Version May 2024
von Willebrand disease: IV:
Note: Individualize dosage and frequency based on patient weight, type and severity of the bleeding episodes/surgical intervention and monitoring of appropriate clinical and laboratory measures. Dosage is expressed in von Willebrand factor:Ristocetin cofactor (VWF:RCo) units (ASH/ISTH/NHF/WFH [Connell 2021]; NHLBI 2007). Refer to product-specific information regarding in vivo recovery.
VWF (recombinant) does not contain factor VIII (FVIII); concomitant FVIII concentrate administration may be necessary based on the urgency of normalizing FVIII activity. Hemostasis cannot be ensured until FVIII activity is ≥40% of normal. A single infusion of VWF (recombinant) alone is expected to increase endogenous FVIII activity to ≥40% within 6 hours in most patients. When FVIII concentrate is indicated, administration within 10 minutes after VWF (recombinant) administration is preferred.
Active bleeding or emergent surgeries: If baseline FVIII activity is <40% or is unknown, administer FVIII concentrate in conjunction with the first infusion of VWF (recombinant). If an immediate rise in FVIII activity is not necessary or if the baseline FVIII activity is sufficient to ensure hemostasis, VWF (recombinant) may be administered alone, without additional FVIII concentrate. When repeated VWF (recombinant) infusions are required, monitor FVIII activity to determine if FVIII is also required. If target laboratory measures of VWF or FVIII activity are not attained or if bleeding persists, evaluate for the presence of VWF or FVIII inhibitors.
Elective surgeries: May assess FVIII and VWF:RCo activity 12 to 24 hours before surgery and administer VWF (recombinant) at that time to allow endogenous FVIII activity to increase to desired goal prior to surgery. Also assess FVIII activity within 3 hours prior to surgery. If FVIII activity is above the desired goal, administer VWF (recombinant) alone within 1 hour prior to surgery. If the FVIII activity is below recommended target levels, administer VWF (recombinant) followed by FVIII concentrate within 10 minutes.
Treatment and control of bleeding episodes or perioperative management:
|
Indication |
Loading doseb |
Maintenance doseb |
Monitoring |
Therapeutic goal (efficacy) |
Therapeutic goal (safety) |
Treatment durationc |
|---|---|---|---|---|---|---|
|
a NHLBI 2007. | ||||||
|
b If known, utilize prior patient-specific dosing information to tailor initial dosing. | ||||||
|
c The duration of therapy can vary for specific types of surgery. Therapy should be individualized based on the patient, type of procedure, and bleeding history. | ||||||
|
Minor bleeding or minor surgery |
30 to 60 VWF:RCo units/kg |
20 to 40 VWF:RCo units/kg every 12 to 48 hours |
VWF:RCo and FVIII peak and trough levels at least once |
Trough levels: VWF:RCo and FVIII >50 units/dL |
Peak levels: Do not exceed VWF:RCo >200 units/dL Or FVIII >250 to 300 units/dL |
3 to 5 days |
|
Major bleeding or major surgery |
40 to 60 VWF:RCo units/kg |
20 to 40 VWF:RCo units/kg every 8 to 24 hours |
VWF:RCo and FVIII peak and trough levels at least daily |
Trough levels: VWF:RCo and FVIII >50 units/dL |
Peak levels: Do not exceed VWF:RCo >200 units/dL Or FVIII >250 to 300 units/dL |
7 to 14 days |
Routine prophylaxis in patients with severe type 3 von Willebrand disease receiving on-demand therapy: IV: Initial: 40 to 60 units/kg twice weekly; may increase to 60 units/kg twice weekly if breakthrough bleeding of the joints or severe bleeding occurs. Doses may vary based on bleeding severity and clinical response.
There are no dosage adjustments provided in the manufacturer’s labeling.
There are no dosage adjustments provided in the manufacturer’s labeling.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Nervous system: Headache (18%)
Neuromuscular & skeletal: Arthralgia (14%)
1% to 10%:
Cardiovascular: Chest discomfort (1%), deep vein thrombosis (1%), hypertension (1%), inversion T wave on ECG (1%), supraventricular tachycardia (5%), tachycardia (1%), ventricular premature contractions (5%)
Dermatologic: Pruritic rash (5%), pruritus (3%)
Endocrine & metabolic: Hot flash (1%)
Gastrointestinal: Diarrhea (5%), dysgeusia (1%), nausea (4%), vomiting (4%)
Hematologic & oncologic: Purpuric disease (5%)
Hepatic: Increased serum alanine aminotransferase (9%), increased serum aspartate aminotransferase (5%)
Immunologic: Antibody development (1%)
Local: Infusion site reaction (paresthesia: 1%), irritation at injection site (5%)
Nervous system: Dizziness (4%), vertigo (3%)
Neuromuscular & skeletal: Joint injury (≥2%), tremor (1%)
Frequency not defined:
Hypersensitivity: Hypersensitivity reaction
Miscellaneous: Infusion related reaction
Postmarketing: Hypersensitivity: Anaphylaxis
Life-threatening hypersensitivity reactions to von Willebrand factor (recombinant), hamster or mouse proteins, or any component of the formulation
Concerns related to adverse effects:
• Antibody formation: Neutralizing antibodies (inhibitors) to von Willebrand factor (VWF) and/or factor VIII may occur. In patients who have high levels of inhibitors to VWF or factor VIII, therapy may not be effective and VWF (recombinant) use may lead severe hypersensitivity reactions; these patients should be managed by an experienced health care provider and alternatives to therapy should be considered. Any patient who has an inadequate response to therapy or a severe adverse reaction should be evaluated for the presence of inhibitors.
• Hypersensitivity reactions: Hypersensitivity reactions, including anaphylaxis, may occur; discontinue if hypersensitivity reactions occur and administer appropriate treatment. Discontinue immediately if signs/symptoms of severe allergic reactions occur. Patients experiencing anaphylactic reactions should be evaluated for the presence of inhibitors.
• Thrombotic events: Thromboembolic reactions, including disseminated intravascular coagulation (DIC), venous thrombosis, pulmonary embolism, myocardial infarction, and stroke may occur, especially in patients with known risk factors for thrombosis (including low ADAMTS13 levels). Risk is increased in patients requiring frequent doses of VWF (recombinant) in combination with factor VIII (recombinant), which may cause a sustained excessive rise in FVIII:C activity; monitor for signs and symptoms of thrombosis.
Dosage form specific issues:
• Mouse/hamster protein: Contains trace amounts of mouse and hamster proteins; hypersensitivity reactions may occur.
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer’s labeling.
Strengths expressed with approximate values. Consult individual vial labels for exact potency within each vial.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [preservative free]:
Vonvendi: 650 units (1 ea); 1300 units (1 ea) [contains mouse (murine) and/or hamster protein, polysorbate 80]
No
Solution (reconstituted) (Vonvendi Intravenous)
650 unit (Price provided is per AHF Unit): $2.38
1300 unit (Price provided is per AHF Unit): $2.38
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
IV: Infuse slowly (maximum rate: 4 mL/minute). If tachycardia occurs, slow infusion rate or interrupt administration. If also administering factor VIII, administer the complete dose of VWF (recombinant) followed by factor VIII within 10 minutes.
von Willebrand disease: Treatment (on demand) and control of bleeding episodes and perioperative management of bleeding in adults with von Willebrand disease (VWD); routine prophylaxis in adult patients with severe type 3 VWD receiving on-demand therapy to reduce the frequency of bleeding episodes.
None known.
There are no known significant interactions.
Based on data from an ex vivo placental perfusion study and the molecular weight, recombinant von Willebrand factor is not expected to cross the placenta (Pastuschek 2021).
Pregnant patients with von Willebrand disease may have an increased risk of bleeding following antenatal procedures, delivery, spontaneous miscarriage, or termination of pregnancy; close surveillance is recommended. Changes in von Willebrand factor levels may vary during pregnancy depending on type. Patients should be monitored at the first antenatal visit, once or twice during the third trimester, at delivery, and prior to surgical or invasive procedures. Factor replacement may be required during pregnancy if concentrations are <0.5 units/mL to prevent maternal bleeding during procedures (including delivery), spontaneous miscarriage, insertion and removal of epidural catheters, or active bleeding. Hemostatic concentrations should be maintained for at least 3 to 5 days following procedures or postpartum. Other agents may be preferred for the treatment of von Willebrand disease in pregnancy; however, when replacement therapy is needed, a recombinant product or a product made from a safe plasma source with viral testing that contains both factor VIII and von Willebrand factor is recommended (AGOG 2013; NHF 2021; RCOG [Pavord 2017]).
It is not known if recombinant von Willebrand Factor (VWF) is present in breast milk. According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
Plasma activity of VWF:RCo and FVIII:C (prior to, during, and after treatment; refer to manufacturer's labeling for details); development of VWF and/or factor VIII inhibitors; signs of bleeding; signs/symptoms of hypersensitivity reactions or thrombosis
von Willebrand Factor (recombinant) promotes platelet aggregation and adhesion to damaged vascular endothelium and acts as a stabilizing carrier protein for factor VIII.
Half-life elimination: 19.1 to 22.6 hours
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
