Afinitor

Afinitor (everolimus) is a targeted cancer medicine that also treats certain tumors and seizures caused by a genetic condition called tuberous sclerosis complex (TSC). It is taken once a day as a tablet.

Afinitor (everolimus) works by blocking a protein called mTOR (mammalian target of rapamycin), which normally helps cells grow, divide, and form new blood vessels. In many cancers and in tuberous sclerosis complex, this pathway is overactive. By binding to a protein inside the cell (FKBP-12) and switching off mTOR activity, everolimus slows cell growth, reduces the blood supply that tumors need, and lowers how much glucose cells take up. In TSC, faults in the TSC1 or TSC2 gene leave mTOR overactive, which is linked to both tumor growth and seizures. Afinitor belongs to the drug class called kinase inhibitors.

Afinitor Disperz (everolimus tablets for oral suspension) is a separate dosage form that is prepared as a suspension in water before it is taken, rather than swallowed whole like an Afinitor tablet, and is used to treat TSC-associated SEGA and TSC-associated partial-onset seizures.

Afinitor (everolimus) first received FDA approval on March 30, 2009. Generic versions are available.

Afinitor is a prescription kinase inhibitor approved for:

• advanced hormone receptor-positive, HER2-negative breast cancer, along with exemestane, in postmenopausal women who have already received certain other medicines for their cancer.
• a type of pancreatic cancer known as pancreatic neuroendocrine tumor (PNET) in adults, that has progressed and cannot be treated with surgery.
• a type of cancer known as neuroendocrine tumor (NET) of the stomach and intestine (gastrointestinal), or lung in adults that has progressed and cannot be treated with surgery.
• advanced kidney cancer (renal cell carcinoma or RCC) in adults when certain other medicines have not worked.
• people with the following types of tumors that are seen with a genetic condition called tuberous sclerosis complex (TSC): adults with a kidney tumor called angiomyolipoma, when their kidney tumor does not require surgery right away adults and children 1 year of age and older with a brain tumor called subependymal giant cell astrocytoma (SEGA) when the tumor cannot be removed completely by surgery.

Afinitor is not for use in people with carcinoid tumors that actively produce hormones.

Afinitor can cause serious side effects, including:

• Lung or breathing problems. In some people lung or breathing problems may be severe and can lead to death. Tell your healthcare provider right away if you have any of these symptoms: New or worsening cough Shortness of breath Chest pain Difficulty breathing or wheezing
• Infections, such as pneumonia, or a bacterial, fungal or viral infection. Viral infections may include active hepatitis B in people who have had hepatitis B in the past (reactivation). In some people (including adults and children) these infections may be severe and can lead to death. You may need to be treated as soon as possible. Tell your healthcare provider right away if you have a temperature of 100.5°F or above, chills, or do not feel well. Symptoms of hepatitis B or infection may include the following: Fever Chills Skin rash Joint pain and swelling Tiredness Loss of appetite Nausea Pale stools or dark urine Yellowing of the skin Pain in the upper right side of the stomach
• Severe allergic reactions. Call your healthcare provider or get medical help right away if you get signs and symptoms of a severe allergic reaction, including: rash, itching, hives, flushing, trouble breathing or swallowing, chest pain or dizziness.
• Possible increased risk for a type of allergic reaction called angioedema, in people who take an Angiotensin-Converting Enzyme (ACE) inhibitor medicine during treatment with Afinitor. Talk with your healthcare provider before taking Afinitor if you are not sure if you take an ACE inhibitor medicine. Get medical help right away if you have trouble breathing or develop swelling of your tongue, mouth, or throat during treatment with Afinitor.
• Mouth ulcers and sores. Mouth ulcers and sores are common during treatment with Afinitor but can also be severe. When you start treatment with Afinitor, your healthcare provider may tell you to also start a prescription mouthwash to reduce the likelihood of getting mouth ulcers or sores and to reduce their severity. Follow your healthcare provider's instructions on how to use this prescription mouthwash. If you develop pain, discomfort, or open sores in your mouth, tell your healthcare provider. Your healthcare provider may tell you to restart this mouthwash or to use a special mouthwash or mouth gel that does not contain alcohol, peroxide, iodine, or thyme.
• Kidney failure. In some people, this may be severe and can lead to death. Your healthcare provider should do tests to check your kidney function before and during your treatment with Afinitor.

If you have any of the serious side effects listed above, you may need to stop taking Afinitor for a while or use a lower dose. Follow your healthcare provider's instructions.

• Your healthcare provider will prescribe the dose of Afinitor that is right for you.
• Take Afinitor exactly as your healthcare provider tells you to.
• Your healthcare provider may change your dose of Afinitor or tell you to temporarily interrupt dosing, if needed.
• Take only Afinitor or Afinitor Disperz. Do not mix Afinitor and Afinitor Disperz together.
• Use scissors to open the blister pack.
• Take Afinitor 1 time each day at about the same time.
• Take Afinitor the same way each time, either with food or without food.
• If you take too much Afinitor, contact your healthcare provider or go to the nearest hospital emergency room right away. Take the pack of Afinitor with you.
• If you miss a dose of Afinitor, you may take it if it is less than 6 hours after the time you normally take it. If it is more than 6 hours after you normally take your Afinitor, skip the dose for that day. The next day, take Afinitor at your usual time. Do not take 2 doses to make up for a missed dose. If you are not sure about what to do, call your healthcare provider.
• You should have blood tests before you start Afinitor and as needed during your treatment. These will include tests to check your blood cell count, kidney and liver function, cholesterol, and blood sugar levels.
• If you take Afinitor to treat SEGA or certain types of seizures with TSC, you will also need to have blood tests regularly to measure how much medicine is in your blood. This will help your healthcare provider decide how much Afinitor you need to take.
• Swallow Afinitor tablets whole with a glass of water. Do not take any tablet that is broken or crushed.

You should not drink grapefruit juice or eat grapefruit during your treatment with Afinitor. It may make the amount of Afinitor in your blood increase to a harmful level.

Afinitor may affect the way other medicines work, and other medicines can affect how Afinitor works. Taking Afinitor with other medicines can cause serious side effects.

Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine. Especially tell your healthcare provider if you take:

• St. John's Wort (Hypericum perforatum)
• Cannabidiol oral solution
• Medicine for: Fungal infections Bacterial infections Tuberculosis Seizures HIV-AIDS Heart conditions or high blood pressure
• Medicines that weaken your immune system (your body's ability to fight infections and other problems)

Ask your healthcare provider or pharmacist if you are not sure if your medicine is one of those taken for the conditions listed above. If you are taking any medicines for the conditions listed above, your healthcare provider might need to prescribe a different medicine or your dose of Afinitor may need to be changed. You should also tell your healthcare provider before you start taking any new medicine.

Do not take Afinitor if you have had a severe allergic reaction to everolimus.

Talk to your healthcare provider before taking this medicine if you are allergic to:

• a medicine that contains sirolimus
• a medicine that contains temsirolimus

Ask your healthcare provider if you do not know.

Before taking Afinitor, tell your healthcare provider about all of your medical conditions, including if you:

• Have or have had kidney problems
• Have or have had liver problems
• Have diabetes or high blood sugar
• Have high blood cholesterol levels
• Have any infections
• Previously had hepatitis B
• Are scheduled to receive any vaccinations. You should not receive a "live vaccine" or be around people who have recently received a "live vaccine" during your treatment with Afinitor. If you are not sure about the type of immunization or vaccine, ask your healthcare provider. For children with TSC and SEGA or certain types of seizures, work with your healthcare provider to complete the recommended childhood series of vaccines before your child starts treatment with Afinitor.
• Are pregnant, can become pregnant, or have a partner who can become pregnant. Afinitor can cause harm to your unborn baby.
• Are breastfeeding or plan to breastfeed
• Are planning to have surgery or if you have had a recent surgery. You should stop taking Afinitor at least 1 week before planned surgery.
• Have received radiation therapy or are planning to receive radiation therapy in the future.

Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Pregnancy

Females who can become pregnant:

• Your healthcare provider will give you a pregnancy test before you start treatment with Afinitor.
• You should use effective birth control during treatment and for 8 weeks after your last dose of Afinitor.

Males with a female partner, you should use effective birth control during treatment and for 4 weeks after your last dose of Afinitor.

Talk to your healthcare provider about birth control methods that may be right for you during this time. If you become pregnant or think you are pregnant, tell your healthcare provider right away.

Breastfeeding

It is not known if Afinitor passes into your breast milk. Do not breastfeed during treatment and for 2 weeks after your last dose of Afinitor.

Serious side effects

Afinitor can cause serious side effects, including:

• See "What is the most important information I should know about Afinitor?" above.
• Risk of wound healing problems. Wounds may not heal properly during Afinitor treatment. Tell your healthcare provider if you plan to have any surgery before starting or during treatment with Afinitor. You should stop taking Afinitor at least 1 week before any planned surgery. Do take it for at least 2 weeks following major surgery and until your wound has healed adequately. Tell your healthcare provider if you have any surgery planned. Your healthcare provider should tell you when you may start taking Afinitor again after surgery.
• Increased blood sugar and fat (cholesterol and triglyceride) levels in the blood. Your healthcare provider should do blood tests to check your fasting blood sugar, cholesterol, and triglyceride levels in the blood before you start and during treatment with Afinitor.
• Decreased blood cell counts. Afinitor can cause you to have decreased red blood cells, white blood cells, and platelets. Your healthcare provider should do blood tests to check your blood cell counts before you start and during treatment with Afinitor.
• Worsening side effects from radiation treatment, that can sometimes be severe. Tell your healthcare provider if you have had or are planning to receive radiation therapy.

Common side effects

The most common side effects of Afinitor in people with advanced hormone receptor-positive, HER2-negative breast cancer, advanced neuroendocrine tumors of the pancreas, stomach, and intestine (gastrointestinal) or lung, and advanced kidney cancer include:

• Infections
• Rash
• Feeling weak or tired
• Diarrhea
• Swelling of arms, hands, feet, ankles, face, or other parts of the body
• Stomach-area (abdominal) pain
• Nausea
• Fever
• Cough
• Headache
• Decreased appetite

The most common side effects of Afinitor in people who have SEGA, renal angiomyolipoma, or certain types of seizures with TSC include respiratory tract infections.

Other side effects that may occur with Afinitor:

• Absence of menstrual periods (menstruation). You may miss 1 or more menstrual periods. Tell your healthcare provider if this happens.
• Afinitor may affect fertility in females and may affect your ability to become pregnant. Talk to your healthcare provider if this is a concern for you.
• Afinitor may affect fertility in males and may affect your ability to father a child. Talk to your healthcare provider if this is a concern for you.

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

These are not all the possible side effects of Afinitor. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• Store Afinitor at room temperature, between 68°F and 77°F (20°C and 25°C).
• Keep Afinitor in the pack it comes in.
• Open the blister pack just before taking Afinitor.
• Keep Afinitor dry and away from light.
• Do not use Afinitor that is out of date or no longer needed.

Keep Afinitor and all medicines out of the reach of children.

Active ingredient: everolimus.

Inactive ingredients: anhydrous lactose, butylated hydroxytoluene, crospovidone, hypromellose, lactose monohydrate, and magnesium stearate.

Inactive ingredients in Afinitor Disperz: butylated hydroxytoluene, colloidal silicon dioxide, crospovidone, hypromellose, lactose monohydrate, magnesium stearate, mannitol, and microcrystalline cellulose.

Distributed by: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936.

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