Orserdu Drug Interactions

ORSERDU is primarily metabolised by CYP3A4 and is a substrate of the Organic Anion Transporting Polypeptide 2B1 (OATP2B1). ORSERDU is an inhibitor of P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) efflux transporters.
Effect of other medicinal products on ORSERDU: CYP3A4 Inhibitors: Co-administration of the strong CYP3A4 inhibitor itraconazole (200 mg once daily for 7 days) with ORSERDU (172 mg once daily for 7 days) increased elacestrant plasma exposure (AUC_inf) and the peak concentration (C_max) in healthy subjects 5.3 and 4.4-fold, respectively.
Physiologically based pharmacokinetic (PBPK) simulations in cancer patients suggested that the concomitant administration of multiple daily doses of elacestrant 345 mg and itraconazole 200 mg may increase elacestrant steady-state AUC and C_max 5.5- and 3.9-fold, respectively, which may increase the risk of adverse reactions.
PBPK simulations in cancer patients suggested that concomitant administration of multiple daily doses of elacestrant 345 mg with moderate CYP3A4 inhibitors may increase elacestrant steady-state AUC and C_max by 2.3- and 1.9-folds, respectively, with fluconazole (200 mg once daily), and by 3.9- and 3.0-folds, respectively, with erythromycin (500 mg four times a day), which may increase the risk of adverse reaction.
CYP3A4 Inducers: Co-administration of the strong CYP3A4 inducer rifampicin (600 mg once daily for 7 days) with a single dose of ORSERDU 345 mg decreased elacestrant plasma exposure (AUC_inf) and the peak concentration (C_max) in healthy subjects by 86% and 73%, respectively, which may decrease elacestrant activity.
PBPK simulations in cancer patients suggested that the concomitant administration of multiple daily doses of elacestrant 345 mg and rifampicin 600 mg may decrease elacestrant steady-state AUC and C_max by 84% and 77%, respectively, which may decrease elacestrant activity.
PBPK simulations in cancer patients suggested that the concomitant administration of multiple daily doses of elacestrant 345 mg and the moderate CYP3A4 inducer efavirenz (600 mg) may decrease elacestrant steady-state AUC and C_max by 57% and 52%, respectively, which may decrease elacestrant activity.
OATP2B1 inhibitors: Elacestrant is a substrate of OATP2B1 in vitro. As it cannot be excluded that the coadministration of OATP2B1 inhibitors may increase the exposure of elacestrant, which may increase the risk of adverse reactions, caution is recommended in case of concomitant use of ORSERDU with OATP2B1 inhibitors.
Effect of ORSERDU on other medicinal products: P-gp substrates: Co-administration of ORSERDU (345 mg, single dose) with digoxin (0.5 mg, single dose) increased digoxin exposure by 27% for C_max and 13% for AUC. Digoxin administration should be monitored and its dose reduced as necessary.
Concomitant use of ORSERDU with other P-gp substrates may increase their concentrations, which may increase the adverse reactions associated with the P-gp substrates. The dose of coadministered P-gp substrates should be reduced according to their package insert.
BCRP substrates: Co-administration of ORSERDU (345 mg, single dose) with rosuvastatin (20 mg, single dose) increased rosuvastatin exposure by 45% for C_max and 23% for AUC. Rosuvastatin administration should be monitored and its dose reduced as necessary.
Concomitant use of ORSERDU with other BCRP substrates may increase their concentrations, which may increase the adverse reactions associated with the BCRP substrates. The dose of coadministered BCRP substrates should be reduced according to their package insert.