Rapamune 1 mg/ml oral solution

Patient Information Leaflet

Introduction

Patient Information Leaflet

Rapamune 1 mg/ml oral solution

sirolimus

Package leaflet contents

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

1. What Rapamune is and what it is used for

Rapamune contains the active substance sirolimus, which belongs to a group of medicines called immunosuppressants. It helps you 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 together with other immunosuppressant medicines called corticosteroids, and initially (the first 2 to 3 months) with cyclosporine.

Rapamune is also used for the treatment of patients with sporadic lymphangioleiomyomatosis (S-LAM) who have moderate lung disease or impaired lung function. S-LAM is a rare, progressive lung disease that primarily affects women of childbearing age. The most common symptom of S-LAM is difficulty breathing.

2. What you need to know before taking Rapamune

Do not take Rapamune

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

Warnings and precautions

Talk to your doctor or pharmacist before taking Rapamune.

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

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

Exposure to sunlight and UV light should be limited by covering the skin with clothing and using a high-protection sunscreen, due to the increased risk of developing 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 is not recommended in this population.

Taking Rapamune with other medicines

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

Some medicines may interfere with the action of Rapamune, and therefore a dose adjustment may be needed. In particular, inform 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. Concomitant use of Rapamune with rifampicin, ketoconazole, or voriconazole is not recommended.
• any medicine used for 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 gynaecological 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 illness).
• cannabidiol (its uses include, among others, the treatment of epileptic seizures).

The use of 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 increased levels of cholesterol and triglycerides in the 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 fiber breakdown (rhabdomyolysis). Inform your doctor if you are taking medicines to lower 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

Take Rapamune in the same way each time, 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 alter the amount of medicine absorbed into the blood; therefore, by taking your medicine consistently the same way, blood levels of Rapamune remain more stable.

Do not take Rapamune with grapefruit juice.

Pregnancy, breast-feeding, and fertility

Rapamune must 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 breast-feeding, think you may be pregnant, or plan 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 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 Rapamune is not expected to 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, 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 or breast-feeding women, children, and high-risk groups such as patients with liver disease or epilepsy. Alcohol may alter or increase the effect of other medicines.

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

3. How to take Rapamune

Follow exactly the administration instructions for this medicine as given by your doctor. If in 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. Always follow your doctor's instructions precisely and never change the dose on your own.

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

Take Rapamune in the same way each time, 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 surgery. 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 the level of Rapamune in your blood. Your doctor will need to perform blood tests to measure Rapamune concentrations.

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

Rapamune is recommended initially to be used in combination with cyclosporine and corticosteroids. After 3 months, your doctor may discontinue either Rapamune or cyclosporine, as it is not recommended to continue taking both medicines together beyond this time.

Sporadic lymphangioleiomyomatosis (S-LAM)

Your doctor will prescribe 2 mg of Rapamune daily until otherwise instructed. Your dose will be adjusted according to the level of Rapamune in your blood. Your doctor will need to perform blood tests to measure Rapamune concentrations.

Instructions for diluting Rapamune

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

2. With the plunger fully depressed, insert one of the dosing syringes into the opening of the adapter.

3. Withdraw the exact amount of Rapamune oral solution prescribed by your doctor by gently pulling the plunger of the dosing syringe until the solution level aligns with the appropriate mark on the syringe. The bottle must remain in an upright position during withdrawal. If bubbles form in the oral solution within the dosing syringe during withdrawal, return the Rapamune solution to the bottle and repeat the withdrawal procedure. You may need to repeat step 3 more than once to obtain your correct dose.

4. Your doctor may have instructed you to take the Rapamune oral solution at a specific time of day. If you need to carry the medicine with you, fill the dosing syringe to the appropriate mark and securely place the cap on it—the cap must fit firmly in place. Then place the capped dosing syringe into the provided transport container. Once drawn into the syringe, the medicine may be stored at room temperature (not exceeding 25°C) or refrigerated and must be used within 24 hours.

5. Empty the contents of the dosing syringe into a glass or plastic cup containing at least 60 ml of water or orange juice. Stir well for one minute and drink immediately in one go. Refill the cup with at least 120 ml of water or orange juice, stir well, and drink immediately. Do not use any other liquid for dilution, including grapefruit juice. The dosing syringe and its cap should be used only once and then discarded.

When refrigerated, the solution in the bottle may become slightly cloudy. If this occurs, simply allow the Rapamune oral solution to reach room temperature and gently shake. The presence of this cloudiness does not affect the quality of Rapamune.

If you take more Rapamune than you should

If you have taken more medicine than prescribed, contact your doctor immediately or go to the nearest hospital emergency department. Always take the medicine bottle with its label, even if empty.

If you forget to take Rapamune

If you forget to take your dose of Rapamune, take it as soon as you remember, but not within 4 hours of your cyclosporine dose. After that, continue taking the medicine as usual. Do not take a double dose to make up for a missed dose, and always take Rapamune and cyclosporine approximately 4 hours apart. If you completely miss a dose of Rapamune, you must inform your doctor.

If you stop taking Rapamune

Do not stop taking Rapamune unless your doctor tells you to do so, as you risk losing your transplanted organ.

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

4. Possible adverse effects

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

Allergic reactions

You must contact your doctor immediately if you experience symptoms such as swelling of the face, tongue and/or back of the mouth (pharynx) and/or difficulty breathing (angioedema), or skin peeling (exfoliative dermatitis). These could be symptoms of a serious allergic reaction.

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

When taken with medicines called calcineurin inhibitors (cyclosporine or tacrolimus), Rapamune may increase the risk of a condition combining kidney damage with low blood platelet and red blood cell counts, with or without skin irritation (thrombocytopenic purpura/hemolytic uremic syndrome). If you experience symptoms such as bruising, skin rashes, 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 may not be as effective as before in fighting infections. Therefore, if you are taking Rapamune, you may develop more infections than usual, such as infections of the skin, mouth, stomach and intestine, lungs, and urinary tract (see list below). You should contact your doctor if you experience symptoms you consider severe, unusual or prolonged.

Frequency of adverse effects

Very common: may 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
• stomach pain, diarrhea, constipation, nausea
• decreased number of red blood cells, decreased number of platelets
• increased blood fats (cholesterol and/or triglycerides), increased blood sugar, decreased blood potassium, decreased blood phosphorus, increased blood lactate dehydrogenase, increased blood creatinine
• joint pain
• acne
• urinary tract infection
• pneumonia and other infections caused by bacteria, viruses, and fungi
• decreased blood cells that fight infections (white blood cells)
• diabetes
• abnormalities in tests measuring liver function, elevated liver enzymes AST and/or ALT
• skin rash
• increased protein in urine
• menstrual disorders (including absent, infrequent or heavy periods)
• slow healing (this may include separation of the layers of a surgical wound or suture line)
• increased heart rate
• general tendency for fluids to accumulate in various tissues

Common: may affect up to 1 in 10 people

• infections (including potentially life-threatening infections)
• blood clots in legs
• blood clots in the lungs
• mouth sores
• fluid accumulation in the abdomen
• kidney injury with decreased platelet and red blood cell counts, with or without skin rash (hemolytic uremic syndrome)
• decreased number of a type of white blood cells called neutrophils
• bone deterioration
• inflammation that may lead to lung injury, fluid accumulation around the lungs
• nosebleeds
• skin cancer
• kidney infection
• ovarian cysts
• fluid accumulation in the membrane surrounding the heart, which in some cases may reduce the heart's ability to pump blood
• inflammation of the pancreas
• allergic reactions
• herpes
• cytomegalovirus infection

Uncommon: may affect up to 1 in 100 people

• cancer of the lymphatic tissue (lymphoma/post-transplant lymphoproliferative disorder), combined decrease in red blood cells, white blood cells, and platelets
• lung hemorrhage
• protein in urine, sometimes severe and associated with adverse effects such as swelling
• scarring process in the kidney that may reduce kidney function
• excess fluid in tissues due to abnormal lymphatic function
• decreased number of platelets in blood, with or without skin rash (thrombocytopenic purpura)
• severe allergic reactions that may cause skin peeling
• tuberculosis
• Epstein-Barr virus infection
• infectious diarrhea due to Clostridium difficile
• severe liver injury

Rare: may affect up to 1 in 1,000 people

• deposition of proteins in the air sacs of the lungs that may interfere with breathing
• severe allergic reactions that may affect blood vessels (see section on allergic reactions)

Frequency not known: cannot be estimated from available data

• Posterior reversible encephalopathy syndrome (PRES), a serious nervous system disorder 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 adverse effects similar to those in kidney transplant patients, with the addition of weight loss, which may affect more than 1 in 10 people.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Rapamune

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

Do not use this medicine after the expiry date stated on the container, following “EXP”. The expiry date refers to the last day of the month indicated.

Store in a refrigerator (between 2°C and 8°C).

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

After opening the bottle, the contents must be kept refrigerated and used within 30 days. If necessary, the bottle may be stored at room temperature up to 25°C for a short period, but not for more than 24 hours.

Once the dosing syringe has been filled with Rapamune oral solution, it should be stored at room temperature, not exceeding 25°C, for a maximum of 24 hours.

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

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging when they are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

Composition of Rapamune

The active substance is sirolimus. Each ml 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 fatty acids and ascorbyl palmitate).

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

Appearance of the product and contents of the pack

Rapamune oral solution is a pale yellow to yellow oral solution supplied in 60 ml bottles.

Each carton contains: 1 bottle (amber glass) containing 60 ml of Rapamune solution, a syringe adapter, 30 dosing syringes (amber plastic), and a carrying case for the syringe.

Marketing Authorization Holder and Manufacturer

You can request further information about this medicinal product by contacting the local representative of the marketing authorization holder:

Date of the most recent review of this leaflet: 01/2025.

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