Itraconazole is a synthetic triazole antifungal agent that is commonly used in the prophylaxis and treatment of fungal infection. A role for itraconazole drug monitoring has been suggested previously; however, the advent of new formulations and increased clinical evidence may aid in further defining this role. Consequently, we have used a previously published decision-making algorithm to determine whether clinical pharmacokinetic monitoring of itraconazole is warranted. First, itraconazole has proven efficacy for the prophylaxis and treatment of fungal infection in immunocompromised individuals such as neutropenic cancer, human immunodeficiency virus (HIV), and solid organ transplant patients. Several assays have been developed to quantify itraconazole and its main metabolite in patient plasma. Measurement of these plasma drug levels in many clinical studies has resulted in no clear definition of a relationship between concentration and efficacy. However, limited evidence suggests a correlation between itraconazole levels greater than 250 or 500 ng/mL and increased efficacy. Clinical monitoring of efficacy is difficult because of the challenges in diagnosis of fungal infections and nonspecific clinical symptoms associated with fungal infections. Pharmacokinetic studies of itraconazole indicate that significant inter- and intrapatient variability exists in both healthy and immunocompromised patient populations, although subpopulations such as neutropenic cancer and HIV patients appear to require more drug than their healthy counterparts to attain similar drug levels. A therapeutic range has not been defined for itraconazole, but because of its relatively minimal side effects, a narrow range is unlikely. Drug interactions can occur with itraconazole because it is both an inhibitor and substrate of the cytochrome P450 3A4 (CYP3A4) enzyme and P-glycoprotein transporter systems. Protein binding alterations could also lead to differences in drug effect. Last, the duration of treatment of prophylaxis is significantly long to propose a potential benefit from drug monitoring. From weighing the available evidence, it appears that itraconazole drug level monitoring would provide more information on efficacy than clinical judgment alone in a subset of patients. Immunosuppressed patients requiring preventative therapy who have suspected poor absorption, are on concomitant enzyme inducers, or are suspected to be noncompliant would have the greatest benefit from itraconazole drug monitoring.
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