Nevirapine + Midazolam = Precautionary

Effect on Concentration

Nevirapine
No change
Applies within class?
No
Midazolam
Decrease
Applies within class?
No

Pharmacologic Effects

Nevirapine
Effect
N/A
Applies within class?
No
Midazolam
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 03-Jul-2018

Summary

Interaction has not been studied, but based upon knowledge of pharmacokinetic parameters, caution is warranted

Sources

Semisimultaneous midazolam administration to evaluate the time course of CYP3A activation by a single oral dose of efavirenz. ^

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.