Drug Interactions between lapatinib and Omeclamox-Pak

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of lapatinib, which is primarily metabolized by the isoenzyme. In healthy subjects, administration of lapatinib in combination with the CYP450 3A4 inhibitor ketoconazole (200 mg twice daily for 7 days) resulted in lapatinib systemic exposure (AUC) and half-life that were approximately 3.6- and 1.7-fold, respectively, of the control values.

MANAGEMENT: Concomitant use of lapatinib with potent CYP450 3A4 inhibitors should generally be avoided. Some authorities recommend avoiding concomitant use of lapatinib during and for 2 weeks after treatment with itraconazole. If coadministration is required, the manufacturer recommends reducing the lapatinib dosage to 500 mg once a day. Based on pharmacokinetic studies, this dosage is predicted to adjust the lapatinib systemic exposure (AUC) to the range observed without inhibitors. However, clinical data are lacking. Following discontinuation of the potent CYP450 3A4 inhibitor, a washout period of approximately one week should be allowed before the lapatinib dosage is adjusted upward to the indicated dosage (i.e., 1250 mg once a day).

MONITOR: Nonclinical data indicate that the solubility of lapatinib is pH-dependent. Therefore, long-term suppression of gastric acid secretion by H2-receptor antagonists or proton pump inhibitors may reduce lapatinib systemic exposure. In study subjects, coadministration with the proton pump inhibitor esomeprazole (40 mg once daily for 7 days) decreased lapatinib exposure by an average of 27% (range 6% to 49%). This effect decreases with increasing age from approximately 40 to 60 years. The clinical significance is unknown.

MANAGEMENT: Caution may be advisable if lapatinib is used in combination with H2-receptor antagonists or proton pump inhibitors. Patients should be monitored for potentially reduced therapeutic response to lapatinib.

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.