title: A potentially hazardous interaction between erythromycin and midazolam.
abstract: Interaction between erythromycin and midazolam was investigated in two double-blind, randomized, crossover studies. In the first study, 12 healthy volunteers were given 500 mg erythromycin three times a day or placebo for 1 week. On the sixth day, the subjects ingested 15 mg midazolam. In the second study, midazolam (0.05 mg/kg) was given intravenously to six of the same subjects, after similar pretreatments. Plasma samples were collected, and psychomotor performance was measured. Erythromycin increased the area under the midazolam concentration-time curve after oral intake more than four times (p < 0.001) and reduced clearance of intravenously administered midazolam by 54% (p < 0.05). In psychomotor tests (e.g., saccadic eye movements), the interaction between erythromycin and orally administered midazolam was statistically significant (p < 0.05) from 15 minutes to 6 hours. Metabolism of both erythromycin and midazolam by the same cytochrome P450IIIA isozyme may explain the observed pharmacokinetic interaction. Prescription of midazolam for patients receiving erythromycin should be avoided or the dose of midazolam should be reduced by 50% to 75%.
authors.affiliation: Department of Clinical Pharmacology, University of Helsinki, Finland.
authors.forename: K T
authors.initials: KT
authors.lastname: Olkkola
authors.forename: K
authors.initials: K
authors.lastname: Aranko
authors.forename: H
authors.initials: H
authors.lastname: Luurila
authors.forename: A
authors.initials: A
authors.lastname: Hiller
authors.forename: L
authors.initials: L
authors.lastname: Saarnivaara
authors.forename: J J
authors.initials: JJ
authors.lastname: Himberg
authors.forename: P J
authors.initials: PJ
authors.lastname: Neuvonen
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D004311:Double-Blind Method; D004357:Drug Synergism; D004917:Erythromycin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008874:Midazolam / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects; D012016:Reference Values
chemical_list: D004917:Erythromycin; D008874:Midazolam