berotralstat dihydrochloride: clinical use

Prescribing considerations

• Not intended for acute HAE treatment; ensure an individualised rescue plan remains available.
• Clinical data are unavailable in HAE with normal C1-inhibitor activity.
• Avoid use below 40 kg because clinical data are unavailable.
• Gastrointestinal adverse effects occur particularly early in treatment and may resolve while treatment continues.

Contraindications and cautions

• Hypersensitivity to berotralstat or any listed excipient.
• Avoid in moderate or severe hepatic impairment.
• Preferably avoid in severe renal impairment and end-stage renal disease requiring haemodialysis.
• Preferably avoid where significant independent QT-prolongation risks or problematic interacting medicines are present.

Monitoring

• Assess breakthrough attack frequency, rescue-treatment use and tolerability.
• Consider liver-function testing where clinically indicated, especially during transitions from androgen therapy or if hepatic symptoms occur.
• Consider ECG monitoring if treatment is necessary despite severe renal impairment, QT-risk factors or relevant interacting medicines.
• Review the complete medication list for CYP3A4, CYP2D6 and P-gp substrates and P-gp/BCRP inducers.

Clinical pharmacology

Berotralstat is an oral plasma kallikrein inhibitor. It is highly protein bound, metabolised mainly through CYP2D6 and CYP3A4, and has a prolonged elimination half-life. It moderately inhibits CYP3A4 and CYP2D6 and weakly inhibits CYP2C9 and P-gp.

Formulation and product differences

• The product is a hard gelatin capsule supplied in blister packaging.
• The capsule contains gelatin, titanium dioxide, indigo carmine, iron oxides and printing-ink excipients.
• No alternative formulation is represented by the product document.

Capsule

Route: Oral

Strengths: 150 mg