Posaconazole oral dose and plasma levels in pediatric hematology-oncology patients.

BACKGROUND: Posaconazole is a triazole with limited pharmacokinetic information in children. This study assessed the correlation between posaconazole oral solution daily dosage/kg/body weight and trough plasma level. METHODS: A total of 97 hematology-oncology pediatric patients with ≥1 posaconazole plasma concentration level (PPC) assessment in the first 6 weeks after the start of posaconazole treatment were included. RESULTS: Posaconazole was used as prophylaxis in 84 of 97 (87%) patients and as therapy in 13 of 97 (13%). The median daily dose/kg/bw ranged from 10 to 12 mg in the prophylaxis group and 12.5 to 16.5 mg in the therapy group. The median value of PPC for the prophylaxis group was 0.9 and 0.8 µg/mL at the first and second/third determinations, respectively. Posaconazole prophylaxis failed in 4 of 84 patients (5%). The median value of PPC for the therapy group was 1.5 and 1.4 µg/mL at the first/second and the third determination, respectively. Posaconazole-related side effects were reported in 6 patients and all regressed with the suspension of the drug. In the prophylaxis group, the use of proton-pump inhibitors was significantly associated with a lower PPC, P = 0.04. CONCLUSIONS: Posaconazole may be a valuable antifungal agent in children despite the incomplete knowledge of its pharmacokinetic characteristics.

Posaconazole in immunocompromised pediatric patients.

INTRODUCTION: Posaconazole is a broad-spectrum triazole widely used to prevent and treat invasive mycoses in adults. Since it received marketing authorization more than a decade ago, many authors have reported on its off-label use in pediatric patients, despite the fact that the pharmacokinetics, safety, and efficacy in children have not been extensively investigated. Areas covered: We reviewed pediatric studies published between 2010 and 2017 describing the prophylactic and therapeutic use of posaconazole, with special attention to the correlation between oral dose, plasma levels, safety, and effectiveness. We found that posaconazole is well tolerated in children with a low incidence of adverse effects. As in adults, posaconazole absorption is hampered by factors such as high gastric pH, mucositis, and concomitant medications, whereas there is no direct correlation between the daily dose and the trough plasma concentration due to saturable absorption. Expert Commentary: Posaconazole has proved safe and effective in preventing and treating fungal infections in immunocompromised children. A body-weight-based dosing regimen and therapeutic drug monitoring are recommended to optimize posaconazole plasma concentration. Absorption can be improved by high-fat foods or avoiding the use of proton-pump inhibitors. Further pediatric studies are needed especially for the new formulations of posaconazole (vials and tablets).