CO-ADMINISTRATION WITH A STRONG CYP3A4 INHIBITOR SUCH AS, BUT NOT LIMITED TO, ATAZANAVIR, CLARITHROMYCIN, INDINAVIR, ITRACONAZOLE, KETOCONAZOLE, NEFAZODONE, NELFINAVIR, RITONAVIR, SAQUINAVIR, TELITHROMYCIN, TROLEANDOMYCIN (TAO), VORICONAZOLE, OR GRAPEFRUIT / GRAPEFRUIT JUICE OR CO-ADMINISTRATION WITH AN INHIBITOR OF BOTH CYP3A4 AND CYP1A2 LIKE CIPROFLOXACIN A DOSE REDUCTION SHOULD BE CONSIDERED IF SEVERE ADVERSE REACTIONS OCCUR.
PRE-TREATMENT WITH THE CYP3A4 INDUCER RIFAMPICIN, RIFABUTIN, RIFAPENTINE, PHENYTOIN, CARBAMAZEPINE, PHENOBARBITAL AND ST. JOHN'S WORT DECREASED ERLOTINIB AUC BY ABOUT 2/3 TO 4/5, SO DOSE INCREMENT OF ERLOTINIB IS TO BE CONSIDERED. THE MAXIMUM DOSE OF ERLOTINIB STUDIED IN COMBINATION WITH RIFAMPICIN IS 450 MG.
CIGARETTE SMOKING HAS BEEN SHOWN TO REDUCE ERLOTINIB EXPOSURE. PATIENTS SHOULD BE ADVISED TO STOP SMOKING. IF A PATIENT CONTINUES TO SMOKE, A CAUTIOUS INCREASE IN THE DOSE OF TARCEVA, NOT EXCEEDING 300 MG MAY BE CONSIDERED.
TARCEVA DECREASED THE AUC OF CYP3A4 SUBSTRATE, MIDAZOLAM, BY 24%.
THE CONCOMITANT USE OF PROTON PUMP INHIBITORS WITH TARCEVA SHOULD BE AVOIDED IF POSSIBLE. THE USE OF ANTACIDS MAY BE CONSIDERED IN PLACE OF HISTAMINE 2 RECEPTOR BLOCKERS (H2 BLOCKERS) OR PROTON PUMP INHIBITORS. IF AN ANTACID IS NECESSARY, THE ANTACID DOSE AND THE TARCEVA DOSE SHOULD BE SEPARATED BY SEVERAL HOURS. CO-ADMINISTRATION OF TARCEVA WITH OMEPRAZOLE, A PROTON PUMP INHIBITOR, DECREASED THE ERLOTINIB AUC BY 46%.