[Drug Name] Lapatinib Ditosylate Tablets (Tykerb)

[Generic Name] Lapatinib Ditosylate Tablets

[Indications/Uses] Lapatinib, in combination with capecitabine, is indicated for the treatment of advanced or metastatic breast cancer patients whose tumors overexpress ErbB-2 and who have previously received 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.

Pazopanib—a small-molecule targeted agent—has demonstrated a certain degree of efficacy when combined with lapatinib for the treatment of advanced cervical cancer. 3) TOR Inhibitors: Clinical results indicate that sirolimus possesses modest activity against cervical cancer.

[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 one hour before a meal or two 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 currently unknown whether the drug is excreted in breast milk; therefore, nursing mothers 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. [Chemical Composition] Chemical Name: N-(3-chloro-4-((3-fluorophenyl)methoxy)phenyl)-6-(5-(((2-(methylsulfonyl)ethyl)amino)methyl)-furan-2-yl)-quinazolin-4-amine ditosylate monohydrate (p-toluenesulfonate). Chemical Structural Formula: Molecular Formula: C29H26ClFN4O4S(C7H8O3S)2·H2O. Molecular Weight: 943.48 (ditosylate, monohydrate).

[Description] Lapatinib Ditosylate Tablets are yellow, film-coated tablets; one side is flat, while the other side bears an engraved imprint: "GS XJG".

[Indications] Breast Cancer.

[Pharmacological Action]

[Drug Interactions] *In vitro*, Lapatinib Tablets can inhibit CYP3A4 and CYP2C8 at therapeutic concentrations. Furthermore, Lapatinib is primarily metabolized by CYP3A4; therefore, drugs that inhibit the activity of this enzyme can significantly increase the plasma concentration of Lapatinib. Ketoconazole (0.2 g per dose, twice daily) administered for 7 days increased the AUC of Lapatinib by 3 to 7-fold and prolonged its half-life by 1.7-fold. In healthy volunteers, oral administration of a CYP3A4 inducer (100 mg per dose, twice daily for 3 days, followed by 200 mg per dose, twice daily) for a total of 17 days... d. Lapatinib AUC decreased by 72%. Lapatinib is a substrate of P-glycoprotein; drugs that inhibit P-glycoprotein may increase the blood concentration of this medication.

【Adverse Reactions】Adverse reactions observed in clinical trials with an incidence greater than 10% primarily involved the gastrointestinal tract, including nausea, diarrhea, stomatitis, and dyspepsia; dermatological reactions included dry skin and rash; other reactions included back pain, dyspnea, and insomnia. When used in combination with capecitabine, adverse reactions included nausea, diarrhea, vomiting, and palmar-plantar erythrodysesthesia. 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—while other side effects include skin-related issues such as redness, swelling, itching, and pain, as well as fatigue. Additionally, there are extremely rare but serious side effects involving the cardiac and pulmonary systems. If a patient experiences a Grade 2 or higher decrease in left ventricular ejection fraction, the medication must be discontinued to prevent the onset of heart failure. Treatment may be resumed at a reduced dose two weeks after the left ventricular ejection fraction returns to normal levels or after the patient becomes asymptomatic. Compared to anthracycline-based chemotherapeutic agents, the cardiotoxicity of lapatinib is reversible; unlike anthracyclines—which cause irreversible cardiotoxicity and have a lifetime maximum cumulative dose—lapatinib does not have a lifetime maximum cumulative dose limit. Since lapatinib is metabolized via the hepatic CYP enzyme system, caution regarding dose adjustment is required when co-administering other drugs that induce or inhibit CYP enzymes. Lapatinib should generally not be used by pregnant women, as it is classified as Pregnancy Category D; therefore, unless there is an absolute necessity or the potential benefit to the mother is substantial, its use is not recommended for pregnant women or those planning to conceive.

【Contraindications】Contraindicated in patients with known hypersensitivity to Tykerb (Tyrelisa) or related compounds.

Product Specifications

Product Name: Novartis Tykerb (Lapatinib Ditosylate Tablets) 0.25g × 30 Tablets

Common Name: Tykerb (Tyrelisa)

Ingredients: Lapatinib Ditosylate Tablets

Dosage Form: Tablets

Specification: 0.25 g × 30 tablets

Manufacturer: Novartis Pharmaceuticals

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 orally 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 either 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 this drug is excreted in human milk; therefore, 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.