Ekterly

The decision to initiate treatment with oral sebetralstat should be made by a healthcare professional experienced in the management of patients with HAE. Posology Adults and adolescents aged 12 years and older The recommended dose is one 300 mg tablet of Ekterly administered at the earliest recognition of an attack.

A second dose may be taken 3 hours after the first dose if response is inadequate, or if symptoms worsen or recur. No more than two doses should be administered in a 24 hour period. 1). 2). 2). Hepatic impairment No dose adjustment is required for patients with mild or moderate hepatic impairment (Child-Pugh A or B).

2). 5). Patients taking CYP3A4 inducers No dose adjustment is required when taking weak CYP3A4 inducers. 5). Paediatric population Safety and efficacy in children less than 12 years have not been established. No data are available. Method of administration Ekterly is intended for oral use.

2).

Summary of the safety profile Ekterly has been administered to a total of 411 healthy subjects and 239 hereditary angioedema patients. In clinical trials used for registration, 1945 HAE attacks have been treated with Ekterly. 2% of patients).

The reported events of headache were generally mild to moderate in severity, non- serious and resolved without any further intervention. Tabulated list of adverse reactions The frequency of all adverse reactions listed in the table below 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).

6 Table 1. Summary of adverse reactions by system organ class and frequency System Organ Class Adverse Reaction Frequency Nervous system disorder Headache Common Dizziness Common Gastrointestinal disorders Vomiting Common Nausea Common Abdominal pain* Common Diarrhoea Common Musculoskeletal and connective tissue disorders Back pain Common Vascular disorders Hot Flush Common * Includes events of abdominal pain and abdominal pain upper.

Paediatric population In 32 adolescent patients aged 12 to < 18 years old, a total of 390 HAE attacks have been treated with sebetralstat. 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 national reporting system listed in Appendix V.

Laryngeal attacks Following treatment of laryngeal attacks, patients should seek immediate medical attention. If laryngeal attack symptoms worsen after treatment, patients should be managed in an appropriate medical institution. Normal C1 esterase inhibitor (nC1-INH) There are no data available on the use of Ekterly in HAE patients with nC1-INH.

Some subcategories of nC1-INH HAE may not respond to treatment due to alternative pathways that do not include plasma kallikrein activation. 1). QT prolongation In a clinical trial dedicated to the assessment of cardiac parameters in healthy subjects, a potential of sebetralstat to extend the QT interval was detected but only at high concentrations that are not expected to be reached with the recommended dose.

There are no data available for the use of sebetralstat in patients with independent risk factors for QT prolongation such as known pre-existing QT prolongation (either acquired or congenital), electrolyte disturbances, hepatic impairment, concomitant use of drugs interacting with the metabolism of sebetralstat or concomitant use of other medicinal products known to prolong the QT interval.

1). 4 Excipients This medicinal product contains less than 1 mmol sodium (23 mg) per dose that is to say essentially “sodium free”.

1.