DAWNZERA

Treatment is to be initiated under the supervision of a physician experienced in the diagnosis and management of patients with HAE. Posology The recommended starting dose in adult and adolescent patients aged 12 years and older is 80 mg donidalorsen by subcutaneous injection once monthly.

, attack free) for at least 3 months while receiving Dawnzera. Based on the clinical data, a gradual reduction in attack rate is seen as early as Week 1 after the initial dose of donidalorsen with an expected maximum effect after 1 month.

1). 4). Missed dose If a dose is missed, the patient or caregiver should be instructed to administer the dose as soon as possible. Thereafter, dosing should be resumed at the prescribed dosing frequency (once monthly or once every 2 months) from the date of the most recently administered dose.

2). 2). Dawnzera has not been studied in patients with moderate or severe impairment. Donidalorsen should only be used in these patients if the anticipated clinical benefit outweighs the risk. Renal impairment No dose adjustment of donidalorsen is required for patients with mild renal impairment.

Dawnzera has not been studied in patients with moderate or severe impairment or end stage renal disease. Donidalorsen should only be used in these patients if the anticipated clinical benefit outweighs the risk. Paediatric population The safety and efficacy of donidalorsen in children aged < 12 years have not yet been established.

No data are available. 1. 1).

Table 1:

Treatment schedule for patients changing from other prophylactic therapy to Dawnzera. Other prophylactic therapy Recommended treatment schedule when changing to Dawnzera Berotralstat Continue taking the current dose of berotralstat for 14 days after initiating treatment with Dawnzera.

C1 esterase inhibitor Continue taking the current dose of C1 esterase inhibitor for 14 days after initiating treatment with Dawnzera. Lanadelumab Administer last dose of lanadelumab 14 days prior to initiating treatment with Dawnzera.

Method of administration Dawnzera is intended for subcutaneous use only. Dawnzera is to be administered as a subcutaneous injection in the abdomen, upper thigh region, or for caregivers only, the back of the upper arm. Rotation of the injection site is recommended.

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 System organ class Adverse drug reaction Frequency Immune system disorders Hypersensitivity (including anaphylaxis) Common General disorders and administration site conditions Injection site reactions a Very common Investigations Hepatic enzyme increased b Very common 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.

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.

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. 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.

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

1.