ALPROLIX Powder and solvent for solution for injection Ref.[9407] Active ingredients: Eftrenonacog alfa

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

Previously untreated patients

The safety and efficacy of ALPROLIX in previously untreated patients have not yet been established. No data are available.

Treatment monitoring

During the course of treatment, appropriate determination of factor IX levels is advised to guide the dose to be administered and the frequency of repeated injections. Individual patients may vary in their response to factor IX, demonstrating different half-lives and recoveries. Dose based on bodyweight may require adjustment in underweight or overweight patients. In the case of major surgical interventions in particular, precise monitoring of the substitution therapy by means of coagulation analysis (plasma factor IX activity) is indispensable.

When using an in vitro thromboplastin time (aPTT)-based one stage clotting assay for determining factor IX activity in patients' blood samples, plasma factor IX activity results can be significantly affected by both the type of aPTT reagent and the reference standard used in the assay. This is of importance particularly when changing the laboratory and/or reagents used in the assay. Measurements with a one-stage clotting assay utilising a kaolin-based aPTT reagent will likely result in an underestimation of activity level.

Posology

Dose and duration of the substitution therapy depend on the severity of the factor IX deficiency, on the location and extent of the bleeding and on the patient’s clinical condition.

The number of units of recombinant factor IX Fc administered is expressed in International Units (IU), which are related to the current WHO standard for factor IX products. Factor IX 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 IX in plasma).

One International Unit (IU) of recombinant factor IX Fc activity is equivalent to that quantity of factor IX in one mL of normal human plasma.

On demand treatment

The calculation of the required dose of recombinant factor IX Fc is based on the empirical finding that 1 International Unit (IU) factor IX per kg body weight raises the plasma factor IX activity by 1% of normal activity (IU/dL). The required dose is determined using the following formula:

Required units = body weight (kg) x desired factor IX rise (%) (IU/dL) x {reciprocal of observed recovery (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. If a repeat dose is required to control the bleed, the prolonged half-life of ALPROLIX should be taken into account (see section 5.2). The time to peak activity is not expected to be delayed.

In the case of the following haemorrhagic events, the factor IX 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 ALPROLIX dosing for treatment of bleeding episodes and surgery:

¹ In some patients and circumstances the dosing interval can be prolonged up to 48 hours (see section 5.2 for pharmacokinetic data).

Prophylaxis

For long term prophylaxis against bleeding, the recommended starting regimens are either:

• 50 IU/kg once weekly, adjust dose based on individual response or
• 100 IU/kg once every 10 days, adjust interval based on individual response. Some patients who are well-controlled on a once every 10 days regimen might be treated on an interval of 14 days or longer.

The highest recommended dose for prophylaxis is 100 IU/kg

Elderly population

There is limited experience in patients ≥ 65 years.

Paediatric population

For children below the age of 12 years, higher or more frequent doses may be required and the recommended starting dose is 50-60 IU/kg every 7 days. For adolescents of 12 years of age and above, the dose recommendations are the same as for adults. See sections 5.1 and 5.2.

The highest recommended dose for prophylaxis is 100 IU/kg.

Method of administration

Intravenous use.

In case of self-administration or administration by a caregiver appropriate training is needed.

ALPROLIX 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.

For instructions on reconstitution of the medicinal product before administration, see section 6.6.

The effects of higher than recommended doses of ALPROLIX have not been characterised.

Shelf life

Unopened vial: 4 years.

During the shelf-life, the product may be stored at room temperature (up to 30°C) for a single period not exceeding 6 months. The date that the product is removed from refrigeration should be recorded on the carton. After storage at room temperature, the product may not be returned to the refrigerator. The product should not be used beyond the expiry date printed on the vial or six months after removing the carton from refrigeration, whichever is earlier.

After reconstitution: Chemical and physical stability has been demonstrated for 6 hours when stored at room temperature (up to 30°C). If the product is not used within 6 hours, it must be discarded. From a microbiological point of view, the product should be used immediately after reconstitution. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user. Protect product from direct sunlight.

Store in a refrigerator (2°C-8°C). Do not freeze. Keep the vial in the outer carton in order to protect from light.

For storage conditions after reconstitution of the medicinal product, see section 6.3.

Each pack contains:

• powder in a type 1 glass vial with a chlorobutyl rubber stopper
• 5 mL solvent in a type 1 glass pre-filled syringe with a bromobutyl rubber plunger stopper
• a plunger rod
• a sterile vial adapter for reconstitution
• a sterile infusion set
• alcohol swab(s)
• plaster(s)
• gauze pad(s).

Pack size of 1.

The powder for injection in each vial must be reconstituted with the supplied solvent (sodium chloride solution) from the pre-filled syringe using the sterile vial adapter for reconstitution.

The vial should be gently swirled until all of the powder is dissolved.

Please see package leaflet, for additional information on reconstitution and administration.

The reconstituted solution should be clear to slightly opalescent and colourless. Reconstituted medicinal product should be inspected visually for particulate matter and discoloration prior to administration. Do not use solutions that are cloudy or have deposits.

This product is for single use only.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.