STUDIES WITH HUMAN LIVER TISSUE INDICATE THAT AMBRISENTAN IS METABOLIZED BY CYP3A4, CYP2C19, AND URIDINE 5'-DIPHOSPHATE GLUCURONOSYLTRANSFERASES (UGTS) 1A9S, 2B7S, AND 1A3S.
THE DRUG INTERACTION POTENTIAL OF AMBRISENTAN IS NOT WELL CHARACTERIZED BECAUSE IN VIVO DRUG INTERACTION STUDIES WERE NOT CONDUCTED WITH THE FOLLOWING TYPES OF DRUGS: STRONG INHIBITORS OF CYP3A4 (ATANAZAVIR, CLARITHROMYCIN, INDINAVIR, ITRACONAZOLE, KETOCONAZOLE, NEFAZODONE, NELFINAVIR, RITONAVIR, SAQUINAVIR, TELITHROMYCIN), AND CYP2C19 (OMEPRAZOLE), STRONG INDUCERS OF CYP3A AND 2C19 (RIFAMPIN), STRONG INHIBITORS OF THE TRANSPORTERS P-GP (CYCLOSPORINE A) AND OATP (CYCLOSPORINE A, RIFAMPIN); AND INDUCERS OF CYPS, UGTS AND P-GP (RIFAMPIN). THE IMPACT OF CO-ADMINISTRATION OF SUCH DRUGS ON AMBRISENTAN EXPOSURE IS THEREFORE UNKNOWN.
CYCLOSPORINE A
USE CAUTION WHEN LETAIRIS IS CO-ADMINISTERED WITH CYCLOSPORINE A .
STRONG CYP3A OR 2C19 INHIBITORS
USE CAUTION WHEN LETAIRIS IS CO-ADMINISTERED WITH STRONG CYP3A-INHIBITORS (E.G., KETOCONAZOLE) OR CYP2C19-INHIBITORS (E.G., OMEPRAZOLE).
INDUCERS OF P-GP, CYPS, AND UGTS
USE CAUTION WHEN LETAIRIS IS CO-ADMINISTERED WITH INDUCERS OF P-GP, CYPS, AND UGTS.
WARFARIN
IN HEALTHY VOLUNTEERS RECEIVING WARFARIN, DAILY DOSES OF LETAIRIS (10 MG ONCE DAILY) DID NOT HAVE A CLINICALLY SIGNIFICANT EFFECT ON PROTHROMBIN TIME ETC.