Drug Interactions between midazolam and telithromycin

GENERALLY AVOID: Coadministration with telithromycin may significantly increase the plasma concentrations of midazolam and other benzodiazepines that are metabolized by CYP450 3A4 and demonstrate a high first-pass effect, such as triazolam. The mechanism is telithromycin inhibition of CYP450 3A4 metabolism in the liver and especially the intestine. When coadministered with telithromycin, midazolam area under the plasma concentration-time curve (AUC) was increased 2.2-fold following intravenous administration and 6.1-fold following oral administration, and midazolam half-life was increased about 2.5-fold. No data are available for other benzodiazepines.

MANAGEMENT: Given the potential for prolonged and/or increased sedation and respiratory depression associated with excessive benzodiazepine blood levels, concomitant use of oral midazolam or triazolam with telithromycin should be avoided if possible. Benzodiazepines that are not CYP450 3A4 substrates such as lorazepam, nitrazepam, and temazepam may be appropriate alternatives during therapy with telithromycin. Depending on organism susceptibility, azithromycin and dirithromycin may be appropriate alternatives during therapy with midazolam or triazolam. Intravenous midazolam may be administered with telithromycin with close monitoring of vital signs and respiratory status, and the dosage adjusted as necessary.