Prospective CYP2C19‐Guided Voriconazole Prophylaxis in Patients With Neutropenic Acute Myeloid Leukemia Reduces the Incidence of Subtherapeutic Antifungal Plasma Concentrations. Issue 3 (1st November 2019)

• Record Type: Journal Article
• Authors: Hicks, J. Kevin; Quilitz, Rod E.; Komrokji, Rami S.; Kubal, Timothy E.; Lancet, Jeffrey E.; Pasikhova, Yanina; Qin, Dahui; So, Wonhee; Caceres, Gisela; Kelly, Kerry; Salchert, Yasmina S.; Shahbazian, Kevin; Abbas‐Aghababazadeh, Farnoosh; Fridley, Brooke L.; Velez, Ana P.; McLeod, Howard L.; Greene, John N.
• Is Part Of: Clinical pharmacology & therapeutics. Volume 107:Issue 3(2020)
• Page Start: 563
• Page End: 570
• Publication Date: 2019-11-01
• Subjects: Pharmacology -- Periodicals; Therapeutics -- Periodicals; 615.5
• DOI: 10.1002/cpt.1641
• Languages: English
• ISSNs: 0009-9236

Abstract

Abstract : A risk mitigation strategy was implemented to determine if a higher prophylactic voriconazole dosage in patients with CYP2C19 rapid metabolizer neutropenic acute myeloid leukemia (AML) reduces the incidence of subtherapeutic trough concentrations. Patients with AML ( n = 263) were preemptively genotyped for CYP2C19*2, *3, and *17 alleles as part of a single‐center prospective, interventional, quality improvement study. CYP2C19 rapid metabolizers ( CYP2C19*1/*17 ) were recommended to receive interventional voriconazole 300 mg twice daily, ultrarapid metabolizers ( CYP2C19*17/*17 ) were recommended to avoid voriconazole, and all others received the standard prophylactic dosage of 200 mg twice daily. In this real‐world setting, 202 patients (76.8%) were prescribed prophylactic voriconazole, and of these patients 176 (87.1%) received CYP2C19 ‐guided prophylactic dosing. Voriconazole trough concentrations were obtained for 41 of the 58 (70.7%) CYP2C19 rapid metabolizers prescribed prophylactic voriconazole. Interventional voriconazole resulted in higher plasma trough concentrations (median 2.7 μg/mL) compared with the standard prophylactic dosage (median 0.6 μg/mL; P = 0.001). Subtherapeutic concentrations were avoided in 83.8% of CYP2C19 rapid metabolizers receiving interventional dosage compared to 46.2% receiving standard dosage ( P = 0.02). CYP2C19 genotyping to preemptively guide prophylactic voriconazole dosing is feasible and may be a potential strategy for reducing the risk of subtherapeutic trough concentrations that potentiate breakthrough fungal infections.