Drug interactions
Diphenoxylate-atropine + Midazolam
Severity: Major
Diphenoxylate-atropine and Midazolam: 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
Combining an opioid with a benzodiazepine increases the risk of profound sedation, respiratory depression and death. Risk is higher with parenteral midazolam and in vulnerable patients.
What this interaction means in plain words
Diphenoxylate-atropine and Midazolam 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.
Diphenoxylate-atropine belongs to Gastrointestinal Tract; Midazolam belongs to Central Nervous System.
Why it happens
Additive CNS and respiratory depression from opioid and GABA-A modulation.
What to do
Avoid combining where possible; if necessary, titrate cautiously and monitor respiratory status and 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 Diphenoxylate-atropine
- Diphenoxylate-atropine + Isocarboxazid Contraindicated
- Diphenoxylate-atropine + Phenelzine Contraindicated
- Diphenoxylate-atropine + Tranylcypromine Contraindicated
- Alfentanil + Diphenoxylate-atropine Major
- Alvimopan + Diphenoxylate-atropine Major
- Amitriptyline + Diphenoxylate-atropine 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 Diphenoxylate-atropine with Midazolam?
MediHelp rates the interaction as major. Diphenoxylate-atropine and Midazolam 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. Combining an opioid with a benzodiazepine increases the risk of profound sedation, respiratory depression and death. Risk is higher with parenteral midazolam and in vulnerable patients.
How serious is the interaction between Diphenoxylate-atropine and Midazolam?
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 combining where possible; if necessary, titrate cautiously and monitor respiratory status and sedation.
What other medicines interact with Diphenoxylate-atropine?
MediHelp also lists interactions of Diphenoxylate-atropine with, for example, Isocarboxazid, Phenelzine, Tranylcypromine. The full list is on the Diphenoxylate-atropine page.
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