Effect of isavuconazole on tacrolimus and sirolimus serum concentrations in allogeneic hematopoietic stem cell transplant patients: A drug-drug interaction study.
Transpl Infect Dis
; 21(1): e13007, 2019 Feb.
Article
em En
| MEDLINE
| ID: mdl-30295407
ABSTRACT
INTRODUCTION:
Isavuconazole, a triazole antifungal, is an inhibitor of cytochrome P450 3A4, which also metabolizes tacrolimus and sirolimus. In previous studies, isavuconazole administration increased tacrolimus and sirolimus area under the curve values by 2.3-fold and 1.8-fold, respectively, in healthy adults and tacrolimus concentration/dose (C/D) ratio by 1.3-fold in solid organ transplant patients. We aimed to determine the magnitude of effect of isavuconazole administration on tacrolimus and sirolimus C/D ratios in allogeneic hematopoietic stem cell transplant (alloHSCT) patients.METHODS:
A retrospective, single-center, single-arm study in adult alloHSCT patients who received at least 10 days of combination therapy with isavuconazole and tacrolimus and/or sirolimus as inpatients or outpatients was conducted. Tacrolimus and sirolimus trough serum concentrations were measured up to twice weekly for up to 4 weeks.RESULTS:
Twenty-two patients receiving tacrolimus and twenty patients receiving sirolimus met the inclusion criteria. The mean C/D ratio increased from baseline by 1.42-fold for tacrolimus during week 1 (P = 0.002) and up to 1.56-fold for sirolimus during week 2 (P = 0.02). For the remaining timepoints, tacrolimus and sirolimus C/D ratios were not statistically significantly different from baseline.CONCLUSION:
In alloHSCT patients, modest increases in tacrolimus and sirolimus C/D ratios from baseline were observed within the first 2 weeks after initiation of isavuconazole.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transplante de Células-Tronco Hematopoéticas
/
Inibidores do Citocromo P-450 CYP3A
/
Doença Enxerto-Hospedeiro
/
Imunossupressores
/
Antifúngicos
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Transpl Infect Dis
Assunto da revista:
TRANSPLANTE
Ano de publicação:
2019
Tipo de documento:
Article