Von Willebrand Factor, Recombinant

Von Willebrand factor, recombinant is used for on-demand treatment and control of bleeding episodes in adults with von Willebrand disease (VWD) and perioperative management of bleeding in adults with VWD.

Von Willebrand factor, recombinant is available under the following different brand names: Vonvendi.

Dosages of Von Willebrand Factor, Recombinant:

Dosage Forms and 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

Dosage Considerations – Should be Given as Follows:

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 (e.g., readily managed nosebleed, orally bleeding, menorrhagia)
  • Initial dose: 40-50 IU/kg
  • Subsequent dose: 40-50 IU/kg every 8-24 hours as clinically required

• Major hemorrhage
  • Major (e.g., severe or refractory epistaxis, menorrhagia, gastrointestinal bleeding, central nervous system (CNS) trauma, hemarthrosis, or traumatic hemorrhage)
  • Initial dose: 40-80 IU/kg
  • Subsequent dose: 40-60 IU/kg every 8-24 hours for 2-3 days as clinically required
  • Maintain trough levels of vWF:RCo greater than 50% for as long as deemed necessary

• Calculating dose of recombinant factor VIII if needed
  • Also, see Dosing Considerations
  • The initial dose of von Willebrand factor (rVWF) should achieve greater than 60% of vWF levels (based on vWF:RCo greater than 0.6 IU/mL) and an infusion of recombinant factor VIII (rFVIII) should achieve factor VIII levels greater than 40% (FVIII:C greater than 0.4 IU/mL)
  • Administer rVWF with rFVIII if required, to control bleeding
  • Dosing should be at a ratio of 1.3:1 (i.e., 30% more rVWF than rFVIII, based on the approximate mean recoveries to 1.5 and 2 IU/dL for rVWF and rFVIII, respectively)
  • Administer a 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 hours before 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 hour before the procedure
  • If FVIII:C level is below the recommended minimum target level, administer complete rVWF dose followed by recombinant factor VIII within 10 min
  • Assess baseline VWF:RCo levels within 3 hours of administration of the 12-24 hours preoperative dose
  • If 12-24 hours preoperative dose is not administered, then assess baseline level VWF:RCo before surgery
  • When possible, measure incremental recovery (IR) before surgery

• Emergency surgery
  • In emergency surgery, a 12-24 hours preoperative dose in subjects requiring emergency surgery
  • Assess baseline VWF:RCo and FVIII:C levels within 3 hours before initiating the surgical procedure if it is feasible
  • Loading dose (1-hour preoperative dose): Calculate 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-hour 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) less than 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 hours 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 through plasma levels and minimum duration of treatment
  • VWF:RCo target through plasma level (up to 72 hours post-surgery): 30 IU/dL (minor) or greater; greater than 50 IU/dL (major)
  • VWF:RCo target through plasma level (greater than 72 hours post-surgery): greater than 30 IU/dL (major)
  • FVIII:C target through plasma level (up to 72 hours post-surgery): greater than 30 IU/dL (minor); greater than 50 IU/dL (major)
  • FVIII:C target through plasma level (greater than 72 hours post-surgery): greater than 30 IU/dL (major)
  • Minimum duration of treatment: 48 hours (minor surgery); 72 hours (major surgery)
  • Frequency of dosing: every 12-24 hours to every other day

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 less than 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 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
• Children under 18 years: Safety and efficacy not established

Side effects of von Willebrand factor, recombinant include:

• Fast heart rate
• Nausea
• Infusion site numbness and tingling
• Chest discomfort
• Generalized itching
• Hot flush
• High blood pressure (hypertension)
• Dizziness
• Changes in taste
• Tremor
• Increased heart rate
• ECG T-wave inversion

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

• Von Willebrand factor, recombinant has no listed severe interactions with other drugs.
• Von Willebrand factor, recombinant has no listed serious interactions with other drugs.
• Von Willebrand factor, recombinant has no listed moderate interactions with other drugs.
• Von Willebrand factor, recombinant has no listed mild interactions with other drugs.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Warnings

This medication contains von Willebrand factor, recombinant. Do not take Vonvendi if you are allergic to von Willebrand factor, recombinant or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

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

Effects of Drug Abuse

• No information is available

Short-Term Effects

• See "What Are Side Effects Associated with Using on Willebrand Factor, Recombinant?”

Long-Term Effects

• See "What Are Side Effects Associated with Using Von Willebrand Factor, Recombinant?”

Cautions

• Thromboembolic reactions [e.g., disseminated intravascular coagulation (DIC), venous thrombosis, pulmonary embolism (PE), heart attack (myocardial infarction), stroke] can occur, particularly in patients with known risk factors for thrombosis; monitor for early signs and symptoms of thrombosis (e.g., pain, swelling, discoloration, shortness of breath, cough, hemoptysis, lightheadedness/fainting)
• Hypersensitivity reactions, including anaphylaxis, may occur; immediately discontinue if a 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 a healthcare provider before travel; while traveling, advise patients to bring an adequate supply of the drug based on a current regimen of treatment

Pregnancy and Lactation

There are no studies of the use of von Willebrand factor, recombinant in pregnant women. Consult your doctor.

There is no information regarding the presence of von Willebrand factor, recombinant 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 von Willebrand factor, recombinant therapy, and any potential adverse effects on the breastfed infant from the therapy or the underlying maternal condition.