Unconsciousness associated with midazolam and erythromycin

An 8-yr-old boy suffering from an asymptomatic ventricular septal defect was given erythromycin for antibiotic prophylaxis before adenoidectomy. Sixty minutes after premedication with oral midazolam 0.5 mg kg-1 and oral atropine 0.03 mg kg-1, an infusion of erythromycin 400 mg was started. When 200 mg of erythromycin had been infused, the patient lost consciousness, but other vital functions remained normal. After 45 min, he awakened spontaneously. At the time the plasma concentration of midazolam was 134 ng ml-1. In order to investigate possible interactions between midazolam and erythromycin, we studied the pharmacokinetics of midazolam in six children of the same age undergoing minor otolaryngological surgery. The plasma concentration of midazolam in the patient who lost consciousness was significantly greater than in six other children without concomitant administration of erythromycin. The altered pharmacokinetics of midazolam may result from reduced hepatic clearance of midazolam caused by an enzyme inhibiting drug, erythromycin.