Takhzyro

This medicinal product should be initiated under the supervision of a physician experienced in the management of patients with hereditary angioedema (HAE). Posology Adults and Adolescents 12 to less than 18 years of age The recommended starting dose is 300 mg lanadelumab every 2 weeks.

In patients who are stably attack free on treatment, a dose reduction to 300 mg lanadelumab every 4 weeks may be considered, especially in patients with low weight. In patients with a body weight less than 40 kg, a starting dose of 150 mg lanadelumab every 2 weeks may also be considered.

In patients who are stably attack free on treatment, a dose reduction to 150 mg lanadelumab every 4 weeks may be considered. 3 Children 2 to less than 12 years of age The recommended dose of lanadelumab for children 2 to less than 12 years of age is based on body weight (see table below) and should only be administered via a pre-filled syringe or vial.

The pre-filled pen has not been studied in children 2 to less than 12 years of age and therefore should not be used. Patients with a body weight of 20 to less than 40 kg who are stably attack free may continue with the same dose when reaching 12 years of age.

Table 1. 1). 4). Missed doses If a dose of TAKHZYRO is missed, the patient or caregiver should be instructed to administer the dose as soon as possible. The subsequent dosing schedule may need adjustment according to the intended dosing frequency to ensure:  at least 10 days between doses for patients on every 2 weeks dosing regimen,  at least 17 days between doses for patients on every 3 weeks dosing regimen,  at least 24 days between doses for patients on every 4 weeks dosing regimen.

Special populations Elderly Age is not expected to affect exposure to lanadelumab. 2). Hepatic impairment No studies have been conducted in patients with hepatic impairment. Hepatic impairment is not expected to affect exposure to lanadelumab.

2). 4 Renal impairment No studies have been conducted in patients with severe renal impairment. Renal impairment is not expected to affect exposure to lanadelumab or the safety profile. 2). Paediatric population The safety and efficacy of TAKHZYRO in children aged less than 2 years have not been established.

No data are available. Method of administration TAKHZYRO is intended for subcutaneous (SC) administration only. 6). 2). Rotation of the injection site is recommended. For adults and adolescents (12 to less than 18 years of age), TAKHZYRO may be self-administered or administered by a caregiver only after training on subcutaneous injection technique by a healthcare professional.

4%) observed adverse reaction associated with TAKHZYRO was injection site reactions (ISR) including injection site pain, injection site erythema and injection site bruising. Of 6 these ISRs, 97% were of mild intensity, 90% resolved within 1 day after onset with a median duration of 6 minutes.

4. Tabulated list of adverse reactions Table 2 summarises adverse reactions observed in the HELP study that included 84 subjects with HAE, who received at least one dose of TAKHZYRO. The frequency of adverse reactions listed in Table 2 is defined using 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).

Table 2. Adverse reactions reported with lanadelumab System organ class Adverse drug reaction Frequency Immune system disorders Hypersensitivity* Common Nervous system disorders Dizziness Common Skin and subcutaneous tissue disorders Rash maculo-papular Common Musculoskeletal and connective tissue disorders Myalgia Common General disorders and administration site conditions Injection site reactions** Very common Investigations Alanine aminotransferase increased Common Aspartate aminotransferase increased Common *Hypersensitivity includes: pruritus, discomfort and tingling of tongue.

**Injection site reactions include: pain, erythema, bruising, discomfort, haematoma, haemorrhage, pruritus, swelling, induration, paraesthesia, reaction, warmth, oedema and rash. Safety data available from the HELP study extension are consistent with the safety data from the HELP study (described in Table 2).

Paediatric population The safety of TAKHZYRO 300 mg/2 ml was evaluated in a subgroup of 23 subjects 12 to less than 18 years of age in the HELP and HELP study extension. 1). 5 years was receiving lanadelumab in the study. No new adverse reactions were identified.

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 Hypersensitivity reactions have been observed.

In case of a severe hypersensitivity reaction, administration of TAKHZYRO must be stopped immediately and appropriate treatment must be initiated. General TAKHZYRO is not intended for treatment of acute HAE attacks. In case of a breakthrough HAE attack, individualized treatment should be initiated with an approved rescue medication.

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 TAKHZYRO. 1). Interference with coagulation test Lanadelumab can increase activated partial thromboplastin time (aPTT) due to an interaction of lanadelumab with the aPTT assay.

The reagents used in the aPTT laboratory test initiate intrinsic coagulation through the activation of plasma kallikrein in the contact system. Inhibition of plasma kallikrein by lanadelumab can increase aPTT in this assay. None of the increases in aPTT in patients treated with TAKHZYRO were associated with abnormal bleeding adverse events.

There were no differences in international normalised ratio (INR) between treatment groups. Sodium content This medicinal product contains less than 1 mmol sodium (23 mg) per pre-filled syringe, pre-filled pen, or vial, that is to say essentially ‘sodium-free’.

1.