Drug interactions
Midazolam + Zaleplon
Severity: Major
Midazolam and Zaleplon: 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
Zaleplon is a sedative-hypnotic that acts at the GABA-A receptor, so combining it with midazolam produces additive sedation and psychomotor impairment. Complex sleep behaviors, falls and respiratory depression are more likely, especially in older patients.
What this interaction means in plain words
Midazolam and Zaleplon 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; Zaleplon belongs to Central Nervous System.
Why it happens
Additive GABA-A receptor-mediated CNS and respiratory depression.
What to do
Avoid combined use where possible; if needed, reduce doses, hold zaleplon around procedural midazolam, and monitor sedation and respiration.
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?
Pro+ members
Unlock the full page
Create an account and start a Pro+ trial to unlock the full management advice for Midazolam and Zaleplon, the additional notes, the evidence detail and the whole-prescription interaction checker.
- Full clinical management advice
- Additional notes
- Evidence detail
- Interaction checker for a whole prescription
Try Pro+ free for 7 days on the web. No card needed.
References
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
Other interactions of Zaleplon
- Calcium / magnesium / potassium / sodium oxybates + Zaleplon Contraindicated
- Sodium oxybate + Zaleplon Contraindicated
- Brexanolone + Zaleplon Major
- Buprenorphine long-acting + Zaleplon Major
- Buprenorphine subdermal implant + Zaleplon Major
- Buprenorphine transdermal + Zaleplon Major
Frequently asked questions
Can I take Midazolam with Zaleplon?
MediHelp rates the interaction as major. Midazolam and Zaleplon 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. Zaleplon is a sedative-hypnotic that acts at the GABA-A receptor, so combining it with midazolam produces additive sedation and psychomotor impairment. Complex sleep behaviors, falls and respiratory depression are more likely, especially in older patients.
How serious is the interaction between Midazolam and Zaleplon?
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 combined use where possible; if needed, reduce doses, hold zaleplon around procedural midazolam, and monitor sedation and respiration.
What other medicines interact with Midazolam?
MediHelp also lists interactions of Midazolam with, for example, Atazanavir, Cobicistat, Darunavir. The full list is on the Midazolam page.
Full monographs, dosing and an interaction checker in the MediHelp app
Open the complete reference, check multi-drug interactions and use dosing tools in the MediHelp app.
