GILOTRIF™ (afatinib) tablets

GILOTRIF tablets for oral administration are available in 40 mg, 30 mg, or 20 mg of afatinib (equivalent to 59.12 mg, 44.34 mg, or 29.56 mg afatinib dimaleate, respectively). The inactive ingredients of GILOTRIF are the following: Tablet Core: lactose monohydrate, microcrystalline cellulose, crospovidone, colloidal silicon dioxide, magnesium stearate. Coating: hypromellose, polyethylene glycol, titanium dioxide, talc, polysorbate 80, FD&C Blue No. 2 (40 mg and 30 mg tablets only).

Afatinib demonstrated inhibition of autophosphorylation and in vitro proliferation of cell lines expressing wild-type EGFR or those expressing selected EGFR exon 19 deletion mutations or exon 21 L858R mutations, including some with a secondary T790M mutation, at afatinib concentrations achieved, at least transiently, in patients. In addition, afatinib inhibited in vitro proliferation of cell lines overexpressing HER2.

Treatment with afatinib resulted in inhibition of tumor growth in nude mice implanted with tumors either overexpressing wild type EGFR or HER2 or in an EGFR L858R/T790M double mutant model.

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

WARNINGS AND PRECAUTIONS:

1. Diarrhea: Diarrhea may result in dehydration and renal failure. Withhold GILOTRIF for severe and prolonged diarrhea not responsive to anti-diarrheal agents.
2. 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.
3. 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.
4. 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.
5. Keratitis: Occurs in 0.8% of patients. Withhold GILOTRIF for keratitis evaluation. Withhold or discontinue GILOTRIF for confirmed ulcerative keratitis.
6. Embryofetal toxicity: Can cause fetal harm. Advise females of the potential hazard to the fetus and to use highly effective contraception.

To report SUSPECTED ADVERSE REACTIONS, contact Boehringer Ingelheim Pharmaceuticals, Inc. at (800) 542-6257 or (800) 459-9906 TTY or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS
Co-administration of P-gp inhibitors can increase afatinib exposure. Reduce GILOTRIF by 10 mg per day if not tolerated. Co-administration of chronic P-gp inducers orally can decrease afatinib exposure. Increase GILOTRIF by 10 mg per day as tolerated.

USE IN SPECIFIC POPULATIONS
Nursing mothers: Discontinue drug or nursing.

See PACKAGE INSERT for PATIENT COUNSELING INFORMATION and Medication Guide.

Tablets: 40 mg, 30 mg, and 20 mg

Distributed by:
Boehringer Ingelheim Pharmaceuticals, Inc.
Ridgefield, CT 06877 USA

Licensed from:
Boehringer Ingelheim International GmbH
GILOTRIF is a trademark of and used under license from Boehringer Ingelheim International GmbH.

Copyright 2013 Boehringer Ingelheim International GmbH
ALL RIGHTS RESERVED
Revised: November 2013

IT5562EK252013
302972-03

Gilotrif™ 20 mg Tablets
NDC: 0597-0141-30

DRUG UPDATE
Drug:  GILOTRIF ® (afatinib) tablets, for oral use
[Drug information  /  PDF]  
Dosing:  Click (+) next to Dosage and Administration section (drug info link)

Initial U.S. Approval:  2013