Afatinib

Take the missed dose as soon as you remember it. However, if it is less than 12 hours before you are scheduled to take your next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Limit your time in the sun. Afatinib 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 afatinib if you have to be in sunlight.

• diarrhea. Diarrhea is common with afatinib 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 afatinib, 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. Afatinib 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. 

• lung or breathing problems. 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 
  • fever 
• liver problems. Your doctor will do blood tests to check your liver function during your treatment with afatinib. 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 

• eye problems. Tell your doctor right away if you have symptoms of eye problems which 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 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

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of afatinib, there are no specific foods that you must exclude from your diet when receiving this medication.

It is not known if afatinib crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. You should not do both.

Tell your doctor about all medicines you use, and those you start or stop using during your treatment with afatinib, especially:

• St. John's wort; or

• an antibiotic--erythromycin, rifampin; antifungal medicine--itraconazole, ketoconazole; HIV or AIDS medicine--nelfinavir, ritonavir, saquinavir; heart or blood pressure medication--amiodarone, quinidine, verapamil; medicine to prevent organ transplant rejection--cyclosporine, tacrolimus; seizure medication--carbamazepine, phenobarbital, phenytoin.

This list is not complete. Other drugs may interact with afatinib, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Afatinib is used to treat metastatic (cancer that has already spread) non-small cell lung cancer or NSCLC that has certain types of abnormal epidermal growth factor receptor (EGFR) genes in patients who have not received any treatments for cancer that has already spread to other parts of the body. afatinib is also used to treat patients with metastatic squamous NSCLC after receiving medicines containing platinum that did not work well.

afatinib is available only with your doctor's prescription.

It is very important that your doctor check your progress at regular visits to make sure that afatinib is working properly. Blood tests may be needed to check for unwanted effects.

Using afatinib while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant during therapy and for 2 weeks after the last dose of afatinib. If you think you have become pregnant while using the medicine, tell your doctor right away.

Check with your doctor right away if diarrhea occurs while taking afatinib. You may need medicines to help manage or prevent the diarrhea.

Skin reactions (eg, acne, rash, or skin redness) may occur while you are using afatinib. Check with your doctor right away if you develop severe skin reactions, such as blistering or peeling of the skin, or severe rash. Also, avoid overexposing your skin to sunlight. Always use sunscreen or sun blocking lotions and wear protective clothing and hats while you are using afatinib.

Check with your doctor right away if you start having breathing problems, shortness of breath, a cough, chest pain, fever, or chills. These could be symptoms of a serious lung problem.

Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, a loss of appetite, nausea, unusual tiredness or weakness, or yellow eyes or skin. These could be symptoms of a serious liver problem.

Check with your doctor immediately if you have vision changes, such as blurred vision, difficulty reading, or eye pain, irritation, or swelling, during or after treatment. Your doctor may want you to have your eyes checked by an eye doctor. Also, tell your doctor if you wear contact lenses.

Check with your doctor right away if you have trouble breathing, cough, fast or uneven heartbeat, rapid weight gain, swelling of your ankles or legs, or unusual tiredness or weakness.

Talk with your doctor before using afatinib if you plan to have children. afatinib may cause infertility in men and women (unable to have children).

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (eg, St. John's wort) or vitamin supplements.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take on an empty stomach. Take 1 hour before or 2 hours after meals.
• Avoid wearing contacts unless told to wear them by your doctor.
• To gain the most benefit, do not miss doses.
• Keep taking afatinib as you have been told by your doctor or other health care provider, even if you feel well.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is less than 12 hours until the next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Itching.
• Dry skin.
• Dry lips.
• Pimples (acne).
• Loose stools (diarrhea).
• Not hungry.
• Mouth irritation or mouth sores.
• Nosebleed.
• Runny nose.
• Weight loss.
• Change in skin or finger nails.
• Upset stomach or throwing up.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Dosage Forms & Strengths

tablet

• 20mg
• 30mg
• 40mg

Non-Small Cell Lung Cancer

40 mg PO qDay 1 hr ac or 2 hr pc

Administer until disease progression or inability to tolerate drug

Indications

• First-line treatment of patients with metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test
• Metastatic squamous NSCLC which has progressed after platinum-based chemotherapy

Dosage Modifications

Withhold dose for any drug-related adverse reactions of:

• NCI CTCAE Grade 3 or higher
• Diarrhea Grade 2 or higher persisting for 2 or more consecutive days while taking anti-diarrhea medication
• Cutaneous reactions Grade 2 that are prolonged (>7 days) or intolerable
• Renal dysfunction Grade 2 or higher
• Decrease dose (ie, 10 mg/day less than previous dose) and resume treatment when adverse reaction fully resolves, returns to baseline, or improves to Grade 1

Permanently discontinue for:

• Life-threatening bullous, blistering, or exfoliative skin lesions
• Confirmed interstitial lung disease
• Severe drug-induced hepatic impairment
• Persistent ulcerative keratitis
• Symptomatic left ventricular dysfunction
• Severe or intolerable adverse reaction occurring at a dose of 20 mg/day

Coadministration with P-gp inhibitors

• For patients who require therapy with a P-gp inhibitor, reduce afatinib daily dose by 10 mg if not tolerated
• Resume previous dose after P-gp inhibitor is discontinued as tolerated

Coadministration with P-gp inducers

• For patients who require chronic therapy with a P-gp inducer, increase afatinib daily dose by 10 mg as tolerated
• Resume the previous dose 2 to 3 days after P-gp inducer is discontinued

Renal impairment

• Mild (CrCl 60-89 mL/min): Adjustment to starting dose not required
• Moderate (CrCl 30-59 mL/min or severe (CrCl <30 mL/min): Closely monitor and adjust dose if not tolerated
• Severe (CrCl 15-30 mL/min): 30 mg once daily
• Severe (CrCl<15 mL/min/1.73 m²): Not studied

Hepatic impairment

• Mild-to-moderate (Child Pugh A or B): Adjustment to starting dose not required
• Severe (Child Pugh C): Closely monitor and adjust dose if not tolerated

Dosing Considerations

Safety and efficacy have not been established in tumors with other EGFR mutations than those listed in the approved indication

Afatinib was approved concurrently with the diagnostic companion test, therascreen EGFR RGQ PCR Kit

Information on FDA-approved tests for the detection of EGFR mutations in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics

CNS Tumors (Orphan)

Orphan designation for treatment of malignant brain and CNS tumors

Sponsor

• Boehringer Ingelheim Pharmaceuticals, Inc; 900 Ridgebury Road, PO Box 368; Ridgefield, CT 06877-0368

Safety and efficacy not established

Applies to afatinib: oral tablet

General

The most frequent serious adverse reactions reported were diarrhea (6.6%); vomiting (4.8%); and dyspnea, fatigue, and hypokalemia (1.7% each). Fatal adverse reactions 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 patients. The most frequent adverse reactions that led to dose reduction were diarrhea (20%), rash/acne (19%), paronychia (14%), and stomatitis (10%).

Discontinuation of therapy for adverse reactions was 14.0%. The most frequent adverse reactions that led to discontinuation were diarrhea (1.3%), ILD (0.9%), and paronychia (0.9%).[Ref]

Gastrointestinal

Very common (10% or more): Diarrhea (96%), stomatitis (71%), cheilitis (12%)[Ref]

Dermatologic

Very common (10% or more): Acneiform rash/dermatitis (90%), paronychia (58%), dry skin (31%), pruritus (21%)[Ref]

Genitourinary

Very common (10% or more): Cystitis (13%)[Ref]

Hepatic

Very common (10% or more): Alanine aminotransferase increased (11%)
Common (1% to 10%): Aspartate aminotransferase increased (8%)[Ref]

Metabolic

Very common (10% or more): Decreased appetite (29%), weight decreased (17%)[Ref]

Ocular

Very common (10% or more): Conjunctivitis (11%)[Ref]

Other

Very common (10% or more): Pyrexia (12%)[Ref]

Respiratory

Very common (10% or more): Epistaxis (17%), rhinorrhea (11%)[Ref]

Some side effects of afatinib may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

-Mild Renal Dysfunction (CrCl 60 to 89 mL/min): No adjustment recommended.
-Moderate Renal Dysfunction (CrCl 30 to 59 mL/min): Closely monitor patients and adjust dose if not tolerated.
-Severe Renal Dysfunction (CrCl less than 30 mL/min): No data available. Closely monitor patients and adjust dose if not tolerated.

Consult WARNINGS section for dosing related precautions.