Triazolam macrolide antibiotics

Nefazodone substantially decreases the clearance rate for triazolam, which results in a 400% increase in triazolam s serum levels (131). Erythromycin can also interfere with the metabolism of triazolam, resulting in decreased clearance and increased plasma levels, possibly causing toxicity. Troleandomycin and other macrolide antibiotics, such as clarithromycin, flurithromycin, josamycin, midecamycin, or roxithromycin, also may inhibit triazolam s metabolism (132). The coadministration of itraconazoie and triazolam can produce a marked elevation of triazolam plasma levels associated with statistically significant impairment of psychomotor tests and a prolongation of other effects (e.g., amnesia, lethargy, and confusion) for hours after awakening ( 133). 

With the important exception of additive effects when combined with other CNS depressants, including alcohol, BZDs interact with very few drugs. Disulfiram (see the section The Alcoholic Patient in Chapter 14) and cimetidine may increase BZD blood levels, and diazepam may increase blood levels of digoxin and phenytoin. Antacids may reduce the clinical effects of clorazepate by hindering its biotransformation to desmethyidiazepam. Coadministration of a BZD and another drug known to induce seizures may possibly increase seizure risk, especially if the BZD is abruptly withdrawn. Furthermore, as noted earlier, important interactions have been reported among nefazodone, erythromycin, troleandomycin, and other macrolide antibiotics, as well as itraconazole. In each case, metabolism is inhibited, and triazolam levels can increase significantly. 

BZD hypnotics such as midazolam and triazolam are primarily metabolized via the P450 3A3/4 microenzyme system. Other BZDs often used as hypnotics, such as diazepam, can also be metabolized by CYP 33/4 and CYP 2C19. Any drugs that act as inhibitors or inducers of these isoenzymes could increase or decrease BZD levels, respectively (350). Thus, ketoconazole, macrolide antibiotics (e.g., erythromycin), SSRIs (e.g., fluoxetine-norfluoxetine and fluvoxamine), and other antidepressants (especially nefazodone) may decrease clearance and increase BZD levels to potentially toxic ranges. Conversely, rifampacin, CBZ, and dexamethasone may increase clearance and decrease BZD levels to potentially subtherapeutic ranges. 

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