Drug interactions affecting the efficacy of corticosteroid therapy a brief review with an illustrative case

A drug interaction that seemed to contribute to sudden worsening of corticosteroid-stabilized vasculitis stimulated this review. A large number of drugs share with corticosteroids critical phase I metabolic steps mediated by hepatic cytochrome P450 (CYP) enzymes, particularly the individual enzyme CYP3A4. In their metabolic interaction with CYP3A4 as substrates, a growing number of these drugs have the potential to induce (upregulate) hepatic CYP3A4 levels, resulting in accelerated clearance (and reduced efficacy) of concomitantly administered glucocorticoids, which are also CYP3A4 substrates. Many other drugs can have the opposite effect, that is, they can inhibit CYP3A4 function by tight binding to its active site. This can result in reduced clearance (and augmented efficacy) of concurrently administered glucocorticoids. Current knowledge of this type of drug interaction, the drugs to watch out for, and multiple clinical reports of altered corticosteroid efficacy, are reviewed after presentation of the case illustrating potential relevance to the management of rheumatic diseases.