Introduction: The Society of Infectious Disease Pharmacists (SIDP) presents its consensus recommendations for primary prevention and therapeutic drug monitoring (TDM) of five commonly used triazole antifungal drugs: voriconazole, posaconazole, itraconazole, fluconazole, and isavuconazole.
With the advancement of medical technology and the growing complexity of clinical cases, the incidence of invasive fungal infections (IFIs) continues to rise, particularly in critically ill and immunocompromised patients. Triazole antifungal drugs—including fluconazole, itraconazole, voriconazole, posaconazole, and isavuconazole—are the mainstays for the treatment and prevention of IFIs due to their broad-spectrum antifungal activity and relatively good safety profiles. However, triazoles exhibit complex pharmacokinetics, requiring precision in clinical management and individualized dose adjustments to optimize efficacy and minimize adverse effects. This expert consensus aims to provide guidance on best practices for using triazoles in primary prevention through a comprehensive analysis of existing literature and clinical experience.
Drug Selection:
For high-risk IFI patients, such as those undergoing hematopoietic stem cell transplantation or long-term immunosuppressive therapy, voriconazole is the preferred drug for primary prevention. Posaconazole is recommended as an alternative to voriconazole due to its efficacy and safety profile, particularly in patients intolerant to voriconazole or those at risk of drug-drug interactions. Itraconazole can also be considered in specific contexts, such as the prevention of candidiasis.
Dose Adjustment and TDM:
The consensus recommends routine TDM for voriconazole, posaconazole, and itraconazole to maintain drug concentrations within an effective and safe therapeutic range. The timing of TDM should consider the pharmacokinetic properties of each drug, patient physiological conditions, and concurrent medications.
The target concentration range for each triazole differs based on its unique pharmacokinetics. For example, the target trough concentration for voriconazole is typically between 1-5.5 μg/mL. For posaconazole, the target concentrations vary based on the dosage form (oral suspension, delayed-release tablets, or intravenous formulation).
Drug-Drug Interactions:
Triazole antifungals interact with a wide range of commonly used medications, affecting their pharmacokinetics. Therefore, when using triazoles for primary prevention, potential drug-drug interactions must be thoroughly assessed, and dose adjustments or therapeutic changes should be made as necessary. Regular monitoring of hepatic, renal, and electrolyte parameters is crucial to detect and manage possible adverse effects, such as hepatotoxicity, nephrotoxicity, and electrolyte imbalances.
