Drug Interactions between bosutinib and Omeclamox-Pak

GENERALLY AVOID: Coadministration with potent and moderate inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of bosutinib, which is primarily metabolized by the isoenzyme. In 24 healthy volunteers, administration of a single 100 mg dose of bosutinib with the potent CYP450 3A4 inhibitor ketoconazole (400 mg/day for 5 days) under fasting conditions resulted in a 5.2-fold increase in bosutinib peak plasma concentration (Cmax) and 8.6-fold increase in systemic exposure (AUC) compared to administration of bosutinib alone. Ketoconazole also decreased the mean apparent clearance of bosutinib by approximately 9-fold and increased the mean terminal half-life from 46.2 hours to 69.0 hours.

MANAGEMENT: Concomitant use of bosutinib with potent or moderate CYP450 3A4 inhibitors should generally be avoided. Some authorities recommend avoiding concomitant use of bosutinib during and for 2 weeks after treatment with itraconazole. If use of a potent or moderate CYP450 3A4 inhibitor is required, an interruption or a dosage reduction of bosutinib therapy should be considered.

GENERALLY AVOID: Coadministration with proton pump inhibitors may decrease the oral bioavailability of bosutinib and reduce its concentrations in plasma. The solubility of bosutinib decreases rapidly when the pH is above 5, resulting in reduced absorption. In 24 healthy volunteers, administration of a single 400 mg oral dose of bosutinib in combination with multiple oral doses of lansoprazole 60 mg under fasting conditions resulted in a 46% decrease in bosutinib peak plasma concentration (Cmax) and 26% decrease in systemic exposure (AUC) compared to administration of bosutinib alone. Since proton pump inhibitors affect pH of the upper gastrointestinal tract for an extended period, separation of doses may not eliminate the interaction.

MANAGEMENT: The concomitant use of bosutinib with proton pump inhibitors should generally be avoided. If acid-suppression therapy is required during bosutinib treatment, an H2-receptor antagonist (e.g., cimetidine, famotidine, ranitidine) or antacid may be taken up to 2 hours before or 2 hours after the bosutinib dose.

Although some in vitro data indicate synergism between macrolide antibiotics and penicillins, other in vitro data indicate antagonism. When these drugs are given together, neither has predictable therapeutic efficacy. Data are available for erythromycin, although theoretically this interaction could occur with any macrolide. Except for monitoring of the effectiveness of antibiotic therapy, no special precautions appear to be necessary.

Clarithromycin may increase and prolong the omeprazole plasma concentration. The mechanism may be related to clarithromycin inhibition of hepatic cytochrome P450 enzymes responsible for omeprazole metabolism. Coadministration of omeprazole may result in an increase in clarithromycin and 14-(R)-hydroxyclarithromycin plasma concentrations. These increases may be due to the effect of omeprazole on gastric pH.