Treatment should be initiated under the supervision of a physician experienced in the treatment of haemophilia. Treatment monitoring During the course of treatment, appropriate determination of factor VIII levels (by one-stage clotting or chromogenic assays) is advised to guide the dose to be administered and the frequency of repeated injections.
Individual patients may vary in their response to factor VIII, demonstrating different half-lives and recoveries. Dose based on bodyweight may require adjustment in underweight and overweight patients. In the case of major surgical interventions in particular, precise monitoring of the substitution therapy by means of coagulation analysis (plasma factor VIII activity) is indispensable.
When using an in vitro thromboplastin time (aPTT)-based one stage clotting assay for determining factor VIII activity in patients’ blood samples, plasma factor VIII activity results can be significantly affected by both the type of the aPTT reagent and the reference standard used in the assay.
Also there can be significant discrepancies between assay results obtained by aPTT-based one stage clotting assay and the chromogenic assay according to Ph. Eur. This is of importance particularly when changing the laboratory and/or reagent used in the assay.
Posology The dose 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 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 recombinant factor VIII Fc activity is equivalent to that quantity of factor VIII in one mL of normal human plasma.
On-demand treatment The calculation of the required dose of recombinant factor VIII Fc 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. 5 (IU/kg per IU/dL) The amount to be administered and the frequency of administration should always be oriented to the clinical effectiveness in the individual case.
In the 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.
Table 1 can be used to guide dosing in bleeding episodes and surgery:
Table 1: Guide to ELOCTA dosing for treatment of bleeding episodes and surgery Degree of haemorrhage / Type of surgical procedure Factor VIII level required (%) (IU/dL) Frequency of doses (hours)/ Duration of therapy (days) Haemorrhage Early haemarthrosis, muscle bleeding or oral bleeding 20-40 Repeat injection every 12 to 24 hours for at least 1 day, until the bleeding episode as indicated by pain is resolved or healing is achieved.
1 More extensive haemarthrosis, muscle bleeding or haematoma 30-60 Repeat injection every 12 to 24 hours for 3- 4 days or more until pain and acute disability are resolved. 1 Life threatening haemorrhages 60-100 Repeat injection every 8 to 24 hours until threat is resolved.
Surgery Minor surgery including tooth extraction 30-60 Repeat injection every 24 hours, for at least 1 day, until healing is achieved. Major surgery 80-100 (pre- and post- operative) Repeat injection every 8 to 24 hours as necessary until adequate wound healing, then therapy at least for another 7 days to maintain a factor VIII activity of 30% to 60% (IU/dL).
1 In some patients and circumstances the dosing interval can be prolonged up to 36 hours. 2 for pharmacokinetic data. Prophylaxis For long term prophylaxis, the recommended dose is 50 IU of factor VIII per kg body weight at intervals of 3 to 5 days.
2). In some cases, especially in younger patients, shorter dosage intervals or higher doses may be necessary. Elderly There is limited experience in patients ≥65 years. 1). For adolescents of 12 years of age and above, the dose recommendations are the same as for adults.
Method of administration ELOCTA is for intravenous use. ELOCTA should be injected intravenously over several minutes. The rate of administration should be determined by the patient’s comfort level and should not exceed 10 mL/min. 6.