RAPAMUNE 0.5 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Rapamune 0.5mg film-coated tablets

Rapamune 1 mg film-coated tablets

Rapamune 2mg film-coated tablets

sirolimus

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Rapamune and what is it used for
2. What you need to know before you take Rapamune
3. How to take Rapamune
4. Possible side effects
5. Storing Rapamune
6. Contents of the pack and other information

1. What is Rapamune and what is it used for

Rapamune contains the active substance sirolimus, which belongs to a group of medicines called immunosuppressants. It helps to control your body's immune system after you have received a kidney transplant.

Rapamune is used in adults to prevent the rejection of transplanted kidneys and is normally used in combination with other immunosuppressive medicines called corticosteroids, and initially (for the first 2 to 3 months) with cyclosporin.

Rapamune is also used to treat patients with sporadic lymphangioleiomyomatosis (S-LAM) with moderate or severe lung disease. S-LAM is a rare, progressive lung disease that mainly affects women of childbearing age. The most common symptom of S-LAM is difficulty breathing.

2. What you need to know before you take Rapamune

Do not take Rapamune

• if you are allergic to sirolimus or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor or pharmacist before you start taking Rapamune.

• If you have any liver problems or have had any disease that may have affected your liver, tell your doctor as this may affect the dose of Rapamune you receive and may be a reason for you to have other blood tests.
• Rapamune, like other immunosuppressive medicines, may reduce your ability to fight infections and may increase the risk of developing cancer of the lymphoid tissues and skin.
• If you have a body mass index (BMI) over 30 kg/m2, you may have a higher risk of abnormal wound healing.
• If you are considered to be at high risk of kidney rejection, for example if you have had a previous transplant that was rejected.

Your doctor will perform tests to monitor your blood levels of Rapamune. Your doctor will also perform tests to monitor your kidney function, to measure your lipid (cholesterol and/or triglyceride) levels in your blood, and possibly your liver function, during treatment with Rapamune.

Exposure to sunlight and UV light should be limited by covering your skin with clothing and using a sunscreen with a high sun protection factor, due to the increased risk of skin cancer.

Children and adolescents

Experience with the use of Rapamune in children and adolescents under 18 years of age is limited. The use of Rapamune in this population is not recommended.

Taking Rapamune with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

Some medicines may interfere with the action of Rapamune and you may need a dose adjustment. In particular, you should tell your doctor or pharmacist if you are taking any of the following medicines:

• any other immunosuppressive medicine.
• antibiotics or antifungal medicines used to treat infections, such as clarithromycin, erythromycin, telithromycin, troleandomycin, rifabutin, clotrimazole, fluconazole, and itraconazole. You should not take Rapamune with rifampicin, ketoconazole, or voriconazole.
• any medicine used to treat high blood pressure or heart problems, including nicardipine, verapamil, and diltiazem.
• antiepileptic medicines, including carbamazepine, phenobarbital, and phenytoin.
• medicines used to treat ulcers or other gastrointestinal problems, such as cisapride, cimetidine, or metoclopramide.
• bromocriptine (used to treat Parkinson's disease and various hormonal disorders), danazol (used to treat gynecological disorders), or protease inhibitors (e.g., for HIV and hepatitis C, such as ritonavir, indinavir, boceprevir, and telaprevir).

• St. John's Wort (Hypericum perforatum).

• letermovir (an antiviral medicine to prevent cytomegalovirus disease).
• cannabidiol (its use includes, among others, the treatment of epileptic seizures).

You should avoid the use of live vaccines during treatment with Rapamune. Before vaccination, tell your doctor or pharmacist that you are receiving Rapamune.

The use of Rapamune may lead to an increase in your blood cholesterol and triglyceride levels, which may require treatment. Medicines known as "statins" and "fibrates" used to treat high cholesterol and triglycerides have been associated with an increased risk of muscle fiber breakdown (rhabdomyolysis). Tell your doctor if you are taking medicines to lower your blood fats.

The combined use of Rapamune and angiotensin-converting enzyme (ACE) inhibitors (a type of medicine used to lower blood pressure) may cause allergic reactions. Tell your doctor if you are taking these medicines.

Taking Rapamune with food and drinks

Always take Rapamune the same way, with or without food. If you prefer to take Rapamune with food, you should always take it with food. If you prefer to take Rapamune without food, you should always take it without food. Food can affect the amount of medicine that gets into your blood, and taking your medicine the same way each time will help keep your blood levels of Rapamune more stable.

Do not take Rapamune with grapefruit juice.

Pregnancy, breastfeeding, and fertility

Rapamune should not be used during pregnancy unless clearly necessary. You must use an effective method of contraception during treatment with Rapamune and for 12 weeks after stopping treatment. If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

It is not known whether Rapamune passes into breast milk. Patients who take Rapamune should not breastfeed.

A reduction in sperm count has been associated with the use of Rapamune, which usually returns to normal after treatment is stopped.

Driving and using machines

Although treatment with Rapamune is not expected to affect your ability to drive, if you are unsure, consult your doctor.

Rapamune contains lactose and sucrose

Rapamune contains 86.4 mg of lactose and up to 215.8 mg of sucrose. If your doctor has told you that you have an intolerance to some sugars, consult your doctor before taking this medicine.

3. How to take Rapamune

Always take this medicine exactly as your doctor has told you. If you are not sure, check with your doctor or pharmacist.

Your doctor will decide the exact dose of Rapamune that you should take and how often you should take it. Follow your doctor's instructions exactly and never change the dose yourself.

Rapamune is for oral use only. Do not crush, chew, or break the tablets. Tell your doctor if you have difficulty taking the tablet.

You should not take multiple 0.5 mg Rapamune tablets as a substitute for the 1 mg and 2 mg tablets, as they are not directly interchangeable.

Always take Rapamune the same way, with or without food.

Kidney transplant

Your doctor will give you an initial dose of 6 mg as soon as possible after your kidney transplant operation. After that, you will need to take 2 mg of Rapamune every day until your doctor tells you otherwise. Your dose will be adjusted based on your blood levels of Rapamune. Your doctor will need to perform blood tests to measure the levels of Rapamune in your blood.

If you are also taking cyclosporin, you should space out the taking of the two medicines by approximately 4 hours.

It is recommended to use Rapamune in combination with cyclosporin and corticosteroids initially. After 3 months, your doctor may stop Rapamune or cyclosporin, as it is not recommended to take these medicines together after this time.

Sporadic lymphangioleiomyomatosis (S-LAM)

Your doctor will give you 2 mg of Rapamune per day, until further notice. Your dose will be adjusted based on your blood levels of Rapamune. Your doctor will need to perform blood tests to measure the levels of Rapamune in your blood.

If you take more Rapamune than you should

If you have taken more medicine than you should, contact your doctor or go to the nearest hospital emergency department immediately. Always take the labelled blister pack with you, even if it is empty.

If you forget to take Rapamune

If you forget to take Rapamune, take it as soon as you remember, but not within 4 hours of your cyclosporin dose. After that, continue taking your medicine as usual. Do not take a double dose to make up for a forgotten dose, and always take Rapamune and cyclosporin with a difference of approximately 4 hours. If you have forgotten to take a dose of Rapamune, you should inform your doctor.

If you stop taking Rapamune

Do not stop taking Rapamune unless your doctor tells you to, as you may be at risk of losing your transplant.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Allergic reactions

You should see a doctor immediatelyif you experience symptoms such as swelling of the face, tongue and/or throat and/or difficulty breathing (angioedema), or skin peeling (exfoliative dermatitis). These may be symptoms of a severe allergic reaction.

Kidney damage with low blood cell counts (thrombocytopenic purpura/hemolytic uremic syndrome)

When taken with medicines called calcineurin inhibitors (cyclosporin or tacrolimus), Rapamune may increase the risk of a condition that combines kidney damage with low blood platelet and red blood cell counts, with or without skin rash (thrombocytopenic purpura/hemolytic uremic syndrome). If you experience symptoms such as bruising, skin rash, changes in urine, mood changes, or any other symptom that you consider serious, unusual, or prolonged, contact your doctor.

Infections

Rapamune reduces your body's defenses. As a result, your body may not be as good at fighting infections as it used to be. Therefore, if you are taking Rapamune, you may get more infections than usual, such as skin, mouth, stomach, and intestine, lung, and urinary tract infections (see list below). You should contact your doctor if you experience symptoms that you consider serious, unusual, or prolonged.

Frequency of side effects

Very common: affects more than 1 in 10 people

• fluid accumulation around the kidney
• body swelling, including hands and feet
• pain
• fever
• headache
• high blood pressure
• stomach pain, diarrhea, constipation, nausea
• decrease in red blood cell count, decrease in platelet count
• increase in blood fats (cholesterol and/or triglycerides), increase in blood sugar, decrease in potassium in the blood, decrease in phosphorus in the blood, increase in lactate dehydrogenase in the blood, increase in creatinine in the blood
• joint pain
• acne
• urinary tract infection
• pneumonia and other bacterial, viral, and fungal infections
• decrease in white blood cells that fight infection
• diabetes
• abnormal liver function tests, elevated liver enzymes AST and/or ALT
• skin rash
• protein in the urine
• menstrual disorders (including absent, infrequent, or heavy periods)
• slow wound healing (this may include the separation of the layers of a surgical wound or suture line)
• increased heart rate
• there is a general tendency for fluids to accumulate in various tissues

Common: affects between 1 and 10 in 100 people

• infections (including potentially life-threatening infections)
• blood clots in the legs
• blood clots in the lungs
• mouth ulcers
• fluid accumulation in the abdomen
• kidney damage with low platelet and red blood cell counts, with or without skin rash (hemolytic uremic syndrome)
• decrease in a type of white blood cell called neutrophils
• bony changes
• inflammation that can lead to lung damage, fluid accumulation around the lungs
• nosebleeds
• skin cancer
• kidney infection
• ovarian cysts
• fluid accumulation in the membrane surrounding the heart, which in some cases can reduce the heart's ability to pump blood
• pancreatitis
• allergic reactions
• herpes
• cytomegalovirus infection

Uncommon: affects between 1 and 10 in 1,000 people

• cancer of the lymphoid tissue (lymphoma/post-transplant lymphoproliferative disorder), decrease in red blood cells, white blood cells, and platelets
• bleeding in the lungs
• protein in the urine, sometimes severe and associated with side effects such as swelling
• scarring of the kidney that can reduce kidney function
• excess fluid in the tissues due to abnormal lymph function
• decrease in platelet count in the blood, with or without skin rash (thrombocytopenic purpura)
• severe allergic reactions that can cause skin peeling
• tuberculosis
• Epstein-Barr virus infection
• infectious diarrhea caused by Clostridium difficile
• severe liver damage

Rare: affects between 1 and 10 in 10,000 people

• protein deposits in the air sacs of the lungs that can interfere with breathing
• severe allergic reactions that can affect the blood vessels (see section on allergic reactions)

Frequency not known: cannot be estimated from the available data

• Posterior reversible encephalopathy syndrome (PRES) which is a serious condition of the nervous system that has the following symptoms: headache, nausea, vomiting, confusion, seizures, and loss of vision. If you experience more than one of these symptoms, contact your doctor.

Patients with S-LAM experienced side effects similar to those of patients with kidney transplants, with the addition of weight loss, which may affect more than 1 in 10 people.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storing Rapamune

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the blister and carton after “EXP”. The expiry date refers to the last day of the month shown.

Do not store above 25°C.

Store the blister in the outer carton to protect from light.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Container Content and Additional Information

Rapamune Composition

The active ingredient is sirolimus.

Each Rapamune 0.5 mg coated tablet contains 0.5 mg of sirolimus.

Each Rapamune 1 mg coated tablet contains 1 mg of sirolimus.

Each Rapamune 2 mg coated tablet contains 2 mg of sirolimus.

The other ingredients are:

Core of the tablets: lactose monohydrate, macrogol, magnesium stearate, talc

Coating of the tablets: macrogol, glycerol monooleate, pharmaceutical varnish, calcium sulfate, microcrystalline cellulose, sucrose, titanium dioxide, poloxamer 188, α-tocopherol, povidone, carnauba wax, printing ink (shellac, iron oxide red, propylene glycol [E1520], concentrated ammonia solution, simethicone). The 0.5 mg and 2 mg tablets also containyellow iron oxide (E172) and brown iron oxide (E172).

Product Appearance and Container Content

Rapamune 0.5 mg is presented in the form of triangular, light brown, coated tablets, engraved on one side with “RAPAMUNE 0.5 mg”.

Rapamune 1 mg is presented in the form of triangular, white, coated tablets, engraved on one side with “RAPAMUNE 1 mg”.

Rapamune 2 mg is presented in the form of triangular, yellow-beige, coated tablets, engraved on one side with “RAPAMUNE 2 mg”.

The tablets are packaged in blisters of 30 and 100 tablets. Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

For further information on this medicinal product, please contact the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet: 01/2025.

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu/.