Zelboraf（vemurafenib）片剂治疗黑色素瘤新药获FDA批准上市
8月17日，美国食品和药物管理局（FDA）批准Zelboraf(vemurafenib)用于治疗晚期转移性或不能切除的黑色素瘤。此药是今年获准的第二个治疗黑色素瘤的药物，它能改善患者的总体生存期。
Zelboraf特别适用于治疗有基因BRAF V600E突变的黑色素瘤。该药尚未在该突变阴性的黑色素瘤病人中进行过研究。
Zelboraf获准的同时，FDA还批准了首个用于检测cobas 4800 BRAF V600突变的试验方法，这一诊断方法将有助于确定病人的黑色素瘤细胞是否存在BRAF V600E突变。
BRAF蛋白通常涉及调节细胞生长，但它在约半数晚期黑色素瘤病人中发生突变。Zelboraf是BRAF抑制剂，能阻断V600E发生突变的BRAF蛋白的功能。
“Zelboraf是FDA批准的第二个治疗黑色素瘤的新药，该药被证明能改善病人的总生存。” FDA药物评价与研究中心肿瘤药物产品办公室主任理查（Richard Pazdur）说：“FDA在3月批准的Yervoy (伊匹木单抗，ipilimumab)，是另一种治疗晚期黑色素瘤的新药，也显示能延长病人的生存期。”
Zelboraf通过了FDA的优先评审项目审查。一项国际化研究确定了Zelboraf的安全性和有效性，该研究纳入675例有晚期黑色素瘤伴BRAF V600E突变病人，这些病人以前未经治疗。病人分别接受Zelboraf或达卡巴嗪治疗，试验设计的测定指标是总生存期。
Zelboraf组病人未达到中位生存期（77%病人仍生存），达卡巴嗪组病人的中位生存期为8个月（64%仍生存）。

Generic Name for ZELBORAF
Vemurafenib 240mg; tabs.

Legal Classification:
Rx

Pharmacological Class for ZELBORAF
Kinase inhibitor.

Manufacturer of ZELBORAF
Genentech, Inc.

Indications for ZELBORAF
Treatment of unresectable or metastatic melanoma with BRAFV600E mutation as detected by an FDA-approved test.

Adult dose for ZELBORAF
Swallow whole with water. Take in the AM and PM (approx. 12 hours apart). ≥18yrs: 960mg twice daily; until disease progression or unacceptable toxicity occurs. Dose modifications for adverse reactions or QTc prolongation: see literature. Dose reductions <480mg twice daily: not recommended.

Children's dosing for ZELBORAF
<18yrs: not recommended.

Warnings/Precautions for ZELBORAF
Not for use in wild-type BRAF melanoma. Confirm BRAFV600E mutation-positive melanoma with FDA-approved test before treating. Risk of cutaneous squamous cell carcinoma (cuSCC): ≥65 years, prior skin cancer, chronic sun exposure; if occurs, do excision and continue without dose adjustment. Do dermatologic eva luation before therapy, every 2 months during, and consider monitoring 6 months after. Long QT syndrome or QTc >500ms, uncorrectable electrolyte abnormalities, or concomitant drugs that prolong the QT interval: not recommended. Monitor electrolytes before therapy and after dose adjustments. Monitor ECG at Day 15 of treatment, monthly during the 1st 3 months, then every 3 months thereafter, or more as needed. If QTc >500ms, interrupt therapy, correct electrolytes, and control cardiac risk factors. Severe hepatic or renal impairment. Monitor liver enzymes, bilirubin before therapy and monthly, or as needed. Monitor for ophthalmologic reactions routinely. Avoid sun exposure. Pregnancy (Cat. D); avoid. Use adequate contraception during therapy and for at least 2 months after. Nursing mothers: not recommended.

Interactions for ZELBORAF
Concomitant CYP3A4, CYP1A2 or CYP2D6 substrates with narrow therapeutic indices: not recommended; if CYP1A2 or CYP2D6 substrates unavoidable, consider dose reduction of substrates. Caution with concomitant strong CYP3A4 inhibitors (eg, azole antifungals, clarithromycin) or inducers (eg, phenytoin, rifampin). May potentiate warfarin; monitor INR.

Adverse Reactions for ZELBORAF
Arthralgia, rash, alopecia, fatigue, photosensitivity, nausea, pruritus, skin papilloma; cuSCC, severe hypersensitivity or dermatologic reactions (discontinue if occurs), prolonged QTc, uveitis.

How is ZELBORAF supplied?
Tabs—120