Nerandomilast

Strong CYP3A Inhibitors : Reduce JASCAYD dosage to 9 mg twice daily. ( 2.2 , 7.1 ) Strong CYP3A Inducers : Avoid concomitant use with JASCAYD. ( 7.1 ) Moderate CYP3A Inducers : Recommended dosage is 18 mg twice daily. Do not reduce dosage to 9 mg twice daily. ( 2.1 , 7.1 )

7.1 Effects of Other Drugs on JASCAYD Strong CYP3A Inhibitors Reduce the dosage of JASCAYD to 9 mg twice daily when used concomitantly with strong CYP3A inhibitors [see Dosage and Administration (2.2) ] . Nerandomilast is a CYP3A substrate. Concomitant use of JASCAYD with a strong CYP3A inhibitor increases exposure of nerandomilast, which may increase the risk of JASCAYD adverse reactions [see Clinical Pharmacology (12.3) ]. Strong or Moderate CYP3A Inducers Avoid concomitant use of strong CYP3A inducers with JASCAYD. Recommended dosage of JASCAYD is 18 mg twice daily when used concomitantly with moderate CYP3A inducers.

Do not reduce the dosage to 9 mg twice daily [see Dosage and Administration (2.1) ]. Nerandomilast is a CYP3A substrate. Concomitant use of JASCAYD with strong or moderate CYP3A inducers decreases exposure of nerandomilast, which may decrease the efficacy of JASCAYD [see Clinical Pharmacology (12.3) ] . Pirfenidone Recommended dosage of JASCAYD is 18 mg twice daily when used concomitantly with pirfenidone. Do not reduce the dosage to 9 mg twice daily [see Dosage and Administration (2.1) ] . Concomitant use of JASCAYD with pirfenidone decreases exposure of nerandomilast [see Clinical Pharmacology (12.3) ] .

When JASCAYD was used concomitantly with pirfenidone in patients with IPF in FIBRONEER-IPF, efficacy was not observed with the JASCAYD 9 mg twice daily dosage [see Clinical Studies (14.1) ] .

8.1 Pregnancy Risk Summary There are no available data on JASCAYD use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. There are maternal and fetal risks associated with untreated idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) during pregnancy (Clinical Considerations). Based on findings from animal reproduction studies, JASCAYD may increase the risk for fetal loss.

In an embryo-fetal development study in rats, oral administration of nerandomilast to pregnant rats during organogenesis at an exposure approximately 5 times the maximum recommended human dose (MRHD) of 36 mg/day resulted in an increase in embryo-fetal losses (see Data ) . Advise pregnant women and females of reproductive potential of the potential risk of fetal loss. 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 is 2% to 4% and miscarriage in clinically recognized pregnancies is 15% to 20%. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Untreated IPF or PPF can lead to respiratory failure and mortality in the mother and intrauterine growth restriction, preterm birth, fetal hypoxia, and neonatal death.

Data Animal Data In an embryo-fetal development study in pregnant rats dosed by the oral route during the period of organogenesis from gestation days 6 to 17, nerandomilast caused an increase in embryo-fetal losses (pre- and post-implantation loss and decreased mean number of live fetuses) at an exposure that was approximately 5 times the MRHD (on an AUC basis with a maternal oral dose of 6 mg/kg/day). Maternal toxicity, as evidenced by decreased body weight gains and adverse clinical signs, was observed at exposures approximately 7 times the MRHD (on an AUC basis with a maternal oral dose of 9 mg/kg/day).

No fetal or maternal toxicities were observed at exposures up to 3 and 5 times the MRHD (on an AUC basis with maternal oral doses of 3 mg/kg/day and 6 mg/kg/day), respectively. In an embryo-fetal development study in pregnant rabbits dosed by the oral route during the period of organogenesis from gestation days 7 to 19, no effects on maternal or fetal development were observed at an exposure that was approximately 4 times the MRHD (on an AUC basis with a maternal oral dose of 15 mg/kg/day). In a prenatal and…