Rapamune

Rapamune is a prescription medication used to prevent kidney transplant rejection.  Rejection is when your body’s immune system recognizes the new organ as a “foreign” threat and attacks it. Rapamune belongs to a group of drugs called immunosuppressants, which prevent the immune system from attacking the transplanted kidney. 

This medication comes in tablet and liquid forms.  Rapamune is taken once a day. The tablets should be swallowed whole, with or without food.  The liquid should be kept refrigerated and mixed with water or orange juice immediately before it is taken.

Common side effects of Rapamune include high blood pressure, pain, diarrhea and headache.

Rapamune is a prescription medicine used to prevent organ rejection in people 13 years of age and older who have received a kidney transplant. Rapamune is used with other medicines called cyclosporine (Gengraf, Neoral, Sandimmune), and corticosteroids.

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

Take Rapamune exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

Dosage of this medicine must be individualized based on weight, risk for transplant rejection, blood levels, response to the medicine, as well as other factors.

The maximum recommended daily dose of Rapamune (sirolimus) is 40 mg.

BOX WARNING: IMMUNOSUPPRESSION, USE IS NOT RECOMMENDED IN LIVER OR LUNG TRANSPLANT PATIENTS

• Increased susceptibility to infection and the possible development of lymphoma and other malignancies may result from immunosuppression

Increased susceptibility to infection and the possible development of lymphoma may result from immunosuppression. Only physicians experienced in immunosuppressive therapy and management of renal transplant patients should use Rapamune. Patients receiving the drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physician responsible for maintenance therapy should have complete information requisite for the follow-up of the patient.

• The safety and efficacy of Rapamune as immunosuppressive therapy have not been established in liver or lung transplant patients, and therefore, such use is not recommended 
• Liver Transplantation – Excess Mortality, Graft Loss, and Hepatic Artery Thrombosis (HAT)

The use of Rapamune in combination with tacrolimus was associated with excess mortality and graft loss in a study in de novo liver transplant patients. Many of these patients had evidence of infection at or near the time of death.

In this and another study in de novo liver transplant patients, the use of sirolimus in combination with cyclosporine or tacrolimus was associated with an increase in HAT; most cases of HAT occurred within 30 days post-transplantation and most led to graft loss or death.

• Lung Transplantation – Bronchial Anastomotic Dehiscence

Cases of bronchial anastomotic dehiscence, most fatal, have been reported in de novo lung transplant patients when Rapamune has been used as part of an immunosuppressive regimen

Rapamune can cause serious side effects, including:

1. increased risk of getting infections
2. increased risk of getting certain cancers

1. Increased risk of getting infections. Serious infections can happen including infections caused by viruses, bacteria, and fungi (yeast). Your doctor may put you on medicine to help prevent some of these infections. Call your doctor right away if you have symptoms of infection including fever or chills while taking sirolimus.

2. Increased risk of getting certain cancers. People who take Rapamune have a higher risk of getting lymphoma, and other cancers, especially skin cancer. Talk with your doctor about your risk for cancer.

Rapamune has not been shown to be safe and effective in people who have had liver or lung transplants. Serious complications and death may happen in people who take Rapamune after a liver or lung transplant. You should not take Rapamune if you have had a liver or lung transplant without talking with your doctor.

• Avoid receiving live vaccines while taking Rapamune. Some vaccines may not work as well while you are taking Rapamune.
• Limit your time in sunlight and UV light. Cover your skin with clothing and use a sunscreen with a high protection factor because of the increased risk for skin cancer with Rapamune.

Rapamune may cause serious side effects, including:

• See “Drug Precautions”.
• Serious allergic reactions. Tell your doctor or get medical help right away if you get any of following symptoms of an allergic reaction:
  • swelling of your face, eyes, or mouth
  • trouble breathing or wheezing
  • throat tightness
  • chest pain or tightness
  • feeling dizzy or faint
  • rash or peeling of your skin
• Swelling (edema). Fluid may collect in your hands and feet and in various tissues of your body, including in the sac around your heart or lungs. Call your doctor if you have trouble breathing.
• Poor wound healing. Rapamune may cause your wounds to heal slowly or not heal well. Tell your doctor if you have any redness or drainage, your wound does not heal, or the wound opens up.
• Increased levels of cholesterol and triglycerides (lipids or fat) in your blood. Your doctor should do blood tests to check your lipids during treatment with Rapamune. Your doctor may prescribe treatment with diet, exercise, or medicine if your lipid levels are too high. During treatment with Rapamune, your blood levels of cholesterol and triglycerides may remain high even if you follow your prescribed treatment plan.
• Effects on kidney function. When Rapamune is taken with cyclosporine (Gengraf, Neoral, Sandimmune), the function of your transplanted kidney may be affected. Your doctor should regularly do tests to check your kidney function while you are taking Rapamune with cyclosporine (Gengraf, Neoral, Sandimmune).
• Increased protein in your urine. Your doctor may regularly test your urine protein.
• Increased risk for viral infections.
  • Certain viruses can live in your body and cause active infections when your immune system is weak. BK virus can affect how your kidney works and cause your transplanted kidney to fail.
  • A certain virus can cause a rare serious brain infection called Progressive Multifocal Leukoencephalopathy (PML). PML usually causes death or severe disability. Call your doctor right away if you notice any new or worsening medical problems such as:
    • confusion
    • sudden change in thinking, walking, strength on one side of your body
    • other problems that have lasted over several days.

• Lung or breathing problems. This can sometimes lead to death. Tell your doctor if you have a new or worsening cough, shortness of breath, difficulty breathing or any new breathing problems. Your doctor may need to stop Rapamune or lower your dose.
• Blood clotting problems. When Rapamune is taken with cyclosporine or tacrolimus, you may develop a blood clotting problem. Tell your doctor if you get any unexplained bleeding or bruising.

Common side effects with Rapamune include:

• high blood pressure
• pain (including stomach and joint pain)
• diarrhea
• headache
• fever
• urinary tract infection
• low red blood cell count (anemia)
• nausea
• low platelet count (cells that help blood to clot)

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

These are not all of the possible side effects of Rapamune. For more information ask your doctor or pharmacist.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements. Using Rapamune with certain medicines may affect each other causing serious side effects.

Rapamune may affect the way other medicines work, and other medicines may affect how Rapamune works.

Especially tell your doctor if you take:

• a medicine to lower your cholesterol or triglycerides
• cyclosporine (including Gengraf, Neoral, Sandimmune) or tacrolimus (Prograf) or other medicines that suppress the immune system
• an antibiotic
• an antifungal medicine
• a medicine for high blood pressure or heart problems
• an anti-seizure medicine
• medicines used to treat stomach acid, ulcers, or other gastrointestinal problems
• bromocriptine mesylate (Parlodel, Cycloset)
• danazol
• an anti-HIV medicine
• St. John’s Wort

This is not a complete list of Rapamune drug interactions. Ask your doctor or pharmacist for more information.

Tell your doctor if you are pregnant or plan to become pregnant. You must use an effective method of birth control during treatment and for 12 weeks after you stop treatment with Rapamune. Tell your doctor right away if you become pregnant or think you are pregnant while taking Rapamune.

Tell your doctor if you are breastfeeding or plan to breastfeed. It is not known whether Rapamune passes into breast milk. You and your doctor should decide if you will take Rapamune or breastfeed. You should not do both.

Avoid receiving live vaccines while taking sirolimus. Some vaccines may not work as well while you are taking sirolimus.

Limit your time in sunlight and UV light. Cover your skin with clothing and use a sunscreen with a high protection factor because of the increased risk for skin cancer with sirolimus.

Grapefruit and grapefruit juice may interact with sirolimus. Discuss the use of grapefruit products with your doctor.

You must use an effective method of birth control during treatment and for 12 weeks after you stop treatment with sirolimus. Tell your doctor right away if you become pregnant or think you are pregnant while taking sirolimus.