IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
GILOTRIF can cause diarrhea which may be severe and can result in
dehydration with or without renal impairment. In clinical studies,
some of these cases were fatal.
For patients who develop Grade 2 diarrhea lasting more than 48 hours
or Grade 3 or greater
diarrhea, withhold GILOTRIF until diarrhea resolves to Grade 1 or
less, and then resume at a
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
until loose stools cease for
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
- Discontinue GILOTRIF in patients who develop life-threatening
bullous, blistering, or
exfoliating 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
- Withhold GILOTRIF during evaluation of patients with suspected ILD,
and discontinue GILOTRIF in
patients with confirmed ILD.
- 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. Treatment should
be discontinued in patients
who develop severe hepatic impairment while taking GILOTRIF.
- Keratitis has been reported in patients taking GILOTRIF.
- Withhold GILOTRIF during evaluation of patients with suspected
keratitis. If diagnosis of
ulcerative keratitis is confirmed, treatment with GILOTRIF should be
discontinued. 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.
- 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 observed in clinical trials were as
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
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
- 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%), 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%).
Effect of P‑glycoprotein (P‑gp) Inhibitors and
- Concomitant use of P-gp inhibitors (including but not limited to
ritonavir, cyclosporine A,
ketoconazole, itraconazole, erythromycin, verapamil, quinidine,
saquinavir, and amiodarone) with GILOTRIF can increase exposure to
- Concomitant use of P-gp inducers (including but not limited to
phenytoin, phenobarbital, and St. John’s wort) with GILOTRIF can
decrease exposure to afatinib.
USE IN SPECIFIC POPULATIONS
- Because of the potential for serious adverse reactions in nursing
infants from GILOTRIF,
lactating women should not breastfeed during treatment with GILOTRIF
and for 2 weeks after the
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.
- 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
- 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.
INDICATIONS AND USAGE
GILOTRIF is indicated for the first-line treatment
patients with metastatic non-small cell lung cancer
(NSCLC) whose tumors have non-resistant epidermal growth
factor receptor (EGFR) mutations as detected by an
Limitation of Use: Safety and efficacy of GILOTRIF have not been
established in patients whose tumors have resistant EGFR mutations.
- GILOTRIF is indicated for the treatment of patients
with metastatic squamous NSCLC progressing after platinum‑based
GF PROF ISI 01.12.18
Accredo® is a registered trademark owned by Accredo Health Group, Inc.
This web site is intended for US residents only. Please visit your country's web site for information applicable
to your local labeling.