RAPAMUNE 1 мг/мл Оральный раствор

Содержание инструкции

1. Rapamune 1 mg/ml oral solution
   1. What is Rapamune and what is it 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
2. Rapamune 0.5 mg film-coated tablets, 1 mg film-coated tablets, 2 mg film-coated tablets
   1. What is Rapamune and what is it 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. Package contents and other information

Rapamune 1 mg/ml oral solution

sirolimus

Read this leaflet carefully before you start taking this medicine as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

• 1. What Rapamune is and what it is used for
• 2. What you need to know before you take 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 is Rapamune and what is it used for

Rapamune contains the active substance sirolimus, which belongs to a group of medicines defined
as immunosuppressants. It helps to control the body's immune system after you have
undergone a kidney transplant.
Rapamune is used in adults to prevent the body from rejecting transplanted kidneys and is
normally used in combination with other immunosuppressant medicines called corticosteroids and
initially (for the first 2 – 3 months) with cyclosporine.
Rapamune is also used for the treatment of patients affected by sporadic lymphangioleiomyomatosis
(S-LAM) with moderate lung disease or decreasing lung function. S-LAM is a
rare progressive lung disease that predominantly affects women of childbearing age. The most common
symptom of LAM is dyspnea.

2. What you need to know before taking Rapamune

Do not take Rapamune:

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

Warnings and precautions
Talk to your doctor or pharmacist before taking Rapamune

• If you have liver problems or have had a disease that may have affected your liver, tell your doctor, as this may affect the dose of Rapamune you receive and further blood tests may be necessary.
• Rapamune, like other immunosuppressant medicines, can decrease the body's ability to fight infections, and may increase the risk of developing tumors of the lymphatic tissues and skin.
• If your body mass index (BMI) is greater than 30 kg/m², there may be a greater risk of abnormal wound healing.
• If you are considered to be at high risk of kidney rejection, such as someone who has already received another organ transplant followed by rejection.

The doctor will perform tests to check the levels of Rapamune in the blood. The doctor will also perform
tests to check kidney function, blood fat 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
suitable clothing and using a sunscreen with a high protection factor, as
the risk of skin cancer is increased.

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

Other medicines and Rapamune
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicine.
Some medicines can interfere with the action of Rapamune and therefore an
adjustment of the Rapamune dose may be necessary. In particular, tell your doctor or pharmacist if you are
taking:

• any other immunosuppressant medicine.
• antibiotic or antifungal medicines used to treat infections, for example clarithromycin, erythromycin, telithromycin, troleandomycin, rifabutin, clotrimazole, fluconazole, itraconazole. Taking Rapamune with rifampicin, ketoconazole or voriconazole is not recommended.
• any antihypertensive medicine or medicines for heart problems, including nicardipine, verapamil and diltiazem.
• anti-epileptic medicines including carbamazepine, phenobarbital, phenytoin.
• medicines used to treat ulcers or other gastrointestinal disorders such as cisapride, cimetidine, metoclopramide.
• bromocriptine (used in the treatment of Parkinson's disease and various hormonal imbalances), danazol (used in the treatment of 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 (uses include, also, the treatment of seizures).

The use of live vaccines during treatment with Rapamune should be avoided. Before any
vaccination, tell your doctor or pharmacist that you are taking Rapamune.
The use of Rapamune may cause an increase in blood levels of cholesterol and triglycerides (fats in
the blood) 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 breakdown (rhabdomyolysis). Tell your doctor if you are taking medicines to lower your blood
fat levels.
The use of Rapamune in combination with angiotensin converting enzyme inhibitors (a
type of medicine used to lower blood pressure) may cause allergic reactions. Tell your
doctor if you are taking one of these medicines.

Rapamune with food and drink
Rapamune should always be taken under the same conditions, with or without
meals. If you prefer to take Rapamune with food, you should then always take it with food. If
you prefer to take Rapamune without food, you should then always take it without food. Food can
affect the amount of medicine in the blood, therefore, if you always take the medicine under the same
conditions, the blood levels of Rapamune will be more stable.
Rapamune should not be taken with grapefruit juice.

Pregnancy, breastfeeding and fertility
Rapamune should not be taken during pregnancy unless strictly necessary.
During treatment with Rapamune and for 12 weeks after stopping treatment
effective contraceptive methods must be used. If you are pregnant, suspect or are
planning a pregnancy, or if you are breastfeeding, ask your doctor or
pharmacist for advice before taking this medicine.
It is not known whether Rapamune is excreted in breast milk. Patients taking Rapamune must
stop breastfeeding.
A decrease in sperm count has been associated with the use of Rapamune and
generally returns to normal after stopping treatment.

Driving and using machines
Although treatment with Rapamune is not expected to affect the ability to drive, if you have any
doubts, consult your doctor.

Rapamune contains ethanol (alcohol)
Rapamune contains up to 3.17% by volume of 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 those suffering from alcoholism and in pregnant or breastfeeding women, in
children and in high-risk groups, such as patients with epilepsy or liver disease. Alcohol can
alter or increase the effect of other medicines.
Maintenance doses of 4 mg or lower contain small amounts of ethanol (100 mg or less
of 100 mg) which are probably too low to be harmful.

3. How to take Rapamune

Take this medicine exactly as your doctor has told you. If you have any doubts, ask your doctor or pharmacist.
Your doctor will decide exactly what dose of Rapamune you need to take and how often.
Follow your doctor's instructions exactly and never change the dose on your own initiative.
Rapamune is for oral use only. Tell your doctor if you have difficulty taking the oral solution.
Rapamune must always be taken under the same conditions, with or without food.
Kidney transplant
Generally, for an adult, your doctor will prescribe an initial dose of 6 mg as soon as possible after
kidney transplant surgery. Afterwards, you will need to take 2 mg of Rapamune every day, unless
your doctor tells you otherwise. Your dose will be adjusted based on the concentration of
Rapamune in your blood. Your doctor will need to perform blood tests to determine the
Rapamune concentrations.
If you are also taking cyclosporine, then you must take the two medicines about 4 hours apart
from each other.
It is recommended to initially take Rapamune in combination with cyclosporine and
corticosteroids. After 3 months, your doctor may stop taking Rapamune or cyclosporine, as it is not recommended to take both medicines together for a longer
period of time.
Sporadic lymphangioleiomyomatosis (S-LAM)
Your doctor will give you 2 mg of Rapamune every day, until otherwise indicated. The dose
will be adjusted based on the level of Rapamune present in your blood. Your doctor will need to perform
blood tests to measure Rapamune concentrations.

Instructions on how to dilute Rapamune

• 1. Remove the safety cap from the bottle by pressing the tabs on the cap and unscrewing. Insert the syringe adapter into the bottle until it is aligned with the top edge of the bottle. Do not try 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. Draw the exact amount of Rapamune oral solution, as prescribed by your doctor, by gently pulling the plunger of the dosing syringe until the level of the oral solution is aligned with the appropriate mark on the dosing syringe. During withdrawal of the solution, the bottle must remain in an upright position. If air bubbles form in the oral solution inside the dosing syringe during withdrawal, empty the Rapamune solution back into the bottle and repeat the withdrawal procedure. You may need to repeat step 3 more than once before administering the dose.

• 4. You may have been prescribed 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 close it securely with a cap – the cap must click. Then put the closed dosing syringe in the provided container for transport. Once in the syringe, the medicine can be kept at room temperature (not exceeding 25°C) or stored in the refrigerator and must be used within 24 hours.

• 5. Pour the contents of the dosing syringe into a container that is only made of glass or plastic, containing at least 60 ml of water or orange juice. Mix well for one minute and drink it immediately. Refill the glass with at least 120 ml of water or orange juice, mix well and drink immediately. No other liquid, including grapefruit juice, should be used for dilution. The dosing syringe and cap must be used only once and then discarded.

When refrigerated, the solution in the bottle may develop a slight opacity. If this occurs,
simply bring Rapamune oral solution to room temperature and shake gently. The
presence of this opacity does not affect the quality of Rapamune.

If you take more Rapamune than you should
If you have taken more medicine than you were told to take, consult a doctor or go
directly to the emergency room of the nearest hospital. Always bring with you the labeled bottle of
the medicine, 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 next dose of cyclosporine. Afterwards, continue to take the medicine as usual. Do not take a double dose to make up for a missed dose and always
take Rapamune and cyclosporine about 4 hours apart. If you completely forget to
take a dose of Rapamune, you should tell your doctor.

If you stop taking Rapamune
Do not stop taking Rapamune unless you have been told to do so by your doctor, as you risk
losing the transplanted organ.
If you have any questions about using 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 must contact your doctor immediatelyif you experience symptoms such as swelling of the face, tongue and/or throat (back of the mouth) and/or difficulty breathing (angioedema) or a skin condition for which it may exfoliate (exfoliative dermatitis). These may be symptoms of a severe allergic reaction.

Kidney damage associated with anemia (thrombocytopenic purpura/hemolytic uremic syndrome)
When taken with medicines called calcineurin inhibitors (cyclosporine or tacrolimus), Rapamune may increase the risk of kidney damage with thrombocytopenia and anemia, with or without rash (thrombocytopenic purpura/hemolytic uremic syndrome). If you experience symptoms such as bruising or rash, changes in urine or changes in behavior or other serious, unusual or prolonged symptoms, contact your doctor.

Infections
Rapamune reduces your body's defense mechanisms. Consequently, your body may not be able to fight infections as normally. Therefore, if you are taking Rapamune, you may get more infections than usual, such as skin, mouth, stomach and intestinal, lung and urinary tract infections (see list below). If your symptoms are severe, unusual or prolonged, you should contact your doctor.

Frequency of side effects
Very common (may affect more than 1 in 10 people)

• Fluid collection around the kidney
• Swelling of the body, including hands and feet
• Pain
• Fever
• Headache
• Increased blood pressure
• Abdominal pain, diarrhea, constipation, nausea
• Anemia, thrombocytopenia
• Increased fats in the blood (cholesterol and/or triglycerides), increased blood sugar, low potassium levels in the blood, low phosphorus levels in the blood, increased lactate dehydrogenase protein in the blood, high creatinine levels in the blood
• Joint pain
• Acne
• Urinary tract infections
• Pneumonia and other bacterial, viral and fungal infections
• Decreased number of white blood cells that fight infections
• Diabetes
• Abnormal liver function tests, increased liver enzymes AST and/or ALT
• Rash (skin rash)
• Increased protein in urine
• Menstrual disorders (including amenorrhea, dysmenorrhea or heavy periods)
• Delayed wound healing (which may include separation of surgical wound flaps or suture line)
• Tachycardia
• General tendency to accumulate fluids in various tissues

Common: (may affect up to 1 in 10 people)

• Infections (including life-threatening infections)
• Blood clots in the leg vessels
• Blood clots in the lung
• Mouth ulcers
• Fluid collection in the abdomen
• Kidney damage with thrombocytopenia and anemia, with or without rash (hemolytic uremic syndrome)
• Decreased number of neutrophils (a type of white blood cells)
• Bone deterioration
• Inflammation that can lead to lung damage, fluid around the lungs
• Nosebleeds
• Skin cancer
• Kidney infection
• Ovarian cysts
• Fluid collection in the sac around the heart, which in some cases may decrease the heart's ability to pump blood
• Pancreatitis
• Allergic reactions
• Herpes Zoster (Shingles)
• Cytomegalovirus infection

Uncommon: (may affect up to 1 in 100 people):

• Cancer of the lymphatic tissue (lymphoma/post-transplant lymphoproliferative disorders), simultaneous decrease in red blood cells, white blood cells and platelets
• Bleeding from the lungs
• Protein in the urine, occasionally severe and associated with side effects such as swelling
• Scarring of the kidney, which may reduce kidney function
• Fluid accumulation in tissues due to irregular lymphatic system function
• Thrombocytopenia, with or without rash (thrombocytopenic purpura)
• Severe allergic reactions that can cause skin peeling
• Tuberculosis
• Epstein-Barr virus infection
• Clostridium difficileinfectious diarrhea
• Severe liver damage

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

• Accumulation of protein in the lung alveoli that can interfere with breathing
• Severe allergic reactions that can affect blood vessels (see the paragraph on allergic reactions above)

Not known: (frequency cannot be estimated based on available data)

• Posterior reversible encephalopathy syndrome (PRES), a serious nervous system syndrome that has the following symptoms: headache, nausea, vomiting, confusion, seizures, and

loss of vision. If these symptoms occur together, please contact your doctor.
Patients with S-LAM have experienced side effects similar to those of kidney transplant patients, with the addition of weight loss, which may affect more than 1 person in 10.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. You can also report side effects directly through the national reporting system detailed in Annex V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Rapamune

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date which is stated on the cardboard package after
“EXP”. The expiry date refers to the last day of the month.
Store in a refrigerator (2°C - 8°C).
Keep Rapamune oral solution in its original bottle to protect the medicine from light.
Once the bottle has been opened, the contents must be stored in a refrigerator and used
within 30 days.
If necessary, you can store the bottle at room temperature up to 25°C for a short period of
time, but for no more than 24 hours.
Once filled with Rapamune oral solution, the dosing syringe must be stored at
room temperature, but not at a temperature above 25°C, for a maximum of 24 hours.
After diluting the contents of the dosing syringe with water or orange juice, the preparation
obtained must be drunk immediately.
Do not dispose of any medicine in the wastewater and household waste. Ask your pharmacist how
to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Rapamune contains
The active ingredient is sirolimus. Each ml of Rapamune oral solution contains 1 mg of sirolimus
The excipients are:
Polysorbate 80 (E433) and Phosal 50 PG (phosphatidylcholine, propylene glycol [E1520], mono- and
diglycerides, ethanol, soybean fatty acids and ascorbyl palmitate).
Each ml of this medicine contains approximately 350 mg of propylene glycol (E1520).

Description of the appearance of Rapamune and contents of the pack
Rapamune oral solution is a solution from pale yellow to yellow supplied in a 60 ml bottle.
Each pack contains: one bottle (amber glass) containing 60 ml of Rapamune solution, one
syringe adapter, 30 dosing syringes (amber, made of polypropylene) and a syringe holder.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Brussels
Belgium

Manufacturer:
Pfizer Service Company BV
Hoge Wei 10,
1930 Zaventem
Belgium
For further information on this medicine, contact the local representative of the marketing
authorisation holder:

België/Belgique/Belgien
Luxembourg/Luxemburg
Pfizer NV/SA
Tél/Tel: +32 (0)2 554 62 11

Lietuva
Pfizer Luxembourg SARL filialas Lietuvoje
Tel. +3705 2514000

България
Пфайзер Люксембург САРЛ, Клон
БългарияTeл: +359 2 970 4333

Magyarország
Pfizer Kft.
Tel: +36 1 488 3700

Česká Republika
Pfizer, spol. s r.o.
Tel: +420 283 004 111

Malta
Vivian Corporation Ltd.
Tel: +35621 344610

Danmark
Pfizer ApS
Tlf: +45 44 201 100

Nederland
Pfizer bv
Tel: +31 (0)800 63 34 636

Deutschland
Pfizer Pharma GmbH
Tel: +49 (0)30 550055-51000

Norge
Pfizer AS
Tlf: +47 67 52 61 00

Eesti
Pfizer Luxembourg SARL Eesti filiaal
Tel: +372 666 7500

Österreich
Pfizer Corporation Austria Ges.m.b.H.
Tel: +43 (0)1 521 15-0

Ελλάδα
PFIZER ΕΛΛΑΣ A.E.
Τηλ.: +30 210 6785 800

Polska
Pfizer Polska Sp. z o.o.,
Tel.: +48 22 335 61 00

España
Pfizer, S.L.
Télf:+34914909900

Portugal
Laboratórios Pfizer, Lda.
Tel: +351 21 423 5500

France
Pfizer
Tél: +33 (0)1 58 07 34 40

România
Pfizer Romania S.R.L
Tel: +40 (0) 21 207 28 00

Hrvatska
Pfizer Croatia d.o.o.
Tel: + 385 1 3908 777

Slovenija
Pfizer Luxembourg SARL, Pfizer, podružnica za
svetovanje s področja farmacevtske dejavnosti,
Ljubljana
Tel: +386 (0)1 52 11 400

Ireland
Pfizer Healthcare Ireland Unlimited Company
Tel: +1800 633 363 (toll free)
Tel: +44 (0)1304 616161

Slovenská Republika
Pfizer Luxembourg SARL, organizačná zložka
Tel: + 421 2 3355 5500

Ísland
Icepharma hf
Tel: +354 540 8000

Suomi/Finland
Pfizer Oy
Puh/Tel: +358 (0)9 430 040

Italia
Pfizer S.r.l.
Tel: +39 06 33 18 21

Sverige
Pfizer AB
Tel: +46 (0)8 550 520 00

Kύπρος
PFIZER ΕΛΛΑΣ A.E. (Cyprus Branch)
T  : +357 22 817690

Latvija
Pfizer Luxembourg SARL filiāle Latvijā
Tel. +371 67035775
More detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu.

Rapamune 0.5 mg film-coated tablets, 1 mg film-coated tablets, 2 mg film-coated tablets

sirolimus

Read 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 questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

• 1. What Rapamune is and what it is used for
• 2. What you need to know before you take 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 is Rapamune and what is it used for

Rapamune contains the active substance sirolimus, which belongs to a group of medicines defined
as immunosuppressants. It helps to control your body's immune system after you have
undergone a kidney transplant.
Rapamune is used in adults to prevent your body from rejecting the transplanted kidneys and is
normally used in association with other immunosuppressant medicines called corticosteroids and
initially (for the first 2 – 3 months) with cyclosporine.
Rapamune is also used for the treatment of patients affected by sporadic lymphangioleiomyomatosis
(S-LAM) with moderate lung disease or decreasing lung function. LAM is a
rare progressive lung disease that predominantly affects women of childbearing age. The most common
symptom of LAM is dyspnea.

2. What you need to know before taking 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 taking Rapamune

• If you have liver problems or have had a disease that may have affected your liver, tell your doctor, as this may affect the dose of Rapamune you receive and further blood tests may be necessary.
• Rapamune, like other immunosuppressant medicines, can decrease your body's ability to fight infections, and may increase the risk of developing tumors of the lymphatic tissues and skin.
• If your body mass index (BMI) is greater than 30 kg/m², there may be a higher risk of abnormal wound healing.
• If you are considered to be at high risk of kidney rejection, such as someone who has already received another organ transplant, which was subsequently lost due to rejection.

The doctor will perform tests to check the levels of Rapamune in your blood. The doctor
will also perform tests to check the function of your kidneys, the levels of fats in the blood
(cholesterol and/or triglycerides) and possibly, the function of your liver during treatment with
Rapamune.
Exposure to sunlight and UV light should be limited, covering your skin with suitable
clothing and using a sunscreen with a high protection factor, as the risk of skin cancer is increased.

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

Other medicines and Rapamune
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicines.
Some medicines can interfere with the action of Rapamune and therefore a
dose adjustment of Rapamune may be necessary. In particular, tell your doctor or pharmacist if you are
taking any of the following:

• any other immunosuppressant medicines.
• antibiotic or antifungal medicines used to treat infections, for example clarithromycin, erythromycin, telithromycin, troleandomycin, rifabutin, clotrimazole, fluconazole, itraconazole, ketoconazole or voriconazole. Taking Rapamune with rifampicin, ketoconazole or voriconazole is not recommended.
• any anti-hypertensive medicines or medicines for heart problems, including nicardipine, verapamil and diltiazem.
• anti-epileptic medicines, including carbamazepine, phenobarbital, phenytoin.
• medicines used to treat ulcers or other gastrointestinal disorders such as cisapride, cimetidine, metoclopramide.
• bromocriptine (used to treat Parkinson's disease and various hormonal imbalances), 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 (uses include, also, the treatment of seizures).

The use of live vaccines during treatment with Rapamune should be avoided. Before any
vaccination, tell your doctor or pharmacist that you are taking Rapamune.
The use of Rapamune may cause an increase in blood levels of cholesterol and triglycerides (fats in
the blood) 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 breakdown (rhabdomyolysis). Tell your doctor if you are taking medicines to lower
blood fat levels.
The use of Rapamune in combination with 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 any of these medicines.

Rapamune with food and drink
Rapamune should always be taken under the same conditions, with or without
food. If you prefer to take Rapamune with food, you should then always take it with food. If
you prefer to take Rapamune without food, you should then always take it without food. Food can
affect the amount of medicine in the blood, therefore, if you always take the medicine under the same
conditions, the blood levels of Rapamune will be more stable.
Rapamune should not be taken with grapefruit juice.

Pregnancy, breastfeeding and fertility
Rapamune should not be taken during pregnancy unless it is strictly necessary.
During treatment with Rapamune and for 12 weeks after stopping treatment
effective contraceptive methods must be used. If you are pregnant, suspect or are
planning a pregnancy or if you are breastfeeding, ask your doctor or
pharmacist for advice before taking this medicine.
It is not known whether Rapamune is excreted in breast milk. Patients taking Rapamune must
stop breastfeeding.
A decrease in sperm count has been associated with the use of Rapamune and
generally returns to normal after stopping treatment.

Driving and using machines
Although treatment with Rapamune is not expected to 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 you have been told by your doctor
that you have an intolerance to some sugars, contact your doctor before taking this medicine.

3. How to take Rapamune

Always take this medicine exactly as your doctor has told you. If you have any doubts, ask your
doctor or pharmacist.
The doctor will decide exactly what dose of Rapamune you should take and how often.
Follow your doctor's instructions exactly and never change the dose on your own initiative.
Rapamune is for oral use only. Do not crush, chew or split the tablets. Tell your doctor if you have
difficulty swallowing the tablet.
Multiples of 0.5 mg tablets should not be used as substitutes for other 1 mg and 2 mg tablet dosages,
as the different dosages are not directly interchangeable.
Rapamune should always be taken under the same conditions, with or without food.
Kidney transplant
The doctor will prescribe an initial dose of 6 mg as soon as possible after the kidney transplant surgery.
Afterwards, you will need to take 2 mg of Rapamune every day, unless your doctor instructs
otherwise. Your dose will be adjusted based on the concentration of Rapamune in your
blood. The doctor will need to perform blood tests to determine the concentrations of
Rapamune.
If you are also taking ciclosporin, then you should take the two medicines approximately 4 hours
apart from each other.
It is recommended to initially take Rapamune in combination with ciclosporin and
corticosteroids. After 3 months, the doctor may stop taking Rapamune or ciclosporin, as it is not
recommended to take both medicines together for a longer period.
Sporadic lymphangioleiomyomatosis (S-LAM)
Your doctor will give you 2 mg of Rapamune every day, until otherwise indicated. The dose
will be adjusted based on the level of Rapamune present in your blood. The doctor will need to perform
blood tests to measure the concentrations of Rapamune.

If you take more Rapamune than you should
If you have taken more medicine than you were told to take, consult a doctor or go
directly to the emergency room of the nearest hospital. Always bring the labeled 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
the next dose of ciclosporin. Afterwards, continue to take the medicine as usual.
Do not take a double dose to make up for the missed dose and always take Rapamune and
ciclosporin approximately 4 hours apart from each other. If you completely forget to take a
dose of Rapamune, you should inform your doctor.

If you stop taking Rapamune
Do not stop taking Rapamune unless you have been told to do so by your doctor, as you risk
losing the transplanted organ.
If you have any further questions on this medicine, ask your doctor or pharmacist.

4. Possible side effects

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

Allergic reactions
You must contact your doctor immediatelyif you experience symptoms such as swelling of the face, tongue and/or throat (back of the mouth) and/or difficulty breathing (angioedema) or a skin condition in which the skin may peel off (exfoliative dermatitis). These may be symptoms of a severe allergic reaction.

Kidney damage associated with anemia (thrombocytopenic purpura/hemolytic uremic syndrome)
When taken with medicines called calcineurin inhibitors (cyclosporine or tacrolimus), Rapamune may increase the risk of kidney damage with thrombocytopenia and anemia, with or without rash (thrombocytopenic purpura/hemolytic uremic syndrome). If you experience symptoms such as bruising or rash, changes in urine, or changes in behavior or other serious, unusual, or prolonged symptoms, contact your doctor.

Infections
Rapamune reduces your body's defenses. Consequently, your body will not be as effective as usual in fighting infections. Therefore, if you are taking Rapamune, you may contract more infections than usual, such as skin, mouth, stomach and intestinal, lung, and urinary tract infections (see list below). If your symptoms are severe, unusual, or prolonged, you should contact your doctor.

Frequency of side effects
Very common: (may affect more than 1 in 10 people)

• Fluid collection around the kidney
• Swelling of the body, including hands and feet
• Pain
• Fever
• Headache
• Increased blood pressure
• Abdominal pain, diarrhea, constipation, nausea
• Anemia, thrombocytopenia
• Increased fats in the blood (cholesterol and/or triglycerides), increased blood sugar, low potassium levels in the blood, low phosphorus levels in the blood, increased lactate dehydrogenase protein in the blood, high creatinine levels in the blood
• Joint pain
• Acne
• Urinary tract infections
• Pneumonia and other bacterial, viral and fungal infections
• Decreased number of white blood cells that fight infections
• Diabetes
• Abnormal liver function tests, increased liver enzymes AST and/or ALT
• Rash (skin rash)
• Increased protein in urine
• Menstrual disorders (including amenorrhea, dysmenorrhea or heavy periods)
• Delayed wound healing (which may include separation of surgical wound flaps or suture line)
• Tachycardia
• General tendency to fluid accumulation in various tissues

Common: (may affect up to 1 in 10 people)

• Infections (including life-threatening infections)
• Blood clots in the leg vessels
• Blood clots in the lung
• Mouth ulcers
• Fluid collection in the abdomen
• Kidney damage with thrombocytopenia and anemia, with or without rash (hemolytic uremic syndrome)
• Decreased number of neutrophils (a type of white blood cells)
• Bone deterioration
• Inflammation that can lead to lung damage, fluid around the lungs
• Nosebleeds
• Skin tumor
• Kidney infection
• Ovarian cysts
• Fluid collection in the sac around the heart, which in some cases may decrease the heart's ability to pump blood
• Pancreatitis
• Allergic reactions
• Shingles
• Cytomegalovirus infection

Uncommon: (may affect up to 1 in 100 people)

• Cancer of the lymphatic tissue (lymphoma/post-transplant lymphoproliferative disorders), simultaneous decrease in red blood cells, white blood cells and platelets
• Bleeding from the lungs
• Protein in the urine, occasionally severe and associated with side effects such as swelling
• Scarring of the kidney that can reduce kidney function
• Collection of too much fluid in the tissues due to irregular lymph function
• Thrombocytopenia, with or without rash (thrombocytopenic purpura)
• Severe allergic reactions that can cause skin peeling
• Tuberculosis
• Epstein-Barr virus infection
• Clostridium difficileinfectious diarrhea
• Severe liver damage
• Rare: (may affect up to 1 in 1000)
• Accumulation of protein in the lung alveoli that can interfere with breathing
• Severe allergic reactions that can affect blood vessels (see the paragraph on allergic reactions above)

Not known: (frequency cannot be estimated based on available data)

• Posterior reversible encephalopathy syndrome (PRES), a serious nervous system syndrome with the following symptoms: headache, nausea, vomiting, confusion, seizures, and vision loss. If these symptoms occur together, please contact your doctor.

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

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. You can also report side effects directly through the national reporting system detailed in Annex V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store 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 the cardboard packaging
after EXP. The expiry date refers to the last day of the month.
Do not store at a temperature above 25°C.
Keep the blister in the outer packaging to protect the medicine from light.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how
to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Rapamune contains
The active ingredient is sirolimus.
Each 0.5 mg film-coated tablet of Rapamune contains 0.5 mg of sirolimus.
Each 1 mg film-coated tablet of Rapamune contains 1 mg of sirolimus.
Each 2 mg film-coated tablet of Rapamune contains 2 mg of sirolimus.
The excipients are:
Tablet core :lactose monohydrate, macrogol, magnesium stearate, talc
Tablet coating :macrogol, glycerol monooleate, pharmaceutical lacquer, calcium sulfate,
microcrystalline cellulose, sucrose, titanium dioxide, poloxamer 188 , -tocopherol, povidone, carnauba wax.
Printing ink (shellac, red iron oxide, propylene glycol [E1520], concentrated ammonia solution, simeticone). The 0.5 mg and 2 mg tablets also contain yellow iron oxide (E172) and brown iron oxide (E172).

Description of Rapamune and package contents
Rapamune 0.5 mg is supplied as light brown, triangular film-coated tablets, marked on one side with "RAPAMUNE 0.5 mg".
Rapamune 1 mg is supplied as white, triangular film-coated tablets, marked on one side with "RAPAMUNE 1 mg".
Rapamune is supplied as yellow to beige, triangular film-coated tablets, marked on one side with " RAPAMUNE 2 mg".
The tablets are provided in packs of 30 and 100 tablets in blisters. Not all pack sizes may be marketed.

Marketing authorisation holder and manufacturer
Marketing authorisation holder:
Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Brussels
Belgium

Manufacturer:
Pfizer Ireland Pharmaceuticals
Little Connell, Newbridge, Co. Kildare
Ireland
Pfizer Manufacturing Deutschland GmbH
Mooswaldallee 1
79108 Freiburg Im Breisgau
Germany
For further information on this medicinal product, contact the local representative of the marketing authorisation holder.

België/Belgique/Belgien
Luxembourg/Luxemburg
Pfizer NV/SA
Tél/Tel: +32 (0)2 554 62 11

Lietuva
Pfizer Luxembourg SARL filialas Lietuvoje
Tel. +3705 2514000

БългарияMagyarország
Пфайзер Люксембург САРЛ, Клон България
Teл: +359 2 970 4333
Pfizer Kft.
Tel: +36 1 488 3700

Česká Republika
Pfizer, spol. s r.o.
Tel: +420 283 004 111

Malta
Vivian Corporation Ltd.
Tel: +35621 344610

Danmark
Pfizer ApS
Tlf: +45 44 201 100

Nederland
Pfizer bvTel: +31 (0)800 63 34 636

Deutschland
Pfizer Pharma GmbH
Tel: +49 (0)30 550055-51000

Norge
Pfizer AS
Tlf: +47 67 52 61 00

Eesti
Pfizer Luxembourg SARL Eesti filiaal
Tel: +372 666 7500

Österreich
Pfizer Corporation Austria Ges.m.b.H.
Tel: +43 (0)1 521 15-0

Ελλάδα
PFIZER ΕΛΛΑΣ A.E.
Τηλ.: +30 210 6785 800

Polska
Pfizer Polska Sp. z o.o.,
Tel.: +48 22 335 61 00

España
Pfizer, S.L.
Télf:+34914909900

Portugal
Laboratórios Pfizer, Lda.
Tel: +351 21 423 5500

France
Pfizer
Tél: +33 (0)1 58 07 34 40

România
Pfizer Romania S.R.L
Tel: +40 (0) 21 207 28 00

Hrvatska
Pfizer Croatia d.o.o.
Tel: + 385 1 3908 777

Slovenija
Pfizer Luxembourg SARL, Pfizer, podružnica za
svetovanje s področja farmacevtske dejavnosti,
Ljubljana
Tel: +386 (0)1 52 11 400

Ireland
Pfizer Healthcare Ireland Unlimited Company
Tel: +1800 633 363 (toll free)
Tel: +44 (0)1304 616161

Slovenská Republika
Pfizer Luxembourg SARL, organizačná zložka
Tel: + 421 2 3355 5500

Ísland
Icepharma hf
Tel: +354 540 8000

Suomi/Finland
Pfizer Oy
Puh/Tel: +358 (0)9 430 040

Italia
Pfizer S.r.l.
Tel: +39 06 33 18 21

Sverige
Pfizer AB
Tel: +46 (0)8 550 520 00

Kύπρος
PFIZER ΕΛΛΑΣ A.E. (Cyprus Branch)
T  : +357 22 817690

Latvija
Pfizer Luxembourg SARL filiāle Latvijā
Tel. +371 67035775
More detailed information on this medicinal product is available on the website of the
European Medicines Agency: http://www.ema.europa.eu.