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Drugs reference index «Lapatinib»


Pronunciation: (la-PA-ti-nib)Class: Tyrosine kinase inhibitor

Trade Names:Tykerb- Tablets 250 mg


Inhibits both epidermal growth factor receptor and human epidermal growth receptor 2–driven tumor cell growth in vitro and in animal models.



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.


Binding to albumin and alpha-1 acid glycoprotein is more than 99%.


Primarily metabolized by CYP3A4 and CYP3A5, with minor metabolism by CYP2C19 and CYP2C8.


The half-life is 24 h with repeated dosing. Elimination is primarily via CYP3A4/5 metabolism, with negligible (less than 2%) renal excretion. Fecal elimination accounts for approximately 27%.

Special Populations

Renal Function Impairment

Because less than 2% of an administered dose is eliminated by the kidneys, renal function impairment is unlikely to affect the pharmacokinetics.

Hepatic Function Impairment

AUC increased after a single dose by approximately 14% and 63% in patients with moderate and severe hepatic impairment, respectively. Use with caution and consider dose reduction in patients with severe hepatic impairment.

Indications and Usage

In combination with capecitabine for the treatment of advanced or metastatic breast cancer in patients whose tumors overexpress human epidermal receptor type 2, and who have received prior therapy, including an anthracycline, a taxane, and trastuzumab.


Standard considerations.

Dosage and Administration


PO 1,250 mg once daily on days 1 to 21 continuously with capecitabine 2,000 mg/m 2 /day on days 1 to 14 in a repeating 21-day cycle. Discontinuation or interruption of dosing may be considered if the patient develops at least grade 2 National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). Restart treatment at 1,250 mg/day when toxicity improves to grade 1 or less. If toxicity recurs, restart at 1,000 mg/day.

Cardiac EventsAdults

PO Discontinue in patients with a decreased left ventricular ejection fraction (LVEF) that is grade 3 or more, and in patients with an LVEF that drops below the lower limit of normal. Restart at a reduced dosage of 1,000 mg/day after a minimum of 2 wk if LVEF recovers to normal and the patient is asymptomatic.

Coadministration With a Strong CYP3A4 InducerAdults

PO Consider gradually increasing dosage from 1,250 to 4,500 mg/day based on tolerability. When the inducer is discontinued, reduce the dose to the indicated dose.

Coadministration With a Strong CYP3A4 InhibitorAdults

PO Consider dosage reduction to 500 mg/day. When the inhibitor is discontinued, allow 1 wk before adjusting dose upward to the indicated dose.

Hepatic Function ImpairmentAdults

PO In patients with severe hepatic function impairment, consider dosage reduction to 750 mg/day.

General Advice

  • Take lapatinib once daily, at least 1 h before or after a meal.
  • The dose of lapatinib should be once daily; dividing the dose is not recommended.


Store at 59° to 86°F.

Drug Interactions

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, grapefruit juice, 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.


Lapatinib plasma concentrations may be decreased.


Lapatinib plasma concentrations may be decreased.

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.

Laboratory Test Interactions

None well documented.

Adverse Reactions

The following adverse reactions were reported with combined use of lapatinib and capecitabine.


Decreased LVEF.


Insomnia (10%).


Palmar-plantar erythrodysesthesia (53%); rash (28%); dry skin (10%).


Diarrhea (65%); nausea (44%); vomiting (26%); stomatitis (14%); dyspepsia (11%).

Lab Tests

Abnormal hemoglobin (56%); abnormal AST (49%); abnormal total bilirubin (45%); abnormal ALT (37%); abnormal neutrophils (22%); abnormal platelets (18%).


Pain in extremities (12%); back pain (11%).


Dyspnea (12%); interstitial lung disease, pneumonitis.


Mucosal inflammation (15%).



Hepatotoxicity, severe and life-threatening, has occurred. The cause of death is uncertain.


Monitor for pulmonary symptoms indicative of interstitial lung disease or pneumonitis.


Category D .




Safety and efficacy not established.


No differences in safety and efficacy have been observed between subjects who were 65 yr of age and older compared with younger subjects.

Renal Function

Because less than 2% of an administered dose is eliminated by the kidneys, renal function impairment is unlikely to affect the pharmacokinetics.

Hepatic Function

Lapatinib dose reduction may be needed in patients with severe hepatic function impairment.


LVEF may be reduced, majority occurring within the first 9 weeks of treatment. Use with caution.


Diarrhea, including severe diarrhea, has been reported. Management with anti-diarrheal agents is important. Severe cases may require oral or IV electrolytes and fluids, as well as withholding or discontinuing therapy.

Interstitial lung disease

Interstitial lung disease and pneumonitis have been reported. Discontinue therapy in patients experiencing pulmonary symptoms that are grade 3 or higher.

QT prolongation

QT prolongation has been measured by automated machine-read evaluation of ECG. Administer with caution in patients who have or may develop prolongation of the QTC interval, including patients taking antiarrhythmic drugs.



Toxicity may be increased; grade 3 diarrhea and vomiting have been reported.

Patient Information

  • Advise patient to read the patient information leaflet before using product the first time and with each refill.
  • Instruct patient to inform health care provider if fatigue, palpitations, severe diarrhea, or shortness of breath occurs.
  • Instruct patient to take lapatinib at least 1 h before or after a meal.
  • Advise patients who have heart or liver problems to inform health care provider of the medical condition.
  • Advise patient not to eat or drink grapefruit products while taking lapatinib.

Copyright © 2009 Wolters Kluwer Health.

  • Lapatinib MedFacts Consumer Leaflet (Wolters Kluwer)
  • lapatinib Advanced Consumer (Micromedex) - Includes Dosage Information
  • Tykerb Prescribing Information (FDA)
  • Tykerb Consumer Overview