Drug interactions
Codeine + Midazolam
Severity: Major
Codeine 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
Midazolam combined with an opioid markedly increases the risk of deep sedation, respiratory depression, hypoxia and death. This is a recognised class warning, especially for parenteral midazolam and in patients with respiratory disease or older age.
What this interaction means in plain words
Codeine 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.
Codeine belongs to Musculoskeletal; Midazolam belongs to Central Nervous System.
Why it happens
Additive CNS and respiratory depression via GABA-A and mu-opioid receptor activity.
What to do
Avoid unless clearly needed; if used, reduce doses, titrate slowly and monitor respiration and oxygen saturation continuously in a setting with resuscitation capability.
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 Codeine
- Alvimopan + Codeine Contraindicated
- Codeine + Isocarboxazid Contraindicated
- Codeine + Olanzapine / samidorphan Contraindicated
- Codeine + Phenelzine Contraindicated
- Codeine + Tranylcypromine Contraindicated
- Alfentanil + Codeine 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 Codeine with Midazolam?
MediHelp rates the interaction as major. Codeine 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. Midazolam combined with an opioid markedly increases the risk of deep sedation, respiratory depression, hypoxia and death. This is a recognised class warning, especially for parenteral midazolam and in patients with respiratory disease or older age.
How serious is the interaction between Codeine 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 unless clearly needed; if used, reduce doses, titrate slowly and monitor respiration and oxygen saturation continuously in a setting with resuscitation capability.
What other medicines interact with Codeine?
MediHelp also lists interactions of Codeine with, for example, Alvimopan, Isocarboxazid, Olanzapine / samidorphan. The full list is on the Codeine page.
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