The pharmacokinetic challenge of voriconazole therapy for cerebral aspergillosis in patients treated with ibrutinib

Excerpt

Ibrutinib is a new Bruton’s tyrosine kinase inhibitor approved for the management of chronic lymphocytic leukemia (CLL) that has recently been associated with an increasing number of cases of invasive aspergillosis (IA). Ghez et al. reported 33 patients with invasive fungal infections, corresponding to IA in 27/33 with cerebral aspergillosis in 40% of these cases [1]. Voriconazole (VRCZ) is the first-line treatment for IA including central nervous system (CNS) infection due to its good penetration across the blood-brain barrier. However, VRCZ requires therapeutic drug monitoring to ensure effective therapy. In the case reported here, CNS aspergillosis was responsible for brain edema requiring corticosteroids. However, corticosteroids have been very recently reported to be a new cause of rapid VRCZ metabolism, inducing low plasma VRCZ concentrations and therefore limited efficacy [2]. …