DAWNZERA Solution for injection Ref.[116238] Active ingredients: Donidalorsen

Hypersensitivity including anaphylaxis

Hypersensitivity reactions including anaphylaxis have been observed (see section 4.8). In case of a severe hypersensitivity reaction, administration of donidalorsen must be stopped immediately and appropriate treatment must be initiated.

Patients must be advised on the signs and symptoms of hypersensitivity reactions and instructed to promptly seek medical attention and to discontinue use of donidalorsen if serious hypersensitivity reactions occur.

General

Dawnzera is not intended for treatment of acute HAE attacks. In case of a breakthrough HAE attack, individualised treatment should be initiated with an approved rescue medicinal product.

There are limited data available on the use of donidalorsen in HAE patients with HAE-nC1INH (see section 5.1). Patients with HAE nC1-INH having mutations that are not associated with the kallikrein-kinin system (KKS) pathway are not expected to respond to Dawnzera.

It is recommended to perform genetic testing, if available, according to current HAE guidelines and to discontinue the treatment if clinical response is not observed (see sections 4.2 and 5.1).

Sodium

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

No clinical drug-drug interaction studies have been performed with donidalorsen. In vitro studies show that donidalorsen is not a substrate or inhibitor of transporters, does not interact with highly plasma protein bound active substances, and is not a substrate or inhibitor/inducer of cytochrome P450 (CYP) enzymes. Donidalorsen is not expected to cause or be affected by drug-drug interactions mediated through drug transporters, plasma protein binding, or CYP enzymes.

Pregnancy

There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of donidalorsen in pregnant women.

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).

As a precautionary measure, it is preferable to avoid the use of donidalorsen during pregnancy.

Breast-feeding

Available pharmacodynamic/toxicological data in animals have shown excretion of donidalorsen/metabolites in milk (see section 5.3).

A risk to the newborns/infants cannot be excluded.

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from donidalorsen therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility

No clinical data on the effect of this medicinal product on human fertility are available. Donidalorsen had no effect on fertility and early embryonic development toxicity in murine models (see section 5.3).

Dawnzera has no or negligible influence on the ability to drive and use machines.

Summary of the safety profile

The most frequently observed adverse drug reactions (ADRs) in patients treated with 80 mg donidalorsen every 4 weeks were injection site reactions (24.4%).

Tabulated list of adverse reactions

Adverse reactions associated with donidalorsen obtained from clinical trials are tabulated below. All ADRs are listed by system organ class and frequency; 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) and 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 drug reactions to donidalorsen:

^a Injection site reactions include also: erythema, discolouration, pain, pruritus, induration, haematoma, bruising, exfoliation, hypersensitivity and swelling.
^b mainly mild, and mostly in alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

Description of selected adverse reactions

Hypersensitivity including anaphylaxis

In clinical trials, a serious hypersensitivity reaction of anaphylaxis was reported in one patient. Symptoms included generalised rash, dyspnoea, chest pain and peri-oral swelling (see sections 4.3 and 4.4).

Injection site reactions

During double-blinded, placebo-controlled trials, injection site reactions were observed. All injection site reactions were non serious, mild to moderate in severity, and generally resolved over time. In some patients, the injection site reactions such as injection site erythema, injection site pruritus, and injection site discolouration persisted for 2 or more days. In one patient who received higher than labelled doses in accordance with the protocol, injection site discoloration led to permanent discontinuation of treatment.

Paediatric population

The safety of donidalorsen was evaluated in a double-blind placebo-controlled clinical trial in a subset of 7 adolescent patients aged 12 to 17 years. The safety profile in these adolescent patients was similar to the profile observed in adult patients.

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.