Vandetanib

IMPORTANT WARNING:

Vandetanib may cause QT prolongation (an irregular heart rhythm that can lead to fainting, loss of consciousness, seizures, or sudden death). Tell your doctor if you or anyone in your family has or has ever had long QT syndrome (an inherited condition in which a person is more likely to have QT prolongation) or you have or have ever had low levels of calcium, potassium or magnesium in your blood, an irregular heartbeat, heart failure, or a heart attack. Tell your doctor and pharmacist if you are taking chloroquine (Aralen); clarithromycin (Biaxin, in Prevpac); haloperidol (Haldol); medications for an irregular heartbeat such as amiodarone (Cordarone, Pacerone), disopyramide (Norpace), dofetilide (Tikosyn), procainamide, and sotalol (Betapace); certain medications for nausea such as dolasetron (Anzemet) and granisetron (Sancuso); methadone (Dolophine, Methadose); moxifloxacin (Avelox); and pimozide (Orap). If you experience any of the following symptoms, stop taking vandetanib and call your doctor immediately or get emergency medical treatment: fast, pounding, or irregular heartbeat; fainting; lightheadedness; or loss of consciousness. Vandetanib may remain in your body for several months after you stop taking the medication, so you may continue to be at risk of side effects during that time.

Keep all appointments with your doctor and the laboratory. Your doctor will order certain tests, such as blood tests and electrocardiograms (EKGs, tests that record the electrical activity of the heart) before and regularly during your treatment to be sure that it is safe for you to take vandetanib. Your doctor will also order these tests any time that your dose of vandetanib is changed or if you begin taking certain new medications.

A program called Caprelsa Risk Evaluation and Mitigation Strategy (REMS) has been set up to manage the risks of this medication. You will only be able to receive vandetanib if the doctor who prescribes your medication is enrolled in the program. You can only receive the medication from a pharmacy that participates in the program. Ask your doctor if you have any questions about participating in the program or how to get your medication.

Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with vandetanib and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm)or the manufacturer's website to obtain the Medication Guide.

Talk to your doctor about the risks of taking vandetanib.

WHY is this medicine prescribed?

Vandetanib is used to treat a certain type of thyroid cancer that cannot be treated by surgery or that has spread to other parts of the body. Vandetanib 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?

Vandetanib comes as a tablet to take by mouth. It is usually taken with or without food once a day. Take vandetanib 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 vandetanib 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 with a glass of water. Do not split, chew, or crush them. If a tablet is accidentally crushed, avoid contact with your skin. If any contact occurs, wash the affected area well with water.

If you are unable to swallow the tablets whole, you may dissolve them in water. Place the tablet in a glass that contains 2 ounces of plain, non-carbonated drinking water. Do not use any other liquid to dissolve the tablet. Stir the mixture for about 10 minutes until the tablet is in very small pieces; the tablet will not dissolve completely. Drink the mixture right away. Rinse the glass with another 4 ounces of non-carbonated water and drink the rinse water to be sure that you swallow all of the medication.

Your doctor may decrease your dose of vandetanib or tell you to stop taking vandetanib for a period of time 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 vandetanib even if you feel well. Do not stop taking vandetanib without talking to your doctor.

What SPECIAL PRECAUTIONS should I follow?

Before taking vandetanib,

• tell your doctor and pharmacist if you are allergic to vandetanib, any other medications, or any of the ingredients in vandetanib 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, and nutritional supplements you are taking or plan to take. Be sure to mention the medications listed in the IMPORTANT WARNING section and any of the following: carbamazepine (Tegretol, Carbatrol, Equetro), dexamethasone, phenobarbital, phenytoin (Dilantin, Phenytek), rifabutin (Mycobutin), rifampin (Rifadin, in Rifamate), rifapentin (Priftin), and thyroid hormones such as levothyroxine (Synthroid). 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 vandetanib, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.

• tell your doctor what herbal products you are taking, especially St. Johns Wort.

• tell your doctor if you have recently coughed up blood or had any other type of bleeding problems and if you have or have ever had high blood pressure, any type of skin disease, seizures, or lung, kidney or liver disease.

• tell your doctor if you are pregnant or plan to become pregnant. You should not become pregnant while you are taking vandetanib and for at least 4 months after your treatment. Talk to your doctor about birth control methods that you can use during your treatment. If you become pregnant while taking vandetanib, call your doctor immediately. Vandetanib may harm the fetus.

• tell your doctor if you are breast-feeding.

• you should know that vandetanib may make you feel drowsy, weak, or cause blurred vision. Do not drive a car or operate machinery until you know how this medication affects you.

• plan to avoid unnecessary or prolonged exposure to sunlight and to wear protective clothing, sunglasses, and sunscreen. Vandetanib may make your skin sensitive to sunlight during your treatment and for at least 4 months after stopping your treatment.

What SPECIAL DIETARY instructions should I follow?

Unless your doctor tells you otherwise, continue your normal diet.

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

If your next dose is due in 12 hours or more, take the missed dose as soon as you remember it. However, if the next dose will be taken in less than 12 hours, 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?

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

• nausea
• vomiting
• heartburn
• loss of appetite
• weight loss
• stomach pain
• runny nose
• extreme tiredness
• weakness
• difficulty falling asleep or staying asleep
• depression

Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING section, call your doctor immediately or get emergency medical treatment:

• diarrhea
• rash or acne
• dry, peeling, or itchy skin
• blisters or sores on the skin or in the mouth
• redness of the face, hands, or soles of the feet
• muscle or joint aches
• fever
• chest pain (which may get worse with deep breaths or cough)
• hiccups or rapid breathing
• sudden shortness of breath
• persistent cough
• swelling of the hands, feet, ankles, or lower legs
• sudden weight gain
• numbness or weakness of the face, arm, or leg, especially on one side of the body
• sudden confusion
• difficulty speaking or understanding
• sudden trouble seeing in one or both eyes
• sudden trouble walking or balancing
• sudden severe headache
• seizures
• unusual bruising or bleeding

Vandetanib 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).

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.

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

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.

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 vandetanib. Your doctor will also check your blood pressure regularly during your treatment with vandetanib.

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.