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Related Experiment Videos

A potentially hazardous interaction between erythromycin and midazolam

K T Olkkola1, K Aranko, H Luurila

  • 1Department of Clinical Pharmacology, University of Helsinki, Finland.

Clinical Pharmacology and Therapeutics
|March 1, 1993
PubMed
Summary

Erythromycin significantly increases midazolam levels and impairs psychomotor function. Avoid co-prescription or reduce midazolam dosage by 50-75% when using erythromycin.

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Area of Science:

  • Pharmacology
  • Drug Interactions
  • Clinical Pharmacy

Background:

  • Midazolam is a commonly used sedative.
  • Erythromycin is a macrolide antibiotic with known drug interaction potential.

Purpose of the Study:

  • To investigate the pharmacokinetic and pharmacodynamic interaction between erythromycin and midazolam.
  • To determine the clinical implications of this drug interaction.

Main Methods:

  • Two double-blind, randomized, crossover studies were conducted.
  • Healthy volunteers received erythromycin or placebo, followed by oral or intravenous midazolam.
  • Plasma concentrations and psychomotor performance were measured.

Main Results:

  • Erythromycin increased oral midazolam exposure over fourfold and reduced intravenous midazolam clearance by 54%.

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  • Significant impairment in psychomotor tests was observed with co-administration.
  • Cytochrome P450IIIA isozyme is implicated in the interaction.

    • Conclusions:

    • Erythromycin significantly alters midazolam pharmacokinetics and pharmacodynamics.
    • Clinicians should avoid co-prescribing erythromycin and midazolam or significantly reduce the midazolam dose.