RESUMO
Antifungal agents may be associated with significant toxicity or drug interactions leading to sub-therapeutic antifungal drug concentrations and poorer clinical outcomes for patients with haematological malignancy. These risks may be minimised by clinical assessment, laboratory monitoring, avoidance of particular drug combinations and dose modification. Specific measures, such as the optimal timing of oral drug administration in relation to meals, use of pre-hydration and electrolyte supplementation may also be required. Therapeutic drug monitoring (TDM) of antifungal agents is warranted, especially where non-compliance, non-linear pharmacokinetics, inadequate absorption, a narrow therapeutic window, suspected drug interaction or unexpected toxicity are encountered. Recommended indications for voriconazole and posaconazole TDM in the clinical management of haematology patients are provided. With emerging knowledge regarding the impact of pharmacogenomics upon metabolism of azole agents (particularly voriconazole), potential applications of pharmacogenomic evaluation to clinical practice are proposed.
Assuntos
Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Neoplasias Hematológicas/imunologia , Micoses/microbiologia , Infecções Oportunistas/microbiologia , Consenso , Esquema de Medicação , Sistemas de Liberação de Medicamentos , Cálculos da Dosagem de Medicamento , Interações Medicamentosas , Monitoramento de Medicamentos , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/terapia , Humanos , Dados de Sequência Molecular , Micoses/tratamento farmacológico , Micoses/imunologia , Infecções Oportunistas/imunologia , Infecções Oportunistas/prevenção & controle , Guias de Prática Clínica como Assunto , Soluções para Reidratação , Triazóis/administração & dosagem , Triazóis/efeitos adversos , Voriconazol/administração & dosagem , Voriconazol/efeitos adversosRESUMO
Antifungal prophylaxis, empirical therapy and treatment of established fungal infections in the haematology population may be associated with significant toxicity or drug interactions leading to sub-therapeutic antifungal drug concentrations and poorer clinical outcomes. These risks may be minimised by clinical assessment, laboratory monitoring of biochemical or haematological indices, avoidance of particular drug combinations and dose modification in certain circumstances. Specific measures, such as the optimal timing of oral drug administration in relation to meals, use of pre-hydration and electrolyte supplementation may also be required. For certain agents, therapeutic drug monitoring (TDM) is warranted where non-compliance, non-linear pharmacokinetics, a narrow therapeutic window, suspected drug interaction or unexpected toxicity are encountered. Pharmacokinetics and pharmacodynamics of clinical relevance to the haematology population are discussed for the azole, polyene and echinocandin classes of antifungal agents. The evidence supporting an association between TDM and enhanced treatment outcomes is presented for individual antifungal drugs, and recommendations for clinical practice are provided. Further randomised study of newer antifungal agents, such as posaconazole, is required to explore the potential for improved clinical outcomes in association with TDM.