Prospective CYP2C19-Guided Voriconazole Prophylaxis in Patients With Neutropenic Acute Myeloid Leukemia Reduces the Incidence of Subtherapeutic Antifungal Plasma Concentrations.
Adult
Aged
Aged, 80 and over
Alleles
Antifungal Agents
/ administration & dosage
Cytochrome P-450 CYP2C19
/ genetics
Dose-Response Relationship, Drug
Female
Genotype
Humans
Incidence
Leukemia, Myeloid, Acute
/ complications
Male
Middle Aged
Mycoses
/ prevention & control
Neutropenia
/ etiology
Prospective Studies
Risk Management
Voriconazole
/ administration & dosage
Young Adult
Journal
Clinical pharmacology and therapeutics
ISSN: 1532-6535
Titre abrégé: Clin Pharmacol Ther
Pays: United States
ID NLM: 0372741
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
04
06
2019
accepted:
14
09
2019
pubmed:
25
9
2019
medline:
29
10
2020
entrez:
25
9
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31549389
doi: 10.1002/cpt.1641
pmc: PMC7018540
mid: NIHMS1051680
doi:
Substances chimiques
Antifungal Agents
0
CYP2C19 protein, human
EC 1.14.14.1
Cytochrome P-450 CYP2C19
EC 1.14.14.1
Voriconazole
JFU09I87TR
Types de publication
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
563-570Subventions
Organisme : NCI NIH HHS
ID : P30 CA076292
Pays : United States
Informations de copyright
© 2019 The Authors Clinical Pharmacology & Therapeutics © 2019 American Society for Clinical Pharmacology and Therapeutics.
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