von Willebrand factor, recombinant (Rx)

Brand and Other Names:Vonvendi

Dosing & Uses


Dosage Forms & Strengths

injection, lyophilized powder for reconstitution

  • 650 or 1300 IU von Willebrand factor ristocetin cofactor (vWF:RCo) per vial
  • Each vial is labeled with precise IU, which is based on the current World Health Organization standard for von Willebrand factor concentrate

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


Adverse Effects




Infusion site paresthesia

Chest discomfort

Generalized pruritus

Hot flush





Increased heart rate

ECG T-wave inversion




Life-threatening hypersensitivity reactions to rVWF or product constituents (ie, trisodium citrate-dihydrate, glycine, mannitol, trehalose-dihydrate, polysorbate 80, hamster or mouse proteins)


Thromboembolic reactions (eg, DIC, venous thrombosis, PE, MI, stroke) can occur, particularly in patients with known risk factors for thrombosis; monitor for early signs and symptoms of thrombosis (eg, pain, swelling, discoloration, dyspnea, cough, hemoptysis, syncope)

Hypersensitivity reactions, including anaphylaxis, may occur; immediately discontinue if severe allergic response occurs

Neutralizing antibodies to vWF and/or FVIII may occur; if the expected plasma levels of vWF activity (vWF:RCo) are not attained, perform an appropriate assay to determine if anti-vWF or anti-FVIII inhibitors are present

Monitor plasma levels of vWF:RCo and FVIII activity to avoid sustained excessive activity

Monitor for development of vWF and/or FVIII inhibitors when suspected

Advise patients to consult with healthcare provider prior to travel; while traveling, advise patients to bring adequate supply of the drug based on current regimen of treatment




There are no studies of use in pregnant women


There is no information regarding the presence of rVWF in human milk, the effects on the breastfed infant, or the effects on milk production

Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for therapy and any potential adverse effects on the breastfed infant from the therapy or from the underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.



Mechanism of Action

Recombinant von Willebrand factor (rVWF)

rVWF promotes platelet aggregation and platelet adhesion on damaged vascular endothelium; vWF also serves as a stabilizing carrier protein for the procoagulant protein FVIII


AUC (0-inf): 1541.4-2939 hr·U/dL


Clearance: 0.03-0.04 dL/kg/hr

Half-life: 49.3-22.6 hr



IV Preparation

Allow rvWF and sterile water for injection (diluent) to reach room temperature

Reconstitute Mix2Vial(s) according to package instruction

With both vials still attached, gently swirl vials or allow reconstituted product to sit for 5 minutes then gently swirl to ensure powder is completely dissolved

Do not shake; shaking adversely affects the integrity of product

Once content is completely dissolved, firmly hold both transparent and blue parts of Mix2Vial and unscrew into 2 separate pieces and discard empty diluent vial and blue part of Mix2Vial

Some flakes or particles may remain in reconstituted vial; filter included in Mix2Vial device will remove extraneous flakes or particles, and resulting solution in syringe should be clear and colorless; discard if it is cloudy or contains flakes or particles after filtration from vial into syringe

Note: Mix2Vial is intended for one-time use with a single vial of rVWF and diluent only

If dose requires >1 vial, reconstitute each vial separately

Do not refrigerate after reconstitution

IV Administration

For IV administration only

Administer immediately after reconstitution; if not, store at room temperature not to exceed 27°C (81°F) for up to 3 hr

Discard after 3 hr

If a patient is to receive >1 vial of rVWF, the contents of each vial must be drawn into individual syringes

Leave syringe attached to the vial until ready to infuse to reduce risk of contamination

Use plastic syringes with this product because proteins in the product tend to stick to the surface of glass syringes

Do not mix with other medicinal products

Prepare infusion site and plastic disposable syringe and infusion set according to package instructions

Infuse IV at a rate that ensures the comfort of the patient, up to a maximum of 4 mL/minute

If tachycardia occurs, reduce injection rate or the administration must be interrupted


Unopened vials

  • Store refrigerated at 2-8°C (36-46°F) in the original box and protect from extreme exposure to light
  • Do not freeze
  • May store at room temperature up to 30°C (86°F) for a period of up to 12 months, not to exceed the expiration date
  • Record on the carton the date removed from refrigeration
  • Do not return to refrigerated temperature after storing at room temperature
  • Do not use beyond the expiration date

Reconstituted vials

  • Administer immediately after reconstitution; if not, store at room temperature not to exceed 27°C (81°F) for up to 3 hr
  • Discard after 3 hr


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