ADZYNMA Powder and solvent for solution for injection Ref.[116244] Active ingredients: Apadamtase alfa

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Hypersensitivity reactions

Allergic-type hypersensitivity including anaphylactic reactions may occur. Patients should be informed of the early signs of hypersensitivity reactions including but not limited to tachycardia, tightness of the chest, wheezing and/or acute respiratory distress, hypotension, generalised urticaria, pruritus, rhinoconjunctivitis, angioedema, lethargy, nausea, vomiting, paraesthesia, restlessness, and may progress to anaphylactic shock. If signs and symptoms of severe allergic reactions occur, the administration of this medicinal product should be discontinued immediately and appropriate supportive care should be provided.

Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity. Patients may develop antibodies to rADAMTS13 following treatment with ADZYNMA which could potentially result in a decreased response to rADAMTS13 (see section 5.1). If such antibodies are suspected and there is a lack of efficacy, consider other therapeutic strategies.

Sodium content

This medicinal product contains less than 1 mmol sodium (23 mg) per mL, that is to say essentially 'sodium free'.

No interaction studies have been performed.

Pregnancy

There are no or limited amount of data from the use of ADZYNMA in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). The use of ADZYNMA during pregnancy may only be considered after a thorough individual risk benefit analysis by the treating physician before and during treatment.

Breast-feeding

There is insufficient information on the excretion of rADAMTS13 in human or animal milk but it is unlikely that it is excreted in human milk due to its high molecular weight. The decision either to discontinue breast-feeding or discontinue ADZYNMA should take into account the importance of this medicinal product to the mother.

Fertility

No human data are available on the effects of rADAMTS13 on male and female fertility. Animal data do not indicate direct or indirect harmful effects with respect to male or female fertility (see section 5.3).

Recombinant ADAMTS13 may have a minor influence on the ability to drive and use machines. Dizziness and somnolence may occur following the administration of ADZYNMA (see section 4.8).

Summary of the safety profile

The most common adverse reactions reported in clinical studies were headache (31.5%), diarrhoea (17.8%), dizziness (16.4%), upper respiratory tract infection (15.1%), nausea (13.7%), and migraine (11%).

Tabulated list of adverse reactions

The adverse drug reactions (ADRs) are listed in Table 1.

Adverse reactions are listed below by MedDRA system organ class and by frequency. Frequencies are defined as follows: 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 System Organ Class (SOC), ADRs are presented in order of decreasing frequency. Within each frequency grouping, ADRs are presented in order of decreasing seriousness.

Table 1. Adverse reactions reported in patients treated with ADZYNMA:

Paediatric population

There is limited information from controlled studies of ADZYNMA in paediatric patients. The safety assessment in paediatric patients is based on the safety data from one phase 3 clinical study comparing ADZYNMA to plasma-based therapies (fresh frozen plasma [FFP], pooled solvent/detergent [S/D] treated plasma, or factor VIII:von Willebrand factor [FVIII-VWF] concentrates, as assigned by the investigator) and one phase 3b study. The studies included 20 and 1 paediatric patients aged 2 to 17 years of age in the prophylactic and on-demand cohorts, respectively. Overall, the safety profile in these paediatric patients was similar to that observed in the adult population.

One neonate aged 36 hours old was treated with ADZYNMA in a compassionate use program and had no reported safety or immunogenicity concerns after 2 years of prophylactic treatment.

Frequency, type and severity of adverse reactions in children are expected to be the same as in adults.

Reporting of suspected adverse reactions

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.