Prophylactic dosing of factor VIII and factor IX from a clinical pharmacokinetic perspective.
The high cost and limited availability of factor concentrates make dosing of factor VIII (FVIII) or factor IX (FIX) a crucial issue in the prophylactic treatment of haemophilia. It has often been recommended that this treatment should aim to maintain a minimum plasma level of 1% of normal coagulation factor activity (FVIII:C or FIX:C). The dosage needed is commonly given as 25-40 U kg(-1) three times weekly for FVIII or twice weekly for FIX. However, these guidelines are valid only with several qualifications. First, the actual trough levels required may vary considerably between patients. The clinical severity of haemophilia may depend on more factors than the endogenous level of FVIII:C or FIX:C. Secondly, interindividual variations in dose requirements are also due to variance in the pharmacokinetics of the coagulation factors. Pharmacokinetic calculations are useful to design optimal dosing schedules to achieve required trough levels of FVIII:C or FIX:C. Moreover, tailoring of the dosing of FVIII or FIX according to their disposition in the individual patient can markedly improve the cost-effectiveness of prophylactic treatment. However, the usefulness of in vivo recovery as a guide for prophylactic dosing seems questionable. It should be clearly understood that maintaining a certain trough level of FVIII:C or FIX:C is not an end in itself. Clinical outcome, not the achieved trough level, determines whether a dosage is adequate. Chiefly for economic reasons, the minimum effective dosage of coagulation factor should be determined and used in every patient. The dose requirement should also be re-evaluated at appropriate times.
Björkman
S
S
Hospital Pharmacy, Malmö University Hospital, Sweden. Sven.Bjorkman@Apoteket.Se
D004334:Drug Administration Schedule; D005164:Factor IX / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005169:Factor VIII / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006467:Hemophilia A / Q000517:prevention & control*; D002836:Hemophilia B / Q000517:prevention & control*; D006801:Humans; D016032:Randomized Controlled Trials as Topic
D005169:Factor VIII; D005164:Factor IX