Presentation and Status in Health Basket
1 x 250 IU
1 x 500 IU
1 x 1,000 IU
Von Willebrand’s disease: Generally, 1 IU/kg VWF:RCo raises the circulating level of VWF:RCo by 0.02 IU/ml (2 %). Levels of VWF:RCo of > 0.6 IU/ml (60%) and of FVIII:C of > 0.4 IU/ml (40%) should be achieved. Usually 40 – 80 IU/kg of von Willebrand factor (VWF:RCo) and 20 – 40 IU FVIII:C/kg of body weight (BW) are recommended to achieve haemostasis. An initial dose of 80 IU/kg von Willebrand factor may be required, especially in patients with type 3 von Willebrand disease where maintenance of adequate levels may require greater doses than in other types of von Willebrand disease. Prevention of haemorrhage in case of surgery or severe trauma: For prevention of excessive bleeding during or after surgery the injection should start 1 to 2 hours before the surgical procedure. An appropriate dose should be re-administered every 12 – 24 hours. The dose and duration of the treatment depend on the clinical status of the patient, the type and severity of bleeding, and both VWF:RCo and FVIII:C levels. When using a FVIII-containing von Willebrand factor product, the treating physician should be aware that continued treatment may cause an excessive rise in FVIII:C. After 24 – 48 hours of treatment, in order to avoid an uncontrolled rise in FVIII:C, reduced doses and/or prolongation of the dose interval should be considered. Dosing in children is based on body weight and is therefore generally based on the same guidelines as for adults. The frequency of administration should always be oriented to the clinical effectiveness in the individual case.
Haemophilia A: The dosage and duration of the substitution therapy depend on the severity of the factor VIII deficiency, on the location and extent of the bleeding and on the patient’s clinical condition. The number of units of factor VIII administered is expressed in International Units (IU), which are related to the current WHO standard for factor VIII products. Factor VIII activity in plasma is expressed either as a percentage (relative to normal human plasma) or in IU (relative to an International Standard for factor VIII in plasma). One IU of factor VIII activity is equivalent to that quantity of factor VIII in one ml of normal human plasma. The calculation of the required dosage of factor VIII is based on the empirical finding that 1 IU factor VIII per kg body weight raises the plasma factor VIII activity by about 2 % of normal activity (2 IU/dl). The required dosage is determined using the following formula: Required units = body weight [kg] x desired factor VIII rise [% or IU/dl] x 0.5. The amount to be administered and the frequency of administration should always be oriented to the clinical effectiveness in the individual case.
For full details see prescribing information.
Congenital and acquired deficiency of blood clotting factor VIII: Severe or moderate hemophilia, prophylaxis during operation, Von Willebrands disease.
Known hypersensitivity to any of the constituents.
As with any intravenous infusion of a plasma-derived protein, allergic type hypersensitivity reactions are possible. Patients should be informed of the early signs of hypersensitivity reactions including hives, generalised urticaria, tightness of the chest, wheezing, hypotension and anaphylaxis. If these symptoms occur, they should be advised to discontinue use of the product immediately and contact their physician. In case of shock, the current medical standards for shock treatment should be observed. Haemate P 250/500/1000 contains up to 70 mg sodium per 1000 IU. To be taken into consideration by patients on a controlled sodium diet.
Von Willebrand Disease: There is a risk of occurrence of thrombotic events, particularly in patients with known clinical or laboratory risk factors. Therefore, patients at risk must be monitored for early signs ofthrombosis. Prophylaxis against venous thromboembolism should be instituted, according to the current recommendations.When using a VWF product, the treating physician should be aware that continued treatment may cause an excessive rise in FVIII:C. In patients receiving FVIII-containing VWF products, plasma levels of FVIII:C should be monitored to avoid sustained excessive FVIII:C plasma levels which may increase the risk of thrombotic events, and antithrombotic measures should be considered.Patients with VWD, especially type 3 patients, may develop neutralising antibodies (inhibitors) to VWF. If the expected VWF:RCo activity plasma levels are not attained, or if bleeding is not controlled with an appropriate dose, an appropriate assay should be performed to determine if a VWF inhibitor is present. In patients with high levels of inhibitor, therapy may not be effective and other therapeutic options should be considered.
Haemophilia A: The formation of neutralising antibodies (inhibitors) to factor VIII is a known complication in the management of individuals with haemophilia A. These inhibitors are usually IgG immunoglobulins directed against the factor VIII procoagulant activity, which are quantified in Bethesda Units (BU) per ml of plasma using the modified assay. The risk of developing inhibitors is correlated to the exposure to anti-haemophilic factor VIII, this risk being highest within the first 20 exposure days. Rarely, inhibitors may develop after the first 100 exposure days. Patients treated with human coagulation factor VIII should be carefully monitored for the development of inhibitors by appropriate clinical observations and laboratory tests. In patients with high levels of inhibitor, therapy may not be effective and other therapeutic options should be considered.
Virus safety: Standard measures to prevent infections resulting from the use of medicinal products prepared from human blood or plasma include selection of donors, screening of individual donations and plasma pools for specific markers of infection and the inclusion of effective manufacturing steps for the inactivation/removal of viruses. Despite this, when medicinal products prepared from human blood or plasma are administered, the possibility of transmitting infective agents cannot be totally excluded. This also applies to unknown or emerging viruses and other pathogens. The measures taken are considered effective for enveloped viruses such as HIV, HBV and HCV and for the non-enveloped virus HAV. The measures taken may be of limited value against non-enveloped viruses such as parvovirus B19. Parvovirus B19 infection may be serious for pregnant women (fetal infection) and for individuals with immunodeficiency or increased erythropoiesis (e.g. haemolytic naemia).Appropriate vaccination (hepatitis A and B) should be considered for patients in regular/repeated receipt of human plasma-derived products.It is strongly recommended that every time that Haemate P 250/500/1000 is administered to a patient, the name and batch number of the product are recorded in order to maintain a link between the patient and the batch of the product.
See prescribing information for full details.
Blood and lymphatic system disorders: When very large or frequently repeated doses are needed, or when inhibitors are present or when pre- and post- surgical care is involved, all patients should be monitored for signs of hypervolemia. In addition, those patients with blood groups A, B and AB should be monitored for signs of intravascular haemolysis and/or decreasing haematocrit values.
General disorders: and administration site conditions On very rare occasions, fever has been observed.
Immune system disorders: Hypersensitivity or allergic reactions (which may include angioedema, burning and stinging at the infusion site, chills, flushing, generalised urticaria, headache, hives, hypotension, lethargy, nausea, restlessness, tachycardia, tightness of the chest, tingling, vomiting, wheezing) have been observed very rarely, and may in some cases progress to severe anaphylaxis (including shock).
Von Willebrand Disease
Blood and lymphatic system disorders: Patients with VWD, especially type 3 patients, may very rarely develop neutralising antibodies (inhibitors) to VWF. If such inhibitors occur, the condition will manifest itself as an inadequate clinical response. Such antibodies are precipitating and may occur concomitantly to anaphylactic reactions. Therefore, patients experiencing anaphylactic reaction should be evaluated for the presence of an inhibitor. In all such cases, it is recommended that a specialised haemophilia centre be contacted.
Vascular system disorders: Very rarely, there is a risk of thrombotic/thromboembolic events (including pulmonary embolism). In patients receiving VWF products sustained excessive FVIII:C plasma levels may increase the risk of thrombotic events.
Blood and lymphatic system disorders: Patients with haemophilia A may very rarely develop neutralising antibodies (inhibitors) to factor VIII. If such inhibitors occur, the condition will manifest itself as an insufficient clinical response. In such cases, it is recommended that a specialised haemophilia centre be contacted. The experience from clinical trials with Haemate P 250/500/1000 in previously untreated patients (PUPs) is very limited. Therefore, no valid figures on incidence of clinically relevant specific inhibitors can be provided.
For full details see prescribing information.
Pregnancy and Lactation
Animal reproduction studies have not been conducted with Haemate P 250/500/1000.Based on the rare occurrence of haemophilia A in women, experience regarding the use of factor VIII during pregnancy and breastfeeding is not available.The situation is different in von Willebrand disease because of its autosomal heredity. Women are even more affected than men, because of additional bleeding risks like menstruation, pregnancy, labour, child birth and gynecological complications. Based on post-marketing experience substitution of VWF in the treatment and prevention of acute bleedings can be recommended. There are no clinical studies available on substitution therapy with VWF in pregnant or lactating women.Therefore, VWF and FVIII should be used during pregnancy and lactation only if clearly indicated.
No symptoms of overdose with VWF and FVIII have been reported. However, the risk of thrombosis cannot be excluded in case of an extremely high overdose, especially of FVIII-containing VWF products with a high FVIII content.