AimsAvapritinib was first approved by the FDA in January 2020 and represents the first precision‐targeted drug for gastrointestinal stromal tumours. However, there is a lack of large‐scale data relating to adverse events (AEs) related to its use. We aimed to explore the avapritinib‐related AEs in real‐world practice based on the post‐marketing data.MethodsWe extracted all avapritinib‐related reports submitted to the FDA Adverse Event Reporting System (FAERS) by June 2022. Based on disproportionality analysis and Bayesian analysis, we then calculated the reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC) and empirical Bayes geometric mean (EBGM) to evaluate whether there is a significant association between avapritinib and AEs. Gender, age and time to onset were comparable between haemorrhage/non‐haemorrhage, serious/non‐serious, death/non‐death AEs, respectively.ResultsIn total, 3120 cases related to avapritinib were documented in the FAERS database, and 44% were reported within 30 days of commencing avapritinib. A total of 331 different AE signals were detected, and no significant differences between males and females was identified. Although the number of AEs associated with an abnormal skin texture and executive dysfunction was small, the signal intensity is high, suggesting that these events are strongly correlated with avapritinib. Subgroup analysis showed that elderly male patients were more likely to suffer from serious AEs compared to females (P < .01), but there was no significant difference between the haemorrhage group and the non‐haemorrhage group. Analysis of fatalities due to avapritinib‐related AEs indicated that sex, age and time‐to‐onset were all significantly related to death (P < .05).ConclusionOur study provides a more precise description of the incidence and characteristics of AEs after using avapritinib, clinicians should be particularly careful when prescribing avapritinib to elderly male patients, especially within the 30 days.

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This study aimed to optimize the dosing regimens of voriconazole (VRC) for pediatric patients after hematopoietic cell transplantation with different cytochrome P450 (CYP) 2C19 phenotypes and body weights, based on pharmacokinetic (PK)/pharmacodynamic (PD) analysis. The PK parameters of VRC were derived from previous literature. Combined with key factors affecting VRC, patients were categorized into 9 subgroups based on different CYP2C19 phenotypes (poor metabolizer/intermediate metabolizer, normal metabolizer, and rapid metabolizer/ultrarapid metabolizer) and typical body weights (15, 40, and 65 kg). Monte Carlo simulation was used to investigate dosing regimens for different groups. The area under the 24‐hour free drug concentration–time curve to the minimum inhibitory concentration (MIC) > 25 was used as the target value for effective treatment. The probability of target achievement and the cumulative fraction of response were determined on the basis of the assumed MICs and MICs distribution frequency of Aspergillus species and Candida species. When the MIC was ≤1 mg/L, 4 mg/kg every 12 hours was sufficient for optimal effects in groups 1‐3 and groups 5 and 6; however, 6 mg/kg every 12 hours was required for group 4, and 8 mg/kg every 12 hours was required for groups 7‐9. In empirical treatment, lower (2‐6 mg/kg every 12 hours) and higher (6‐12 mg/kg every 12 hours) dosing regimens were recommended for Candida spp. and Aspergillus spp., respectively. Our findings will assist in selecting appropriate dosing regimens of VRC for pediatric patients after hematopoietic cell transplantation with different CYP2C19 phenotypes and body weights. Clinically, it is better to continuously adjust the dosing on the basis of the therapeutic drug monitoring.