Berotralstat

ORLADEYO ® is indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adults and pediatric patients 2 years of age and older. ORLADEYO is a plasma kallikrein inhibitor indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adults and pediatric patients 2 years and older. Limitations of Use: ORLADEYO should not be used for treatment of acute HAE attacks. Limitations of Use: The safety and effectiveness of ORLADEYO for the treatment of acute HAE attacks have not been established. ORLADEYO should not be used for treatment of acute HAE attacks. Additional doses or doses of ORLADEYO higher than the prescribed once-daily dose are not recommended due to the potential for QTc interval prolongation.

Berotralstat is a plasma kallikrein inhibitor that binds to plasma kallikrein and inhibits its proteolytic activity. Plasma kallikrein is a protease that cleaves high-molecular-weight kininogen (HMWK) to generate cleaved HMWK (cHMWK) and bradykinin, a potent vasodilator that increases vascular permeability resulting in swelling and pain associated with HAE. In patients with HAE due to C1-inhibitor (C1-INH) deficiency or dysfunction, normal regulation of plasma kallikrein activity is not present, which leads to uncontrolled increases in plasma kallikrein activity and results in angioedema attacks. Berotralstat decreases plasma kallikrein activity to control excess bradykinin generation in patients with HAE.

Recommended dosage in adult and pediatric patients aged 12 years and older: 150 mg orally once daily with food. Recommended dosage in pediatric patients aged 2 to less than 12 years is based on body weight as follows: Weight Recommended Dosage (oral pellets) Administration Instructions 12 kg to less than 24 kg 72 mg once daily Pour directly in mouth and swallow immediately with non-acidic liquid, or, Sprinkle over 1 tablespoon (15 mL) of non-acidic soft food and consume immediately. A meal should be consumed just before or after administration. 24 kg to less than 32 kg 96 mg once daily 32 kg to less than 40 kg 108 mg once daily 40 kg or greater 132 mg once daily See full prescribing information for recommended dosage in patients with hepatic impairment and dosage modification in patients with persistent gastrointestinal adverse reactions.

None. None.

An increase in QTc interval prolongation can occur at dosages higher than the recommended dosage. Additional doses or doses of ORLADEYO higher than the recommended dosage are not recommended.

The following clinically significant adverse reaction is described elsewhere in the labeling: QTc Interval Prolongation. Most common adverse reactions (≥10%) are abdominal pain, vomiting, diarrhea, back pain, and gastroesophageal reflux disease.

P-gp inducers: Avoid use with ORLADEYO. CYP2D6, CYP3A4 or P-gp Substrates: When used concomitantly with ORLADEYO, closely monitor or modify the dosage of the substrates where minimal increases in concentration may lead to serious adverse reactions.

Store at 20°C to 25°C (68°F to 77°F). Excursions permitted between 15°C and 30°C (59°F to 86°F).