Source: European Medicines Agency (EU) Revision Year: 2020 Publisher: Bayer AG, 51368, Leverkusen, Germany
In order to improve traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
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.
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 (see section 4.2).
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.
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 factor VIII. Elevation of factor VIII 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.
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.
The listed warnings and precautions apply both to adults and children.
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’.
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’.
No interactions of human coagulation factor VIII (rDNA) products with other medicinal products have been reported.
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.
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 animal fertility studies have been conducted with Kovaltry and its effect on human fertility has not been established in controlled clinical trials. Since Kovaltry is a replacement protein of endogenous factor VIII, no adverse effects on fertility are expected.
If patients experience dizziness or other symptoms affecting their ability to concentrate and react, it is recommended that they do not drive or use machines until the reaction subsides.
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 (FVIII), 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.
The table presented below is according to the MedDRA system organ classification (SOC and Preferred Term Level). Frequencies have been evaluated according to the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Table 2. Frequency of adverse drug reactions in clinical trials:
Common: Lymphadenopathy
Very common (PUPs)*: FVIII inhibition
Uncommon (PTPs)*: FVIII inhibition
Common: Palpitation, sinus tachycardia
Common: Abdominal pain, abdominal discomfort, dyspepsia
Common: Pyrexia, chest discomfort, injection site reactions**
Uncommon: Hypersensitivity
Common: Headache, dizziness
Uncommon: Dysgeusia
Common: Insomnia
Common: Pruritus, rash***, dermatitis allergic
Uncommon: Urticaria
Uncommon: Flushing
In completed clinical studies with 71 paediatric previously treated patients, the frequency, type and severity of adverse reactions in children were found to be similar to those in adults.
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. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Only the provided infusion sets should be used for reconstitution and injection because treatment failure can occur as a consequence of human recombinant coagulation factor VIII adsorption to the internal surfaces of some infusion equipment.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
