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Buy Tarceva (Erlotinib HCl) anticancer medication
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Erlotinib is metabolized predominantly by CYP3A4, and inhibitors of CYP3A4 would be expected to increase exposure. Co-treatment with the potent CYP3A4 inhibitor ketoconazole increases erlotinib AUC by 2/3. When Erlotinib (Tarceva) was co-administered with ciprofloxacin, an inhibitor of both CYP3A4 and CYP1A2, the erlotinib exposure [AUC] and maximum concentration [Cmax] increased by 39% and 17% respectively. Caution should be used when administering or taking Tarceva (Erlotinib Hydrochloride) with ketoconazole and other strong CYP3A4 inhibitors such as, but not limited to, clarithromycin, atazanavir, indinavir, nefazodone, itraconazole, nelfinavir, saquinavir, ritonavir, telithromycin, troleandomycin (TAO), voriconazole and grapefruit or grapefruit juice.

Pre-treatment with the CYP3A4 inducer rifampicin for 7 days prior to Erlotinib Hydrochloride (Tarceva) decreased erlotinib AUC by about 2/3 to 4/5, which is equivalent to a dose of about 30 to 50 mg in NSCLC patients. In a separate study, treatment with rifampicin for 11 days, with co-administration of a single 450 mg dose of Tarceva (Erlotinib HCl) on day 8 resulted in a mean erlotinib exposure (AUC) that was 57.6% of that observed following a single 150 mg Erlotinib HCl (Tarceva) dose in the absence of rifampicin treatment. Use of alternative treatments lacking CYP3A4 inducing activity is strongly recommended. If an alternative treatment is unavailable, adjusting the starting dose should be considered. If the Tarceva (Erlotinib HCl) tablets dose is adjusted upward, the dose will need to be reduced immediately to the indicated starting dose upon discontinuation of rifampicin or other inducers. Other CYP3A4 inducers include, but are not limited to, rifapentine, rifabutin, phenytoin, carbamazepine, phenobarbital and St. John's Wort.

Cigarette smoking has been shown to reduce erlotinib AUC. Patients should be advised to stop smoking; however, if they continue to smoke, a cautious increase in the dose of Erlotinib HCl (Tarceva) tablets may be considered, while monitoring the patient's safety. If the Tarceva tablets dose is adjusted upward, the dose should be reduced immediately to the indicated starting dose upon cessation of smoking.

Pretreatment and co-administration of Erlotinib tablets decreased the AUC of CYP3A4 substrate, midazolam, by 24%. The mechanism is not clear.

In a study, there were no significant effects of gemcitabine on the pharmacokinetics of erlotinib nor were there significant effects of erlotinib on the pharmacokinetics of gemcitabine.

Drugs that alter the pH of the upper GI tract may alter the solubility of erlotinib and reduce its bioavailability. Increasing the dose of Tarceva when coadministered with such agents is not likely to compensate for the loss of exposure. Co-administration of Erlotinib with omeprazole, a proton pump inhibitor, decreased the erlotinib AUC by 46%. Since proton pump inhibitors affect pH of the upper GI tract for an extended period, separation of doses may not eliminate the interaction. The concomitant use of proton pump inhibitors with Tarceva (Erlotinib) should be avoided if possible. Co-administration of Erlotinib (Tarceva) with 300 mg ranitidine, an H2 receptor antagonist, decreased erlotinib AUC by 33%. When Tarceva (Erlotinib Hydrochloride) was administered with ranitidine 150 mg twice daily (at least 10 h after the previous ranitidine evening dose and 2 h before the ranitidine morning dose), the erlotinib AUC decreased by 15%. If patients need to be treated with an H2-receptor antagonist such as ranitidine, it should be used in a staggered manner. Erlotinib Hydrochloride (Tarceva) must be taken once a day, 10 hours after the H2-receptor antagonist dosing and at least 2 hours before the next dose of H2-receptor antagonist. Although the effect of antacids on erlotinib pharmacokinetics has not been evaluated, the antacid dose and the Tarceva (Erlotinib HCl) dose should be separated by several hours, if an antacid is necessary.

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