Factor VIII Concentrate

VERBATIM UK SPC §4.2 (ADVATE 1000 IU POWDER AND SOLVENT FOR SOLUTION FOR INJECTION, PLGB060090023, Takeda Manufacturing Austria AG; §2 covers the 250, 500, 1000 and 1500 IU vials, each reconstituted with 2 ml solvent): '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.' '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. In some cases, especially in younger patients, shorter dosage intervals or higher doses may be necessary.' Table 1 (factor VIII level required; frequency/duration): early haemarthrosis, muscle bleeding or oral bleeding 20-40 - 'Repeat injections every 12 to 24 hours ... 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 haematoma 30-60 - 'every 12 to 24 hours ... for 3 - 4 days or more until pain and acute disability are resolved'; life-threatening haemorrhages 60-100 - 'every 8 to 24 hours ... until threat is resolved'; minor surgery including tooth extraction 30-60 - 'Every 24 hours ..., at least 1 day, until healing is achieved'; major surgery 80-100 (pre- and post-operative) - 'Repeat injections every 8 to 24 hours ... 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 shorter intervals printed in brackets for patients under the age of 6 are NOT adult intervals and are given in paedDose. 'The amount to be administered and the frequency of administration should always be oriented to the clinical effectiveness 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.' 'In case of the following haemorrhagic events, the factor VIII activity should not fall below the given plasma activity level.' §4.1: 'Treatment and prophylaxis of bleeding in patients with haemophilia A (congenital factor VIII deficiency). ADVATE is indicated in all age groups.' SUPERVISION: 'Treatment should be initiated under the supervision of a physician experienced in the treatment of haemophilia and with resuscitation support immediately available in case of anaphylaxis.' MONITORING: 'appropriate determination of factor VIII levels is advised to guide the dose to be administered and the frequency of repeated infusions'; individual patients differ in half-life and recovery; dose based on bodyweight may need adjustment in underweight or overweight patients; for major surgery 'precise monitoring of the substitution therapy by means of coagulation analysis (plasma factor VIII activity) is indispensable'. Method: intravenous use; 'The rate of administration should be determined to ensure the comfort of the patient up to a maximum of 10 ml/min.' CLASS PAGE: the page lists Advate, Recombinate, Helixate, Kogenate and Octanate; this card is ADVATE only and the other products differ and are not covered. The SPC prints no maximum total dose, so none is given. Some sections of the product information we used were incomplete — check the full SPC.

THESE ARE THE LABEL'S OWN PAEDIATRIC FIGURES (ADVATE UK SPC §4.2), NOT SCALED ADULT DOSES. VERBATIM: 'For on demand treatment dosing in paediatric patients (0 to 18 years of age) 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.' Table 1 intervals in brackets for patients under the age of 6: early haemarthrosis, muscle bleeding or oral bleeding '8 to 24 hours'; more extensive haemarthrosis, muscle bleeding or haematoma '8 to 24 hours'; life-threatening haemorrhages '6 to 12 hours'; minor surgery '12 to 24 hours'; major surgery '6 to 24 hours'. The factor VIII level targets are the same as in adults. The SPC gives no prophylaxis figure for patients aged 6 years and over other than the adult prophylaxis range (which it says may need shorter intervals or higher doses in younger patients), and no neonate-specific figure; none is implied. Product-specific: ADVATE only. Verify any under-18 dose against a children's formulary and local haemophilia centre protocol before use.