Drug interactions
Midazolam + Promethazine
Severity: Major
Midazolam and Promethazine: 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
Promethazine adds to the sedative and respiratory depressant effects of midazolam, which can lead to deep sedation, hypotension and airway compromise. The risk is higher in elderly patients, those with respiratory disease and at higher doses.
What this interaction means in plain words
Midazolam and Promethazine 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 belongs to Central Nervous System; Promethazine belongs to Respiratory.
Why it happens
Additive CNS and respiratory depression via H1 blockade and GABA-A potentiation.
What to do
Reduce midazolam dose and titrate slowly, with continuous monitoring of sedation level, oxygen saturation and respiratory rate. Ensure airway management equipment is 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
Other interactions of Promethazine
- Cabergoline + Promethazine Contraindicated
- Dopamine + Promethazine Contraindicated
- Ibutilide + Promethazine Contraindicated
- Pimozide + Promethazine Contraindicated
- Promethazine + Thioridazine Contraindicated
- Alfentanil + Promethazine Major
Other interactions of Midazolam
- Atazanavir + Midazolam Contraindicated
- Cobicistat + Midazolam Contraindicated
- Darunavir + Midazolam Contraindicated
- Elvitegravir / cobicistat / emtricitabine / tenofovir df + Midazolam Contraindicated
- Fosamprenavir + Midazolam Contraindicated
- Indinavir + Midazolam Contraindicated
Frequently asked questions
Can I take Midazolam with Promethazine?
MediHelp rates the interaction as major. Midazolam and Promethazine 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. Promethazine adds to the sedative and respiratory depressant effects of midazolam, which can lead to deep sedation, hypotension and airway compromise. The risk is higher in elderly patients, those with respiratory disease and at higher doses.
How serious is the interaction between Midazolam and Promethazine?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Reduce midazolam dose and titrate slowly, with continuous monitoring of sedation level, oxygen saturation and respiratory rate. Ensure airway management equipment is available.
What other medicines interact with Promethazine?
MediHelp also lists interactions of Promethazine with, for example, Cabergoline, Dopamine, Ibutilide. The full list is on the Promethazine page.
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