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Prospective CYP2C19 ‐Guided Voriconazole Prophylaxis in Patients With Neutropenic Acute Myeloid Leukemia Reduces the Incidence of Subtherapeutic Antifungal Plasma Concentrations
Author(s) -
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,
AbbasAghababazadeh Farnoosh,
Fridley Brooke L.,
Velez Ana P.,
McLeod Howard L.,
Greene John N.
Publication year - 2020
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.1641
Subject(s) - voriconazole , cyp2c19 , medicine , dosing , myeloid leukemia , incidence (geometry) , pharmacology , gastroenterology , antifungal , dermatology , physics , cytochrome p450 , metabolism , optics
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.