Presentation and Status in Health Basket
5 ml X 500 IU
5 ml X 1000 IU
The calculation of the required dose 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 2 IU/dl. The required dose is determined using the following formula: Required units (IU) = body weight (kg) x desired factor VIII rise (%) x 0.5 In case of the following haemorrhagic events, the factor VIII activity should not fall below the given plasma activity level (in % of normal or IU/dl) in the corresponding period.
Guide for dosing in bleeding episodes and surgery:
Haemorrhage: Early haemarthrosis, muscle bleeding or oral bleeding: 20-40 Factor VIII level required (% or IU/dl), Repeat injections every 12 to 24 hours (8 to 24 hours for patients under the age of 6) for at least 1 day, until the bleeding episode, as indicated by pain, is resolved or healing is achieved.
More extensive haemarthrosis, muscle bleeding or hematoma: 30 – 60 Factor VIII level required (% or IU/dl), Repeat injections every 12 to 24 hours (8 to 24 hours for patients under the age of 6) for 3 – 4 days or more until pain and acute disability are resolved.
Life-threatening haemorrhages: 60 – 100 Factor VIII level required (% or IU/dl), Repeat injections every 8 to 24 hours (6 to 12 hours for patients under the age of 6) until threat is resolved.
Surgery: Minor (Including tooth extraction): 30 – 60 Factor VIII level required (% or IU/dl), Every 24 hours (12 to 24 hours for patients under the age of 6), at least 1 day, until healing is achieved.
Major: 80 – 100 (pre- and postoperative) Factor VIII level required (% or IU/dl), every 24 hours (12 to 24 hours for patients under the age of 6), at least 1 day, until healing is achieved. Repeat injections every 8 to 24 hours (6 to 24 hours for patients under the age of 6) until adequate wound healing then continue therapy for at least another 7 days to maintain a factor VIII activity of 30% to 60% (IU/dl). The dose and frequency of administration should be adapted to the clinical response in the individual case. Under certain circumstances (e.g. presence of a low-titre inhibitor), doses larger than those calculated using the formula may be necessary. During the course of treatment, appropriate determination of plasma factor VIII levels is advised to guide the dose to be administered and the frequency of repeated injections. In the case of major surgical interventions in particular, precise monitoring of the substitution therapy by means of plasma factor VIII activity assay is indispensable. Individual patients may vary in their response to factor VIII, achieving different levels of in vivo recovery and demonstrating different half-lives.
Prophylaxis: For long-term prophylaxis against bleeding in patients with severe haemophilia A, the usual doses are 20 to 40 IU of factor VIII per kg body weight at intervals of 2 to 3 days.
Pediatric population: The safety and efficacy of this drug in all pediatric age groups has been established. For on demand treatment dosing in pediatric patients does not differ from adult patients. In patients under the age of 6, doses of 20 to 50 IU of factor VIII per kg body weight 3 to 4 times weekly are recommended for prophylactic therapy.
Method of administration: This agent should be administered via the intravenous route. In case of administration by a non health care professional appropriate training is needed. The rate of administration should be determined to ensure the comfort of the patient up to a maximum of 10 ml/min.
Treatment and prophylaxis of bleeding in patients with Haemophilia A (congenital factor VIII deficiency).
Hypersensitivity to the active substance or to any of the excipients or to mouse or hamster proteins.
Hypersensitivity: Allergic type hypersensitivity reactions, including anaphylaxis, have been reported with this drug. The product contains traces of mouse and hamster proteins. If symptoms of hypersensitivity occur, patients should be advised to discontinue use of the product immediately and contact their physician. Patients should be informed of the signs of the early signs of hypersensitivity reactions including hives, generalised urticaria, tightness in the chest, wheezing, hypotension, and anaphylaxis. In case of shock, standard medical treatment for shock should be implemented.
Inhibitors: The formation of neutralising antibodies (inhibitors) against 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. In patients who develop inhibitors to factor VIII, the condition may manifest itself as an insufficient clinical response. In such cases, it is recommended that a specialised haemophilia centre be contacted. The risk of developing inhibitors is correlated to the extent of exposure to factor VIII, the risk being highest within the first 20 exposure days, and to other genetic and environmental factors. Rarely, inhibitors may develop after the first 100 exposure days.
Cases of recurrent inhibitor (low titre) have been observed after switching from one factor VIII product to another in previously treated patients with more than 100 exposure days who have a previous history of inhibitor development. Therefore, it is recommended to monitor all patients carefully for inhibitor occurrence following any product switch.
In general, all patients treated with coagulation factor VIII should be carefully monitored for the development of inhibitors by appropriate clinical observations and laboratory tests. If the expected factor VIII activity plasma levels are not attained, or if bleeding is not controlled with an appropriate dose, testing for factor VIII inhibitor presence should be performed. In patients with high levels of inhibitor, factor VIII substitution therapy may not be effective and other therapeutic options should be considered. The management of such patients should be directed by physicians with experience in the care of patients with haemophilia and factor VIII inhibitors.
If central venous access device (CVAD) is required, risk of CVAD-related complications including local infections, bacteremia and catheter site thrombosis should be considered.
Excipient related considerations: After reconstitution this medicinal product contains 0.45 mmol sodium (10 mg) per vial. To be taken into consideration by patients on a controlled sodium diet. It is strongly recommended that every time ADVATE 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 medicinal product.
Pediatric population: The listed warnings and precautions apply to both adults and children.
For full details see prescribing information.
The ADRs that occurred in the highest frequency were development of neutralising antibodies to factor VIII (inhibitors), headache and fever.
See prescribing information for full details.
No interaction studies have been performed with ADVATE.
Pregnancy and Lactation
Animal reproduction studies have not been conducted with factor VIII. Based on the rare occurrence of haemophilia A in women, experience regarding the use of Factor VIII during pregnancy and breast-feeding is not available. Therefore, factor VIII should be used during pregnancy and lactation only if clearly indicated.
No symptoms of overdose with recombinant coagulation factor VIII have been reported.
Incompatibilities: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products or solvents.
After reconstitution: Chemical and physical in-use stability has been demonstrated for 3 hours at 25°C. From a microbiological point of view, the product should be used immediately after reconstitution.
Storage: Store in a refrigerator (2ċ– 8 ċ). Do not freeze. During the shelf life, the product may be kept at room temperature (up to 25°C) for a single period not exceeding 6 months. The beginning of storage at room temperature should be recorded on the product carton. The product may not be returned to refrigerated storage again. Keep the vial in the outer carton in order to protect from light.