Danicopan

7 DRUG INTERACTIONS BCRP substrates: Monitor patients more frequently for adverse reactions and consider dose reduction of the BCRP substrate drug. For rosuvastatin, the dose should not exceed 10 mg once daily ( 7.1 ). P-gp substrates: Dose adjustment might be necessary for P-gp substrates where minimal concentration changes may lead to serious adverse reactions ( 7.2 ).

7.1 BCRP Substrates Danicopan is a Breast Cancer Resistance Protein (BCRP) inhibitor. Concomitant use of VOYDEYA with a BCRP substrate increases the plasma concentrations of the BCRP substrate [see Clinical Pharmacology (12.3) ] , which may increase the risk for adverse reactions associated with the BCRP substrate. If used together, monitor patients more frequently for adverse reactions associated with the BCRP substrate, and consider dose reduction of the BCRP substrate according to its prescribing information. Rosuvastatin Danicopan significantly increased rosuvastatin exposure.

The dose of rosuvastatin should not exceed 10 mg once daily when concomitantly used with VOYDEYA [see Clinical Pharmacology (12.3) ] .

7.2 P-gp Substrates Danicopan is an inhibitor of P-glycoprotein (P-gp). Concomitant administration of VOYDEYA with a P-gp substrate may increase the plasma concentration of the P-gp substrate. Dose adjustment might be necessary for P-gp substrates where minimal concentration changes may lead to serious adverse reactions [see Clinical Pharmacology (12.3) ] .

8.1 Pregnancy Risk Summary There are no available data on VOYDEYA use in pregnant individuals to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with untreated PNH in pregnancy (see Clinical Considerations ) . The use of VOYDEYA in pregnant women or women planning to become pregnant may be considered following an assessment of the risks and benefits.

In animal reproduction studies, oral administration of danicopan to pregnant New Zealand White (NZW) rabbits and Wistar Hans (WH) rats during organogenesis at exposures 18 or 25-times, respectively, above the human exposure at the maximum recommended human dose (MRHD) of 200 mg three times a day (based on AUC) resulted in no adverse developmental effects (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 miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Fetal/Neonatal Risk PNH in pregnancy is associated with adverse maternal outcomes, including worsening cytopenias, thrombotic events, infections, bleeding, miscarriages, and increased maternal mortality, and adverse fetal outcomes, including fetal death and premature delivery.

Data Animal Data There were no effects on early embryonic development and fetal development in NZW rabbits (where danicopan is pharmacodynamically active) up to a mean maternal systemic exposure 18-times the exposure at the MRHD (based on AUC) or during post-natal development up to a mean maternal systemic exposure 9-times the exposure at the MRHD (based on AUC). In WH rats (where danicopan lacks pharmacodynamic activity), there were no effects on embryo-fetal development up to a mean maternal exposure 25-times the exposure at the MRHD (based on AUC).