FANHDI

Treatment should be initiated under the supervision of a physician experienced in the treatment of haemophilia. Posology 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.

On demand treatment 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 International Units (relative to an International Standard for factor VIII in plasma).

One International Unit (IU) of factor VIII activity is equivalent to that quantity of factor VIII in one ml of normal human plasma. 4% of normal activity. 5 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.

The following table can be used to guide dosing in 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 every 12 to 24 hours.

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 Repeat infusion every 12-24 hours for 3-4 days or more until pain and acute disability are resolved.

Life threatening haemorrhages 60 - 100 Repeat infusion every 8 to 24 hours until threat is resolved. Surgery Minor including tooth extraction 30 - 60 Every 24 hours, at least 1 day, until healing is achieved. Major 80 - 100 (pre-and postoperative) Repeat infusion every 8-24 hours until adequate wound healing, then therapy for at least another 7 days to maintain a factor VIII activity of 30% to 60% (IU/dl).

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. In some cases, especially in younger patients, shorter dosage intervals or higher doses may be necessary.

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 infrequently, and may in some cases progress to severe anaphylaxis (including shock).

On rare occasions, fever has been observed. The adverse drug reactions reported are summarised and categorised according to the MedDRA system organ class in the table below. Within each frequency grouping, undesirable effects are presented in order of decreasing of seriousness.

) System Organ Class Body System Preferred Term ADR frequency evaluation Blood and lymphatic system disorders FVIII inhibitors Uncommon (PTPs)* Very common (PUPs)* General disorders and administration site conditions Pyrexia Rare * Frequency is based on studies with all FVIII products which included patients with severe haemophilia A.

1). 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. 4. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk.

As with any intravenous protein product, allergic type hypersensitivity reactions are possible. The product contains traces of human proteins other than factor VIII. 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. 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. The measures taken may be of limited value against non-enveloped viruses such as HAV and parvovirus B19. g. haemolytic anaemia). Inhibitors 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 severity of the disease as well as the exposure to factor VIII, this risk being highest within the first 20 exposure days.

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.

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