Midazolam drug interactions

Gascon MP, Dayer P, Waldvogel F. Les interactions medicamenteuses du midazolam. [Drug interactions of midazolam.] Schweiz Med Wochenschr 1989 119(50) 1834-6. 

Yuan R, Flockhart DA, Balian JD Pharmacokinetic and pharmacodynamic consequences of metabolism-based drug interactions with alprazolam, midazolam, and triazolam. J Clin Pharmacol 1999,39 1109-1125. 

Hypersensitivity to any component of the product. Coadministration of nelfinavir is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events (eg, amiodarone, quinidine, ergot derivatives, pimozide, midazolam, triazolam, lovastatin, simvastatin see Drug Interactions). 

Do not administer concurrently with cisapride, midazolam, triazolam, or ergot derivatives. Competition for CYP3A4 by efavirenz could result in inhibition of metabolism of these drugs and create the potential for serious or life-threatening adverse events (eg, cardiac arrhythmias, prolonged sedation, respiratory depression see Drug Interactions). 

The importance of these enzymes for drug interactions is that enzyme inducers and inhibitors may preferentially affect certain isoforms and consequently may only affect the metabolism of selected drugs. For example, ketoconazole has the potential to inhibit the metabolism of drugs metabolised to a great extent by the sub-family 3A (e.g. midazolam) but not of those metabolised by sub-family 1A (e.g. theophylline), 2C (e.g. diazepam), or 2D (e.g. metaprolol). In contrast, although fluconazole is a weaker inhibitor of the sub-family 3A than ketoconazole, it also inhibits the sub-family 2C, and so the interactions of fluconazole differ from those of ketoconazole. 

For most child psychiatrists, the drug interactions most frequently encountered are interactions with other psychotropics. Fluoxetine inhibits the CYP3A isozymes and thus increase the plasma concentration of the tria-zolobenzodiazepines (alprazolam, midazolam, and triazolam), causing increased psychomotor effects (Shader and Greenblatt, 1995). To avoid unwanted psychomotor effects, the dosage of alprazolam should be decreased when it is coadministered with fluoxetine (Chouinard et ah, 1999). Nefazadone has also been shown to increase the pharmacodynamic effects of triazolam and, to a lesser extent, alprazolam (Chouinard et ah, 1999). 

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