Prospect: information for the user

Rapamune 0.5mg coated tablets

Rapamune 1 mg coated tablets

Rapamune 2mg coated tablets

sirolimus

Read this prospect carefully before starting to take this medicine, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed to you alone, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this prospect. See section 4.

Rapamunecontains the active ingredient sirolimus, whichbelongs to a group of medications called immunosuppressants. It helps control your body's immune system after receiving a kidney transplant.

Rapamune is used in adults to prevent rejection of transplanted kidneys and is usually used in combination with other immunosuppressant medicationscalled corticosteroids, and initially(the first2 to3 months)with cyclosporine.

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

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 starting to take Rapamune.

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

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

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

Children and adolescents

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

Taking Rapamune with other medicines

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medicine.

• any other immunosuppressant.
• antibiotics or antifungal medicines used to treat infections, for example, clarithromycin, erythromycin, telithromycin, troleandomycin, rifabutin, clotrimazole, fluconazole, and itraconazole. Rapamune should not be taken 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 (such as for HIV and hepatitis C, for example, ritonavir, indinavir, boceprevir, and telaprevir).

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

• letmovir (an antiviral medicine to prevent infection with cytomegalovirus).
• cannabidiol (its use includes, among others, the treatment of epilepsy seizures).

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 cholesterol and triglyceride levels in the blood (blood fats) that 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 rupture (rhabdomyolysis). Inform your doctor if you are taking medicines to reduce 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 drinks

Take Rapamune always in the same way, with or without food. If you prefer to take Rapamune with food, take it always with food. If you prefer to take Rapamune without food, take it always without food. Food may alter the amount of medicine that enters the blood, and by taking your medicine always in the same way, Rapamune blood levels are maintained more stable.

Do not take Rapamune with grapefruit juice.

Pregnancy, breastfeeding, and fertility

Rapamune should not be used during pregnancy unless clearly necessary. You should use an effective contraceptive method during treatment with Rapamune and for 12 weeks after stopping treatment. If you are pregnant or breastfeeding, or think you may be pregnant, or intend to become pregnant, consult your doctor or pharmacist before using this medicine.

It is not known whether Rapamune passes into breast milk. Patients taking Rapamune should stop breastfeeding.

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

Driving and operating machinery

Although it is not expected that treatment with Rapamune will affect your ability to drive, if you have any doubts, 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 certain sugars, consult with them before taking this medicine.

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

Your doctor will decide the exact dose of Rapamune you should take and how often you should take it. Follow exactly the instructions of your doctor and never change the dose on your own.

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

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

Take Rapamune always in the same way, with or without food.

Renal Transplant

Your doctor will give you an initial dose of 6 mg as soon as possible after the renal transplant surgery. 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 the level of Rapamune in your blood. Your doctor will need to perform blood tests to measure the Rapamune concentrations.

If you are also taking cyclosporine, you must space the intake of the two medications approximately 4 hours apart.

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

Sporadic Lymphangioleiomyomatosis (S-LAM)

Your doctor will give you 2 mg of Rapamune per day, until they tell you otherwise. Your dose will be adjusted based on the level of Rapamune in your blood. Your doctor will need to perform blood tests to measure the Rapamune concentrations.

If you take more Rapamune than you should

If you have taken more medication than you were told, contact your doctor as soon as possible or go to the nearest hospital emergency room. Always carry the labeled blister pack of the medication 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 the cyclosporine dose. After that, continue taking the medication in the usual way. Do not take a double dose to compensate for the missed doses, and always take Rapamune and cyclosporine with a difference of approximately 4 hours. If you completely forget to take a dose of Rapamune, you must inform your doctor.

If you interrupt the treatment with Rapamune

Do not stop taking Rapamune unless your doctor tells you to, as you would risk losing the transplant.

If you have any other doubts about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Allergic reactions

You should go to your doctor immediately if you experience symptoms such as swelling of the face, tongue and/or the back of the mouth (pharynx) and/or difficulty breathing (angioedema), or skin peeling (dermatitis exfoliativa). It could be a sign of a severe allergic reaction.

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

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

Infections

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

Frequency of side effects

Very common: affects more than 1 in 10 patients

• Fluid accumulation around the kidney
• Swelling of the body, including hands and feet
• Pain
• Fever
• Headache
• Increased blood pressure
• Abdominal pain, diarrhea, constipation, nausea
• Decreased red blood cell count, decreased platelet count
• Increased blood fats (cholesterol and/or triglycerides), increased blood sugar, decreased potassium levels, decreased phosphorus levels, increased lactate dehydrogenase levels, increased creatinine levels
• Joint pain
• Acne
• Urinary tract infection
• Pneumonia and other bacterial, viral and fungal infections
• Decreased white blood cell count
• Diabetes
• Abnormal liver function test results, elevated liver enzymes AST and/or ALT
• Skin rash
• Proteinuria
• M menstrual disorders (including absent, infrequent or heavy periods)
• Slow wound healing (this may include separation of the layers of a surgical wound or suture line)
• Increased heart rate
• Tendency for fluids to accumulate in various tissues

Common: affects between 1 and 10 in 100 patients

• Infections (including potentially life-threatening infections)
• Deep vein thrombosis
• Pulmonary embolism
• Mouth sores
• Abdominal fluid accumulation
• Renal damage with decreased platelet and red blood cell counts, with or without skin rash (hemolytic uremic syndrome)
• Decreased neutrophil count
• Bone deterioration
• Pulmonary inflammation that may lead to lung damage, fluid accumulation around the lungs
• Nasal bleeding
• Skin cancer
• Renal infection
• Ovarian cysts
• Fluid accumulation in the membrane surrounding the heart, which in some cases may reduce the heart's ability to pump blood
• Pancreatitis
• Allergic reactions
• Herpes
• Cytomegalovirus infection

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

• Pulmonary alveolar proteinosis, which may interfere with breathing
• Severe allergic reactions that may affect blood vessels (see allergic reactions section)

Unknown frequency: cannot be estimated from available data

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

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

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the blister pack and on the outer case after “EXP”. The expiration date is the last day of the month indicated.

Do not store at a temperature above25°C.

Store the blister pack in the outer packaging to protect it from light.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. By doing so, you will help protect the environment.

Composition of Rapamune

The active ingredient is sirolimus.

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

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

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

The other components are:

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

Coating of the tablets : macrogol, monooleate of glycerol, pharmaceutical varnish, calcium sulfate, microcrystalline cellulose, saccharose, titanium dioxide, poloxamer 188, α-tocopherol, povidone, carnauba wax, printing ink (shellac, iron oxide red, propylene glycol [E1520], concentrated ammonia solution, simethicone).

The tablets of 0.5 mg and 2 mg also contain iron oxide yellow (E172) and iron oxide brown (E172).

Appearance of the product and contents of the package

Rapamune 0.5 mg is presented in the form of coated triangular tablets of light brown color, which are engraved on one side with "RAPAMUNE 0.5 mg".

Rapamune 1 mg is presented in the form of coated triangular tablets of white color, which are engraved on one side with "RAPAMUNE 1 mg".

Rapamune 2 mg is presented in the form of coated triangular tablets of yellow-beige color, which are engraved on one side with "RAPAMUNE 2 mg".

The tablets are packaged in blisters of 30 and 100 tablets. Only some package sizes may be commercially available.

Holder of the marketing authorization and responsible for manufacturing

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Last review date of this leaflet: 01/2025.

The detailed information about this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu /.