Indications for: ADVATE
In patients with Hemophilia A: to control and prevent hemorrhagic episodes, for perioperative management, and routine prophylaxis to prevent or reduce the frequency of hemorrhagic episodes.
Safety and Efficacy Study
Safety and efficacy trial evaluated the pharmacokinetics (double-blinded, randomized, cross-over), safety, immunogenicity, and hemostatic efficacy (open-label) of Advate in 111 patients.
- The trial included previously treated patients (PTPs with ≥150 exposure days) diagnosed with moderate to severe hemophilia A (FVIII level ≤2% of normal) who were ≥10 years of age.
- Patients self-administered Advate for routine prophylaxis (≥25 IU/kg body weight 3-4 times per week) and for on-demand treatment of bleeding episodes.
- A total of 510 bleeding episodes were reported; 439 (86%) were rated excellent or good in their response to treatment with Advate.
- A total of 411 (81%) bleeding episodes were managed with a single infusion.
- The rate of new bleeding episodes during the 75-exposure-day prophylactic regimen was calculated as a function of the etiology of bleeding episodes for 107 evaluable patients (n=274 bleeding episodes).
- The overall rate of new bleeding episodes in the prophylaxis study was 0.52 ± 0.71.
Perioperative Management Study
Safety and efficacy of Advate for perioperative management was investigated in 59 patients (7-65 years old) with severe or moderately severe hemophilia A (factor VIII ≤2%).
- 57 patients completed the study.
- Patients received a pre-operative loading dose aimed at increasing the plasma factor VIII level to 60% to 100% of normal for dental procedures or 80% to 120% of normal for all other surgical procedures.
- During the surgery, patients received replacement therapy by either bolus or continuous infusion.
- After discharge, patients continued to receive Advate for control of hemostasis for up to 6 weeks for major orthopedic procedures and up to 2 weeks for all other procedures.
- Intraoperative efficacy was rated as excellent or good for 61 (93.9%) of the 65 procedures.
- Postoperative efficacy was rated as excellent or good for 62 (95.4%) of the 65 procedures.
Routine Prophylaxis Study
In a multicenter, open-label, prospective, randomized, controlled postmarketing clinical trial of Advate use in 2 prophylactic treatment regimens compared to that of on-demand treatment, 53 PTPs with severe to moderately severe hemophilia A (FVIII level ≤2 IU/dL) were analyzed in the per-protocol group.
- Patients were initially treated for 6 months of on-demand therapy and then randomly assigned to 12 months of either a standard prophylaxis regimen (20-40 IU/kg every 48 hours) or PK-driven prophylaxis regimen (20-80 IU/kg every 72 hours).
- The median annual bleed rate during the on-demand therapy period was 44 bleeds per patients per year compared with 1 bleed per patient per year while on either prophylaxis regimen, which was a statistically significant difference (P <.0001).
- 42% of patients experienced no bleeding episodes while on prophylaxis for 1 year.
Adults and Children:
Dosage Required (IU) = Body Weight (kg) × Desired % Factor VIII Increase × 0.5. Infuse over ≤5 minutes (max infusion rate 10mL/min); monitor pulse; if increased significantly, reduce infusion rate or hold. Hemorrhage: Mild: obtain 20–40% FVIII increase; give every 12–24hrs for 1–3 days until resolved. Moderate: obtain 30–60% FVIII increase; give every 12–24hrs for 3 days or until pain or disability resolved. Major: obtain 60–100% FVIII increase; give every 8–24hrs until resolved. Perioperative: Minor: obtain 60–100% FVIII increase; give single bolus infusion within 1 hour of surgery, then every 12–24hrs as needed to control bleeding; Major: pre- and post-op: obtain 80–120% FVIII increase; give 1 dose preoperative to achieve 100% activity, then repeat every 8–24hrs based on healing. Routine prophylaxis: give 20–40 IU/kg every other day (3–4 times weekly). Or, alternatively, an every 3rd day dosing regimen may be followed. Adjust based on response.
Hypersensitivity reactions to mouse or hamster protein or other constituents of the product (mannitol, trehalose, sodium chloride, histidine, Tris, calcium chloride, polysorbate 80, and/or glutathione).
Not for von Willebrand's disease. Confirm Factor VIII deficiency prior to treatment. Monitor for development of Factor VIII inhibitors. Labor & delivery. Pregnancy (Cat.C). Nursing mothers.
Pyrexia, headache, cough, nasopharyngitis, arthralgia,
vomiting, upper respiratory tract infection, limb injury, nasal congestion, diarrhea; antibody formation, hypersensitivity reactions.
Half-life: ~12 hours.
Generic Drug Availability:
Single-dose vial—1 (w. diluent, Baxject II needleless transfer device)