Dosing and uses of Vonvendi, von Willebrand factor, recombinant (vonicog alfa)
Adult dosage forms and strengths
injection, lyophilized powder for reconstitution
- 650 or 1300 IU 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 (vWD)
Indicated for on-demand treatment and control of bleeding episodes in adults aged ≥18 yr with 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
Calculating dose of recombinant factor VIII if needed
- Also see Dosing Considerations
- The initial dose of vWFr 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)
- In major bleeding episodes, maintain trough levels of vWF:RCo >50% for as long as deemed necessary
- Administer vWFr with rFVIII if required, to control bleeding
- Dosing should be at a ratio of 1.3:1 (ie, 30% more vWFr than rFVIII, based on the approximate mean recoveries to 1.5 and 2 IU/dL for vWRr and rFVIII, respectively)
- Administer the complete dose of vWFr followed by rFVIII within 10 minutes
- vWFr dose = dose (IU/kg) x weight (kg)
- rFVIII dose = vWFr dose divided by 1.3
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 vWFr 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, vWFr may be administered without recombinant factor VIII
Pediatric dosage forms and strengths
Safety and efficacy not established
Vonvendi, von Willebrand factor, recombinant (vonicog alfa) adverse (side) effects
<1%
Tachycardia
Nausea
Infusion site paresthesia
Chest discomfort
Generalized pruritus
Hot flush
Hypertension
Dizziness
Dysgeusia
Tremor
Increased heart rate
ECG T-wave inversion
Warnings
Contraindications
Life-threatening hypersensitivity reactions to vWFr or product constituents (ie, trisodium citrate-dihydrate, glycine, mannitol, trehalose-dihydrate, polysorbate 80, hamster or mouse proteins)
Cautions
Thromboembolic reactions, including DIC, venous thrombosis, PE, MI, and 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
Pregnancy
Pregnancy
There are no studies of use in pregnant women
Lactation
Unknown if distributed in human breast milk
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.
Pharmacology of Vonvendi, von Willebrand factor, recombinant (vonicog alfa)
Mechanism of action
Recombinant von Willebrand factor (vWF)
vWF promotes platelet aggregation and platelet adhesion on damaged vascular endothelium; vWF also serves as a stabilizing carrier protein for the procoagulant protein FVIII
Pharmacokinetics
AUC, mean: 1541-2890 h·U/dL
Clearance, mean: 0.03-0.04 dL/kg/hr
Half-life, mean: ~20 hr
Administration
IV Preparation
Allow vWFr and sterile water for injection (diluent) to reach room temperature
Reconstitute Mix2Vial(s) according to package instruction
With both vials still attached, gently swirl the vials or allow the reconstituted product to sit for 5 minutes then gently swirl to ensure the powder is completely dissolved
Do not shake; shaking adversely affects the integrity of the product
Once the content is completely dissolved, firmly hold both the transparent and blue parts of the Mix2Vial and unscrew into 2 separate pieces and discard the empty diluent vial and the blue part of the Mix2ViaL
Note: The Mix2Vial is intended for one-time use with a single vial of vWFr and diluent only
If the 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 vWFr, 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, the injection speed must be reduced or the administration must be interrupted
Storage
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
