Major
Probable
Description
Fluconazole inhibits hydroxychloroquine metabolism and both drugs prolong the QT interval, creating compounded arrhythmia risk.
Mechanism
Fluconazole inhibits CYP2D6 and CYP3A4 pathways involved in hydroxychloroquine metabolism; both drugs independently block hERG channels.
Clinical Significance
Increased hydroxychloroquine plasma levels combined with additive hERG blockade significantly elevates torsades de pointes risk.
Management
Avoid combination; use antifungal agents with minimal CYP inhibitory effect or alternative antimalarial/rheumatologic therapy.