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

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 (t(1/2)), 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 t(1/2) differed among patients receiving LDP of FVIII twice weekly, with a median of t(1/2) 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.