GILOTRIF

Generic Name/API: afatinib

Manufacturer: Boehringer Ingelheim

Dosage Forms & Strength & Pack Size:
Tablets: 40 mg, 30 mg, and 20 mg, 28’s

Storage:
Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F) [see USP Controlled Room
Temperature]. Dispense medication in the original container to protect from exposure to high humidity and light.

  • INDICATION
  • IMPORTANT SAFETY INFORMATION

GILOTRIF is a kinase inhibitor indicated for:
First-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have non-resistant epidermal growth factor
receptor (EGFR) mutations as detected by an FDA-approved test.

Limitation of Use: Safety and efficacy of GILOTRIF were not established in patients whose tumors have resistant EGFR mutations.
Treatment of patients with metastatic, squamous NSCLC progressing after platinum-based chemotherapy.

5 WARNINGS AND PRECAUTIONS

5.1 Diarrhea
Diarrhea has resulted in dehydration with or without renal impairment across the clinical experience; some
cases were fatal. Grade 3-4 diarrhea occurred in 697 (16%) of the 4257 patients who received GILOTRIF across
44 clinical trials. In LUX-Lung 3, diarrhea occurred in 96% of patients treated with GILOTRIF (n=229), of
which 15% were Grade 3 in severity and occurred within the first 6 weeks. Renal impairment as a consequence
of diarrhea occurred in 6% of patients treated with GILOTRIF, of which 1.3% were Grade 3. In LUX-Lung 8,
diarrhea occurred in 75% of patients treated with GILOTRIF (n=392), of which 10% were Grade 3 in severity
and 0.8% were Grade 4 in severity. Renal impairment as a consequence of diarrhea occurred in 7% of patients
treated with GILOTRIF, of which 2% were Grade 3 [see Adverse Reactions (6.1)].

 

For patients who develop prolonged Grade 2 diarrhea lasting more than 48 hours, or greater than or equal to
Grade 3 diarrhea, withhold GILOTRIF until diarrhea resolves to Grade 1 or less, and resume GILOTRIF with
appropriate dose reduction [see Dosage and Administration (2.3)]. Provide patients with an anti-diarrheal agent
(e.g., loperamide) for self-administration at the onset of diarrhea and instruct patients to continue anti-diarrheal
therapy until loose bowel movements cease for 12 hours.
5.2 Bullous and Exfoliative Skin Disorders
Grade 3 cutaneous reactions characterized by bullous, blistering, and exfoliating lesions, occurred in 0.2% of
the 4257 patients who received GILOTRIF across clinical trials. In LUX-Lung 3, the overall incidence of
cutaneous reactions consisting of rash, erythema, and acneiform rash was 90%, and the incidence of Grade 3
cutaneous reactions was 16%. In addition, the incidence of Grade 1-3 palmar-plantar erythrodysesthesia
syndrome was 7%. In LUX-Lung 8, the overall incidence of cutaneous reactions consisting of rash, erythema,
and acneiform rash was 70%, and the incidence of Grade 3 cutaneous reactions was 7%. In addition, the
incidence of Grade 1-3 palmar-plantar erythrodysesthesia syndrome was 1.5% [see Adverse Reactions (6.1)].
Discontinue GILOTRIF in patients who develop life-threatening bullous, blistering, or exfoliating lesions. For
patients who develop prolonged Grade 2 cutaneous adverse reactions lasting more than 7 days, intolerable
Grade 2, or Grade 3 cutaneous reactions, withhold GILOTRIF until the adverse reaction resolves to Grade 1 or
less, and resume GILOTRIF with appropriate dose reduction [see Dosage and Administration (2.3)].
Postmarketing cases consistent with toxic epidermal necrolysis (TEN) and Stevens Johnson syndrome (SJS)
have been reported in patients receiving GILOTRIF. The cases of TEN and SJS bullous skin reactions result
from a distinct and separate mechanism of toxicity than the bullous skin lesions secondary to the pharmacologic
action of the drug on the epidermal growth factor receptor. Discontinue GILOTRIF if TEN or SJS is suspected
[see Dosage and Administration (2.3)].
5.3 Interstitial Lung Disease (ILD)
Interstitial lung disease or ILD-like adverse reactions (e.g., lung infiltration, pneumonitis, acute respiratory
distress syndrome, or alveolitis allergic) occurred in 1.6% of the 4257 patients who received GILOTRIF across
clinical trials; of these, 0.4% were fatal. The incidence of ILD appeared to be higher in Asian patients (2.3%;
38/1657) as compared to Whites (1.0%; 23/2241). In LUX-Lung 3, the incidence of Grade ≥3 ILD was 1.3%
and resulted in death in 1% of GILOTRIF-treated patients. In LUX-Lung 8, the incidence of Grade ≥3 ILD was
0.9% and resulted in death in 0.8% of GILOTRIF-treated patients.
Withhold GILOTRIF during evaluation of patients with suspected ILD, and discontinue GILOTRIF in patients
with confirmed ILD [see Dosage and Administration (2.3)].
5.4 Hepatic Toxicity
In 4257 patients who received GILOTRIF across clinical trials, 9.7% had liver test abnormalities, of which
0.2% were fatal. In LUX-Lung 3, liver test abnormalities of any grade occurred in 17.5% of the patients treated
with GILOTRIF, of which 3.5% had Grade 3-4 liver test abnormalities. In LUX-Lung 8, liver test abnormalities
of any grade occurred in 6% of the patients treated with GILOTRIF, of which 0.2% had Grade 3-4 liver test
abnormalities.
Obtain periodic liver testing in patients during treatment with GILOTRIF. Withhold GILOTRIF in patients who
develop worsening of liver function [see Dosage and Administration (2.3)]. In patients who develop severe
hepatic impairment while taking GILOTRIF, treatment should be discontinued.
Reference ID: 4207081
6
5.5 Keratitis
Keratitis, characterized as acute or worsening eye inflammation, lacrimation, light sensitivity, blurred vision,
eye pain, and/or red eye occurred in 0.7% of patients treated with GILOTRIF among 4257 patients across
clinical trials, of which 0.05% of patients experienced Grade 3 keratitis. Keratitis was reported in 2.2% patients
in LUX-Lung 3, with Grade 3 in 0.4%. In LUX-Lung 8, keratitis was reported in 0.3% patients; there were no
patients with ≥Grade 3 keratitis.
Withhold GILOTRIF during evaluation of patients with suspected keratitis, and if diagnosis of ulcerative
keratitis is confirmed, treatment with GILOTRIF should be interrupted or discontinued [see Dosage and
Administration (2.3)]. If keratitis is diagnosed, the benefits and risks of continuing treatment should be carefully
considered. GILOTRIF should be used with caution in patients with a history of keratitis, ulcerative keratitis, or
severe dry eye [see Adverse Reactions (6.1)]. Contact lens use is also a risk factor for keratitis and ulceration.
5.6 Embryo-Fetal Toxicity
Based on findings from animal studies and its mechanism of action, GILOTRIF can cause fetal harm when
administered to a pregnant woman. Administration of afatinib to pregnant rabbits during organogenesis at
exposures approximately 0.2 times the exposure in humans at the recommended dose of 40 mg daily resulted in
embryotoxicity and, in rabbits showing maternal toxicity, increased abortions at late gestational stages. Advise
pregnant women and females of reproductive potential of the potential risk to a fetus.
Advise females of reproductive potential to use effective contraception during treatment, and for at least 2
weeks after the last dose of GILOTRIF [see Use in Specific Populations (8.1 and 8.3)].

Scroll to Top