Everolimus

Brand Name(s):

• Afinitor®
• Zortress®

Other Name(s):

• RAD001

IMPORTANT WARNING

Taking everolimus may decrease your ability to fight infection from bacteria, viruses, and fungi and increase the risk that you will get a serious or life-threatening infection. This includes infection with the BK virus, a serious virus that may damage the kidneys and cause a transplanted kidney to fail. Tell your doctor if you have or have ever had hepatitis B (a type of liver disease) or if you have or think you may have any type of infection now. Tell your doctor and pharmacist if you are taking other medications that suppress the immune system such as azathioprine (Imuran), cyclosporine (Gengraf, Neoral, Sandimmune), dexamethasone (Decadron, Dexpak), methotrexate (Rheumatrex, Trexall), prednisolone (Orapred, Pediapred, Prelone), prednisone (Sterapred), sirolimus (Rapamune), and tacrolimus (Prograf). If you experience any of the following symptoms, call your doctor immediately: excessive tiredness; yellowing of the skin or eyes; loss of appetite; nausea; joint pain; dark urine; pale stools; pain in the upper right part of the stomach; rash; difficult, painful, or frequent urination; ear pain or drainage; sinus pain and pressure; or sore throat, cough, fever, chills, feeling unwell or other signs of infection.

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

Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide [Zortress] or patient information leaflet [Afinitor]) when you begin treatment with everolimus 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 ( Web Site) or the manufacturer's website to obtain the Medication Guide.

Talk to your doctor about the risks of taking everolimus.

For patients who are taking everolimus to prevent transplant rejection:

You must take everolimus under the supervision of a doctor who is experienced in taking care of transplant patients and giving medications that suppress the immune system.

The risk that you will develop cancer, especially lymphoma (cancer of a part of the immune system) or skin cancer is increased. Tell your doctor if you or anyone in your family has or has ever had skin cancer or if you have fair skin. To reduce your risk of skin cancer, plan to avoid unnecessary or prolonged exposure to sunlight or ultraviolet light (tanning beds and sunlamps) and to wear protective clothing, sunglasses, and sunscreen during your treatment. If you experience any of the following symptoms, call your doctor immediately: a red, raised, or waxy area on the skin; new sores, bumps, or discoloration on the skin; sores that do not heal; lumps or masses anywhere in your body; skin changes; night sweats; swollen glands in the neck, armpits, or groin; trouble breathing; chest pain; weakness or tiredness that does not go away.

Everolimus may cause a blood clot in the blood vessels of your transplanted kidney. This is most likely to happen within the first 30 days after your kidney transplant and may cause the transplant to be unsuccessful. If you experience any of the following symptoms, call your doctor immediately: pain in your groin, lower back, side, or stomach; decreased urination or no urination; blood in your urine; dark-colored urine; fever; nausea; or vomiting.

Taking everolimus in combination with cyclosporine could cause damage to your kidneys. In order to reduce this risk, your doctor will adjust the dose of cyclosporine and monitor the levels of the medications and how your kidneys are working. If you experience either of the following symptoms, call your doctor immediately: decreased urination or swelling of the arms, hands, feet, ankles, or lower legs.

WHY is this medicine prescribed?

Everolimus (Afinitor) is used to treat advanced renal cell carcinoma (RCC; cancer that begins in the kidneys) that has already been treated unsuccessfully with other medications. Everolimus (Afinitor) is also used to treat subependymal giant cell astrocytoma (SEGA; a type of brain tumor) that cannot be treated with surgery in patients with tuberous sclerosis (TS; a genetic condition that causes tumors to grow in many organs). Everolimus (Zortress) is used with other medications to prevent transplant rejection (attack of the transplanted organ by the immune system of the person who received the organ) in certain adults who have received kidney transplants. Everolimus is in a class of medications called kinase inhibitors. Everolimus treats cancer by stopping cancer cells from reproducing and by decreasing blood supply to the cancer cells. Everolimus prevents transplant rejection by decreasing the activity of the immune system.

HOW should this medicine be used?

Everolimus comes as a tablet to take by mouth. When everolimus is taken to treat RCC or SEGA, it is usually taken once a day. When everolimus is taken to prevent transplant rejection, it is usually taken twice a day (every 12 hours) at the same time as cyclosporine. Everolimus should either always be taken with food or always without food. Take everolimus at around the same time(s) 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 everolimus exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Everolimus tablets come in individual blister packs that can be opened with scissors. Do not open a blister pack until you are ready to swallow the tablet it contains.

Swallow the tablets whole with a full glass of water; do not split, chew, or crush them.

If you are not able to swallow the tablets, ask your doctor or pharmacist what to do.

Your doctor may adjust your dose of everolimus during your treatment depending on the results of your blood tests, your response to the medication, side effects you experience, and changes in other medications that you take with everolimus. If you are taking everolimus to treat SEGA, your doctor will adjust your dose not more often than once every 2 weeks, and if you are taking everolimus to prevent transplant rejection, your doctor will adjust your dose not more often than once every 4-5 days. Your doctor may stop your treatment for a time if you experience severe side effects. Talk to your doctor about how you are feeling during your treatment with everolimus.

Are there OTHER USES for this medicine?

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

What SPECIAL PRECAUTIONS should I follow?

Before taking everolimus,

• tell your doctor and pharmacist if you are allergic to everolimus, sirolimus (Rapamune), temsirolimus (Torisel), any other medications, or any of the ingredients in everolimus tablets. Ask your pharmacist for a list of the ingredients.
• tell your doctor and pharmacist what 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: angiotensin-converting enzyme (ACE) inhibitors; aprepitant (Emend); certain antibiotics such as clarithromycin (Biaxin, in Prevpac), erythromycin (E.E.S., E-Mycin, Erythrocin), rifabutin (Mycobutin), rifampin (Rifadin, in Rifamate, in Rifater), rifapentine (Priftin), and telithromycin (Ketek); certain antifungals such as fluconazole (Diflucan), itraconazole (Sporanox), ketoconazole (Nizoral), and voriconazole (Vfend); cholesterol-lowering medications such as lovastatin (Altoprev, Mevacor, in Advicor) and simvastatin (Zocor, in Simcor, in Vytorin); digoxin (Digitek, Lanoxicaps, Lanoxin); diltiazem (Cardizem, Dilacor, Tiazac); certain medications for human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) including amprenavir (Agenerase), atazanavir (Reyataz), efavirenz (in Atripla, Sustiva), fosamprenavir (Lexiva), indinavir (Crixivan), nelfinavir (Viracept), nevirapine (Viramune), ritonavir (Norvir, in Kaletra), and saquinavir (Invirase); certain medications for seizures such as carbamazepine (Carbatrol, Epitol, Tegretol), phenobarbital (Luminal), and phenytoin (Dilantin, Phenytek); medications that suppress the immune system; nefazodone; nicardipine (Cardene); and verapamil (Calan, Covera, Isoptin, Verelan). 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 everolimus, 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. John's wort.
• tell your doctor if you have or have ever had diabetes; high levels of cholesterol or triglycerides in your blood; liver disease; or any condition that prevents you from digesting foods containing sugar, starch, or dairy products normally.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. You should not become pregnant during your treatment with everolimus or for 8 weeks after your treatment. You must use birth control during this time. Talk to your doctor about methods of birth control that will work for you. If you become pregnant while taking everolimus, call your doctor. Everolimus may harm the fetus.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking everolimus.
• do not have any vaccinations without talking to your doctor. During your treatment with everolimus, you should avoid close contact with other people who have recently been vaccinated.
• you should know that you may develop sores or swelling in your mouth during your treatment with everolimus. Tell your doctor if you develop sores or feel pain in your mouth. Your doctor may recommend a mouthwash or gel to relieve your symptoms. However, you should not use any mouthwash without talking to your doctor or pharmacist because certain types of mouthwash that contain alcohol or peroxide can worsen the sores and swelling.
• you should know that wounds or cuts, including the cut in the skin made during a kidney transplant may heal more slowly than normal or may not heal properly during your treatment with everolimus. Call your doctor right away if the cut in the skin from your kidney transplant or any other wound becomes warm, red, painful, or swollen, fills with blood, fluid, or pus, or begins to open.

What SPECIAL DIETARY instructions should I follow?

Do not eat star fruit, Seville oranges, grapefruit or drink grapefruit juice while taking this medication.

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

If you remember the missed dose within 6 hours of the time you were scheduled to take it, take the missed dose right away. However, if more than 6 hours have passed since the scheduled time, 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?

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

Keep this medication in the blister pack it came in, tightly closed, and out of reach of children. Store it at room temperature and away from light and excess heat and moisture (not in the bathroom). Keep the blister packs and tablets dry. Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.

What should I do in case of OVERDOSE?

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

What OTHER INFORMATION should I know?

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.

AHFS® Consumer Medication Information. © Copyright, The American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland. All Rights Reserved. Duplication for commercial use must be authorized by ASHP.

Selected Revisions: March 16, 2011.