Source: European Medicines Agency (EU) Revision Year: 2019 Publisher: Baxalta Innovations GmbH, Industriestrasse 67, A-1221, Vienna, Austria
Hypersensitivity to the active substance, to the parent molecule octocog alfa or to any of the excipients listed in section 6.1.
Known allergic reaction to mouse or hamster protein.
Allergic type hypersensitivity reactions are possible with ADYNOVI. The medicinal product contains traces of mouse and hamster proteins. If symptoms of hypersensitivity occur, patients should be advised to discontinue use of the medicinal product immediately and contact their physician. Patients should be informed of the early signs of hypersensitivity reactions including hives, generalised urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis.
In case of anaphylactic 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 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. Therefore, it is recommended to monitor all patients carefully for inhibitor occurrence following any product switch.
The clinical relevance of inhibitor development will depend on the titre of the inhibitor, with low titre inhibitors which are transiently present or remain consistently 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.
No clinical data for use of ADYNOVI in ITI are available.
In patients with existing cardiovascular risk factors, substitution therapy with factor VIII may increase the cardiovascular risk.
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.
After reconstitution this medicinal product contains 0.45 mmol sodium (10 mg) per vial. To be taken into consideration by patients on a controlled sodium diet.
It is strongly recommended that every time that ADYNOVI is administered to a patient, the name and batch number of the product are recorded in order to maintain a link between the patient and the batch of the medicinal product.
The listed warnings and precautions apply both to adults and children.
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 and breast-feeding is not available. Therefore, factor VIII should be used during pregnancy and lactation only if clearly indicated.
ADYNOVI has no influence on the ability to drive and use machines.
Hypersensitivity or allergic reactions (which may include angioedema, burning and stinging at the injection site, chills, flushing, generalised urticaria, headache, hives, hypotension, lethargy, nausea, restlessness, tachycardia, tightness of the chest, tingling, vomiting, wheezing) have been observed rarely and may in some cases progress to severe anaphylaxis (including shock).
Development of neutralising antibodies (inhibitors) may occur in patients with haemophilia A treated with factor VIII, including with ADYNOVI. 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.
The safety of ADYNOVI was evaluated in 243 previously treated patients with severe haemophilia A (factor VIII less than 1% of normal), who received at least one dose of ADYNOVI in 3 completed multi-center, prospective, open label clinical studies and 2 ongoing clinical studies. The median number of exposure days to ADYNOVI per subject was 103.5 (min-max: 1-278).
The table presented below is according to the MedDRA system organ classification (System Organ Class 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); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Table 2. Adverse reactions reported for ADYNOVI:
Uncommon (PTPs)*: Factor VIII inhibition
Uncommon: Hypersensitivity
Common: Headache
Uncommon: Flushing
Common: Diarrhoea, Nausea
Common: Rash
The observed event of hypersensitivity was a mild transient non-serious rash, occurring in one 2-year-old patient who had developed a previous rash while on ADYNOVI.
Frequency, type and severity of adverse reactions in children are expected to be the same as in adults. The safety of ADYNOVI was evaluated in 38 subjects <6 years and 34 subjects 6 to <12 years of age having accumulated a total of 2880 EDs and 2975 EDs respectively. The mean (SD) age was 3.3 (1.55) and 8.1 (1.92) years respectively.
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.
© 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.
