Orladeyo

Posology The recommended dose for adults and adolescents aged 12 years and older weighing ≥ 40 kg is 150 mg berotralstat once daily. Missed doses If a dose of berotralstat is missed, the patient should take the forgotten dose as soon as possible without exceeding one dose per day.

4). 2). Renal impairment No dose adjustment is required for patients with mild or moderate renal impairment. In patients with severe renal impairment, it is preferable to avoid the use of berotralstat. g. 4). There are no available clinical data for the use of berotralstat in patients with end stage renal disease (ESRD) requiring haemodialysis.

2). 3 Hepatic impairment No dose adjustment is required for patients with mild hepatic impairment. 2). Paediatric population The safety and efficacy of berotralstat in children under 12 years of age have not yet been established. No data are available.

Method of administration Orladeyo is for oral use. 2).

Summary of the safety profile The most common adverse reactions are abdominal pain (all locations) (reported by 21% of patients), diarrhoea (reported by 15% of patients), and headache (reported by 13% of patients). The gastrointestinal events were reported primarily in the first 1-3 months of Orladeyo use (median day of onset was day 66 for abdominal pain and day 45 for diarrhoea) and resolved without medicinal product while Orladeyo treatment was continued.

5 days (95% CI 2-8 days). 2 days (95% CI 2-8 days). Tabulated list of adverse reactions The safety of Orladeyo has been evaluated in long term clinical studies in patients with HAE (both uncontrolled, open-label and placebo-controlled, blinded) in 381 patients.

Adverse reactions obtained from clinical studies and post-marketing surveillance are listed below by MedDRA system organ class and by frequency. Frequencies are defined as follows: 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).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 6 Table 1: Adverse reactions observed in clinical studies and post-marketing surveillance System organ class Frequency Adverse reactions Nervous system disorders Very common Headachea Gastrointestinal disorders Very common Abdominal painb, Diarrhoeac Common Vomiting, Gastroesophageal reflux, Flatulence Not known Nausea Skin and subcutaneous tissue disorders Common Rash Investigationsd Common ALT increased, AST increased a Includes the events of Headache, Sinus headache b Includes the events of Abdominal pain, Abdominal discomfort, Abdominal pain upper, Abdominal pain lower, Epigastric discomfort, Abdominal tenderness c Includes the events of Diarrhoea, Faeces soft, Frequent bowel movements d LFT elevations, which generally improved with or without discontinuation of berotralstat, were observed in some patients, primarily in those who discontinued androgen therapy within 14 days of initiating Orladeyo treatment.

General Orladeyo is not intended for treatment of acute HAE attacks, individualised treatment should be initiated with an approved rescue medicinal product. There are no available clinical data on the use of berotralstat in HAE patients with normal C1 esterase inhibitor (C1-INH) activity.

There are no available data on the use of berotralstat in patients weighing less than 40 kg and use of berotralstat in these patients should be avoided. 1). Patients with moderate or severe hepatic impairment may develop increased serum berotralstat concentrations that are associated with a risk of prolonged QT.

Use of berotralstat in these patients should be avoided. Patients with severe renal impairment may be at risk of prolonged QT. It is preferable to avoid the use of berotralstat in these patients. g. ECGs) should be considered. 2), or concomitant use of other medicinal products known to prolong the QT.

It is preferable to avoid the use of berotralstat in these patients. g. ECGs) should be considered.

1.