Interaction is expected based upon what is known of pharmacokinetic parameters, and caution is warranted even if a direct interaction study has not been completed. Delavirdine may induce CYP3A, which could increase effects of the benzodiazepine, including respiratory depression.
Semisimultaneous midazolam administration to evaluate the time course of CYP3A activation by a single oral dose of efavirenz.
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Study Design
The interaction potential between midazolam and efavirenz has not been studied, and conclusions regarding the management of these interactions are based upon theoretical interactions based upon what is known of the metabolic pathways of these drugs
Study Results
Midazolam is extensively metabolized by CYP3A4/5. Efavirenz, an inducer of CYP3A4, could potentially decrease midazolam exposure.
Study Conclusions
The significance of potential interactions is unknown, but these drugs should not be used together unless benefit outweighs known risks. European guidelines suggest that concomitant use may actually increase midazolam levels due to competitive inhibition of metabolism. This would result in an increase in benzodiazepine related adverse events, including respiratory depression.
References
Mikus G, Heinrich T, Bodigheimer J, Roder C, Matthee AK, Weiss J, Haefeli WE. Semisimultaneous midazolam administration to evaluate the time course of cyp3a activation by a single oral dose of efavirenz. Journal Of Clinical Pharmacology. 2017; 7: 899-905.
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