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Afatinib(阿法替尼片，GILOTRIF，Giotrif)

2014-10-08 00:35:16 来源: 作者: 【大中小】浏览:1630次评论:0条

25 July 2013
EMA/CHMP/447957/2013
Committee for Medicinal Products for Human Use (CHMP)
Summary of opinion1 (initial authorisation)
Giotrif
afatinib

On 25 July 2013, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for the medicinal product Giotrif 20 mg, 30 mg, 40 mg and 50 mg film-coated tablets intended for the treatment of EGFR TKI-naïve adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating EGFR mutation(s). The applicant for this medicinal product is Boehringer Ingelheim International GmbH. They may request a re-examination of any CHMP opinion, provided they notify the European Medicines Agency in writing of their intention within 15 days of receipt of the opinion.
The active substance of Giotrif is afatinib, an antineoplastic agent, protein kinase inhibitor (L01XE13), that covalently binds to and irreversibly blocks signalling from all homo- and heterodimers formed by the ErbB family members EGFR (ErbB1), HER2 (ErbB2), ErbB3 and ErbB4.
The benefits with Giotrif have been shown in a phase III, randomised, open-label study of afatinib versus chemotherapy in patients with locally advanced or metastatic non-small cell lung cancer with activating EGFR mutation(s). In this study efficacy has been shown in terms of an increased progression free survival in patients receiving afatinib compared to chemotherapy. The most common side effects are diarrhea, stomatitis, rash, dermatitis acneiform, pruritus, dry skin, paronychia, decreased apetite and epistaxis.

A pharmacovigilance plan for Giotrif will be implemented as part of the marketing authorisation.
The approved indication is: " GIOTRIF as monotherapy is indicated for the treatment of Epidermal Growth Factor Receptor (EGFR) TKI-naïve adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating EGFR mutation(s) (see section 5.1).”
It is proposed that Giotrif be initiated and supervised by a physician experienced in the use of anticancer therapies.
Detailed recommendations for the use of this product will be described in the summary of product characteristics (SmPC), which will be published in the European public assessment report (EPAR) and
1 Summaries of positive opinion are published without prejudice to the Commission decision, which will normally be issued 67 days from adoption of the opinion.
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made available in all official European Union languages after the marketing authorisation has been granted by the European Commission.
The CHMP, on the basis of quality, safety and efficacy data submitted, considers there to be a favourable benefit-to-risk balance for Giotrif and therefore recommends the granting of the marketing authorisation.
Giotrif
EMA/CHMP/447957/2013 Page 2/2
GILOTRIF (afatinib) tablet, film coated
[Boehringer Ingelheim Pharmaceuticals, Inc.]

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use GILOTRIF safely and effectively. See full prescribing information for GILOTRIF.
GILOTRIF™ (afatinib) tablets, for oral use
Initial U.S. Approval: 2013

INDICATIONS AND USAGE

GILOTRIF is a kinase inhibitor indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test (1)

Limitation of Use: Safety and efficacy of GILOTRIF have not been established in patients whose tumors have other EGFR mutations (1)

DOSAGE AND ADMINISTRATION

Recommended dose: 40 mg orally, once daily (2.2)
Instruct patients to take GILOTRIF at least 1 hour before or 2 hours after a meal (2.2)

DOSAGE FORMS AND STRENGTHS

Tablets: 40 mg, 30 mg, and 20 mg (3)

CONTRAINDICATIONS

None (4)

WARNINGS AND PRECAUTIONS

Diarrhea: Diarrhea may result in dehydration and renal failure. Withhold GILOTRIF for severe and prolonged diarrhea not responsive to anti-diarrheal agents. (2.3, 5.1)
Bullous and Exfoliative Skin Disorders: Severe bullous, blistering, and exfoliating lesions occurred in 0.15% of patients. Discontinue for life-threatening cutaneous reactions. Withhold GILOTRIF for severe and prolonged cutaneous reactions. (2.3, 5.2)
Interstitial lung disease (ILD): Occurs in 1.5% of patients. Withhold GILOTRIF for acute onset or worsening of pulmonary symptoms. Discontinue GILOTRIF if ILD is diagnosed. (2.3, 5.3)
Hepatic toxicity: Fatal hepatic impairment occurs in 0.18% of patients. Monitor with periodic liver testing. Withhold or discontinue GILOTRIF for severe or worsening liver tests. (2.3, 5.4)
Keratitis: Occurs in 0.8% of patients. Withhold GILOTRIF for keratitis eva luation. Withhold or discontinue GILOTRIF for confirmed ulcerative keratitis. (2.3, 5.5)
Embryofetal toxicity: Can cause fetal harm. Advise females of the potential hazard to the fetus and to use highly effective contraception. (5.6)