CONCOMITANT USE OF STRONG CYP3A4 INHIBITORS SHOULD BE AVOIDED (E.G., KETOCONAZOLE, ITRACONAZOLE, CLARITHROMYCIN, ATAZANAVIR, INDINAVIR, NEFAZODONE, NELFINAVIR, RITONAVIR, SAQUINAVIR, TELITHROMYCIN, VORICONAZOLE). GRAPEFRUIT MAY ALSO INCREASE PLASMA CONCENTRATIONS OF LAPATINIB AND SHOULD BE AVOIDED.
CONCOMITANT USE OF STRONG CYP3A4 INDUCERS SHOULD BE AVOIDED (E.G., DEXAMETHASONE, PHENYTOIN, CARBAMAZEPINE, RIFAMPIN, RIFABUTIN, RIFAPENTIN, PHENOBARBITAL, ST. JOHN'S WORT). IF PATIENTS MUST BE COADMINISTERED A STRONG CYP3A4 INDUCER, BASED ON PHARMACOKINETIC STUDIES, THE DOSE OF LAPATINIB SHOULD BE TITRATED GRADUALLY FROM 1,250 MG/DAY UP TO 4,500 MG/DAY BASED ON TOLERABILITY.
LAPATINIB IS A SUBSTRATE OF THE EFFLUX TRANSPORTER P-GLYCOPROTEIN (PGP, ABCB1). IF LAPATINIB IS ADMINISTERED WITH DRUGS THAT INHIBIT PGP, INCREASED CONCENTRATIONS OF LAPATINIB ARE LIKELY, AND CAUTION SHOULD BE EXERCISED.