von Willebrand factor, recombinant (Rx)

von Willebrand Disease, Bleeding Episodes

Control bleeding episodes

• Indicated for on-demand treatment and control of bleeding episodes in adults with von Willebrand disease (VWD)
• Initial: 40-80 IU/kg

• Minor hemorrhage

  • Minor (eg, readily managed epistaxis, PO bleeding, menorrhagia)
  • Initial dose: 40-50 IU/kg
  • Subsequent dose: 40-50 IU/kg q8-24hr as clinically required

• Major hemorrhage

  • Major (eg, severe or refractory epistaxis, menorrhagia, GI bleeding, CNS trauma, hemarthrosis, or traumatic hemorrhage)
  • Initial dose: 40-80 IU/kg
  • Subsequent dose: 40-60 IU/kg q8-24hr for 2-3 days as clinically required
  • Maintain trough levels of vWF:RCo >50% for as long as deemed necessary

• Calculating dose of recombinant factor VIII if needed

  • Also see Dosing Considerations
  • Initial dose of von Willebrand factor (rVWF) should achieve >60% of vWF levels (based on vWF:RCo >0.6 IU/mL) and an infusion of recombinant factor VIII (rFVIII) should achieve factor VIII levels >40% (FVIII:C >0.4 IU/mL)
  • Administer rVWF with rFVIII if required, to control bleeding
  • Dosing should be at a ratio of 1.3:1 (ie, 30% more rVWF than rFVIII, based on the approximate mean recoveries to 1.5 and 2 IU/dL for rVWF and rFVIII, respectively)
  • Administer complete dose of rVWF followed by rFVIII within 10 minutes
  • rVWF dose = dose (IU/kg) x weight (kg)
  • rFVIII dose = rVWF dose divided by 1.3

Perioperative bleeding

• Indicated for perioperative management of bleeding in adults with VWD

• Elective surgical procedures

  • rVWF dose may be given 12-24 hr prior to surgery to allow the endogenous factor VIII levels to increase to at least 30 IU/dL (minor surgery) or 60 IU/dL (major surgery)
  • If FVIII:C levels are at or above the recommended minimum target levels, administer rVWF alone (without factor VIII treatment) within 1 hr prior to procedure
  • If FVIII:C level is below recommended minimum target level, administer complete rVWF dose followed by recombinant factor VIII within 10 min
  • Assess baseline VWF:RCo levels within 3 hr of administration of the 12-24 hr preoperative dose
  • If 12-24 hr preoperative dose is not administered, then assess baseline level VWF:RCo prior to surgery
  • When possible, measure incremental recovery (IR) before surgery

• Emergency surgery

  • In emergency surgery, a 12-24 hr preoperative dose in subjects requiring emergency surgery
  • Assess baseline VWF:RCo and FVIII:C levels within 3 hr prior to initiating the surgical procedure if it is feasible
  • Loading dose (1 hr preoperative dose): Calculate as the difference in the target peak and baseline plasma VWF:RCo levels divided by the IR
  • If baseline VWF:RCo and FVIII:C is not available, loading dose (1 hr preoperative dose) of rvWF 40-60 IU/kg VWF:RCo
  • Additionally, recombinant factor VIII at a dose of 30-45 IU/kg may be infused sequentially, preferably within 10 min after rvWF infusion in patients whose factor VIII plasma levels already are (or are highly likely to be) <40 to 50 IU/dL (minor surgery) or 80-100 IU/dL (major surgery)

• Calculation of rvWF dose

  • Difference plasma VWF:RCo: Target peak plasma VWF:RCo – baseline plasma VWF:RCo
  • Difference plasma VWF:RCo x body weight [BW] (kg) divided by incremental recovery as measured in the subject (if IR is not available, assume IR of 2.0 IU/dL per IU/kg)
  • Also see prescribing information for further information

• Recommended BW based dosing in the absence of baseline FVIII:C, VWF:RCo and incremental recovery

  • VWF:RCo: 25-30 IU/kg (minor); 50±10 IU/kg (major)
  • FVIII:C: 20-25 IU/kg (minor); 40-50 IU/kg (major)
  • Frequency dosing range between BID and q48hr

• Recommended target peak plasma levels for the perioperative management of bleeding

  • VWF:RCo target peak plasma level: 50-60 IU/dL (minor); 100 IU/dL (major)
  • FVIII:C target peak plasma level: 40-50 IU/dL (minor); 80-100 IU/dL (major)
  • Monitor VWF:RCo and FVIII:C plasma levels starting 12-24 hr after surgery and at least q24hr in the perioperative period
  • Individualize intra- and postoperative maintenance regimen according to the pharmacokinetic results and intensity and duration of the hemostatic challenge

• Recommended target trough plasma levels and minimum duration of treatment

  • VWF:RCo target trough plasma level (≤72 hr post-surgery): ≥30 IU/dL (minor); >50 IU/dL (major)
  • VWF:RCo target trough plasma level (>72 hr post-surgery): >30 IU/dL (major)
  • FVIII:C target tough plasma level (≤72 hr post-surgery): >30 IU/dL (minor); >50 IU/dL (major)
  • FVIII:C target trough plasma level (>72 hr post-surgery): >30 IU/dL (major)
  • Minimum duration of treatment: 48 hr (minor surgery); 72 hr (major surgery)
  • Frequency of dosing: q12-24hr to every other day

von Willebrand Disease, Routine Prophylaxis

Indicated for routine prophylaxis to reduce bleeding episode frequency in patients with severe Type 3 VWD receiving on-demand therapy

Initial: 40-60 IU/kg IV twice weekly

Adjust prophylaxis dose up to 60 IU/kg twice weekly if breakthrough bleeding occurs in joints or if severe bleeding occurs

Treat breakthrough bleeding as per dosing guidelines for minor and major bleeding episodes

Dosing Considerations

Hemostasis cannot be ensured until factor VIII coagulation activity (FVIII:C) has reached 0.4 IU/mL (40% of normal activity)

If the patient's baseline plasma FVIII:C level is <40% or is unknown, it is necessary to administer an approved recombinant (non-von Willebrand factor containing) factor VIII with the first infusion of rVWF in order to achieve a hemostatic plasma level of FVIII:C

However, if an immediate rise in FVIII:C is not necessary or if the baseline FVIII:C level is sufficient to ensure hemostasis, rVWF may be administered without recombinant factor VIII

<18 years: Safety and efficacy not established