RAPAMUNE 2 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 ciclosporin.

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

Consult your doctor or pharmacist before you start taking Rapamune.

• If you have any liver problems or have had any disease which may have affected your liver, inform your doctor as this may affect the dose of Rapamune you receive and may mean you need 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) of over 30 kg/m2, you may have a higher risk of abnormal wound healing.
• If you are considered to be at high risk of rejection, for example if you have had a previous transplant which 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 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, for example clarithromycin, erythromycin, telithromycin, troleandomycin, rifabutin, clotrimazole, fluconazole and itraconazole. You should not take Rapamune with rifampicin, ketoconazol or voriconazol.
• any medicine used for high blood pressure or heart problems, including nicardipine, verapamil and diltiazem.
• antiepileptic medicines, including carbamazepine, phenobarbital and phenytoin.
• medicines used for the treatment of ulcers or other gastrointestinal problems, such as cisapride, cimetidine or metoclopramide.
• bromocriptine (used in the treatment of Parkinson's disease and various hormonal disorders), danazol (used in the treatment of gynaecological disorders) or protease inhibitors (for example for HIV and hepatitis C such as ritonavir, indinavir, boceprevir and telaprevir).

• St John's Wort (Hypericum perforatum).

• letermovir (an antiviral medicine to prevent illness due to cytomegalovirus).

Live vaccines should be avoided during treatment with Rapamune. Before vaccination, inform your doctor or pharmacist that you are receiving Rapamune.

The use of Rapamune may lead to an increase in your cholesterol and triglyceride levels in your blood (blood fats) 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 fibre 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. Inform your doctor if you are taking these medicines.

Taking Rapamune with food and drink

Always take Rapamune in 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 by taking your medicine in the same way, the levels of Rapamune in your blood will be more even.

Do not take Rapamune with grapefruit juice.

Pregnancy, breast-feeding and fertility

Rapamune should not be used during pregnancy unless clearly necessary. You should use effective contraception during treatment with Rapamune and for 12 weeks after stopping treatment. If you are pregnant or breast-feeding, 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 if Rapamune passes into breast milk. Patients who take Rapamune should not breast-feed.

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

Driving and using machines

Although it is not expected that treatment with Rapamune will affect your ability to drive, if you are in any doubt, 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. Always follow your doctor's instructions exactly and never change the dose yourself.

Your doctor will give you an initial dose of 6 mg as soon as possible after your kidney transplant operation. After this, you will need to take 2 mg of Rapamune every day until your doctor tells you otherwise. Your dose will be adjusted depending 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 ciclosporin, you should space the taking of the two medicines by approximately 4 hours.

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

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

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

Rapamune should be taken with food, or without food, but always in the same way.

If you take more Rapamune than you should

If you have taken more medicine than you should, contact your doctor or go to the casualty department of your nearest hospital 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 ciclosporin dose. After this, continue to take your medicine as normal. Do not take a double dose to make up for a forgotten dose, and always take Rapamune and ciclosporin with a difference of approximately 4 hours. If you have forgotten to take a dose of Rapamune altogether, 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 your doctor immediatelyif you experience symptoms such as swelling of the face, tongue and/or the back of the throat (pharynx) and/or difficulty breathing (angioedema), or skin peeling (exfoliative dermatitis). These could 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 (ciclosporin or tacrolimus), Rapamune may increase the risk of a condition that combines kidney damage with low blood cell counts and skin rash. 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 defences to prevent it from rejecting the transplanted organ. As a result, your body will not be as good at fighting infections as it used to be. Therefore, if you are taking Rapamune, you may catch more infections than usual, such as infections of the skin, mouth, stomach and gut, lungs and urinary tract (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: may affect 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, diarrhoea, constipation, nausea
• reduced red blood cell count, reduced platelet count
• increased blood fats (cholesterol and/or triglycerides), high blood sugar, low blood potassium, low blood phosphorus, high blood lactate dehydrogenase, high blood creatinine
• joint pain
• acne
• urinary tract infection
• pneumonia and other bacterial, viral and fungal infections
• reduced white blood cell count
• diabetes
• abnormal liver function tests, elevated liver enzymes AST and/or ALT
• skin rash
• high levels of protein in the urine
• menstrual disorders (including absent, infrequent or heavy periods)
• slow wound healing (this may include the separation of layers of a surgical wound or suture line)
• increased heart rate
• there is a general tendency for fluid to accumulate in various tissues

Common: may affect up to 1 in 10 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 blood cell counts and skin rash (hemolytic uremic syndrome)
• reduced neutrophil count
• bony damage
• 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: may affect up to 1 in 100 people

• cancer of the lymphoid tissues (lymphoma/post-transplant lymphoproliferative disorder), reduced red blood cell count, reduced white blood cell count and reduced platelet count
• bleeding in the lungs
• high levels of 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
• reduced platelet count, with or without skin rash (thrombocytopenic purpura)
• severe allergic reactions that can cause skin peeling
• tuberculosis
• Epstein-Barr virus infection
• infectious diarrhoea caused by Clostridium difficile
• severe liver damage

Rare: may affect up to 1 in 1,000 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 with symptoms such as headache, nausea, vomiting, confusion, convulsions and loss of vision. If you experience more than one of these symptoms, contact your doctor.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. 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: https://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 on the carton after “EXP”. The expiry date refers to the last day of that month.

Do not store above 25°C.

Store the blister in the outer carton in order 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 to 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 components 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 (gum lacquer, red iron oxide, propylene glycol, ammonium hydroxide, 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 face with “RAPAMUNE 0.5 mg”.

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

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

The tablets are packaged in blisters of 30 and 100 tablets. Only some 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/.