"The U.S. Food and Drug Administration today approved Gilotrif (afatinib) for patients with late stage (metastatic) non-small cell lung cancer (NSCLC) whose tumors express specific types of epidermal growth factor receptor (EGFR) gene mutations, a"...
Gilotrif Side Effects Center
Medical Editor: John P. Cunha, DO, FACOEP
Gilotrif (afatinib) a tyrosine kinase inhibitor used to treat non-small cell lung cancer (NSCLC) that has spread (metastasized), whose tumors have a genetic mutation called epidermal growth factor receptor (EGFR). Common side effects include diarrhea, rash, blisters or other skin lesions, inflammation of the mouth, infection of the skin around fingernails or toenails, dry skin, decreased appetite, or itching.
The recommended dose of Gilotrif is 40 mg orally once daily at least 1 hour before or 2 hours after a meal, until the disease progresses or the drug is no longer tolerated. Gilotrif may interact with ritonavir, cyclosporine A, ketoconazole, itraconazole, erythromycin, verapamil, quinidine, tacrolimus, nelfinavir, saquinavir, amiodarone, rifampicin, carbamazepine, phenytoin, phenobarbital, or St. John's wort. Tell your doctor all medications and supplements you use. Gilotrif should not be used during pregnancy. It can harm a fetus. It is unknown if this drug passes into breast milk. Consult your doctor before breastfeeding.
Our Gilotrif (afatinib) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
What is Prescribing information?
The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.
Gilotrif FDA Prescribing Information: Side Effects
The following adverse reactions are discussed in greater detail in other sections of the labeling:
- Diarrhea [see WARNINGS AND PRECAUTIONS]
- Bullous and Exfoliative Skin Disorders [see WARNINGS AND PRECAUTIONS]
- Interstitial Lung Disease [see WARNINGS AND PRECAUTIONS]
- Hepatic Toxicity [see WARNINGS AND PRECAUTIONS]
- Keratitis [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety evaluation of GILOTRIF is based on the data from more than 3800 patients, including 2135 NSCLC patients receiving GILOTRIF monotherapy at or above the recommended dose.
The data in Tables 1 and 2 below reflect exposure of 229 EGFR-TKI naïve GILOTRIF-treated patients with EGFR mutation-positive, metastatic, non-squamous, NSCLC enrolled in a randomized, multicenter, open-label trial (Study 1). Patients received GILOTRIF 40 mg daily until documented disease progression or intolerance to the therapy. A total of 111 patients were treated with pemetrexed/cisplatin. Patients were treated with pemetrexed 500 mg/m² followed after 30 minutes by cisplatin 75 mg/m² every three weeks for a maximum of six treatment courses.
The median exposure was 11.0 months for patients treated with GILOTRIF and 3.4 months for patients treated with pemetrexed/cisplatin. The overall trial population had a median age of 61 years; 61% of patients in the GILOTRIF arm and 60% of patients in the pemetrexed/cisplatin arm were younger than 65 years. A total of 64% of patients on GILOTRIF and 67% of pemetrexed/cisplatin patients were female. More than two-thirds of patients were from Asia (GILOTRIF 70%; pemetrexed/cisplatin 72%).
Serious adverse reactions were reported in 29% of patients treated with GILOTRIF. The most frequent serious adverse reactions reported in patients treated with GILOTRIF were diarrhea (6.6%); vomiting (4.8%); and dyspnea, fatigue, and hypokalemia (1.7% each). Fatal adverse reactions in GILOTRIF-treated patients in Study 1 included pulmonary toxicity/ILD-like adverse reactions (1.3%), sepsis (0.43%), and pneumonia (0.43%).
Dose reductions due to adverse reactions were required in 57% of GILOTRIF-treated patients. The most frequent adverse reactions that led to dose reduction in the patients treated with GILOTRIF were diarrhea (20%), rash/acne (19%), paronychia (14%), and stomatitis (10%).
Discontinuation of therapy in GILOTRIF-treated patients for adverse reactions was 14.0%. The most frequent adverse reactions that led to discontinuation in GILOTRIF-treated patients were diarrhea (1.3%), ILD (0.9%), and paronychia (0.9%).
Clinical trials of GILOTRIF excluded patients with an abnormal left ventricular ejection fraction (LVEF), i.e., below the institutional lower limit of normal. In Study 1, all patients were evaluated for LVEF at screening and every 9 weeks thereafter in the GILOTRIF-treated group and as needed in the pemetrexed/cisplatin group. More GILOTRIF-treated patients (2.2%; n=5) experienced ventricular dysfunction (defined as diastolic dysfunction, left ventricular dysfunction, or ventricular dilation; all < Grade 3) compared to chemotherapy-treated patients (0.9%; n=1).
Table 1 : Adverse Reactions Reported in ≥ 10% of
GILOTRIF-Treated Patients in Study 1
|All Grades (%)||Grade 3* (%)||All Grades (%)||Grade 3* (%)|
|Skin and subcutaneous tissue disorders|
|Infections and infestations|
|Metabolism and nutrition disorders|
|Respiratory, thoracic and mediastinal disorders|
|General disorders and administration site conditions|
|*None of the adverse reactions
in this table except stomatitis (one patient on GILOTRIF [0.4%]) were Grade 4
1Includes stomatitis, aphthous stomatitis, mucosal inflammation, mouth ulceration, oral mucosa erosion, mucosal erosion, mucosal ulceration
2Includes group of rash preferred terms, acne, acne pustular, dermatitis acneiform
3Includes paronychia, nail infection, nail bed infection
Table 2 : Adverse Reactions
of Laboratory Abnormalities from the Investigations SOC Reported in ≥ 5%
of GILOTRIF-Treated Patients in Study 1
|All Grades (%)||Grades 3-4 (%)||All Grades (%)||Grades 3-4 (%)|
|Alanine aminotransferase increased||11||2||4||0|
|Aspartate aminotransferase increased||8||2||2||1|
|1Includes hypokalemia, blood potassium decreased
SOC=system organ class
Read the entire FDA prescribing information for Gilotrif (Afatinib Tablets, for Oral Use)
Additional Gilotrif Information
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