Análisis de concentraciones plasmáticas de voriconazol y su perfil de seguridad en pacientes oncológicos pediátricos

Abstract

112 through levels from 26 patients were analyzed and the average age was 9.3 years-old. The SDL obtained from the IV route were 43.7%. There were more SDL ≥ 0.5 mg/L and ≥ 1.0 mg/L with the IV route than the PO route (p < 0.05). Patients younger than 12-years-old received a higher dosage than those ≥ 12 years old (median 18.6 and 9.2 mg/kg/d, respectively, p < 0.05). To reach SDL ≥ 0,5 mg/L with the PO route, a dosage of 200 mg every 12 hours showed the best results for all patients (80-100% SDL ≥ 0.5 mg/L). With an IV dosage between 14 and 20 mg/kg/day in patients > 12-years-old, 80% of the SDL were ≥ 1 mg/L and ≥ 2 mg/L. In patients younger than 12-year-old, dosages between 8-30 mg/ kg/day showed similar results (50-63% of SDL ≥ 1 mg/L and 36-40% of SDL ≥ 2 mg/L). Eight patients (30.8%) presented an adverse drug reaction and no relationship with the SDL was found. Conclusión: A VCZ standard dosage of 200 mg every 12 hours PO showed the best results for IA prophylaxis in all patients. Patients younger than 12-years-old would require higher dosages than the doses used in this study to attain adequate SDL for IA treatment. No relation with SDL and adverse reactions was found.

Voriconazole Use in Children: Therapeutic Drug Monitoring and Control of Inflammation as Key Points for Optimal Treatment

“…The available paediatric data on voriconazole safety are heterogeneous, as the criteria for classifying AEs and attributing them to the drug vary widely between studies. However, the percentage of AEs we detected is similar to the values reported in other studies using the same AE classification [29,[44][45][46]72]. We mention that our recording of up to four liver function parameters, including changes with no clinical impact, may have led to an overestimation of hepatic AEs in our study.…”

“…As is seen in Table 7, voriconazole PC often fell outside the therapeutic range. Adequate levels were described in 34% to 50% of patients in older studies using the previous dosage [17,29,30,[44][45][46][47]50]. With the new dosing recommendations, our findings indicate an improvement in this regard.…”

“…The main paediatric studies focussed on plasma voriconazole variability and monitoring published since 2012 are summarized in Table 7. Most of these studies include a relatively small sample (11 to 74 patients) [17,29,30,[32][33][34]41,[44][45][46][47][48][49]]. An exception is the article by Liu et al [50] with 107 patients (75 younger than 2 y) and the study by Allegra et al [51] with 237 patients, although 150 received voriconazole as prophylaxis.…”

“…It is reported that genetic polymorphisms conditioning voriconazole metabolism may differ depending on the patients' ethnicity, and this is especially relevant in Asian patients [27,[52][53][54][55]. Many of the paediatric studies cited above included a predominantly Asian population or did not describe the patients' ethnicity [30,32,41,[44][45][46][47][48][49][50].…”

Importancia de la monitorización de concentraciones plasmáticas de voriconazol y dificultad en ajuste de dosis en un paciente pediátrico

“…Por otra parte su cinética se ve afectada por interacciones con otros fármacos que pueden aumentar o disminuir las concentraciones plasmáticas de voriconazol, con el consiguiente riesgo de toxicidad y disminución de la efectividad por niveles supra o subterapéuticos; respectivamente. Otros factores que influyen en la variabilidad del metabolismo de voriconazol son: polimorfismos de la enzima CYP2C19, edad, sexo y enfermedades hepáticas, que son de relevancia al momento de seleccionar la dosificación y posteriores ajustes del fármaco 12 . En este contexto, se recomienda fuertemente la monitorización de concentraciones plasmáticas de voriconazol, ya que los niveles subterapéuticos (bajo 1 μg/ml) se han asociado a mayor mortalidad en pediatría 13 .…”