Name: Atebrioz (zilurgisertib) in Fibrodysplasia ossificans progressiva: Effects of other drugs on zilurgisertib
Published: 2026-09-27T12:28:00-04:00

Strong CYP3A4 inhibitors

“Reduce the ATEBRIOZ dosage to 50 mg once daily when used concomitantly with a strong CYP3A4 inhibitor” (opens the prescribing information at this quote)
“ATEBRIOZ is a CYP3A4 substrate. Strong CYP3A4 inhibitors increase zilurgisertib exposure” (opens the prescribing information at this quote)
“Coadministration of itraconazole (a strong CYP3A4 inhibitor) increased the geometric mean Cmax and AUC of zilurgisertib 1.28-fold and 2.13-fold, respectively” (opens the prescribing information at this quote)

“Participants in Cohort 1 (n = 18) received zilurgisertib 100 mg on Days 1 and 10 and itraconazole 200 mg once daily on Days 6-13.” (opens the source at this quote in a new tab)
“With the concomitant administration of itraconazole, the geometric mean maximum plasma drug concentration (Cmax) and area under the concentration-time curve from time 0 to infinity (AUC0-inf) of zilurgisertib increased by 1.28- and 2.13-fold, respectively.” (opens the source at this quote in a new tab)

CYP3A4/5 estimated to account for about half of zilurgisertib clearance

“Assuming itraconazole completely inhibited CYP3A4/5 activity and had no effect on the bioavailability of zilurgisertib, CYP3A4/5 is therefore estimated to be responsible for approximately 53% of the overall clearance of zilurgisertib.” (opens the source at this quote in a new tab)
“In addition to CYP3A4/5 inhibitors, itraconazole and hydroxy-itraconazole are also P-glycoprotein (P-gp) inhibitors.” (opens the source at this quote in a new tab)

More potent strong CYP3A4 inhibitors may increase exposure more than itraconazole did

“Strong CYP enzymes are known to vary in their magnitude of inhibition.” (opens the source at this quote in a new tab)
“such as ritonavir and ketoconazole, may cause even larger increases in its exposure than the approximately 2-fold effect seen here.” (opens the source at this quote in a new tab)
“This may require even greater zilurgisertib dose reductions, and coadministration of zilurgisertib with these drugs may not be appropriate.” (opens the source at this quote in a new tab)

Mild and moderate CYP3A4 inhibitors

“No change in ATEBRIOZ dosage is needed when used concomitantly with a mild or moderate CYP3A4 inhibitor” (opens the prescribing information at this quote)
“Coadministration of zilurgisertib with moderate CYP3A4 inhibitors (ciprofloxacin, erythromycin, and fluconazole) is predicted to increase the Cmax and AUC of zilurgisertib 1.09-1.13 and 1.50-1.78-fold, respectively.” (opens the prescribing information at this quote)

Strong and moderate CYP3A4 inducers

“Avoid concomitant use of ATEBRIOZ with strong or moderate CYP3A4 inducers. Strong or moderate CYP3A4 inducers decrease zilurgisertib plasma concentrations” (opens the prescribing information at this quote)
“Coadministration of rifampin (a strong CYP3A4 inducer) decreased zilurgisertib Cmax and AUC by 56% and 79%, respectively” (opens the prescribing information at this quote)
“Concomitant use of efavirenz (a moderate CYP3A4 inducer) is predicted to decrease zilurgisertib Cmax and AUC by 25% and ~60%, respectively” (opens the prescribing information at this quote)

“With the concomitant administration of rifampin, there was a 2.27- and 4.76-fold reduction in the geometric mean Cmax and AUC0-inf of zilurgisertib, respectively.” (opens the source at this quote in a new tab)
“Zilurgisertib dose adjustment may be necessary with concomitant administration of strong CYP3A4 inhibitors, and coadministration of zilurgisertib with strong CYP3A4 inducers is not recommended.” (opens the source at this quote in a new tab)

Rifampin as a broad-spectrum, potent inducer represents a worst-case interaction

“Rifampin is the most potent inducer of P-gp” (opens the source at this quote in a new tab)
“Therefore, the effect of rifampin on the zilurgisertib exposure in this study represents a worst-case scenario for when zilurgisertib is coadministered with a CYP3A4/5 inducer.” (opens the source at this quote in a new tab)
“Given the significant decrease in zilurgisertib AUC (4.76-fold) when coadministered with rifampin, concomitant use of zilurgisertib and rifampin should be avoided.” (opens the source at this quote in a new tab)

CYP2D6 inhibitors

“Coadministration of paroxetine (a strong CYP2D6 inhibitor) and duloxetine is predicted to have negligible effect on zilurgisertib exposure.” (opens the prescribing information at this quote)

Transporter inhibitors

“Zilurgisertib is a substrate of P-gp, BCRP and MRP2, but P-gp, BCRP or MRP2 inhibitors are not expected to affect zilurgisertib exposure at clinically relevant concentrations. Zilurgisertib is not a substrate of key hepatic transporters OATP, OAT, or OCT families. Zilurgisertib is not a substrate for renal transporters MATE1 and MATE2-K.” (opens the prescribing information at this quote)

Grapefruit and pomelo

“Do not administer ATEBRIOZ with grapefruit, pomelo, or juices containing these fruits.” (opens the prescribing information at this quote)