Impact of dose adaptations following voriconazole therapeutic drug monitoring in pediatric patients.
Med Mycol
; 57(8): 937-943, 2019 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-30759261
ABSTRACT
Voriconazole is the mainstay of treatment for invasive aspergillosis in immunocompromised pediatric patients. Although Therapeutic Drug Monitoring (TDM) of voriconazole is recommended, it remains unknown if TDM-based dose adaptations result in target attainment. Patients <19 years from two pediatric hematologic-oncology wards were retrospectively identified based on unexplained high voriconazole trough concentrations (Cmin > 6 mg/l). Patient demographics, clinical characteristics, treatment, voriconazole dosing information, voriconazole Cmin before and after adjustment based on TDM were obtained. Twenty-one patients, median (range) age 7.0 (1.2-18.5) years, were identified in two centers. First Cmin (3.1 mg/l [0.1-13.5]) was obtained after 3 days (1-27) of treatment. The median of all Cmin (n = 485, median 11 per patient) was 2.16 mg/l (0.0 (undetectable)-28.0), with 24.1% of Cmin < 1 mg/l, 48.9% 1-4 mg/l, 9.3% 4-6 mg/l, and 17.7% > 6 mg/l. Intrapatient variability was large (94.1% for IV, 88.5% for PO). Dose increases at Cmin < 1 mg/l resulted in an increased Cmin in 76.4%, with 60% between 1 and 4 mg/l. Dose decreases at Cmin > 6 mg/l resulted in a decreased Cmin in 80%, with 51% between 1 and 4 mg/l. Overall, in 45% of the cases (33 out of 55 and 12 out of 45) therapeutic targets were attained after dose adjustment. Fifty-five percent of initial Cmin was outside the therapeutic target of 1-4 mg/l, with multiple dose adaptations required to achieve therapeutic concentrations. Only 60% and 51% of dose adaptations following sub- and supra-therapeutic Cmin, respectively, did result in target attainment. Intensive and continuous TDM of voriconazole is a prerequisite for ensuring adequate exposure in pediatric patients.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Monitoramento de Medicamentos
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Aspergilose Pulmonar Invasiva
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Voriconazol
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Antifúngicos
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adolescent
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Child
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Child, preschool
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Female
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Humans
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Infant
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Male
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Newborn
Idioma:
En
Revista:
Med Mycol
Assunto da revista:
MEDICINA VETERINARIA
/
MICROBIOLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Holanda