[Drug Name]

Generic Name: Lapatinib Ditosylate Tablets

Brand Name: Tykerb

[Manufacturer]

Natco Pharma Ltd

[Composition]

Lapatinib Ditosylate

[Indications]

Indicated for use in combination with capecitabine for the treatment of advanced or metastatic breast cancer in patients with ErbB-2 overexpression who have previously received therapy including anthracyclines, taxanes, and trastuzumab (Herceptin).

[Specification] 0.25 g × 30 tablets/box

[Dosage and Administration]

The recommended dose is 1250 mg, taken once daily on Days 1 through 21, in combination with capecitabine at a dose of 2000 mg/day (administered in two divided doses) on Days 1 through 14. Lapatinib should be taken once daily; divided doses are not recommended. It should be taken 1 hour before a meal or 2 hours after a meal. If a dose is missed, the dose should not be doubled the following day. Pregnancy Category D; contraindicated in pregnant women. It is not known whether the drug is excreted in human milk; nursing women should discontinue breastfeeding. No significant differences in safety or efficacy were observed between elderly patients and younger patients. Clinical trials have not been conducted in patients with severe renal impairment or those undergoing dialysis; a dose reduction should be considered for patients with moderate to severe hepatic impairment.

[Adverse Reactions]

Adverse reactions observed in clinical trials with an incidence greater than 10% primarily involved the gastrointestinal system, including nausea, diarrhea, stomatitis, and dyspepsia; other reactions included dry skin, rash, back pain, dyspnea, and insomnia. When used in combination with capecitabine, adverse reactions included nausea, diarrhea, vomiting, and palmar-plantar erythrodysesthesia (hand-foot syndrome). In individual patients, a decrease in left ventricular ejection fraction or interstitial pneumonia may occur.

The most common side effects are gastrointestinal in nature—specifically symptoms such as nausea, vomiting, and diarrhea. Other side effects include skin-related reactions such as redness, swelling, itching, and pain, as well as fatigue. Additionally, there are very rare but serious side effects, including those affecting the heart and lungs. If a patient experiences a decline in Left Ventricular Ejection Fraction (LVEF) accompanied by symptoms of New York Heart Association (NYHA) Class 2 heart failure or higher, treatment must be discontinued to prevent the development of overt heart failure. Treatment may be resumed at a reduced dosage two weeks after the LVEF returns to normal levels or the patient becomes asymptomatic. Unlike anthracycline-based chemotherapeutic agents—which are associated with irreversible cardiotoxicity and a lifetime cumulative dose limit—the cardiotoxicity associated with lapatinib is reversible; consequently, lapatinib does not carry a lifetime cumulative dose limit.

Since lapatinib is metabolized via the hepatic cytochrome P450 (CYP) enzyme system, careful dose adjustments are required when co-administering other medications known to induce or inhibit CYP enzymes. Lapatinib is generally contraindicated in pregnant women, as it is classified as Pregnancy Category D; therefore, its use in pregnant women or women of childbearing potential is not recommended unless there is an absolute necessity or the potential benefit to the mother significantly outweighs the risks.

【Drug Interactions】

In vitro studies indicate that, at therapeutic concentrations, lapatinib inhibits CYP3A4 and CYP2C8 enzymes. Furthermore, lapatinib is primarily metabolized by CYP3A4; consequently, drugs that inhibit the activity of this enzyme can significantly increase lapatinib plasma concentrations. For instance, the administration of ketoconazole (0.2 g orally, twice daily) for 7 days resulted in a 3- to 7-fold increase in lapatinib's Area Under the Curve (AUC) and a 1.7-fold prolongation of its elimination half-life. Conversely, in healthy volunteers, the oral administration of a CYP3A4 inducer—initiated at a dosage of 100 mg twice daily for 3 days, followed by 200 mg twice daily for an additional 14 days (totaling 17 days of treatment)—resulted in a 72% reduction in lapatinib AUC. Additionally, lapatinib serves as a substrate for P-glycoprotein (P-gp); therefore, drugs that inhibit P-gp activity may lead to increased plasma concentrations of lapatinib. **Product Specifications**

**Product Name:** Lapatinib Tablets (Tykerb) 250 mg × 30 Tablets (Herduo)

**Common Name:** Lapatinib Ditosylate Tablets

**Composition:** Lapatinib Ditosylate

**Dosage Form:** Tablets

**Specification:** 0.25 g × 30 tablets/box

**Manufacturer:** Natco Pharma Ltd

**Indications:** Lapatinib, in combination with capecitabine, is indicated for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress ErbB-2 and who have received prior therapy including anthracyclines, taxanes, and trastuzumab. Note: This product must be used in patients with recurrent or metastatic disease that has progressed following treatment with trastuzumab. No data currently support its use in patient populations outside of this specific indication.

**Dosage and Administration:** The recommended dose is 1250 mg, taken once daily on Days 1 through 21, in combination with capecitabine at a dose of 2000 mg/day (administered in two divided doses) on Days 1 through 14. Lapatinib should be taken once daily; administration in divided doses is not recommended. It should be taken either 1 hour before a meal or 2 hours after a meal. If a dose is missed, the dose should not be doubled on the following day. Pregnancy Category D; contraindicated in pregnant women. It is not known whether this drug is excreted in human milk; therefore, nursing women should discontinue breastfeeding. No significant differences in safety or efficacy have been observed between elderly patients and younger patients. Clinical trials have not been conducted in patients with severe renal impairment or those undergoing dialysis; a dose reduction should be considered for patients with moderate to severe hepatic impairment.