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Evaluation of CYP 2C19 Genotype‐Guided Voriconazole Prophylaxis After Allogeneic Hematopoietic Cell Transplant
Author(s) -
Patel Jai N.,
Hamadeh Issam S.,
Robinson Myra,
Shahid Zainab,
Symanowski James,
Steuerwald Nury,
Hamilton Alicia,
Reese Emily S.,
Plesca Dragos C.,
Arnall Justin,
Taylor Margaret,
Trivedi Jigar,
Grunwald Michael R.,
Gerber Jonathan,
Ghosh Nilanjan,
Avalos Belinda,
Copelan Edward
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.1642
Subject(s) - voriconazole , dosing , medicine , pharmacology , trough concentration , cyp2c19 , genotype , gastroenterology , therapeutic drug monitoring , hematopoietic stem cell transplantation , pharmacokinetics , pharmacogenetics , cytochrome p450 , biology , transplantation , antifungal , biochemistry , dermatology , metabolism , gene
There is a high risk of voriconazole failure in those with subtherapeutic drug concentrations, which is more common in CYP 2C19 (cytochrome P450 2C19) rapid/ultrarapid metabolizers ( RMs / UM s). We evaluated CYP 2C19 genotype‐guided voriconazole dosing on drug concentrations and clinical outcomes in adult allogeneic hematopoietic cell transplant recipients. Poor ( PM s), intermediate ( IM s), and normal metabolizers ( NM s) received voriconazole 200 mg twice daily; RMs / UM s received 300 mg twice daily. Steady‐state trough concentrations were obtained after 5 days, targeting 1.0–5.5 mg/L. Of 89 evaluable patients, 29% had subtherapeutic concentrations compared with 50% in historical controls ( P < 0.001). Zero, 26%, 50%, and 16% of PM s, IM s, NM s, and RMs / UM s were subtherapeutic. Voriconazole success rate was 78% compared with 54% in historical controls ( P < 0.001). No patients experienced an invasive fungal infection ( IFI ). Genotype‐guided dosing resulted in $4,700 estimated per patient savings as compared with simulated controls. CYP 2C19 genotype‐guided voriconazole dosing reduced subtherapeutic drug concentrations and effectively prevented IFI s.