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Absorption
Oral absorption is incomplete and variable. C max occurs approximately 4 h after administration, and steady state is reached in 6 to 7 days. Following a dose of 1,250 mg daily, the C max was 2.43 mcg/mL. The AUC is 2-fold higher with divided daily doses compared with single-dose administration. When taken with a low-fat or high-fat meal, AUC is increased 3- and 4-fold, respectively.
Distribution
Binding to albumin and alpha-1 acid glycoprotein is greater than 99%.
Metabolism
Primarily metabolized by CYP3A4 and CYP3A5, with minor metabolism by CYP2C19 and CYP2C8.
Elimination
The t ½ is 24 h with repeated dosing. Elimination is primarily via CYP3A4/5 metabolism, with negligible renal excretion. Fecal elimination accounts for approximately 27%.
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Antiarrhythmic agents or drugs that prolong the QTc interval
Because lapatinib may prolong the QTc interval, use with caution in patients receiving medications that produce QT prolongation.
CYP2C8 (eg, paclitaxel) and CYP3A4 (eg, cyclosporine) substrates
Because lapatinib inhibits CYP2C8 and CYP3A4, use with caution with drugs that are substrates for these isozymes, especially when medication has a narrow therapeutic window.
CYP3A4 inducers (eg, carbamazepine, dexamethasone, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, St. John's wort)
Lapatinib plasma concentrations may be reduced, decreasing efficacy. A lapatinib dose increase may be needed.
CYP3A4 inhibitors (eg, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole)
Lapatinib plasma concentrations may be elevated, increasing the risk of toxicity. Lapatinib dose reduction may be needed.
P-glycoprotein inhibitors (eg, quinidine)
Lapatinib plasma concentrations may be elevated, increasing the risk of toxicity. Use with caution.
P-glycoprotein substrates (eg, amiodarone, digoxin)
Because lapatinib inhibits P-glycoprotein, increased concentrations of drugs that are substrates for P-glycoprotein may occur. Use with caution.
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