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  • Title: Effect of lapatinib on oral digoxin absorption in patients.
    Author: Koch KM, Smith DA, Botbyl J, Arya N, Briley LP, Cartee L, White JH, Beyer J, Dar MM, Chung HC, Chu Q, Bang YJ.
    Journal: Clin Pharmacol Drug Dev; 2015 Nov; 4(6):449-53. PubMed ID: 27137717.
    Abstract:
    The potential for an interaction between lapatinib and absorption of the P-glycoprotein (ABCB1) substrate digoxin at a therapeutic dose in breast cancer patients was characterized. Seventeen women with HER2-positive metastatic breast cancer received a single oral 0.5-mg dose of digoxin on days 1 and 9 and oral lapatinib 1500 mg once daily on days 2 through 9. Digoxin pharmacokinetic parameters were determined on day 1 (digoxin administration alone) and on day 9 (coadministration of lapatinib and digoxin), and parameters were compared to determine the effects of lapatinib on digoxin absorption. Concomitant medications that could affect ABCB1 were accounted for. Lapatinib 1500 mg/day increased digoxin absorption approximately 80%, implicating lapatinib inhibition of intestinal ABCB1-mediated efflux. In summary, coadministration of lapatinib with narrow therapeutic index drugs that are substrates of ABCB1 should be undertaken with caution and dose adjustment should be considered.
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