Drug-Drug Interactions in the Critically Ill

• Critically Ill ED patients are at risk for drug-drug interactions (DDIs) due to altered organ function, polypharmacy, and altered drug kinetics.
• DDIs involving the cytochrome isoenzyme CYP3A4 are of particular importance.
• CYP3A4 inhibitors, such as macrolides and azoles (fluconazole, voriconazole), can cause serious DDIs when given concomitantly with meds that are a subtrate for CYP3A4 - midazolam, cyclosporine, tacrolimus, diltiazem, amiodarone.
• Pay particular attention to your transplant patients, as administration of an azole can result in significant cyclosporine or tacrolimus toxicity.

References

Papadopoulos J, Smithburger PL. Common drug interactions leading to adverse drug events in the intensive care unit: Management and pharmacokinetic considerations. Crit Care Med 2010;38(S):S126-S135.