Evaluation dosing intravenous voriconazole three times a day vs twice daily for the treatment of invasive aspergillosis in immunocompromised children: therapeutic drugs monitoring and safety

Abstract

Background: Voriconazole is the antifungal of choice for the treatment of invasive aspergillosis (IA). Plasma concentrations (PCs) ≥1mg / mL have been associated with better therapeutic results which have not always been achieved during treatment in immunocompromised children. In the necessity to initiate early and effective therapy for the infection, it is relevant to establish the voriconazole administration regimen that is associated with optimal PCs in this population. Aim: To compare the PC and safety of intravenous (IV) voriconazole, dosed BID and TID in immunocompromised children with indication of antifungal treatment. Method: Retrospective observational study since January 2015 until July 2018 in a highly complex pediatric hospital in Santiago of Chile, in patients aged 0 to 17 years who received treatment with IV voriconazole. Those with renal replacement therapy, liver failure and / or renal failure were excluded. Trough CPs were compared between a group with BID dosing regimen versus another group with TID administration. Adverse reactions were evaluated in both groups. Results: 137 trough CPs were obtained in 76 children, with a median age of 9 years (0-17 years) in the BID group and 9 years (0-16) in the TID group with a median weight of 27 kg (6-83 kg) and 28kg (9.3-60 kg), respectively. Patients <12 years old exposed to TID dosages are 4.65 times (OR: 4.65, 95% CI 1.93-11.2) more likely to have PC ≥1mg / mL compared to BID administration (P = 0.001). Eight adverse reactions were reported, mainly photophobia, with no significant difference found between the BID and TID groups. Conclusion: TID dosages are associated with a greater probability of obtaining adequate exposure to voriconazole in patients <12 years old compared to BID dosages, with a low frequency of adverse reactions.