Neratinib

WHY is this medicine prescribed?

Neratinib is used to treat a certain type of hormone receptor-positive breast cancer (breast cancer that depends on hormones such as estrogen to grow) in adults after treatment with trastuzumab (Herceptin) and other medications. Neratinib is used along with capecitabine (Xeloda) to treat a certain type of advanced hormone receptor-positive breast cancer or breast cancer that has spread to other parts of the body after treatment with at least two other medications. Neratinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells.

Are there OTHER USES for this medicine?

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

HOW should this medicine be used?

Neratinib comes as a tablet to take by mouth. When neratinib is taken alone to treat breast cancer, it is usually taken with food once daily for one year. When neratinib is taken with capecitabine to treat advanced breast cancer or breast cancer that has spread to other parts of the body, it is usually taken once daily with food on days 1 to 21 of a 21-day cycle until your condition worsens or you develop serious side effects. Take neratinib at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take neratinib exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Swallow the tablets whole; do not split, chew, or crush them.

Your doctor may decrease your dose or temporarily or permanently stop your treatment of neratinib during your treatment. This depends on how well the medication works for you and the side effects you experience. Talk to your doctor about how you are feeling during your treatment. Continue to take neratinib even if you feel well. Do not stop taking neratinib without talking to your doctor.

What SPECIAL PRECAUTIONS should I follow?

Before taking neratinib,

• tell your doctor and pharmacist if you are allergic to neratinib, any other medications, or any of the ingredients in neratinib tablets. Ask your pharmacist or check the Medication Guide for a list of the ingredients.

• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: certain antibiotics including as ciprofloxacin (Cipro), clarithromycin (Biaxin, in Prevpac), erythromycin (E.E.S., E-Mycin, Erythrocin), and troleandomycin (no longer available in U.S.); certain antifungals including clotrimazole (Mycelex), fluconazole (Diflucan), itraconazole (Sporanox), ketoconazole (Nizoral), posaconazole (Noxafil), and voriconazole (Vfend); aprepitant (Emend); bosentan (Tracleer); certain calcium channel blockers including diltiazem (Cardizem, Tiazac, others) and verapamil (Calan, Verelan, others); cobicistat (Tybost); conivaptan (Vaprisol); crizotinib (Xalkori); cyclosporine (Gengraf, Neoral, Sandimmune); dabigatran (Pradaxa); digoxin (Lanoxin); dronedarone (Multaq); enzalutamide (Xtandi); fexofenadine (Allegra); fluvoxamine (Luvox); idelalisib (Zydelig); imatinib (Gleevec); certain medications for hepatitis C including boceprevir (no longer available in U.S., Victrelis), dasabuvir (in Viekira Pak), ombitasvir (in Technivie, in Viekira XR), and paritaprevir (in Technivie, in Viekira XR); certain medications for human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) including efavirenz (Sustiva, in Atripla), elvitegravir (in Genvoya, in Stribild), etravirine (Intelence), indinavir (Crixivan), lopinavir (in Kaletra), nelfinavir (Viracept), ritonavir (Norvir, in Kaletra), saquinavir (Invirase), and tipranavir (Aptivus); mitotane (Lysodren); modafinil (Provigil); nefazodone; proton pump inhibitors such as esomeprazole (Nexium), lansoprazole (Prevacid), omeprazole (Prilosec), pantoprazole (Protonix), and rabeprazole (AcipHex); rifampin (Rifadin, Rimactane, in Rifater); and certain medications for seizures including carbamazepine (Carbatrol, Epitol, Tegretol) and phenytoin (Dilantin, Phenytek). Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Many other medications may also interact with neratinib, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.

• if you are taking an antacid, take it at least 3 hours before or 3 hours after taking neratinib.

• if you are taking neratinib and a medication for indigestion, heartburn, or ulcers (an H₂ blocker) such as cimetidine, famotidine (Pepcid, in Duexis), nizatidine (Axid), or ranitidine (Zantac), take neratinib at least 2 hours before or at least 10 hours after taking the H₂ blocker.

• tell your doctor what herbal products you are taking, especially St. John's wort.

• tell your doctor if you have or have ever had liver disease.

• tell your doctor if you are pregnant, plan to become pregnant, or if you plan on fathering a child. You should not become pregnant while you are taking neratinib. If you are female, you will need to take a pregnancy test before you start treatment and should use birth control to prevent pregnancy during your treatment with neratinib and for at least 1 month after taking the final dose. If you are a male, you and your female partner should use birth control during your treatment with neratinib and continue for 3 months after your final dose. Talk to your doctor about birth control methods that you can use during your treatment. If you become pregnant while taking neratinib, call your doctor immediately. Neratinib may harm the fetus.

• tell your doctor if you are breastfeeding or plan to breastfeed. You should not breastfeed while taking neratinib and for up to 1 month after your final dose.

• you should know that neratinib often causes diarrhea, which can be severe. Your doctor will probably tell you to take loperamide (Imodium AD), an anti-diarrhea medication, to prevent dehydration (loss of too much water from your body) for the first 56 days of your treatment with neratinib. After 56 days of treatment, your doctor will adjust your loperamide dose so that you have 1 to 2 bowel movements every day while taking neratinib. Your doctor may also tell you to drink plenty of liquids, make changes in your diet, or take other medications to control the diarrhea. Call your doctor immediately if you have severe diarrhea (more than 2 bowel movements in 1 day or diarrhea that does not stop) or diarrhea along with weakness, dizziness, or fever while taking neratinib. Call your doctor immediately if you experience any of the following symptoms of dehydration: extreme thirst, dry mouth and/or skin, decreased urination, or fast heartbeat.

What SPECIAL DIETARY instructions should I follow?

Do not eat grapefruit or drink grapefruit juice while taking this medication.

What should I do IF I FORGET to take a dose?

Skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

What SIDE EFFECTS can this medicine cause?

Neratinib may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• diarrhea
• stomach pain
• heartburn
• bloating
• mouth ulcers
• loss of appetite
• weight loss
• nose bleeding
• nail problems or changes
• muscle spasms

Some side effects can be serious. If you experience any of these symptoms or those listed in the SPECIAL PRECAUTIONS section, call your doctor immediately:

• yellow eyes and skin
• dark urine
• pain or discomfort in the right upper stomach area
• tiredness
• nausea
• vomiting
• rash
• fever, difficulty urinating, pain when urinating, and other signs of infection

Neratinib may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

What should I know about STORAGE and DISPOSAL of this medication?

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

What should I do in case of OVERDOSE?

In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911.

Symptoms of overdose may include the following:

• diarrhea
• nausea
• vomiting
• stomach pain

What OTHER INFORMATION should I know?

Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests to check your body's response to neratinib.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.