ANDEMBRY

This medicinal product should be initiated under the supervision of a physician experienced in the management of patients with HAE. Posology The recommended dose in adults and adolescents aged 12 years and older is an initial loading dose of 400 mg ANDEMBRY administered subcutaneously as two 200 mg injections on the first day of treatment followed by a monthly dose of 200 mg garadacimab.

4) Missed doses If a dose of ANDEMBRY is missed, the patient should be instructed to administer the dose as soon as possible. 2). 2). 2). Paediatric population The safety and efficacy of garadacimab in children less than 12 years have not been established.

No data are available. Method of administration ANDEMBRY is intended for subcutaneous administration only. 6). 2). Rotation of the injection site is recommended. ANDEMBRY may be self-administered or administered by a caregiver only after training on subcutaneous injection technique by a healthcare professional.

1%) observed adverse reactions were injection site reactions (ISR) including injection site erythema, injection site bruising, and injection site pruritus. Tabulated list of adverse reactions Adverse reactions reported in the clinical trial are listed below in Table 1.

The adverse reactions are listed by MedDRA System Organ Class and categories of frequency. Frequencies are defined as: 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).

Table 1:

Adverse reactions System organ class Adverse drug reaction Frequency General disorders and administration site conditions Injection site reaction* Common Nervous system disorders Headache Common Gastrointestinal disorders Abdominal pain Common *Injection site reactions include erythema, bruising, pruritus and injection site urticaria Paediatric population The safety of ANDEMBRY was evaluated in a subgroup of 11 adolescent patients aged 12 to < 18 years old.

The safety profile was similar to that observed 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 UK Yellow Card Scheme. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

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 Hypersensivity reactions have not been observed but may theoretically occur.

In case of a severe hypersensitivity reaction, discontinue ANDEMBRY administration and institute appropriate treatment. General ANDEMBRY is not intended for treatment of acute HAE attacks. In case of breakthrough HAE attack, individualized treatment should be initiated with an approved rescue medicinal product.

1). Some subcategories of nC1-INH HAE may not respond to the treatment with garadacimab due to the alternative pathways involved that do not include FXII- dependent bradykinin production. 1). Interference with coagulation test ANDEMBRY can prolong activated partial thromboplastin time (aPTT) due to an interaction of garadacimab with the aPTT assay.

The extent of aPTT prolongation could be variable depending on drug exposure as well as additional parameters, such as natural variation in FXII levels, and other coagulation factors. The reagents used in the aPTT laboratory test initiate intrinsic coagulation through the activation of FXII in the contact system, therefore inhibition of plasma FXIIa by ANDEMBRY can prolong aPTT in this assay.

None of the increases in aPTT in patients treated with ANDEMBRY were associated with abnormal bleeding adverse events. There were no relevant differences in international normalized ratio (INR) between treatment groups. Garadacimab has not been studied in patients with clinically significant bleeding due to coagulopathy.

There is very limited clinical data on the use of concomitant antiplatelet/anticoagulant medication with garadacimab. Garadacimab inhibits the activity of activated FXII. FXII activation initiates the intrinsic pathway of the coagulation cascade.

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