通用名：
拉帕替尼
商標名
Tykerb Tablets 250mg
（Lapatinib Tosilate Hydrate）
タイケルブ錠250mg

葛兰素史克公司研发的Tykerb（TM）（lapatinib tosilate hydrate，甲苯磺酸拉帕替尼；250mg片剂）已经在日本上市。本品是一种抗肿瘤药物，用于治疗过度表达HER2且不能手术或复发的乳腺癌。获批的适应证包括肿瘤细胞中过度表达HER2的HER2阳性乳腺癌的治疗。
注：使用参照原处方：http://www.info.pmda.go.jp/go/pack/4291022F1026_1_05/
附：
英文药品说明书
Company:
GlaxoSmithKline
Pharmacologic class:
Antineoplastic (tyrosine kinase inhibitor)
Active ingredient:
Lapatinib 250mg; tabs.
Indication:
In combination with capecitabine, for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 and who have received prior therapy including an anthracycline, a taxane, and trastuzumab.
Pharmacology:
Overexpression of epidermal growth factor receptor (EGFR) and human epidermal receptor type 2 (HER2) has been reported in a variety of tumors. Lapatinib works by inhibiting the tyrosine kinase components of the EGFR and HER2 receptors.
Clinical trials:
Lapatinib was evaluated in combination with capecitabine in the treatment of breast cancer in a randomized, Phase 3 trial that enrolled 399 patients. The patients had HER2 overexpressing locally-advanced or metastatic breast cancer that had progressed following prior treatment with anthracyclines, taxanes, and trastuzumab. Capecitabine was given on Days 1?4 on a 21-day cycle, and lapatinib was given once daily continuously. The endpoint was time to progression (time from randomization to tumor progression or death due to breast cancer). An interim analysis revealed that, according to an independent assessment, the median time to progression in the group given lapatinib + capecitabine was 27.1 weeks compared to 18.6 weeks for capecitabine only. The response rate was 23.7% for the lapatinib + capecitabine group compared to 13.9% for the capecitabine-only group. Data results from investigator assessment was significant as well.
Adults:
Take 1 hour before or 1 hour after a meal. Take once daily on Days 1?1 continuously with capecitabine (see literature for capecitabine dose) in a repeating 21 day cycle. 1250mg (5 tablets). Severe hepatic dysfunction (Child-Pugh Class C): 750mg (no clinical data for this dose adjustment). After recovery from left ventricular ejection fraction (LVEF) decrease: 1g. Concomitant potent CYP3A4 inhibitors: 500mg (no clinical data for this dose adjustment). Concomitant potent CYP3A4 inducers: may titrate up to 4500mg (no clinical data for this dose adjustment). Discontinue if ≥Grade 2 NCI CTC toxicity occurs; may restart at 1250mg if toxicity improves to grade 1; if recurs, may restart at 1g.
Children:
Not recommended.
Contraindications:
Renal disease or dysfunction. Metabolic acidosis, ketoacidosis. Concomitant intravascular iodinated contrast agents (suspend during and for 48 hours after use). Type 1 diabetes.
Precautions:
Discontinue if ≥Grade 2 decrease in LVEF occurs, or if LVEF falls below institution抯 lower limit of normal; may restart after at least 2 weeks at reduced dose if asymptomatic and LVEF recovers. Conditions that impair left ventricular function, or risk factors for QT prolongation (eg, hypokalemia, hypomagnesemia, congenital long QT syndrome, concomitant antiarrhythmics, cumulative high dose anthracyclines); correct electrolyte disturbances before starting. Severe hepatic impairment. Pretreat for diarrhea with antimotility drugs. Monitor ECG. Pregnancy (Cat.D). Nursing mothers: not recommended.
Interactions:
Avoid potent CYP3A4 inhibitors (eg, ketoconazole), grapefruit; reduce dose if unavoidable. Avoid potent CYP3A4 inducers (eg, carbamazepine); slowly titrate dose up if unavoidable. May affect drugs that are affected by p-glycoprotein, CYP2C8.
Adverse reactions:
Diarrhea (may be severe), nausea, vomiting, hand/foot syndrome, rash, fatigue; decreased LVEF, QT prolongation