Sirolimus is an immunosuppressant agent. It is normally used along with corticosteroid medications and cyclosporine to prevent the rejection of kidney organ transplants. Together, these medications suppress (decrease) the body's natural defense, the immune system.

Sirolimus works by preventing the formation of cells (white blood cells) that would normally attack the transplanted organ.

Your doctor may have suggested this medication for conditions other than those listed in these drug information articles. If you have not discussed this with your doctor or are not sure why you are taking this medication, speak to your doctor. Do not stop taking this medication without consulting your doctor.

Do not give this medication to anyone else, even if they have the same symptoms as you do. It can be harmful for people to take this medication if their doctor has not prescribed it.

Sirolimus is normally started as soon as possible after transplant. The dose prescribed will depend on your situation. The recommended first dose of sirolimus for new transplant recipients is 6 mg followed by a regular dose of 2 mg daily. For people who have previously had a transplant rejection or are at high risk of rejecting the transplant, the first dose is often 15 mg with a regular dose of 5 mg per day.

Many things can affect the dose of medication that a person needs, such as body weight, other medical conditions, and other medications. If your doctor has recommended a dose different from the ones listed here, do not change the way that you are using the medication without consulting your doctor.

Do not stop taking this medication without talking with your doctor.

Sirolimus is normally given along with cyclosporine and corticosteroids. Sirolimus should be taken approximately 4 hours after the cyclosporine.

Sirolimus should be taken at the same time each day, and taken the same way, either with or without food. It should not be taken with grapefruit juice.

Sirolimus is available as an oral (by mouth) solution and in tablet form. If you are taking the tablets, do not crush, chew, or split them.

The oral solution bottles have oral dose syringes which should be used to withdraw the prescribed amount of sirolimus from the bottle. Empty the correct amount of sirolimus from the syringes into a glass or plastic container holding at least 2 ounces (60 mL) of water or orange juice. No other liquids should be used for dilution. Stir vigorously and drink at once. Rinse the container with an additional volume (minimum of 4 ounces or 120 mL) of water or orange juice, stir vigorously, and drink at once. This ensures that all the medication is rinsed from the container and that the entire dose is taken.

The preparation should be used immediately after dilution and the syringe discarded after one use.

Sirolimus solutions provided in bottles may develop a slight haze when refrigerated. If this occurs, allow the bottle to stand at room temperature and shake gently until the haze disappears. The presence of this haze does not affect the quality of the product.

Do not allow water or juice to contaminate the medication in the bottle. If the mouth of the bottle needs to be cleaned, wipe the bottle with a dry cloth.

The tablets should only be taken with water or orange juice.

It is extremely important to take this medication exactly as prescribed, since missing even a few doses of sirolimus may cause your body to reject the organ. Check with your doctor or pharmacist for the proper way to take sirolimus.

If you miss a dose, take the missed dose as soon as you remember, but not within 4 hours of your cyclosporine dose. If it is less than four hours until your next scheduled dose of sirolimus, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a missed one. If you are not sure what to do after missing a dose, contact your doctor or pharmacist for advice.

Store sirolimus solution in the refrigerator, protect it from light, and keep it out of the reach of children. Once the bottle is opened, it should be kept in a refrigerator and the contents used within one month. If left at room temperature, the opened bottle must be used within 5 days. If the amber syringe is pre-filled, it may be kept at room temperature or in the refrigerator for a maximum of 24 hours.

Store sirolimus tablets at room temperature (15°C to 30°C), protect them from light and moisture, and keep out of the reach of children.

Tablets

1 mg
Each white, triangular-shaped tablet, marked "RAPAMUNE 1 mg" on one side, contains 1 mg of sirolimus. Nonmedicinal ingredients: calcium sulfate anhydrous NF, carnauba wax NF, glyceryl monooleate, ink, lactose monohydrate NF, magnesium stearate NF, microcrystalline cellulose NF, pharmaceutical glaze NF, polaxamer 188, polyethylene glycol 8000 powdered NF, polyethylene glycol type 20 000, povidone USP, sucrose NF, talc USP, titanium dioxide USP, and vitamin E (dl-alpha tocopherol).

Oral solution
Each mL of oral solution contains 1 mg of sirolimus. The solution is supplied in amber glass 60 mL bottles with oral syringes for measuring the dose. Nonmedicinal ingredients: Phosal 50 PG® (phosphatidylcholine, propylene glycol, sunflower mono- and diglycerides, ascorbyl palmitate, ethanol, and soybean oil fatty acids) and polysorbate 80.

Do not use this medication if you are allergic to sirolimus or any ingredients of the medication.

Many medications can cause side effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent.

The side effects listed below are not experienced by everyone who takes this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor.

The following side effects have been reported by at least 1% of people taking this medication. Many of these side effects can be managed, and some may go away on their own over time.

Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.

• acne
• constipation
• diarrhea
• headache
• heartburn
• increased growth of body hair
• nausea
• sleeping problems (insomnia)
• stomach pain
• trembling
• weakness
• weight gain

Although most of the side effects listed below don't happen very often, they could lead to serious problems if you do not seek medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

• anxiousness
• bone pain
• change in menstrual periods
• dizziness when rising from a sitting or lying position
• fever or chills
• high blood pressure
• increased occurrence of infections
• irregular or rapid heartbeat
• joint pain
• lower back or side pain
• lump in neck, armpit, collarbone, or groin regions
• muscle pain or cramps
• new skin lesions or changes to existing skin lesions
• rash
• shortness of breath
• slowed healing
• signs of anemia (low red blood cells; e.g., pale skin, unusual tiredness, or weakness)
• signs of bleeding (e.g., bloody nose, blood in urine, coughing blood, bleeding gums, cuts that don't stop bleeding)
• signs of fluid build-up (e.g., breathing problems; swelling of hands, ankles, feet, or lower legs; swollen abdomen)
• signs of liver problems (e.g., nausea, vomiting, diarrhea, loss of appetite, weight loss, yellowing of the skin or whites of the eyes, dark urine, pale stools)
• signs of a urinary tract infection such as difficult or painful urination, blood in the urine or cloudy urine
• symptoms of high blood sugar (e.g., frequent urination, increased thirst, excessive eating, unexplained weight loss, poor wound healing, infections, fruity breath odour)
• symptoms of lung infection (e.g., cough, shortness of breath, coughing up blood, fever, chills, cold or flu-like symptoms)
• symptoms of ovarian cysts (e.g., pelvic pain or heaviness, pain during intercourse, frequent need to urinate, changed menstrual periods, bloating)
• symptoms of too much or too little potassium in the body (e.g., muscle fatigue, weakness, difficulty moving, abnormal heart rhythms, nausea)
• swelling of the hands, feet, or lower legs
• swollen abdomen
• swollen glands
• vision changes
• vomiting
• weakness or heaviness of legs

Stop taking the medication and seek immediate medical attention if any of the following occur:

• flu-like symptoms (sudden lack of energy, fever, cough, sore throat)
• severe watery diarrhea, rapid heart rate, fever, nausea, abdominal cramps
• signs of a serious allergic reaction (e.g., abdominal cramps, difficulty breathing, nausea and vomiting, or swelling of the face and throat)
• signs of a severe skin reaction such as blistering, peeling, a rash covering a large area of the body, a rash that spreads quickly, or a rash combined with fever or discomfort
• signs of bleeding in the stomach (e.g., bloody, black, or tarry stools; spitting up of blood; vomiting blood or material that looks like coffee grounds)
• signs of heart problems (e.g., fast, irregular heartbeat or pulse, chest pain, difficulty breathing)
• signs of infection (symptoms may include fever or chills, severe diarrhea, shortness of breath, prolonged dizziness, headache, stiff neck, swollen glands, weight loss, or listlessness)
• signs of pancreatitis (e.g., abdominal pain on the upper left side, back pain, nausea, fever, chills, rapid heartbeat, swollen abdomen)

Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are taking this medication.

Before you begin using a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should use this medication.

Alcohol: Sirolimus solution contains up to 3.17% alcohol. A 2 mg dose of the solution would contain about the same amount of alcohol as half a teaspoon of light beer. Discuss any concerns you have about the alcohol content with your doctor.

Cancer: Sirolimus increases the risk of skin cancer. You should limit your exposure to sunlight and wear protective clothing and sunscreen when outside.

Sirolimus has also been associated with lymphoma, cancer of the lymphatic cells of the immune system. Lymphatic cells are responsible for producing the body's defenses against bacteria, viruses, and other infections.

Report any unusual infections, swelling or persistent pain, or unintentional weight loss to your doctor as soon as possible.

Delayed wound healing: Sirolimus may affect the speed with which your body heals. If you notice that wounds are taking longer than usual to heal or signs of infection, such as redness and warmth of an injured area, contact your doctor as soon as possible.

Diabetes: Sirolimus may cause a loss of control of diabetes by increasing blood glucose (sugar). It may also cause the onset of diabetes for people who are at risk.

If you have diabetes, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. You may need to check your blood glucose levels more often.

If you experience signs of uncontrolled blood sugar, such as increased thirst, the need to urinate more often at night, a fruity odour on your breath or poor wound healing, contact your doctor as soon as possible.

Drug interactions: Many medications can interfere with how sirolimus behaves in the body. These medications may decrease the effectiveness of sirolimus or cause increased side effects. If you are taking any other medications, discuss with your doctor or pharmacist how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Fluid and electrolyte balance: Sirolimus may cause the levels of electrolytes such as potassium, sodium, magnesium, chloride, and calcium in the blood to change while taking this medication. If you experience symptoms of fluid and electrolyte imbalance such as muscle pains or cramps; dry mouth; numb hands, feet, or lips; or racing heartbeat, contact your doctor as soon as possible. Your doctor will do blood tests regularly to monitor the levels of these electrolytes in your blood while you are taking this medication.

Grapefruit juice: Grapefruit juice interferes with how the sirolimus is processed and removed from the body. The combination may cause an increase in the amount of sirolimus in the body, and increase the severity and frequency of side effects.

High cholesterol: Sirolimus may cause an increase in serum cholesterol and triglycerides. If you have high cholesterol or are at risk for developing high cholesterol, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Hypersensitivity syndrome: A severe allergic reaction called hypersensitivity syndrome has occurred for some people with the use of sirolimus. Although not common, angioedema (a serious allergic reaction that causes the area around the throat and tongue to swell) can occur. Stop taking the medication and get immediate medical attention if you have symptoms of a severe allergic reaction, including fever, swollen glands, yellowing of the skin or eyes, or flu-like symptoms with skin rash or blistering.

Infection: Sirolimus reduces the number of cells that fight infection in the body (white blood cells). If possible, avoid contact with people who have contagious infections. Tell your doctor immediately if you notice signs of an infection such as fever or chills, severe diarrhea, shortness of breath, prolonged dizziness, headache, stiff neck, weight loss, or listlessness.

Your doctor will do blood tests regularly to monitor the number of specific types of blood cells in your blood. Other medications may be prescribed to reduce the risk of developing severe, life-threatening infections.

Kidney function: Sirolimus may cause or worsen kidney problems. If you have reduced kidney function or kidney disease, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Liver function: Sirolimus is removed from the body by the liver and may cause liver problems. Liver disease or reduced liver function may cause a build-up of sirolimus in the body and cause side effects. You may need to take a lower dose.

If you have liver disease or decreased liver function, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

If you experience symptoms of liver problems (e.g., abdominal pain, persistent vomiting, feeling unwell, fever, itching, yellowing of the skin and eyes, dark urine), contact your doctor immediately.

Lung inflammation: Lung inflammation (interstitial lung disease), causing difficulty breathing has occurred rarely in some people taking this medication. This complication can be serious and sometimes fatal. If you experience new or worsening shortness of breath or cough (with or without fever) at any time while you are taking sirolimus contact your doctor immediately.

Oral hygiene: Sirolimus can cause an increased growth of the gum tissue. While taking this medication, it is important to maintain good oral hygiene and to visit a dentist regularly for teeth cleaning.

Vaccination: If you are taking immunosuppressants you should not receive live or live-attenuated (modified) vaccines, as there is a risk of infection and poor immune response to the vaccine.

Pregnancy: There are no adequate studies on the use of this medication by pregnant people, but some studies suggest that it increases the risk for toxicity in the unborn child. This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.

Effective birth control should be used before starting sirolimus, during treatment with it, and for 12 weeks after the medication has been stopped.

Breast-feeding: It is not known if sirolimus passes into breast milk. If you are breast-feeding and taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding.

Children: The safety and effectiveness of sirolimus have not been established for children less than 13 years old.

Seniors: People over the age of 65 may require lower doses of sirolimus due to age-related decreases in kidney function.

For a full list of interactions, use the Drug Interaction Checker available on the Drugs.com website.

If you are taking other medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:

• stop taking one of the medications,
• change one of the medications to another,
• change how you are taking one or both of the medications, or
• leave everything as is.

An interaction between two medications does not always mean that you must stop taking one of them. Speak to your doctor about how any drug interactions are being managed or should be managed.

Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications you are taking. Also tell them about any supplements you take. Since caffeine, alcohol, the nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.