Bullous and Exfoliative Skin Disorders
- GILOTRIF can result in cutaneous reactions consisting of rash, erythema, and acneiform rash.
In addition, palmar-plantar erythrodysesthesia syndrome was observed in clinical trials in patients taking GILOTRIF.
- Discontinue GILOTRIF in patients who develop life-threatening bullous, blistering, or exfoliating skin lesions.
For patients who develop Grade 2 cutaneous adverse reactions lasting more than 7 days, intolerable Grade 2, or
Grade 3 cutaneous reactions, withhold GILOTRIF. When the adverse reaction resolves to Grade 1 or less,
resume GILOTRIF with appropriate dose reduction.
- Postmarketing cases of toxic epidermal necrolysis (TEN) and Stevens Johnson syndrome (SJS) have been reported
in patients receiving GILOTRIF. Discontinue GILOTRIF if TEN or SJS is suspected.
Interstitial Lung Disease
- Interstitial Lung Disease (ILD) or ILD-like adverse reactions (e.g., lung infiltration, pneumonitis, acute respiratory
distress syndrome, or alveolitis allergic) occurred in patients receiving GILOTRIF in clinical trials. In some cases,
ILD was fatal. The incidence of ILD appeared to be higher in Asian patients as compared to white patients.
- Withhold GILOTRIF during evaluation of patients with suspected ILD, and discontinue GILOTRIF in patients with confirmed ILD.
Hepatic Toxicity
- Hepatic toxicity as evidenced by liver function tests abnormalities has been observed in patients taking GILOTRIF.
In 4257 patients who received GILOTRIF across clinical trials, 9.7% had liver test abnormalities,
of which 0.2% were fatal.
- Obtain periodic liver testing in patients during treatment with GILOTRIF. Withhold GILOTRIF in patients who develop
worsening of liver function. Discontinue treatment in patients who develop severe hepatic impairment while taking GILOTRIF.
Gastrointestinal Perforation
- Gastrointestinal (GI) perforation, including fatal cases, has occurred with GILOTRIF. GI perforation has been reported
in 0.2% of patients treated with GILOTRIF among 3213 patients across 17 randomized controlled clinical trials.
- Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), or anti-angiogenic
agents, or patients with increasing age or who have an underlying history of GI ulceration, underlying diverticular
disease, or bowel metastases may be at an increased risk of perforation.
- Permanently discontinue GILOTRIF in patients who develop GI perforation.
Keratitis
- Keratitis has been reported in patients taking GILOTRIF.
- Withhold GILOTRIF during evaluation of patients with suspected keratitis. If diagnosis of ulcerative keratitis is confirmed,
interrupt or discontinue GILOTRIF. 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. Contact lens use is also a risk factor for keratitis and ulceration.
Embryo-Fetal Toxicity
- GILOTRIF can cause fetal harm when administered to a pregnant woman. 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. Advise female patients to contact their healthcare provider
with a known or suspected pregnancy.
ADVERSE REACTIONS
Adverse Reactions observed in clinical trials were as follows:
First-line treatment of EGFR mutation-positive, metastatic NSCLC
- In GILOTRIF-treated patients (n=229) the most common adverse reactions (≥20% all grades & vs pemetrexed/cisplatin-treated
patients (n=111)) were diarrhea (96% vs 23%), rash/acneiform dermatitis (90% vs 11%), stomatitis (71% vs 15%), paronychia
(58% vs 0%), dry skin (31% vs 2%) and pruritus (21% vs 1%). Other clinically important adverse reactions observed in patients
treated with GILOTRIF include: decreased appetite (29%), nausea (25%), and vomiting (23%).
- 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 included pulmonary toxicity/ILD-like adverse
reactions (1.3%), sepsis (0.43%), and pneumonia (0.43%).
- More GILOTRIF-treated patients (2.2%) experienced ventricular dysfunction (defined as diastolic dysfunction, left
ventricular dysfunction, or ventricular dilation; all < Grade 3)
compared to chemotherapy-treated patients (0.9%).
Previously Treated, Metastatic Squamous NSCLC
- In GILOTRIF-treated patients (n=392) the most common adverse reactions (≥20% all grades & vs erlotinib-treated
patients (n=395)) were diarrhea (75% vs 41%), rash/acneiform dermatitis (70% vs 70%), stomatitis (30% vs 11%),
decreased appetite (25% vs 26%), and nausea (21% vs 16%).
- Serious adverse reactions were reported in 44% of patients treated with GILOTRIF. The most frequent serious adverse
reactions reported in patients treated with GILOTRIF were pneumonia (6.6%), diarrhea (4.6%), and dehydration and
dyspnea (3.1% each). Fatal adverse reactions in GILOTRIF-treated patients included ILD (0.5%), pneumonia (0.3%),
respiratory failure (0.3%), acute renal failure (0.3%), and general physical health deterioration (0.3%).
DRUG INTERACTIONS
Effect of P-glycoprotein (P-gp) Inhibitors and Inducers
- Concomitant use of P-gp inhibitors (including but not limited to ritonavir, cyclosporine A, ketoconazole, itraconazole,
erythromycin, verapamil, quinidine, tacrolimus, nelfinavir, saquinavir, and amiodarone) with
GILOTRIF can increase exposure to afatinib.
- Concomitant use of P-gp inducers (including but not limited to rifampicin, carbamazepine, phenytoin, phenobarbital,
and St. John's wort) with GILOTRIF can decrease exposure to afatinib.
USE IN SPECIFIC POPULATIONS
Lactation
Because of the potential for serious adverse reactions in breastfed infants from GILOTRIF, advise women not to
breastfeed during treatment with GILOTRIF and for 2 weeks after the final dose.
Females and Males of Reproductive Potential
GILOTRIF may reduce fertility in females and males of reproductive potential. It is not known if the effects on fertility are reversible.
Renal Impairment
Patients with severe renal impairment (estimated glomerular filtration rate [eGFR] 15 to 29 mL/min/1.73 m2) have a
higher exposure to afatinib than patients with normal renal function. Administer GILOTRIF at a starting dose of
30 mg once daily in patients with severe renal impairment. GILOTRIF has not been studied in patients
with eGFR <15 mL/min/1.73 m2 or who are on dialysis.
Hepatic Impairment
GILOTRIF has not been studied in patients with severe (Child Pugh C) hepatic impairment. Closely monitor
patients with severe hepatic impairment and adjust GILOTRIF dose if not tolerated.
GF PROF ISI 10.21.19
Please see the Full Prescribing Information,
including Patient Information.