Drug interactions
Midazolam + Primidone
Severity: Moderate
Midazolam and Primidone: moderate interaction.
Last updated
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
Primidone, and its active metabolite phenobarbital, induces CYP3A4 and can substantially lower midazolam exposure, particularly after oral dosing, so sedative or anticonvulsant effect may be reduced. Both drugs also depress the central nervous system, so additive sedation is possible.
What this interaction means in plain words
Midazolam and Primidone can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken.
Midazolam belongs to Central Nervous System; Primidone belongs to Central Nervous System.
Why it happens
Enzyme induction of CYP3A4 by primidone/phenobarbital increases midazolam clearance, together with additive CNS depressant effects.
What to do
Titrate midazolam to clinical effect, expecting higher dose requirements, especially with oral use. Monitor sedation and respiratory status and reassess dose if primidone is started or stopped.
What to ask your pharmacist
- Should I take them at different times of day?
- Does the dose of either medicine need to change?
- Is there anything I should avoid, such as alcohol or certain foods, while on both?
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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 Primidone
- Lorlatinib + Primidone Contraindicated
- Lurasidone + Primidone Contraindicated
- Primidone + Ranolazine Contraindicated
- Primidone + Sofosbuvir-velpatasvir-voxilaprevir Contraindicated
- Primidone + Voriconazole Contraindicated
- Abiraterone + Primidone Major
Frequently asked questions
Can I take Midazolam with Primidone?
MediHelp rates the interaction as moderate. Midazolam and Primidone can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken. Primidone, and its active metabolite phenobarbital, induces CYP3A4 and can substantially lower midazolam exposure, particularly after oral dosing, so sedative or anticonvulsant effect may be reduced. Both drugs also depress the central nervous system, so additive sedation is possible.
How serious is the interaction between Midazolam and Primidone?
MediHelp rates it moderate, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Titrate midazolam to clinical effect, expecting higher dose requirements, especially with oral use. Monitor sedation and respiratory status and reassess dose if primidone is started or stopped.
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.
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