depressants, and the combination can cause deep sedation, hypoventilation, airway obstruction or apnea. Effects may be profound and prolonged, particularly if other sedatives are also present.
How serious is the interaction between Esketamine and Midazolam intranasal?
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 unmonitored co-use. If both are needed, reduce the midazolam dose and provide continuous pulse oximetry with airway and resuscitation equipment available.
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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