Treatment on demand –in vivodose finding studies

Abstract

Since the discovery of replacement therapy the goal of treatment for haemophilia patients has always been the prevention of haemorrhagic episodes. However, the "ideal"" plasma level needed to prevent hemathrosis or treat haemorrhages is still unknown. It seems that the doses of treatment have been arrived at by trial and error based in the pharmacokinetics of the factors and the characteristics of the replacement product. This review provides some guidelines for the treatment of haemophilia, however the doses are not based in randomized trials.

Population pharmacokinetics of plasma-derived factor IX in adult patients with haemophilia B: implications for dosing in prophylaxis

“…Our study establishes that the average elimination half-life of plasma-derived FIX is approximately 30 h, thereby confirming that the average half-life is longer for plasma-derived FIX than the 18-24 h generally found [8] for recombinant FIX. Incremental in vivo recovery, a parameter traditionally used in coagulation factor PK and ubiquitously [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]22] estimated or discussed, was also calculated. It represents the FIX:C level observed immediately after infusion in relationship to the administered dose, that is, recovery equals C 0 (IU/dL) divided by dose (IU/kg).…”

“…Treatment or prevention of bleeding events in patients with haemophilia B requires that an adequate plasma level of coagulation factor is obtained by infusion of a FIX concentrate. In the cases of spontaneous bleedings, trauma or surgery, FIX procoagulant activity (FIX:C) levels of between 0.30 and 1.0 IU/mL are aimed for, depending on the site and severity of the bleeding [1,2]. Prophylactic treatment, on the other hand, theoretically requires the long-term maintenance of a "protective" FIX:C plasma level.…”

Treatment trends for haemophilia A and haemophilia B in the United States: results from the 2010 practice patterns survey

“…The high variability in on-demand dosing regimens observed in this survey, suggests a need for standardized treatment guidelines. Current practices for on-demand factor replacement therapy are based largely on uncontrolled, observational data [15], with the result that the optimal plasma level of factor to treat haemorrhages or prevent the development of haemarthroses remains unknown [16]. Existing recommendations are based on product characteristics, pharmacokinetics and product half-life rather than on randomized clinical trials [16].…”

Products Used To Treat Hemophilia: Dosing

“…Dosing for hemophilia treatment has been arrived at by empiric assessment, essentially "trial and error" based on the pharmacokinetics of the factors and the characteristics of replacement product [1]. However, the "ideal" dose of factor VIII (FVIII) or factor IX (FIX) that needs to be admin istered to invariably achieve hemostasis without "overtreating" is unknown.…”

“…Reproduced from[1].Table 25.2 Guidelines for factor replacement in severe and moderate hemophilia A and B. Reproduced from [1]. Reproduced from[1].Table 25.2 Guidelines for factor replacement in severe and moderate hemophilia A and B. Reproduced from [1].…”