Kovaltry

/ Bayer

Treatment should be under the supervision of a physician experienced in the treatment of haemophilia.
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.
On Demand Treatment: 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. For guide dosing in bleeding episodes and surgery, please refer to Table 1 at the attached doctor’s leaflet.
Prophylaxis: 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.
Previously untreated patients: The safety and efficacy of Kovaltry in previously untreated patients have not yet been established. Limited data are available.
Paediatric population: A safety and efficacy study has been performed in children of 0-12 years; 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.
Method of administration: 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).

Treatment and prophylaxis of bleeding in patients with haemophilia A (congenital factor VIII deficiency). Kovaltry can be used for all age groups.

Hypersensitivity to the active substance or to any of the excipients.
Known allergic reactions to mouse or hamster proteins.

Traceability: In order to improve traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Hypersensitivity: Allergic type hypersensitivity reactions are possible with Kovaltry.
If symptoms of hypersensitivity occur, patients should be advised to discontinue the use of the medicinal product immediately and contact their physician.
Patients should be informed of the early signs of hypersensitivity reactions including hives, nausea, generalised urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis.
In case of shock, standard medical treatment for shock should be implemented.
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 50 exposure days but continues throughout life although the risk is uncommon.
The clinical relevance of inhibitor development will depend on the titre of the inhibitor, with low titre posing less of a risk of insufficient clinical response than high titre inhibitors.
In general, all patients treated with coagulation factor VIII products should be carefully monitored for the development of inhibitors by appropriate clinical observations and laboratory tests.
If the expected factor VIII activity plasma levels are not attained, or if bleeding is not controlled with an appropriate dose, testing for factor VIII inhibitor presence should be performed. In patients with high levels of inhibitor, factor VIII therapy may not be effective and other therapeutic options should be considered. Management of such patients should be directed by physicians with experience in the care of haemophilia and factor VIII inhibitors.
Cardiovascular events: Haemophilic patients with cardiovascular risk factors or diseases may be at the same risk to develop cardiovascular events as non-haemophilic patients when clotting has been normalised by treatment with FVIII. Elevation of FVIII levels following administration, in particular in those with existing cardiovascular risk factors, might cause a patient to have the same risk for vessel closure or myocardial infarction as for the non-haemophilic population. Consequently, patients should be evaluated for cardiac risk factors.
Catheter-related complications: If a central venous access device (CVAD) is required, risk of CVAD-related complications including local infections, bacteraemia and catheter site thrombosis should be considered. These complications have not been associated with the product itself.
Paediatric population: The listed warnings and precautions apply both to adults and children.
Sodium content: For 250/500/1000 IU strength: After reconstitution this medicinal product contains 0.081 mmol sodium per vial of reconstituted solution (corresponding to 1.86 mg per vial). This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium- free’.
For 2000 IU strength: After reconstitution this medicinal product contains 0.156 mmol sodium per vial of reconstituted solution (corresponding to 3.59 mg per vial). This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium- free’.

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 and may in some cases progress to severe anaphylaxis (including shock).
Development of antibodies to mouse and hamster protein with related hypersensitivity reactions may occur.
Development of neutralising antibodies (inhibitors) may occur in patients with haemophilia A treated with factor VIII, including with Kovaltry. If such inhibitors occur, the condition may manifest itself as an insufficient clinical response. In such cases, it is recommended that a specialised haemophilia centre be contacted.
See prescribing information for full details.

No interactions of human coagulation factor VIII (rDNA) products with other medicinal products have been reported.

Pregnancy: Animal reproduction studies have not been conducted with factor VIII. Based on the rare occurrence of haemophilia A in women, experience regarding the use of factor VIII during pregnancy is not available.
Therefore, factor VIII should be used during pregnancy only if clearly indicated.
Lactation: It is unknown whether Kovaltry is excreted in human milk. The excretion in animals has not been studied. Therefore, factor VIII should be used during breast-feeding only if clearly indicated.

No symptoms of overdose with recombinant human coagulation factor VIII have been reported.

Storage: 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.
See prescribing information for full details.