Label: information for the user

Rapamune 1 mg/ml oral solution

sirolimus

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 women of childbearing age. 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 components of this medication (listed in section 6)
• if you are allergic to peanuts or soy

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) of 30 kg/m2 or higher, you may be at a higher risk of abnormal wound healing.
• If you are considered a high-risk patient for renal rejection, for example if you had a previous transplant that was rejected.

Your doctor will perform tests to monitor your Rapamune blood levels. They will also perform tests to monitor your kidney function, measure your blood lipid levels (cholesterol and/or triglycerides), 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 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. The use of Rapamune in this population is not recommended.

Taking Rapamune with other medications

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

• any other immunosuppressant medication
• antibiotics or antifungal medications used to treat infections, for example, clarithromycin, erythromycin, telithromycin, troleandomycin, rifabutin, clotrimazole, fluconazole, and itraconazole.Do not take Rapamune with rifampicin, ketoconazole, or voriconazole.
• any medication used to treat high blood pressure or heart problems, including nicardipine, verapamil, and diltiazem.
• antiepileptic medications, including carbamazepine, phenobarbital, and phenytoin.
• medications 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 (for example, for HIV and hepatitis C, such as ritonavir, indinavir, boceprevir, and telaprevir).
• St. John's Wort (Hypericum perforatum).
• letmovir (an antiviral medication to prevent cytomegalovirus infection).
• 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 blood cholesterol and triglyceride levels (blood fats) that may require treatment. Medications 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 medications to reduce blood fats.

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

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 medication that enters the bloodstream, and by taking your medication always in the same way, Rapamune blood levels remain more stable.

Do not take Rapamune with grapefruit juice.

Pregnancy, breastfeeding, and fertility

Rapamune should not be used during pregnancy unless clearly necessary.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 plan to become pregnant, consult your doctor or pharmacist before using this medication.

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 ethanol (alcohol)

Rapamune contains up to 3.17% ethanol (alcohol). An initial dose of 6 mg contains up to 150 mg of alcohol, which is equivalent to 3.80 ml of beer or 1.58 ml of wine. This amount of alcohol may be harmful to people with alcoholism, as well as to pregnant women, breastfeeding women, children, and high-risk groups, such as patients with liver disease or epilepsy. Alcohol may modify or increase the effect of other medications.

Maintenance doses of 4 mg or less contain small amounts of ethanol (100 mg or less), which are probably too low to be harmful.

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

Rapamune is only for oral use. Inform your doctor if you have difficulties taking the oral solution.

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 Rapamune blood level. Your doctor will need to perform blood tests to measure the Rapamune concentrations.

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

It is recommended to use Rapamune first in combination with ciclosporin and corticosteroids. After 3 months, your doctor may suspend Rapamune or ciclosporin, 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 Rapamune blood level. Your doctor will need to perform blood tests to measure the Rapamune concentrations.

Instructions on how to dilute Rapamune

1. Remove the safety cap from the vial by pressing the cap tabs and turning. Insert the syringe adapter into the vial until it reaches the top of the vial. Do not attempt to remove the syringe adapter from the vial once it is inserted.

1. With the plunger fully pressed, insert one of the dosing syringes into the opening of the adapter.

1. Draw out the exact amount of oral solution of Rapamune as prescribed by your doctor by gently pulling the plunger of the dosing syringe until the level of the oral solution is equal to the appropriate mark on the dosing syringe. The vial must remain in a vertical position while drawing out the solution. If bubbles form in the oral solution in the dosing syringe during the drawing process, return the Rapamune solution to the vial and repeat the procedure. You may need to repeat step 3 more than once to obtain your dose.

1. Your doctor may have instructed you to take the oral solution of Rapamune at a specific time of the day. If you need to carry the medication with you, fill the dosing syringe to the appropriate mark and securely place the cap – the cap must be securely fixed in place. Then, place the dosing syringe with the cap on in the transport box provided. Once in the syringe, the medication can be stored at room temperature (not exceeding 25°C) or refrigerated and must be used within a period of 24 hours.

1. Empty the contents of the dosing syringe into a glass or plastic cup with at least 60 ml of water or orange juice. Shake well for one minute and drink it immediately. Fill the cup with at least 120 ml of water or orange juice, shake well, and drink it immediately. Do not use any other liquid for dilution, including grapefruit juice. The dosing syringe and its cap must be used only once and then discarded.

When refrigerated, the solution in the vial may become slightly turbid. If this occurs, simply place Rapamune oral solution at room temperature and shake gently. The presence of this turbidity does not affect the quality of Rapamune.

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 medication vial with the label, 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 ciclosporin dose. After that, continue taking the medication in the usual manner. Do not take a double dose to compensate for the missed doses, and always take Rapamune and ciclosporin 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 treatment with Rapamune

Do not stop taking Rapamune unless your doctor tells you to, as you 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 shouldvisit your doctor immediatelyif you experience symptoms such as facial swelling, tongueand/or 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 the list below). You should contact your doctor if you experience symptoms that you consider severe, unusual, or prolonged.

Frequency of side effects

Very common: can affect more than 1 in 10 people

• 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 infections caused by bacteria, viruses, and fungi
• Decreased white blood cell count
• Diabetes
• Abnormal liver function test results, elevated liver enzymes AST and/or ALT
• Skin rash
• Proteinuria
• Menstrual disorders (including absent, infrequent, or excessive 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: can affect up to 1 in 10 people

• Infections (including potentially life-threatening infections)
• Deep vein thrombosis
• Pulmonary embolism
• Mouth ulcers
• Abdominal fluid accumulation
• Renal damage with decreased platelet and red blood cell counts, with or without skin rash (thrombotic thrombocytopenic purpura)
• Decreased neutrophil count
• Bone deterioration
• Pulmonary inflammation that may lead to lung injury, 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: can affect up to 1 in 1,000 people

• Pulmonary alveolar proteinosis, which may interfere with breathing
• Severe allergic reactions that may affect blood vessels (see the 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 side effects

If you experienceany type of side effect, consult your doctor, pharmacist, or nurse, even if it is apossibleside effect that does not appear in this prospectus.You can also report them directly through theSpanish System for the Pharmacovigilance of Medicinal Products 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 packaging after“EXP”. The expiration date is the last day of the month indicated.

Store in the refrigerator (between2°Cand8°C).

Keep Rapamune oral solution in its original container to protect it from light.

Once the container is opened, the contents must be kept refrigerated and used within 30 days. If necessary, the container can be stored at room temperature up to25°Cfor a short period, but not more than 24 hours.

Once the dosing syringe has been filled with Rapamune oral solution, it must be stored at room temperature, but not above25°C, for a maximum period of 24 hours.

Once the contents of the dosing syringe have been diluted with water or orange juice, the preparation must be consumed immediately.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. This will help protect the environment.

Composition of Rapamune

The active ingredient is sirolimus. Each milliliter of Rapamune oral solution contains 1 mg of sirolimus.

The other components are:

Polysorbate 80 (E433) and phosal 50 PG (phosphatidylcholine, propylene glycol [E1520], mono and diglycerides, ethanol, soybean and palmitoyl ascorbate).

This medicine contains approximately 350 mg of propylene glycol (E1520) in each milliliter.

Appearance of the product and contents of the package

Rapamune oral solution is a pale yellow to yellow solution that is presented in 60 ml amber glass bottles.

Each carton contains: 1 amber glass bottle containing 60 ml of Rapamune oral solution, a syringe adapter, 30 pre-filled syringes (plastic amber) and a syringe transport case.

Marketing Authorization Holder and Responsible Manufacturer

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 /