WILATE - VON WILLEBRAND FACTOR/COAGULATION FACTOR VIII COMPLEX (HUMAN)- antihemophilic factor human and von willebrand factor human powder, for solution
Octapharma Pharmazeutika Produktionsgesellschaft m.b.H.
1 INDICATIONS AND USAGE
Wilate is a von Willebrand Factor/Coagulation Factor VIII Complex (Human) indicated for the treatment of spontaneous and trauma-induced bleeding episodes in patients with severe von Willebrand disease (VWD) as well as patients with mild or moderate VWD in whom the use of desmopressin is known or suspected to be ineffective or contraindicated.
Clinical trials to evaluate the safety and efficacy of prophylactic dosing with Wilate to prevent spontaneous bleeding have not been conducted in VWD subjects.
Wilate is not indicated for the prevention of excessive bleeding during and after surgery in VWD patients.
Wilate is not indicated for Hemophilia A.
2 DOSAGE AND ADMINISTRATION
For Intravenous Use after Reconstitution
Treatment should be initiated under the supervision of a physician experienced in the treatment of coagulation disorders.
Each vial of Wilate contains the labeled amount in International Units (IU) of von Willebrand factor (VWF) activity as measured with the Ristocetin cofactor assay (VWF:RCo), and coagulation factor VIII (FVIII) activity measured with the chromogenic substrate assay.
The number of units of VWF:RCo and FVIII activities administered is expressed in IU, which are related to the current WHO standards for VWF and FVIII products. VWF:RCo and FVIII activities in plasma are expressed either as a percentage (relative to normal human plasma) or in IU (relative to the International Standards for VWF:RCo and FVIII activities in plasma).
2.1 Dosage in von Willebrand Disease
The ratio between VWF:RCo and FVIII activities in Wilate is approximately 1:1.
The dosage should be adjusted according to the extent and location of the bleeding. In VWD type 3 patients, especially in those with gastro-intestinal (GI) bleedings, higher doses may be required.
2.2 Dosing Schedule
Physician supervision of the treatment regimen is required. A guide for dosing in the treatment of major and minor hemorrhages is provided in Table 1 .
The careful control of replacement therapy is especially important in life-threatening hemorrhages. When using a FVIII-containing VWF product, the treating physician should be aware that continued treatment may cause an excessive rise in FVIII activity
DOSAGE FORMS AND STRENGTHS
Wilate is a sterile, lyophilized powder for reconstitution for intravenous injection, provided in the following nominal strengths per vial:
500 IU VWF:RCo and 500 IU FVIII activities in 5-mL
1000 IU VWF:RCo and 1000 IU FVIII activities in 10-mL
4 CONTRAINDICATIONS
Wilate is contraindicated for patients who have known anaphylactic or severe systemic reaction to plasma-derived products, any ingredient in the formulation, or components of the container. For a complete listing of ingredients
DESCRIPTION
Wilate is a human plasma-derived, sterile, purified, double virus inactivated von Willebrand Factor/Coagulation Factor VIII Complex (Human). Wilate is supplied as a lyophilized powder for reconstitution for intravenous injection.
Wilate is labeled with the actual VWF:RCo and FVIII activities in IU per vial. The VWF activity (VWF:RCo) is determined using a manual agglutination method referenced to the current "WHO International Standard for von Willebrand Factor Concentrate". The FVIII activity is determined using a chromogenic substrate assay referenced to the current "WHO International Standard for Human Coagulation Factor VIII Concentrate". The assay methodologies are according to European Pharmacopoeia (Ph.Eur.).
Wilate contains no preservative. The diluent for reconstitution of the lyophilized powder is Water for Injection with 0.1% Polysorbate 80.
No albumin is added as a stabilizer. The resulting specific activity of Wilate is ≥ 60 IU VWF:RCo and ≥ 60 IU FVIII activities per mg of total protein.
CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
VWF and FVIII are normal constituents of human plasma. VWF is a multimeric protein with two key functions. It is an adhesive molecule, which mediates the binding between platelets and damaged sub-endothelial tissues. It is also a carrier protein, involved in the transport and stabilization of FVIII. Patients suffering from VWD have a deficiency or abnormality of VWF. This reduction in VWF concentration in the bloodstream result in a correspondingly low FVIII activity and an abnormal platelet function thereby resulting in excessive bleeding. [ 8 ]
The VWF in Wilate is derived from normal human plasma and is expected to behave in the same way as endogenous VWF. Thus, administration of VWF allows correction of the hemostatic abnormalities in VWD patients at two levels:
The VWF re-establishes platelet adhesion to the vascular sub-endothelium at the site of vascular damage (as it binds both to the vascular sub-endothelium and to the platelet membrane), providing primary hemostasis, as shown by the shortening of the bleeding time. This effect occurs immediately.
The VWF induces correction of the associated FVIII deficiency in VWD. Administered intravenously, VWF binds endogenous FVIII (which is produced normally by the patient), and by stabilizing this factor, avoids its rapid degradation. This action is slightly delayed. However, administration of a FVIII-containing VWF preparation like Wilate rapidly restores the FVIII activity level to normal.