Pharmacokinetic profile of children with haemophilia A receiving low‐dose FVIII prophylaxis in Indonesia: A single centre experience

Abstract

Background Pharmacokinetic (PK) studies of low‐dose prophylaxis (LDP) of coagulation factor VIII (FVIII) in children with severe haemophilia A (SHA) are scarce. Objective This study aims to investigate the PK profile of children with SHA receiving LDP of FVIII. Methods Paediatric patients receiving FVIII infusions (10 IU/kg twice weekly) were included. PK profiles were estimated using the Web Accessible Population Pharmacokinetic Service for Haemophilia (WAPPS‐Haemo). The primary outcomes were the terminal half‐life (t1/2), concentration–time profile, and time to reach an FVIII level of < 1%. The secondary outcome was the suggested dosing interval of FVIII prophylaxis based on the individual PK profile. Results Twenty‐five patients were recruited; their mean age was 12.3 ± 3.0 years. The t1/2 differed among patients receiving LDP of FVIII twice weekly, with a median of t1/2 was 14.8 h (IQR 12.6–16). The median time to reach an FVIII level of < 1% was 73.8 h (IQR 58.8–80.3). Most patients could maintain a trough level of FVIII > 1% longer than 48 h. At 72–96 h, patients needed a second dose of FVIII infusion because the FVIII level was < 1%. The suggested dosing interval of FVIII prophylaxis ranged from daily to every 96 h, depending on the individual PK profile. Conclusion Our study identified inter‐individual differences in the PK parameters using LDP of FVIII twice weekly. The inter‐individual results in different dosing intervals advise the timing of LDP. Estimating individual PK parameters enables the identification of the optimal prophylaxis frequency to prevent bleedings.

Real pandemic world results of pharmacokinetic-tailored personalized prophylaxis of bleeds in Polish children and adolescents with severe hemophilia A

“…In the recently published study, Huang et al reported that in pediatric patients, personalized and based on individualized target trough level (which is also a PK-related parameter), bleeding prophylaxis protocols are effective in reducing bleeds (6). Other studies also support this statement (19).…”