sebetralstat 300 MG Oral Tablet [Ekterly]

INDICATIONS AND USAGE EKTERLY® is indicated for the treatment of acute attacks of hereditary angioedema (HAE) in adult and pediatric patients aged 12 years and older. EKTERLY ® is a plasma kallikrein inhibitor indicated for the treatment of acute attacks of hereditary angioedema (HAE) in adult and pediatric patients aged 12 years and older. ( 1 )

DOSAGE AND ADMINISTRATION Recommended Dosage : one dose of 600 mg (2 tablets) taken orally at the earliest recognition of an HAE attack. ( 2.1 ) A second dose of 600 mg (2 tablets) may be taken 3 hours after the first dose if response is inadequate, or if symptoms worsen or recur. ( 2.1 ) Maximum Recommended Dosage: 1,200 mg in any 24-hour period. ( 2.1 ) See full prescribing information for dosage modification for concomitant use with CYP3A4 inhibitors and inducers. ( 2.2 ) See full prescribing information for recommended dosage for patients with hepatic impairment. ( 2.3 ) 2.1 Recommended Dosage The recommended dosage of EKTERLY is one dose of 600 mg (two tablets) orally at the earliest recognition of an acute HAE attack. A second dose of 600 mg (two tablets) may be taken at least 3 hours after the first dose if response is inadequate, or if symptoms worsen or recur. Maximum recommended dosage is 1,200 mg (four tablets) in any 24-hour period. 2.2 Dosage Modification for CYP3A4 Inhibitors and Inducers Refer to Table 1 for dosage modification of EKTERLY when used concomitantly with CYP3A4 inhibitors and inducers. Table 1: Dosage Modification of EKTERLY for Concomitant use with CYP3A4 Inhibitors and Inducers Dosage Modification for Concomitant use of EKTERLY with CYP3A4 Inhibitors Strong CYP3A4 Inhibitors Avoid concomitant use with EKTERLY. Moderate CYP3A4 Inhibitors Reduce EKTERLY dosage to 300 mg (one tablet) orally at earliest recognition of an acute HAE attack. A second dose of 300 mg (one tablet) may be taken at least 3 hours after first dose if response is inadequate or if symptoms worsen or recur [ see Drug Interactions ( 7.1 ) and Clinical Pharmacology ( 12.3 ) ] . Weak CYP3A4 Inhibitors No dosage modification of EKTERLY [ see Dosage and Administration ( 2.1 ) ] . Dosage Modification for Concomitant use of EKTERLY with CYP3A4 Inducers Strong and Moderate CYP3A4 Inducers Avoid concomitant use with EKTERLY. Weak CYP3A4 Inducers No dosage modification of EKTERLY [ see Dosage and Administration ( 2.1 ) ] . 2.3 Recommended Dosage in Patients with Hepatic Impairment Refer to Table 2 for recommended dosage of EKTERLY in patients with hepatic impairment. Table 2: Recommended Dosage of EKTERLY in Patients with Hepatic Impairment Recommended Dosage of EKTERLY in Patients with Hepatic Impairment Severe Hepatic Impairment (Child-Pugh Class C) Avoid use of EKTERLY [ see Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.3 ) ] . Moderate Hepatic Impairment (Child-Pugh Class B) Recommended dosage of EKTERLY is one dose of 300 mg (one tablet) orally at the earliest recognition of an acute HAE attack. A second dose of 300 mg (one tablet) may be taken at least 3 hours after the first dose if response is inadequate, or if symptoms worsen or recur [ see Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.3 ) ] . Mild Hepatic Impairment (Child-Pugh Class A) Recommended dosage is the same as the recommended dosage in patients with normal hepatic function [ see Dosage and Administration ( 2.1 ) ] . 2.1 Recommended Dosage The recommended dosage of EKTERLY is one dose of 600 mg (two tablets) orally at the earliest recognition of an acute HAE attack. A second dose of 600 mg (two tablets) may be taken at least 3 hours after the first dose if response is inadequate, or if symptoms worsen or recur. Maximum recommended dosage is 1,200 mg (four tablets) in any 24-hour period. 2.2 Dosage Modification for CYP3A4 Inhibitors and Inducers Refer to Table 1 for dosage modification of EKTERLY when used concomitantly with CYP3A4 inhibitors and inducers. Table 1: Dosage Modification of EKTERLY for Concomitant use with CYP3A4 Inhibitors and Inducers Dosage Modification for Concomitant use of EKTERLY with CYP3A4 Inhibitors Strong CYP3A4 Inhibitors Avoid concomitant use with EKTERLY. Moderate CYP3A4 Inhibitors Reduce EKTERLY dosage to 300 mg (one tablet) orally at earliest recognition of an acute HAE attack. A second dose of 300 mg (one tablet) may be taken at least 3 hours after first dose if response is inadequate or if symptoms worsen or recur [ see Drug Interactions ( 7.1 ) and Clinical Pharmacology ( 12.3 ) ] . Weak CYP3A4 Inhibitors No dosage modification of EKTERLY [ see Dosage and Administration ( 2.1 ) ] . Dosage Modification for Concomitant use of EKTERLY with CYP3A4 Inducers Strong and Moderate CYP3A4 Inducers Avoid concomitant use with EKTERLY. Weak CYP3A4 Inducers No dosage modification of EKTERLY [ see Dosage and Administration ( 2.1 ) ] . 2.3 Recommended Dosage in Patients with Hepatic Impairment Refer to Table 2 for recommended dosage of EKTERLY in patients with hepatic impairment. Table 2: Recommended Dosage of EKTERLY in Patients with Hepatic Impairment Recommended Dosage of EKTERLY in Patients with Hepatic Impairment Severe Hepatic Impairment (Child-Pugh Class C) Avoid use of EKTERLY [ see Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.3 ) ] . Moderate Hepatic Impairment (Child-Pugh Class B) Recommended dosage of EKTERLY is one dose of 300 mg (one tablet) orally at the earliest recognition of an acute HAE attack. A second dose of 300 mg (one tablet) may be taken at least 3 hours after the first dose if response is inadequate, or if symptoms worsen or recur [ see Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.3 ) ] . Mild Hepatic Impairment (Child-Pugh Class A) Recommended dosage is the same as the recommended dosage in patients with normal hepatic function [ see Dosage and Administration ( 2.1 ) ] .

CONTRAINDICATIONS None. None ( 4 )

Mechanism of Action Sebetralstat is a competitive, reversible inhibitor of plasma kallikrein. Plasma kallikrein is a serine protease that cleaves high molecular weight kininogen (HK) releasing bradykinin which increases vascular permeability through activation of bradykinin receptors causing edema. Sebetralstat inhibits the cleavage of HK and reduces production of bradykinin, thereby treating the clinical symptoms of an acute, episodic attack of HAE. Sebetralstat also inhibits the positive feedback mechanism of the kallikrein kinin system by plasma kallikrein, thereby reducing factor XIIa and additional plasma kallikrein generation.