Midazolam macrolides

Like fluoxetine, erythromycin and other macrolides inhibit the CYP-3A isoenzyme and increase the levels and effects of the triazolobenzodiazepines (Shader and Greenblatt, 1995 Chouinard et ah, 1999). Midazolam should be avoided or the dosage dropped by 50% in patients receiving erythromycin (Olkkola et ah, 1993). Ketoconazole and itraconazole may also interact with triazolam and midazolam, and combinations of these drugs should be avoided (Varhe et ah, 1994 Chouinard et ah, 1999). 

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. 

A4 Acetaminophen, alfentanil, amiodarone, astemizole, cocaine, cortisol, cyclosporine, dapsone, diazepam, dihydroergotamine, dihydropyridines, diltiazem, ethinyl estradiol, gestodene, indinavir, lidocaine, lovastatin, macrolides, methadone, miconazole, midazolam, mifepristone (RU 486), paclitaxel, progesterone, quinidine, rapamycin, ritonavir, saquinavir, spironolactone, sulfamethoxazole, sufentanil, tacrolimus, tamoxifen, terfenadine, testosterone, tetrahydro-cannabinol, triazolam, troleandomycin, verapamil Barbiturates, carbamazepine, macrolides, glucocorticoids, pioglitazone, phenytoin, rifampin Erythromycin, 613-hydroxy cortisol... 

The in vivo interactions between midazolam and several macrolides were predicted using PBPK modeling of drug concentration and the time course of active enzyme concentration in the liver (123). Using a value for kE of 0.0005 min-1, the AUC of midazolam after oral administration was predicted to increase 2.9- or 3.0-fold following pretreatment with erythromycin (500 mg t.i.d. 

Ito K, Ogihara K, Kanamitsu S, et al. Prediction of the in vivo interaction between midazolam and macrolides based on in vitro studies using human liver microsomes. Drug Metab Dispos 2003 31(7) 945-954. 

Macrolides cause increases in the serum concentrations, AUCs, and half-lives and reductions in the clearance of triazolam and midazolam (138-140). These changes can result in clinical effects, such as prolonged psychomotor impairment, amnesia, or loss of consciousness (141). Erythromycin can increase concentrations of midazolam and triazolam by inhibition of CYP3A4, and dosage reductions of 50% have been proposed if concomitant therapy is unavoidable (142). 

MIDAZOLAM, TRIAZOLAM, POSSIBLY ALPRAZOLAM MACROLIDES -ERYTHROMYCIN, CLARITHROMYCIN, TELITHROMYCIN t BZD levels Inhibition of CYP3A4-mediated metabolism 1 dose of BZD by 50% warn patients not to perform skilled tasks such as driving for at least 10 hours after the dose of BZD... 

CYP3A4/3A5/3A7 Macrolides, cyclosporine, tacrohmus, Ca + channel blockers, midazolam, terfenadine, hdocaine, dapsone, quinidine, triazolam, etoposide, teniposide, lovastatin, alfentanU, tamoxifen, steroids Efficacy of immunosuppressive effects of tacrolimus... 

The serum levels and effects of midazolam, triazolam and zopi-clone are markedly increased and prolonged by erythromycin. The same interaction has been seen with clarithromycin, josamy-cin, or troleandomycin but not azithromycin. Alprazolam would be expected to be similarly affected. Other benzodiazepines, and the related hypnotic zaleplon, appear not to interact with the macrolides to a clinically significant extent... 

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