Rapamune

Rapamune (Sirolimus) is normally started as soon as possible after transplant. The dose prescribed will depend on your situation. The recommended first dose of Rapamune (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 Rapamune (Sirolimus) without talking with your doctor.

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

Rapamune (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.

Rapamune (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 Rapamune (Sirolimus) from the bottle. Empty the correct amount of Rapamune (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.

Rapamune (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 Rapamune (Sirolimus) exactly as prescribed, since missing even a few doses of Rapamune (Sirolimus) may cause your body to reject the organ. Check with your doctor or pharmacist for the proper way to take Rapamune (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 Rapamune (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 Rapamune (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 Rapamune (Sirolimus) tablets at room temperature (15°C to 30°C), protect them from light and moisture, and keep out of the reach of children.

Do not dispose of medications in wastewater (e.g. down the sink or in the toilet) or in household garbage. Ask your pharmacist how to dispose of medications that are no longer needed or have expired.

In addition to its desired action, this medication may cause some adverse effects, notably: it may cause pimples (acne); it may cause constipation - to prevent this, drink plenty of water or juice, and eat more dietary fibre; it may cause joint pain; it may cause nausea and vomiting; it may cause leg swelling or water retention; it may cause weight gain, mostly with prolonged use. Each person may react differently to a treatment. If you think this medication may be causing adverse effects (including those described here, or others), talk to your health care professional. He or she can help you to determine whether or not the medication is the source of the problem.

Tablets

1 mg
Each white, triangular-shaped tablet, marked "RAPAMUNE 1 mg" on one side, contains 1 mg of Rapamune (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).

2 mg
Each yellow-to-beige triangular-shaped tablet, marked "RAPAMUNE 2 mg" on one side, contains 2 mg of Rapamune (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, vitamin E (dl-alpha tocopherol), Brown #70 Iron Oxide NF and Yellow #10 Iron Oxide NF.

5 mg
Each tan, triangular-shaped tablet, marked "RAPAMUNE 5 mg" on one side, contains 5 mg of Rapamune (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, vitamin E (dl-alpha tocopherol), Brown #75 Iron Oxide NF and Yellow #10 Iron Oxide NF.

Oral solution

Each mL of oral solution contains 1 mg of Rapamune (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 Rapamune (Sirolimus) if you are allergic to Rapamune (Sirolimus) or any ingredients of the medication.

There may be an interaction between Rapamune (Sirolimus) and any of the following:

• acitretin
• Amiodarone
• angiotensin-converting enzyme inhibitors (ACEIs; e.g., Captopril, Enalapril, Ramipril)
• Aprepitant
• Atorvastatin
• "azole" antifungals (e.g., ketoconazole, posaconazole, Voriconazole)
• BCG
• Bicalutamide
• Bosentan
• calcium channel blockers (e.g., Amlodipine, Diltiazem, Nifedipine, Verapamil)
• Carbamazepine
• Carvedilol
• Clozapine
• Cobicistat
• conivaptan
• cyclosporine
• Dabrafenib
• Deferasirox
• Denosumab
• Dexamethasone
• diabetes medications (e.g., chlorpropamide, glipizide, Glyburide, insulin, Metformin, Rosiglitazone)
• dipyrone
• Dronedarone
• echinacea
• Enzalutamide
• Fingolimod
• grapefruit juice
• Haloperidol
• Hepatitis C antivirals (e.g., ombitasvir, paritaprevir, ritonavir, dasabuvir, simeprevir)
• HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs; e.g., delavirdine, efavirenz, etravirine, nevirapine)
• HIV protease inhibitors (e.g., darunavir, indinavir, lopinavir, saquinavir, tipranavir)
• Ivacaftor
• Leflunomide
• Lomitapide
• macrolide antibiotics (e.g., clarithromycin, erythromycin, telithromycin)
• Mefloquine
• Metoclopramide
• mifepristone
• Mitotane
• Modafinil
• Natalizumab
• nefazodone
• Nivolumab
• Norfloxacin
• Phenobarbital
• Phenytoin
• Pimecrolimus
• Pimozide
• primidone
• rifabutin
• rifampin
• Roflumilast
• St. John's wort
• Stiripentol
• Tacrolimus
• Tocilizumab
• tyrosine kinase inhibitors (e.g., Crizotinib, Dasatinib, imatinib, Nilotinib)
• vaccines
• Venetoclax

If you are taking any of these 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.

Medications other than those listed above may interact with Rapamune (Sirolimus). Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications that 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.

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 Rapamune (Sirolimus).

Cancer: Rapamune (Sirolimus) increases the risk of Skin Cancer. You should limit your exposure to sunlight and wear protective clothing and sunscreen when outside.

Rapamune (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: Rapamune (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: Rapamune (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 Rapamune (Sirolimus) may affect your medical condition, how your medical condition may affect the dosing and effectiveness of Rapamune (Sirolimus), 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.

Fluid and electrolyte balance: Rapamune (Sirolimus) may cause the levels of electrolytes such as potassium, sodium, magnesium, chloride, and calcium in the blood to change while taking Rapamune (Sirolimus). 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 Rapamune (Sirolimus).

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

High Cholesterol: Rapamune (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 Rapamune (Sirolimus) may affect your medical condition, how your medical condition may affect the dosing and effectiveness of Rapamune (Sirolimus), and whether any special monitoring is needed.

Hypersensitivity syndrome: A Anaphylaxis (severe allergic reaction) called hypersensitivity syndrome has occurred for some people with the use of Rapamune (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: Rapamune (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 Disease: Rapamune (Sirolimus) may cause or worsen kidney problems. If you have reduced kidney function or kidney disease, discuss with your doctor how Rapamune (Sirolimus) may affect your medical condition, how your medical condition may affect the dosing and effectiveness of Rapamune (Sirolimus), and whether any special monitoring is needed.

Liver disease: Rapamune (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 Rapamune (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 Rapamune (Sirolimus) may affect your medical condition, how your medical condition may affect the dosing and effectiveness of Rapamune (Sirolimus), 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 Rapamune (Sirolimus). 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 Rapamune (Sirolimus) contact your doctor immediately.

Oral hygiene: Rapamune (Sirolimus) can cause an increased growth of the gum tissue. While taking Rapamune (Sirolimus), 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 Rapamune (Sirolimus) by pregnant women, but some studies suggest that it increases the risk for toxicity in the unborn child. Rapamune (Sirolimus) should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking Rapamune (Sirolimus), contact your doctor immediately.

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

Breast-feeding: It is not known if Rapamune (Sirolimus) passes into breast milk. If you are a breast-feeding mother and are taking Rapamune (Sirolimus), it may affect your baby. Talk to your doctor about whether you should continue breast-feeding.

Children: The safety and effectiveness of Rapamune (Sirolimus) have not been established for children less than 13 years old.

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

This medication is typically used only once a day. However, your pharmacist may have suggested a different schedule that is more appropriate for you. Take it regularly and continuously to maintain its beneficial effects. Important: Follow the instructions on the label. Do not use more of this product, or more often, than prescribed. To ensure exact dosage, measure each dose with an accurate measuring device. If you forget a dose, take it as soon as you remember -- unless it is almost time for your next dose. In that case, skip the missed dose. Do not double the next dose to catch up. Avoid grapefruit and grapefruit juice during your treatment. Grapefruit can seriously affect how this medication works.