Selumetinib

Selumetinib is used to treat neurofibromatosis type 1 (NF1; a nervous system disorder that causes tumors to grow on nerves) in children 2 years of age and older who have plexiform neurofibromas (PN; soft tumors) that cannot be completely removed by surgery. Selumetinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals the tumors to grow. This helps to stop or slow tumor growth.

Selumetinib comes as a capsule to take by mouth. It is usually taken twice a day on an empty stomach. Do not eat any food 2 hours before or for 1 hour after each dose. Take selumetinib at around the same time(s) every day, approximately 12 hours apart. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take selumetinib exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Swallow the capsules whole with water; do not open, chew, or crush them.

If you vomit after taking selumetinib, do not take another dose. Continue your regular dosing schedule.

Your doctor may decrease your dose or temporarily or permanently stop your treatment if you experience certain side effects. Be sure to tell your doctor how you are feeling during your treatment with selumetinib.

Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.

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

Before taking selumetinib,

• tell your doctor and pharmacist if you are allergic to selumetinib, any other medications, or any of the ingredients in selumetinib capsules. Ask your pharmacist 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: anticoagulants ('blood thinners') such as warfarin (Coumadin, Jantoven); antifungals such as fluconazole (Diflucan), itraconazole (Sporanox), ketoconazole (Nizoral), and voriconazole (Vfend); aprepitant (Emend); clarithromycin (Biaxin, in Prevpac); clopidogrel (Plavix); corticosteroids such as betamethasone (Celestone), budesonide (Entocort), cortisone (Cortone), dexamethasone (Decadron, Dexpak, Dexasone, others), hydrocortisone (Cortef, Hydrocortone), methylprednisolone (Medrol, Meprolone, others), prednisolone (Prelone, others), and prednisone (Rayos); diltiazem (Cardizem, Dilacor, Tiazac, others); erythromycin (E.E.S., E-Mycin, Erythrocin); certain medications for HIV including indinavir (Crixivan), nelfinavir (Viracept), ritonavir (Norvir, in Kaletra), and saquinavir (Fortovase, Invirase); idelalisib (Zydelig); nefazodone; phenobarbital; rifabutin (Mycobutin); rifampin (Rifadin, Rimactane, in Rifamate, in Rifater); verapamil (Calan, Covera); and vitamin E supplements. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor what herbal products you are taking, especially St. John's wort.
• tell your doctor if you have or have ever had vision problems, difficulty swallowing, or heart or liver disease.
• tell your doctor if you are pregnant, plan to become pregnant, or if you plan on fathering a child. If you are female, you will need to take a pregnancy test before you start treatment and use birth control to prevent pregnancy during your treatment and for at least 1 week after your final dose. If you are a male, you and your partner should use birth control during your treatment with selumetinib and for 1 week after your final dose. Talk to your doctor about birth control methods that you can use during your treatment. If you or your partner become pregnant while taking selumetinib, call your doctor immediately. Selumetinib may harm the fetus.
• tell your doctor if you are breastfeeding. You should not breastfeed while you are taking selumetinib and for 1 week after the final dose.

Avoid eating grapefruit or drinking grapefruit juice while taking this medication.

Take the missed dose as soon as you remember it. However, if it is within 6 hours of the 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.

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

• vomiting
• constipation
• stomach pain
• nausea
• dry skin
• headache
• mouth ulcers
• itching
• redness around the fingernails
• nose bleeding
• fatigue
• loss of appetite
• hair loss or hair color changes

Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately or get emergency medical treatment:

• fever
• unusual bleeding
• pale skin or tiredness
• blurred vision; loss of vision; dark spots in your vision; or other vision changes
• diarrhea
• rash, skin blisters or peeling
• muscle pain, aches, or weakness; or dark urine
• coughing or wheezing; shortness of breath; swelling of ankles and feet; or extreme tiredness

Selumetinib 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).

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). Do not remove the desiccant (small packet included with the capsules to absorb moisture) from your bottle.

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.

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.

Keep all appointments with your doctor, eye doctor, and the laboratory. Your doctor will order certain lab tests, including eye exams, before, during, and after your treatment to check your body's response to selumetinib.

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.

• Koselugo^®