Sebetralstat

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 )] . Sebetralstat is a substrate of CYP3A4. Concomitant use of sebetralstat with a strong CYP3A4 inhibitor increases sebetralstat exposure, which may increase the risk of sebetralstat adverse reactions. Moderate and Weak CYP3A4 Inhibitors Reduce dose of EKTERLY to one dose of 300 mg (one tablet) orally at the earliest recognition of an HAE attack when used concomitantly with moderate CYP3A4 inhibitors.

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 Dosage and Administration ( 2.2 ) and Clinical Pharmacology ( 12.3 )] . Sebetralstat is a substrate of CYP3A4. Concomitant use of sebetralstat with a moderate CYP3A4 inhibitor increases sebetralstat exposure, which may increase the risk of sebetralstat adverse reactions. No dose modification is recommended when EKTERLY is used concomitantly with a weak CYP3A4 inhibitor [see Dosage and Administration ( 2.1 ) and Clinical Pharmacology ( 12.3 )] .

Strong and Moderate CYP3A4 Inducers Use of EKTERLY with strong or moderate CYP3A4 inducers is not recommended. Sebetralstat is a substrate of CYP3A4. Concomitant use of sebetralstat with a strong or moderate CYP3A4 inducer decreases sebetralstat exposure, which may decrease efficacy. Weak CYP3A4 Inducers No dose modification is recommended when EKTERLY is used concomitantly with weak CYP3A4 inducers [see Clinical Pharmacology ( 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 )] . Sebetralstat is a substrate of CYP3A4. Concomitant use of sebetralstat with a strong CYP3A4 inhibitor increases sebetralstat exposure, which may increase the risk of sebetralstat adverse reactions. Moderate and Weak CYP3A4 Inhibitors Reduce dose of EKTERLY to one dose of 300 mg (one tablet) orally at the earliest recognition of an HAE attack when used concomitantly with moderate CYP3A4 inhibitors.

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 Dosage and Administration ( 2.2 ) and Clinical Pharmacology ( 12.3 )] . Sebetralstat is a substrate of CYP3A4. Concomitant use of sebetralstat with a moderate CYP3A4 inhibitor increases sebetralstat exposure, which may increase the risk of sebetralstat adverse reactions. No dose modification is recommended when EKTERLY is used concomitantly with a weak CYP3A4 inhibitor [see Dosage and Administration ( 2.1 ) and Clinical Pharmacology ( 12.3 )] .

Strong and Moderate CYP3A4 Inducers Use of EKTERLY with strong or moderate CYP3A4 inducers is not recommended. Sebetralstat is a substrate of CYP3A4. Concomitant use of sebetralstat with a strong or moderate CYP3A4 inducer decreases sebetralstat exposure, which may decrease efficacy. Weak CYP3A4 Inducers No dose modification is recommended when EKTERLY is used concomitantly with weak CYP3A4 inducers [see Clinical Pharmacology ( 12.3 )] .

8.1 Pregnancy Risk Summary There are no available data on EKTERLY in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. In animal reproduction studies, oral administration of sebetralstat to pregnant rats and rabbits during organogenesis produced no evidence of fetal harm with dose exposures up to approximately 15 and 11 times, respectively, the human exposure at the maximum recommended human dose (MRHD) of up to 1,200 mg (on an area under the curve [AUC] basis). Sebetralstat produced an increase in embryofetal losses and fetal malformations in rats at an exposure that was 60 times the MRHD (see Data) .

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data Animal Data In an embryofetal development study with pregnant rats dosed by the oral route during the period of organogenesis from gestation days 6 to 17, sebetralstat caused a dose-related increase in the incidence of external and visceral malformations, described as cleft palates and ventricular septal defects and an increase in embryofetal losses (early and late fetal deaths, mean number of live fetuses, and post-implantation loss at an exposure that was 60 times the MRHD (on an AUC basis with a maternal dose of 600 mg/kg/day)).

Maternal toxicity, as evidenced by decreased body weight gains, was observed at exposures 60 times the MRHD (on an AUC basis with a maternal oral dose of 600 mg/kg/day). No fetal or maternal toxicities were observed at exposures up to 15 times the MRHD (on an AUC basis with a maternal oral dose of 300 mg/kg/day). In an embryofetal development study with pregnant rabbits dosed by the oral route during the period of organogenesis from gestation days 6 to 18, maternal toxicity was evidenced by a decrease in body weight gain at an exposure that was 11 times the MRHD (on an AUC basis with a maternal dose of 300 mg/kg/day).

No adverse effects on maternal toxicity were observed at an exposure that was 2 times the MRHD (on an AUC basis with a maternal dose of 100 mg/kg/day). No adverse effects on fetal toxicity were observed at an exposure that was 11 times the MRHD (on an AUC basis with a maternal oral dose of 300 mg/kg/day). In a prenatal and postnatal development study…