Fig. 2

Low dose prophylaxis in economically constrained environment: Influence of FVIII infusion frequency on trough level and factor consumption. (Modeled based on an average FVIII recovery of 2 IU dL⁻¹ per IU kg⁻¹ infused and a T_1/2 of 12 h). a A dosage of 10 IU kg⁻¹ two-times a week as well as 5 IU kg⁻¹ three-times a week (weekly consumption 20 and 15 IU kg⁻¹ per week respectively) each results in a trough level <1 IU dL⁻¹ in 3–4 of the 7 days in the week (but with trough levels always higher with three-times a week than with two-times a week prophylaxis even at lower dose with lower consumption), whereas as little as 2 IU kg⁻¹ daily (qd, weekly consumption 14 IU kg⁻¹ per week) produces daily trough of ~1.33 IU dL⁻¹. [For three-times weekly prophylaxis, doubling the infusion dose from 5 to 10 IU kg⁻¹ will double the day 2, 4 and 6 trough levels to ~1.33 IU dL⁻¹, but still leave trough level on day 7 at 0.66 IU dL⁻¹ (i.e. <1 IU dL⁻¹, figure not shown)]. Prophylaxis at 10 IU kg⁻¹ every-two-day (q2d) is shown in Fig. 2b. b In order for an every-three-day (q3d) regimen to produce a trough level similar to that obtained by every-two-day (q2d) infusion (e.g.1.33 IU/dL), the dosage per infusion has to be increased, whereas daily infusion requires a lower per infusion dosage. Compared to the q2d regimen, factor consumption is 2.8× more for the q3d regimen but 2.5× less for the qd regimen. These relative consumption multiples are the same for other target trough levels and other PK handling of clotting factors for a particular individual. (Figures not drawn to scale. Peak and trough levels will be different for different patients depending on their individual pharmacokinetic handling of the particular clotting factor, but the principles remain the same. Peak and trough levels tend to increase slightly with infusions but remain more or less constant after the first few infusions and steady state is achieved. Values for peak levels represent value range during steady state with each regimen)