What is Rapamune?

Rapamune weakens your body’s immune system, to help keep it from “rejecting” a transplanted organ such as a kidney. Organ rejection happens when the immune system treats the new organ as an invader and attacks it.

Rapamune is a prescription medicine used to prevent rejection (anti-rejection medicine) in people 13 years of age and older who have received a kidney transplant. Rejection is when your body’s immune system recognizes the new organ as a “foreign” threat and attacks it. Rapamune is used with other medicines called cyclosporine (Gengraf, Neoral, Sandimmune), and corticosteroids.

Rapamune is also given without other medicines to treat a rare lung disorder called lymphangioleiomyomatosis (LAM). LAM affects predominantly women of childbearing age. This disorder happens mostly in women and causes lung tumors that are not cancerous but can affect breathing.

Warnings

You should not use Rapamune if you have ever had a lung transplant or liver transplant.

Rapamune may cause your body to overproduce white blood cells. This can lead to cancer, severe brain infection causing disability or death, or a viral infection causing kidney transplant failure.

Call your doctor right away if you have: fever, flu symptoms, burning when you urinate, a new skin lesion, any change in your mental state, decreased vision, weakness on one side of your body, problems with speech or walking, or pain around your transplant.

Before taking this medicine

You should not use Rapamune if you are allergic to sirolimus, or if you have ever had a lung transplant or liver transplant.

Talk with your doctor about the risks and benefits of using this medicine. Rapamune can affect your immune system, and may cause overproduction of certain white blood cells. This can lead to cancer, severe brain infection causing disability or death, or a viral infection causing kidney transplant failure.

To make sure Rapamune is safe for you, tell your doctor if you have ever had:

• high cholesterol or triglycerides;
• cytomegalovirus (CMV);
• liver disease; or
• a family history of skin cancer (melanoma).

Do not use Rapamune if you are pregnant. Use effective birth control to prevent pregnancy while you are taking this medicine, and for at least 12 weeks after your last dose.

You should not breast-feed while using this medicine.

Rapamune should not be given to a child younger than 13 years old.

How should I take Rapamune?

Take Rapamune exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose.

Rapamune is usually taken once a day. If you also take cyclosporine, take it at least 4 hours before you take this medicine.

You may take Rapamune with or without food, but take it the same way every time.

Do not crush, chew, or break a Rapamune tablet. Tell your doctor if you have trouble swallowing the tablet whole.

Read and carefully follow any Instructions for Use provided with your medicine. Ask your doctor or pharmacist if you do not understand these instructions.

Rapamune oral liquid must be mixed only with water or orange juice, no other juices or liquids. Measure the liquid carefully. Use the dosing syringe provided, or use a medicine dose-measuring device (not a kitchen spoon).

Sirolimus can increase your risk of infection by changing the way your immune system works. You will need frequent medical tests. Your dosing schedule may be delayed based on the results of these tests.

You should not stop using Rapamune without your doctor’s advice. Stopping suddenly could make your condition worse.

Store the tablets at room temperature, away from heat, moisture, and light.

Store the oral liquid in the refrigerator. Do not freeze. You may notice a slight haze to the liquid. This haze should disappear when the liquid reaches room temperature.

If you are using Rapamune oral liquid with a disposable syringe, you may store a loaded syringe in the carrying case provided. Keep the case at room temperature and use the medicine within 24 hours. Use a disposable syringe only once and then throw it away.

Dosing information

Usual Adult Dose of Rapamune for Organ Transplant — Rejection Prophylaxis:

FOR PATIENTS AT LOW TO MODERATE IMMUNOLOGIC RISK:
Dosing by body weight:
-Less than 40 kg:
Loading dose: 3 mg/m2 on day 1
Maintenance: 1 mg/m2 once daily
-Greater than or equal to 40 kg:
Loading dose: 6 mg orally on day 1
Maintenance: 2 mg orally once daily

IN PATIENTS AT HIGH IMMUNOLOGIC RISK (defined as Black transplant recipients and/or repeat renal transplant recipients who lost a previous allograft for immunologic reason and/or patients with high-panel reactive antibodies [PRA; peak PRA level greater than 80%]):
-For patients receiving sirolimus with cyclosporine:
Loading Dose: Up to 15 mg on day one post-transplantation
Maintenance Dose: Beginning on day 2, an initial maintenance dose of 5 mg/day should be given. A trough level should be obtained between days 5 and 7, and the daily dose of sirolimus should be adjusted thereafter.
-Antibody induction therapy may be used.

Comments:
-It is recommended that this sirolimus be used in a regimen with cyclosporine and corticosteroids.
-Sirolimus should be taken consistently with or without food.
-Once the sirolimus maintenance dose is adjusted, patients should continue on the new maintenance dose for at least 7 to 14 days before further dosage adjustment with concentration monitoring.

MAINTENANCE THERAPY AFTER WITHDRAWAL OF CYCLOSPORINE:
-Cyclosporine withdrawal is not recommended in high-immunological risk patients. Following 2 to 4 months of combined therapy, withdrawal of cyclosporine may be considered in low-to-moderate risk patients. Cyclosporine should be discontinued over 4 to 8 weeks, and a necessary increase in the dosage of sirolimus (up to 4-fold) should be anticipated due to removal of metabolic inhibition by cyclosporine and to maintain adequate immunosuppressive effects. -Dose-adjusted trough target concentrations are typically 16 to 24 ng/mL for the first year post-transplant and 12 to 20 ng/mL thereafter (measured by chromatographic methodology).

Usual Adult Dose of Rapamune for Pulmonary Lymphangioleiomyomatosis:

-Initial dose: 2 mg/day
-Sirolimus whole blood trough concentrations should be measured in 10 to 20 days, with dosage adjustment to maintain concentrations between 5 and 15 ng/mL.

Comment:
-This drug should be taken consistently with or without food.

Usual Pediatric Dose of Rapamune for Organ Transplant — Rejection Prophylaxis:

FOR PATIENTS AT LOW TO MODERATE IMMUNOLOGIC RISK:
Greater than or equal to 13 years of age:
Dosing by body weight:
-Less than 40 kg:
Loading dose: 3 mg/m2 on day 1
Maintenance: 1 mg/m2 once daily
-Greater than or equal to 40 kg:
Loading dose: 6 mg orally on day 1
Maintenance: 2 mg orally once daily

What happens if I miss a dose?

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line .

What should I avoid while taking Rapamune?

Avoid exposure to sunlight or tanning beds. Rapamune may increase your risk of skin cancer. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

Avoid getting Rapamune oral liquid on your skin. Wash the skin with soap and water if this happens. If the medicine gets into your eyes, rinse them with plain water.

Grapefruit may interact with sirolimus and lead to unwanted side effects. Avoid the use of grapefruit and grapefruit juice while taking Rapamune.

Do not receive a “live” vaccine while using Rapamune. The vaccine may not work as well during this time, and may not fully protect you from disease. Live vaccines include measles, mumps, rubella (MMR), polio, rotavirus, typhoid, yellow fever, varicella (chickenpox), and zoster (shingles).

Rapamune side effects

Rapamune may cause a serious brain infection that can lead to disability or death. Call your doctor right away if you have any change in your mental state, decreased vision, weakness on one side of your body, or problems with speech or walking. These symptoms may start gradually and get worse quickly.

Get emergency medical help if you have signs of an allergic reaction to Rapamune: hives, rash, or peeling skin; wheezing, difficulty breathing, chest pain or tightness; feeling like you might pass out; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• redness, oozing, or slow healing of a skin wound;
• a new skin lesion, or a mole that has changed in size or color;
• unusual bleeding or bruising;
• sudden chest pain or discomfort, cough, feeling short of breath;
• tenderness around the transplanted kidney;
• signs of infection – fever, chills, painful mouth sores, skin sores, cold or flu symptoms, pain or burning when you urinate; or
• low red blood cells (anemia) – pale skin, unusual tiredness, feeling light-headed or short of breath, cold hands and feet.

Common Rapamune side effects may include:

• fever, cold symptoms such as stuffy nose, sneezing, sore throat;
• mouth sores;
• nausea, stomach pain, diarrhea;
• headache, muscle aches;
• chest pain;
• dizziness; or
• acne.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

What other drugs will affect Rapamune?

Tell your doctor about all your current medicines. Many drugs can interact with Rapamune, especially:

• bromocriptine (Cycloset, Parlodel);
• cyclosporine;
• danazol;
• St. John’s wort;
• tacrolimus;
• cholesterol-lowering medication;
• an antibiotic or antifungal medicine;
• antiviral medicine to treat HIV or hepatitis C;
• heart or blood pressure medication;
• medicine to reduce stomach acid or treat an ulcer; or
• seizure medicine.

What is Afinitor?

Afinitor is a cancer medicine that interferes with the growth of cancer cells and slows their spread in the body.

Afinitor is used to treat certain types of kidney cancer, breast cancer, or brain tumor. It is also used to treat certain types of advanced or progressive tumors of the stomach, intestines, or pancreas.

Afinitor is also used to treat certain types of seizures or non-cancerous (benign) tumors of the brain or kidney in people with a genetic condition called tuberous sclerosis complex.

This medication guide provides information about the Afinitor brand of everolimus. Zortress is another brand of everolimus used to prevent organ rejection after a kidney transplant.

Warnings

Afinitor can cause serious and sometimes fatal side effects. Call your doctor right away if you have: signs of infection–fever, chills, skin rash, joint pain, tiredness; lung problems–cough, chest pain, wheezing, shortness of breath; kidney problems–swelling, little or no urination; or liver problems–loss of appetite, dark urine, yellowing of your skin or eyes, or upper stomach pain.

If you have ever had hepatitis B, Afinitor can cause this condition to come back or get worse.

You may be more likely to have an allergic reaction if you take an “ACE inhibitor” heart or blood pressure medication while you are taking Afinitor. Tell your doctor about all your current medicines and any you start or stop using.

Before taking this medicine, tell your doctor if you have a breathing disorder such as asthma or COPD, liver disease (or a history of hepatitis B), an active infection, diabetes or high blood sugar, or high cholesterol.

Do not use everolimus if you are pregnant. It could harm the unborn baby. Use effective birth control while you are using this medicine and for at least 8 weeks after your treatment ends.

Before taking this medicine

You should not use Afinitor if you are allergic to everolimus, sirolimus (Rapamune), or temsirolimus (Torisel).

To make sure Afinitor is safe for you, tell your doctor if you have ever had:

• an active or chronic infection;
• liver disease, especially hepatitis B;
• kidney disease;
• diabetes or high blood sugar;
• high cholesterol;
• if you are scheduled to receive any vaccine; or
• high blood pressure.

Afinitor can harm an unborn baby or cause birth defects if the mother or the father is using this medicine.

• If you are a woman, do not use Afinitor if you are pregnant. You may need to have a negative pregnancy test before starting this treatment. Use effective birth control to prevent pregnancy while you are using this medicine and for at least 8 weeks after your last dose.
• If you are a man, use effective birth control if your sex partner is able to get pregnant. Keep using birth control for at least 4 weeks after your last dose.
• Tell your doctor right away if a pregnancy occurs while either the mother or the father is using Afinitor.

This medicine may affect fertility (ability to have children) in both men and women. However, it is important to use birth control to prevent pregnancy because Afinitor can harm an unborn baby.

You should not breastfeed while using this medicine and for at least 2 weeks after your last dose.

How should I take Afinitor?

Take Afinitor exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose.

Take Afinitor at the same time each day. You may take the medicine with or without food, but take it the same way each time.

Do not take a regular tablet together with a dispersible tablet. Use only one form of this medicine.

Read and carefully follow any Instructions for Use provided with your medicine. Ask your doctor or pharmacist if you do not understand these instructions.

Afinitor can increase your risk of bleeding or infection by changing the way your immune system works. You will need frequent medical tests.

If you’ve ever had hepatitis B, using Afinitor can cause this virus to become active or get worse. You may need frequent liver function tests while using this medicine and for several months after you stop.

Surgical incisions or other wounds may take longer to heal while you are taking Afinitor. You may need to stop taking this medicine for 1 week before and 2 weeks after a surgery. Follow your doctor’s instructions.

Store at room temperature in the original container, away from moisture, heat, and light. Keep unused dispersible tablets in the foil blister pack.

What happens if I miss a dose?

Use the medicine as soon as you can, but skip the missed dose if you are more than 6 hours late for the dose. Do not use two doses at one time.

What to avoid

Do not receive a “live” vaccine while using Afinitor, and avoid coming into contact with anyone who has recently received a live vaccine. There is a chance that the virus could be passed on to you. Live vaccines include measles, mumps, rubella (MMR), polio, rotavirus, typhoid, yellow fever, and varicella (chickenpox)

Grapefruit may interact with everolimus and lead to unwanted side effects. Avoid the use of grapefruit products.

If you develop mouth sores or ulcers, avoid using mouthwashes or applying medicines that contain alcohol, peroxide, iodine, or thyme. Your doctor may prescribe a steroid mouthwash if your mouth sores are severe.

Afinitor side effects

Get emergency medical help if you have signs of an allergic reaction to Afinitor: hives; chest pain, difficult breathing; swelling of your face, lips, tongue, or throat. You may be more likely to have some of these symptoms if you also take an “ACE inhibitor” heart or blood pressure medication.

Call your doctor at once if you have:

• blisters or ulcers in your mouth, red or swollen gums, trouble swallowing;
• lung problems – new or worsening cough, chest pain, wheezing, feeling short of breath;
• signs of infection – fever, chills, tiredness, joint pain, skin rash;
• kidney problems – little or no urination; swelling in your feet or ankles;
• liver problems – nausea, loss of appetite, stomach pain (upper right side), dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
• low blood cell counts – flu-like symptoms, skin sores, easy bruising, unusual bleeding, pale skin, cold hands and feet, feeling light-headed;
• any wound that will not heal; or
• a surgical incision that is red, warm, swollen, painful, bleeding, or oozing pus.

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

Common Afinitor side effects may include:

• fever, cough, infections, feeling weak or tired;
• mouth sores;
• nausea, loss of appetite;
• swelling anywhere in your body;
• rash;
• missed menstrual periods;
• headache; or
• high blood sugar – increased thirst, increased urination, dry mouth, fruity breath odor.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Afinitor?

Tell your doctor about all your current medicines. Many drugs can affect Afinitor, especially:

• an antibiotic or antifungal medicine;
• heart or blood pressure medication;
• medicine to treat hepatitis C, or HIV/AIDS;
• seizure medicine;
• St. John’s wort;
• tuberculosis medication; or
• drugs that weaken the immune system, such as cancer medicine, steroids, and medicines to prevent organ transplant rejection.