Sebetralstat

Brand Names: Ekterly

Drug Class: Plasma Kallikrein Inhibitor

Overview

11 DESCRIPTION The active ingredient of EKTERLY is sebetralstat, a plasma kallikrein inhibitor. The chemical name of sebetralstat is N-[(3-fluoro-4-methoxypyridin-2-yl) methyl]-3-(methoxymethyl)-1-({4-[(2-oxo-1,2-dihydropyridin-1-yl) methyl]phenyl}methyl)-1H-pyrazole-4-carboxamide. The chemical structure of sebetralstat is: The molecular formula is C 26 H 26 FN 5 O 4 and molecular weight is 491.5.

Mechanism of Action

12 CLINICAL PHARMACOLOGY 12.1 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. 12.

Indications

  • 1 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 )

Common Doses

  • 600 mg
  • 200 mg
  • 300 mg

Dosage

2 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.

Contraindications

  • 4 CONTRAINDICATIONS None. None ( 4 )

Side Effects

  • 6 ADVERSE REACTIONS The most common adverse reaction (incidence ≥2%) is headache. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact KalVista Pharmaceuticals, Inc. at 1-855-258-4782 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Interactions

  • 7 DRUG INTERACTIONS Strong and Moderate CYP3A4 Inhibitors : Avoid use with strong CYP3A4 inhibitors. In patients taking moderate CYP3A4 inhibitors, take one dose of 300 mg. A second dose of 300 mg may be taken at least 3 hours after the first dose if response is inadequate, or if symptoms worsen or recur. ( 2.2 , 7.1 , 12.3 ) CYP3A4 Inducers : Avoid use with moderate or strong CYP3A4 inducers. ( 2.2 , 7.1 , 12.3 ) 7.1 Effect of Other Drugs on EKTERLY Strong CYP3A4 Inhibitors Avoid use of EKTERLY with strong CYP3A4 inhibitors [see Clinical Pharmacology ( 12.3 )] .