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Tykerb (Lapatinib) - Drug Interactions, Contraindications, Overdosage, etc



Effects of Lapatinib on Drug Metabolizing Enzymes and Drug Transport Systems

Lapatinib inhibits CYP3A4 and CYP2C8 in vitro at clinically relevant concentrations. Caution should be exercised and dose reduction of the concomitant substrate drug should be considered when dosing lapatinib concurrently with medications with narrow therapeutic windows that are substrates of CYP3A4 or CYP2C8. Lapatinib did not significantly inhibit the following enzymes in human liver microsomes: CYP1A2, CYP2C9, CYP2C19, and CYP2D6 or UGT enzymes in vitro, however, the clinical significance is unknown.

Lapatinib inhibits human P-glycoprotein. If TYKERB is administered with drugs that are substrates of Pgp, increased concentrations of the substrate drug are likely, and caution should be exercised.

Drugs that Inhibit or Induce Cytochrome P450 3A4 Enzymes

Lapatinib undergoes extensive metabolism by CYP3A4, and concomitant administration of strong inhibitors or inducers of CYP3A4 alter lapatinib concentrations significantly (see Ketoconazole and Carbamazepine sections, below) . Dose adjustment of lapatinib should be considered for patients who must receive concomitant strong inhibitors or concomitant strong inducers of CYP3A4 enzymes [see Dosage and Administration].


In healthy subjects receiving ketoconazole, a CYP3A4 inhibitor, at 200 mg twice daily for 7 days, systemic exposure (AUC) to lapatinib was increased to approximately 3.6-fold of control and half-life increased to 1.7-fold of control.


In healthy subjects receiving the CYP3A4 inducer, carbamazepine, at 100 mg twice daily for 3 days and 200 mg twice daily for 17 days, systemic exposure (AUC) to lapatinib was decreased approximately 72%.

Drugs that Inhibit Drug Transport Systems

Lapatinib is a substrate of the efflux transporter P-glycoprotein (Pgp, ABCB1). If TYKERB is administered with drugs that inhibit Pgp, increased concentrations of lapatinib are likely, and caution should be exercised.

Other Chemotherapy Agents

In a separate study, concomitant administration of lapatinib with capecitabine did not meaningfully alter the pharmacokinetics of either agent (or the metabolites of capecitabine).


There is no known antidote for overdoses of TYKERB. The maximum oral doses of lapatinib that have been administered in clinical trials are 1,800 mg once daily. More frequent ingestion of TYKERB could result in serum concentrations exceeding those observed in clinical trials and could result in increased toxicity. Therefore, missed doses should not be replaced and dosing should resume with the next scheduled daily dose.

There has been a report of one patient who took 3,000 mg of TYKERB for 10 days. This patient had Grade 3 diarrhea and vomiting on Day 10. The event resolved following IV hydration and interruption of treatment with TYKERB and letrozole.

Because lapatinib is not significantly renally excreted and is highly bound to plasma proteins, hemodialysis would not be expected to be an effective method to enhance the elimination of lapatinib.



See manufacturer’s prescribing information for capecitabine contraindications.

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