Cytochrome P450 interactions and clinical implication in rheumatology

There are many potential drug interactions that involve the complex cytochromes P450 (CYP) enzyme system when treatments for chronic inflammatory rheumatic diseases are used. This iatrogenic risk is increased in patients taking multiple drugs such as those with rheumatoid arthritis or gout, whatever the type of CYP interaction (substrate, inducer, or inhibitor of one of the CYP isoenzymes). Some of these CYP interactions may have clinical consequences, sometimes serious (overdose or therapeutic failure) and are often unrecognized by clinicians. The aim of this article is first of all to act as a reminder of the metabolic role of membrane-bound CYP enzymes in the liver in the oxidation of drugs and the potential types of interaction (drug substrate, inducer, or inhibitor or indirectly by the modulation of CYP activity through its powerful antiinflammatory activity). Secondly, the different factors that modulate the enzymatic activity of CYP will be described that may contribute to variations in drug metabolism and therefore modify the benefit-risk ratio of the drug. Thirdly, an analysis based on a review of the literature will present the different known interactions via CYP for drugs used in clinical practice in rheumatic diseases: analgesics, antiinflammatory drugs, conventional disease-modifying antirheumatic drugs and biologic agents. To limit the clinical consequences of these CYP interactions, it is recommended to focus on drugs that are really essential, to systematically identify the rheumatic patients most at risk before prescribing, and thus to adopt therapeutic strategies that reduce iatrogenic risk.