Sirolimus

Sirolimus 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. Sirolimus 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.  Sirolimus 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 sirolimus include high blood pressure, pain, diarrhea and headache.

Sirolimus is a prescription medicine used to prevent organ rejection in people 13 years of age and older who have received a kidney transplant. Sirolimus 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.

Sirolimus may be found in some form under the following brand names:

• Rapamune

Sirolimus may cause serious side effects, including:

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

Sirolimus may affect the way other medicines work, and other medicines may affect how sirolimus 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 sirolimus drug interactions. Ask your doctor or pharmacist for more information.

Sirolimus 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 sirolimus have a higher risk of getting lymphoma, and other cancers, especially skin cancer. Talk with your doctor about your risk for cancer.

Sirolimus 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 sirolimus after a liver or lung transplant. You should not take sirolimus if you have had a liver or lung transplant without talking with your doctor.

• 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 and lead to potentially dangerous effects. Discuss the use of grapefruit products with your doctor.

Before taking sirolimus, tell your doctor if you:

• have liver problems
• have skin cancer or it runs in your family
• have high cholesterol or triglycerides (fat in your blood)
• 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 sirolimus. Tell your doctor right away if you become pregnant or think you are pregnant while taking sirolimus.
• It is not known whether sirolimus passes into breast milk. You and your doctor should decide if you will take sirolimus or breastfeed. You should not do both.

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

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 sirolimus. Tell your doctor right away if you become pregnant or think you are pregnant while taking sirolimus.

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

• Take sirolimus exactly as your doctor tells you to take it.
• Your doctor will tell you how much sirolimus to take and when to take it. Do not change your dose of sirolimus unless your doctor tells you to.
• If you also take cyclosporine (Gengraf, Neoral, Sandimmune), you should take your sirolimus and cyclosporine about 4 hours apart.
• Do not stop taking sirolimus or your other anti-rejection medicines unless your doctor tells you to.
• Your doctor will check the levels of sirolimus in your blood. Your doctor may change your dose of sirolimus depending on your blood test results.
• Sirolimus is taken by mouth once a day.
• Do not crush, chew, or split sirolimus tablets. Tell your doctor if you cannot swallow sirolimus tablets. Your doctor can prescribe sirolimus as a solution.
• Take each dose of sirolimus the same way, either with or without food. Food can affect the amount of medicine that gets into your bloodstream. Taking each dose of sirolimus the same way helps keep your blood levels of sirolimus more stable. Do not take sirolimus with grapefruit juice.
• Sirolimus oral solution can develop a slight haze when it is refrigerated. If this happens, bring the sirolimus Oral Solution to room temperature and then gently shake the bottle until the haze goes away.
• If you get sirolimus oral solution on your skin, wash the area with soap and water.
• If you get sirolimus oral solution in your eyes, rinse your eyes with water.
• If you have taken more medicine than you were told, contact a doctor or go to the nearest hospital emergency department right away.

Oral Solution:

Each sirolimus oral solution carton contains: 

• a 2 oz. (60 mL fill) amber glass bottle of sirolimus (concentration of 1 mg/mL)
• 1 oral syringe adapter for fitting into the neck of the bottle
• enough disposable amber oral syringes and caps for daily dosing
• 1 carrying case

You will also need:

• glass or plastic cup 
• 6 oz. of water or orange juice only

Open the solution bottle.

• Remove the safety cap by squeezing the tabs on the cap and twisting counterclockwise
• The first time you use a bottle of sirolimus oral solution insert the oral syringe adapter (plastic tube with stopper) tightly into the bottle until it is even with the top of the bottle. 

• Do not remove the oral syringe adapter from the bottle once inserted.
• Use a new disposable amber oral syringe for each dose of sirolimus oral solution.
• Fully push down (depress) on the plunger of the disposable amber oral syringe.
• Then, tightly insert the oral syringe into the opening in the adapter.
• Withdraw the prescribed amount of sirolimus oral solution.
• Gently pull back the plunger of the syringe until the bottom of the black line of the plunger is even with the appropriate mark on the syringe.
• Always keep the bottle in an upright position.
• If bubbles form in the syringe, empty the syringe into the bottle and repeat previous steps.
• If your doctor tells you to carry your medicine with you and you need to carry your sirolimus Oral Solution in a filled syringe, place a cap securely on the syringe. The cap should snap into place.
• Place the capped syringe in the enclosed carrying case.

Taking a dose of sirolimus oral solution:

• Empty the syringe into a glass or plastic cup containing at least 2 ounces (1/4 cup, 60 mL) of water or orange juice, stir vigorously for 1 minute and drink right away. 
• Refill the container with at least 4 ounces (1/2 cup, 120 mL) of water or orange juice, stir vigorously again and drink the rinse solution. Do not mix sirolimus oral solution with apple juice, grapefruit juice, or other liquids. Only glass or plastic cups should be used to mix sirolimus oral solution. 
• The syringe and cap should be used only one time and then thrown away

Always store the bottles of medication in the refrigerator.

Take sirolimus 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 sirolimus is 40 mg.

If you take too much sirolimus, call your local Poison Control Center or seek emergency medical attention right away.

Sirolimus tablets:

• Store sirolimus tablets at room temperature between 68°F to 77°F (20°C to 25°C).
• Blister cards and strips:
  • Keep the tablets in the original blister container and use the outer carton to protect blister cards and strips from light.
• Bottles
  • Keep the bottle of sirolimus tablets tightly closed.

Sirolimus oral solution:

• Store bottles of sirolimus oral solution in the refrigerator at 36°F to 46°F (2°C to 8°C). Protect from light.
• If necessary, bottles of sirolimus oral solution can be stored at room temperature up to 77°F (25°C) for up to 15 days.
• When a bottle of sirolimus oral solution is opened, it should be used within 1 month.
• Use any diluted sirolimus oral solution right away.

Do not use sirolimus after the expiration date, which is located on the blister and carton. The expiration date refers to the last day of that month.

Safely throw away medicine that is out of date or no longer needed.

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

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 sirolimus. 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 sirolimus 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 sirolimus 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 sirolimus has been used as part of an immunosuppressive regimen