Source: European Medicines Agency (EU) Revision Year: 2020 Publisher: Bayer AG, 51368, Leverkusen, Germany
Treatment and prophylaxis of bleeding in patients with haemophilia A (congenital factor VIII deficiency). Kovaltry can be used for all age groups.
Treatment should be under the supervision of a physician experienced in the treatment of haemophilia.
During the course of treatment, appropriate determination of factor VIII levels is advised to guide the dose to be administered and the frequency of repeated infusions. 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 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 VIII activity) is indispensable.
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 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.
The calculation of the required dose of factor VIII is based on the empirical finding that 1 International Unit (IU) factor VIII per kg body weight raises the plasma factor VIII activity by 1.5% to 2.5% of normal activity.
The required dose is determined using the following formulae:
Required units = body weight (kg) x desired factor VIII rise (% or IU/dL) x reciprocal of observed recovery (i.e. 0.5 for recovery of 2.0%).
The amount to be administered and the frequency of administration should always be targeted to the clinical effectiveness required in the individual case.
In the case of the following haemorrhagic events, the factor VIII activity should not fall below the given level (in % of normal) in the corresponding period. The following table can be used to guide dosing in bleeding episodes and surgery:
Table 1. Guide for 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 surgery including tooth extraction | 30-60 | Every 24 hours, at least 1 day, until healing is achieved. |
| Major surgery | 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). |
For long term prophylaxis against bleeding in patients with severe haemophilia A, the usual doses for adolescents (≥12 years age) and adult patients are 20 to 40 IU of Kovaltry per kg body weight two to three times per week. In some cases, especially in younger patients, shorter dose intervals or higher doses may be necessary.
A safety and efficacy study has been performed in children of 012 years (see section 5.1); limited data are available for children below 1 year. The recommended prophylaxis doses are 20-50 IU/kg twice weekly, three times weekly or every other day according to individual requirements. For paediatric patients above the age of 12, the dose recommendations are the same as for adults.
Intravenous use.
Kovaltry should be injected intravenously over 2 to 5 minutes depending on the total volume. The rate of administration should be determined by the patient’s comfort level (maximal rate of infusion: 2 mL/min).
For instructions on reconstitution of the medicinal product before administration, see section 6.6 and the package leaflet.
No symptoms of overdose with recombinant human coagulation factor VIII have been reported.
30 months.
The chemical and physical in-use stability after reconstitution has been demonstrated for 3 hours at room temperature. After reconstitution, from a microbiological point of view, the product should be used immediately. If not used immediately, in use storage times and conditions prior to use are the responsibility of the user.
Do not refrigerate after reconstitution.
Store in a refrigerator (2°C-8°C).
Do not freeze.
Keep the vial and the pre filled syringe in the outer carton in order to protect from light.
Within its overall shelf life of 30 months the product when kept in its outer carton, may be stored up to 25°C for a limited period of 12 months. In this case, the product expires at the end of this 12 month period or the expiry date on the product vial, whichever is earlier. The new expiry date must be noted on the outer carton.
For storage conditions after reconstitution of the medicinal product, see section 6.3.
Each single package of Kovaltry contains:
Pack sizes:
Not all pack sizes may be marketed.
Detailed instructions for preparation and administration are contained in the package leaflet provided with Kovaltry.
The reconstituted medicinal product is a clear and colourless solution.
Kovaltry powder should only be reconstituted with the supplied solvent (2.5 mL or 5 mL water for injections) in the prefilled syringe and the vial adapter. For infusion, the product must be prepared under aseptic conditions. If any component of the package is opened or damaged, do not use this component.
After reconstitution the solution is clear. Parenteral medicinal products should be inspected visually for particulate matter and discoloration prior to administration. Do not use Kovaltry if you notice visible particulate matter or turbidity.
After reconstitution, the solution is drawn back into the syringe. Kovaltry should be reconstituted and administered with the components (vial adapter, prefilled syringe, venipuncture set) provided with each package.
The reconstituted product must be filtered prior to administration to remove potential particulate matter in the solution. Filtering is achieved by using the vial adapter.
The venipuncture set provided with the product must not be used for drawing blood because it contains an in line filter.
For single use only.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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