• Advanced or metastatic breast cancer with tumor overexpression of the human epidermal receptor type 2 (HER2) and past therapy with an anthracycline, a taxane and trastuzumab (in combination with capecitabine).
• Hormone-receptor positive metastatic breast cancer that overexpresses HER2 in postmenopausal women for whom hormonal therapy is indicated (in combination with letrozole).

Contraindicated in:

• Hypersensitivity
• ↓left ventricular ejection fraction (LVEF) (Grade 2 or greater)
• OB: Pregnancy
• Lactation: Lactation.

Use Cautiously in:

• Severe hepatic impairment (dose ↓ recommended)
• Known QTc interval prolongation or coexisting risk factors for QTc interval prolongation including hypokalemia, hypomagnesemia, concurrent antiarrhythmics or medications that are known to prolong the QTc interval
• Rep: Women of reproductive potential and men with female partners of reproductive potential
• Pedi: Safety and effectiveness not established in children
• Geri: Older adults may be more sensitive to effects.

CV: ↓LVEF, QT interval prolongation.

Derm: palmar-plantar erythrodysesthesia, rash, dry skin, ERYTHEMA MULTIFORM (EM), nail disorders, STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN).

GI: nausea, vomiting, ↑ liver enzymes, DIARRHEA, dyspepsia, HEPATOTOXICITY, stomatitis.

Hemat: neutropenia.

MS: pain.

Neuro: fatigue, insomnia.

Resp: dyspnea, INTERSTITIAL LUNG DISEASE (ILD).

Drug-Drug:

• May ↑ effects of midazolam, paclitaxel, and digoxin.
• Strong CYP3A4 inhibitors, including ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, nelfinavir, ritonavir, and voriconazole may ↑ levels and risk of toxicity; avoid concurrent use; if concurrent use unavoidable, ↓ lapatinib dose.
• Strong CYP3A4 inducers, including dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, and phenobarbital, may ↓ levels and effectiveness; avoid concurrent use; if concurrent use unavoidable, ↑ lapatinib dose.

Drug-Natural Products:

• St. John's wort may ↓ levels and effectiveness; avoid concurrent use; if concurrent use unavoidable, ↑ lapatinib dose.

Drug-Food:

• Grapefruit juice may ↑ levels and risk of toxicity; avoid concurrent use.

(Generic available)

• Tablets: 250 mg;

HER2–Positive Metastatic Breast Cancer (Past Therapy with an Anthracycline, a Taxane and Trastuzumab)

• PO (Adults): 1250 mg once daily on Days 1–21 of 21-day cycle; continue until disease progression or unacceptable toxicity; Concurrent use of strong CYP3A4 inhibitors: 500 mg once daily on Days 1–21 of 21-day cycle; continue until disease progression or unacceptable toxicity; Concurrent use of strong CYP3A4 inducers: Gradually titrate dose from 1250 mg once daily up to 4500 mg once daily as tolerated; administer dose on Days 1–21 of 21-day cycle and continue until disease progression or unacceptable toxicity.

Hormone Receptor-Positive, HER2–Positive Metastatic Breast Cancer (Hormone Therapy Indicated)

• PO (Adults): 1500 mg once daily on Days 1–21 of 21-day cycle; continue until disease progression or unacceptable toxicity; Concurrent use of strong CYP3A4 inhibitors: 500 mg once daily on Days 1–21 of 21-day cycle; continue until disease progression or unacceptable toxicity; Concurrent use of strong CYP3A4 inducers: Gradually titrate dose from 1500 mg once daily up to 5500 mg once daily as tolerated; administer dose on Days 1–21 of 21-day cycle and continue until disease progression or unacceptable toxicity.

Tykerb

• Acts as an inhibitor of intracellular tyrosine kinase affecting epidermal growth factor (EGFR, ErbB1) and HER2 (ErbB2). Inhibits the growth of ErbB-driven tumors. Effect is additive with capecitabine.

• Decreased/slowed spread of metastatic breast cancer.

Therapeutic Classification: antineoplastics

Pharmacologic Classification: enzyme inhibitors, kinase inhibitors

Absorption: Incompletely and variably absorbed following oral administration; levels ↑ by food.

Distribution: Unknown.

Protein Binding: >99%.

Metabolism/Excretion: Extensively metabolized by the liver via the CYP3A4 and CYP3A5 isoenzymes; <2% excreted by kidneys.

Half-life: 24 hr.

(plasma concentrations)

• Instruct patient to take lapatinib as directed and to review the Patient Information Sheet prior to therapy and with each refill for new information. If a dose is missed take as soon remembered that day. If a day is missed, skip the dose; do not double doses. Caution patient not to share this medication with others, even with same condition; may be harmful.
• Advise patient to avoid drinking grapefruit juice or eating grapefruit during therapy.
• Advise patient to report signs or decreased LVEF (shortness of breath, palpitations, fatigue) and skin rash to health care professional promptly.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially St. John's wort.
• Advise patient that lapatinib may cause diarrhea, which may become severe. Instruct patient in how to prevent and manage diarrhea and to notify health care professional if severe.
• Rep: May cause fetal harm. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during and for 1 wk after last dose and to avoid breastfeeding for 1 wk after last dose. Advise patient to notify health care professional if pregnancy is planned or suspected.

la-PAT-i-nib

NDC Code^*

• 0078- Novartis Pharmaceuticals Corporation
  • 0078-0671- TYKERB
    • 0078-0671-19- 150 TABLET in 1 BOTTLE (0078-0671-19)