IMPORTANT SAFETY INFORMATION FOR GILOTRIF

IMPORTANT SAFETY INFORMATION FOR PATIENTS ABOUT GILOTRIF® (afatinib) TABLETS

What is GILOTRIF?


GILOTRIF is a prescription medicine used to treat people with non-small cell lung cancer (NSCLC):

  • that has certain types of abnormal epidermal growth factor receptor (EGFR) genes. Your doctor will perform a test to check for certain types of abnormal EGFR genes, and make sure that GILOTRIF is right for you. GILOTRIF may be used when you have not had previous treatment for cancer that has spread to other parts of the body. It is not known if GILOTRIF is safe and effective in treating lung cancer with other abnormal EGFR genes

or

  • that is squamous type and has spread to other parts of the body after you have tried chemotherapy that contains platinum

It is not known if GILOTRIF is safe and effective in children.

IMPORTANT SAFETY INFORMATION ABOUT GILOTRIF

Before you take GILOTRIF, tell your doctor if you:

  • have kidney or liver problems
  • have lung or breathing problems other than lung cancer
  • have a history of severe dry eye or any other eye problems. Tell your doctor if you wear contact lenses.
  • have heart problems
  • have any other medical conditions
  • are pregnant or plan to become pregnant. GILOTRIF can harm your unborn baby. You should not become pregnant while taking GILOTRIF.
    • Women who are able to become pregnant should use effective birth control during treatment with GILOTRIF and for at least 2 weeks after your last dose of GILOTRIF. Talk to your doctor about birth control methods that may be right for you.
    • Tell your doctor right away if you become pregnant while taking GILOTRIF.
  • are breastfeeding or plan to breastfeed. It is not known if GILOTRIF passes into your breast milk. Do not breastfeed while taking GILOTRIF and for 2 weeks after your last dose of GILOTRIF. Talk to your doctor about the best way to feed your baby if you take GILOTRIF.

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. GILOTRIF may affect the way other medicines work, and other medicines may affect the way GILOTRIF works.

What to avoid while taking GILOTRIF

Limit your time in the sun. GILOTRIF can make your skin sensitive to the sun. You could get or have worsening rash or acne. You could get a severe sunburn. Use sunscreen and wear a hat and clothes that cover your skin while you are taking GILOTRIF if you have to be in sunlight.

GILOTRIF may cause serious side effects, including: 

  • Diarrhea. Diarrhea is common with GILOTRIF and may sometimes be severe. Severe diarrhea can cause loss of body fluid (dehydration) and kidney problems that can sometimes lead to death. During your treatment with GILOTRIF, your doctor should prescribe medicines to treat diarrhea. Take this medicine exactly as your doctor tells you to. Tell your doctor if you have diarrhea. Get medical attention right away if your diarrhea does not go away or becomes severe.
  • Skin reactions. GILOTRIF can cause redness, rash, and acne. It is important to get treatment for skin reactions as soon as you notice them. Take medicines to help skin reactions exactly as your doctor tells you to. Get medical attention right away if you develop severe skin reactions such as peeling or blistering of the skin, or blisters in your mouth. 
  • Lung or breathing problems. GILOTRIF may cause inflammation of the lung that may lead to death. Symptoms may be similar to those symptoms from lung cancer. Tell your doctor right away if you have any new or worsening lung problems, or any combination of the following symptoms: trouble breathing or shortness of breath, cough, or fever.
  • Liver problems. GILOTRIF can cause liver problems that can sometimes lead to death. Tell your doctor right away if you have any symptoms of a liver problem which may include:
    • yellowing of your skin or the white part of your eyes (jaundice)
    • dark or brown (tea colored) urine
    • pain on the upper right side of your stomach area (abdomen)
    • bleeding or bruising more easily than normal
    • feeling very tired

Your doctor will do blood tests to check your liver function during your treatment with GILOTRIF.

  • Eye problems. Tell your doctor right away if you have symptoms of eye problems. Symptoms may include:
    • eye pain, swelling, redness, or tearing
    • blurred vision
    • sensitivity to light
    • other changes in your vision
  • Heart problems. Tell your doctor right away if you have any symptoms of a heart problem which may include:
    • new or worsening shortness of breath while at rest or with activity
    • cough
    • tiredness
    • swelling of your ankles, feet, or legs
    • feeling that your heart is pounding or racing (palpitations)
    • sudden weight gain

The most common side effects of GILOTRIF include diarrhea, rash, mouth sores, nail inflammation, dry skin, acne, decreased appetite, nausea, vomiting, itching.

GILOTRIF may cause decreased fertility in females and males. Talk to your doctor if you have concerns about your fertility.

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all of the possible side effects of GILOTRIF. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit   www.fda.gov/medwatch   or call 1-800-FDA-1088.


IMPORTANT SAFETY INFORMATION FOR GILOTRIF® (afatinib) TABLETS

 

INDICATION AND USAGE

GILOTRIF is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test.

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

GILOTRIF is indicated for the treatment of patients with metastatic squamous NSCLC progressing after platinum-based chemotherapy.

WARNINGS AND PRECAUTIONS

Diarrhea

  • 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 reduced dose.
  • 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 12 hours.

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 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. Treatment should be discontinued in patients who develop severe hepatic impairment while taking GILOTRIF.

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, treatment with GILOTRIF should be interrupted or 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.

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 non-small cell lung cancer (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%). 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%), 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%); vomiting (4.8%); 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%).


Postmarketing Experience
 
 

Pancreatitis has been reported during post-marketing use of GILOTRIF. The frequency and causal relationship of pancreatitis to GILOTRIF has not been established.

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 nursing infants from GILOTRIF, lactating women should not 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 May 2016