Author: Wyeth Europa Ltd


Long information

What is it and how is it used?

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.

It is used to prevent your body from rejecting transplanted kidneys and is normally used with other immunosuppressant medicines called corticosteroids and initially (the first 2 to 3 months) with ciclosporin.

Table of Contents
What do you have to consider before using it?
How is it used?
What are possible side effects?
How should it be stored?
Further information

What do you have to consider before using it?

Do not take Rapamune

if you are allergic (hypersensitive) to sirolimus or any of the other ingredients of Rapamune (section 6 contains a list of these ingredients).
if you are allergic to peanut or soya

Take special care with Rapamune

- If you have any liver problems or have had a disease which may have affected your liver, please tell your doctor as this may affect the dose of Rapamune that you receive and may result in your having additional blood tests.- Rapamune, like other immunosuppressive medicines, may decrease your body?s ability to fight infection, and may increase the risk of developing cancer of the lymphoid tissues and skin.- If you have a body mass index (BMI) greater than 30 kg/m 2, you may be at increased risk of abnormal wound healing.- If you are considered to be at high risk for rejection, such as if you had a previous transplant that was lost to rejection.

Your doctor will perform tests to monitor the levels of Rapamune in your blood. Your doctor will also perform tests to monitor your kidney function, your blood fat (cholesterol and/or triglycerides) levels 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 because of the increased risk for skin cancer.

Use in children
There is limited experience on the use of Rapamune in children and adolescents less than 18 years of age. The use of Rapamune is not recommended in this population.

Taking other medicines

Please tell your doctor or pharmacist if you are taking, or have recently taken any other medicines, including those obtained without a prescription.
Some medicines can interfere with the action of Rapamune and, therefore, dose adjustment of Rapamune may be required. In particular, you should inform your doctor or pharmacist if you are taking any of the following:

any other immunosuppressant medicines antibiotics or antifungal medicines used to treat infection e.g. clarithromycin, erythromycin, telithromycin, troleandomycin, rifabutin, clotrimazole, fluconazole, itraconazole. It is not recommended that Rapamune be taken with rifampicin, ketoconazole or voriconazole. any high blood pressure 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 in the treatment of Parkinsons disease and various hormonal disorders, danazol used in the treatment of gynaecological disorders, or protease inhibitors used in the treatment of HIV St. Johns Wort Hypericum perforatum

The use of live vaccines should be avoided with the use of Rapamune. Before vaccinations, please inform your doctor or pharmacist that you are receiving Rapamune.

The use of Rapamune may lead to increased levels of cholesterol and triglycerides (blood fats) in your blood that may require treatment. Medicines known as ?statins? and ?fibrates? used to treat elevated cholesterol and triglycerides have been associated with an increased risk of muscle breakdown (rhabdomyolysis). Please inform your doctor if you are taking medicines to lower your blood fats.

The combined use of Rapamune with angiotensin-converting enzyme (ACE) inhibitors (a type of medicine used to lower blood pressure) may result in allergic reactions. Please inform your doctor if you are taking any of these medicines.

Taking Rapamune with food and drink

Rapamune should be taken consistently, either with or without food. If you prefer to take Rapamune with food, then you should always take it with food. If you prefer to take Rapamune without food, then you should always take it without food. Food can affect the amount of medicine that gets into your bloodstream, and taking your medicine in a consistent way means that the blood levels of Rapamune remain more stable.

Rapamune should not be taken with grapefruit juice.

Pregnancy and breast-feeding

Rapamune should 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 treatment has stopped. If you are unsure, or think you may have become pregnant, talk to your doctor.

It is not known whether Rapamune passes into breast milk. Patients taking Rapamune should discontinue breast-feeding.

Decreased sperm count has been associated with the use of Rapamune and usually returns to normal once treatment is stopped.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

Although Rapamune treatment is not expected to affect your ability to drive, if you have any concerns please consult your doctor.

Important information about some of the ingredients of Rapamune

Rapamune contains up to 2.5 vol % ethanol (alcohol). An initial dose of 6 mg contains up to 150 mg of alcohol which isequivalent to 3 ml beer or 1.25 ml wine. This amount of alcohol may be harmful for those suffering from alcoholism as well as for children and high-risk groups such as patients with liver disease, or epilepsy. Alcohol may modify or increase the effect of other medicines. Maintenance doses of 4 mg or less contain small amounts of ethanol (100 mg or less) that are likely to be too low to be harmful.

How is it used?

Always take Rapamune exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

Your doctor will decide exactly what dose of Rapamune you must take and how often to take it. Follow your doctor?s instructions exactly, and never change the dose yourself.

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Your doctor will give you an initial dose of 6 mg as soon as possible after the kidney transplant operation. Then you will need to take 2 mg of Rapamune each day, until otherwise directed by your doctor. 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 ciclosporin, then you must take the two medicines approximately 4 hours apart.

It is recommended that Rapamune be used first in combination with ciclosporin and corticosteroids. After 3 months, your doctor may discontinue either Rapamune or ciclosporin, as it is not recommended that these medicines be taken together beyond this period.

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

Rapamune should be taken consistently, either with or without food.

Instructions on how to dilute Rapamune

1. Remove the safety cap from the bottle by squeezing the tabs on the cap and twisting. Insert the syringe adapter into the bottle until it is flush with 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 in the adapter.

3. Withdraw the exact amount of Rapamune oral solution as prescribed by your doctor by gently pulling out the plunger of the dosing syringe until the bottom of the black line of the plunger is level with the appropriate mark on the dosing syringe. The bottle should remain in an upright position when withdrawing the solution. If bubbles form in the dosing syringe during withdrawal, empty the Rapamune solution back into the bottle and repeat the withdrawal procedure.

4. You may have been instructed to take your Rapamune oral solution at a particular time of day. If it is necessary to carry your medication with you, fill the dosing syringe to the appropriate mark and place a cap securely on it ? the cap should snap into place. Then place the capped dosing syringe in the carrying case provided. Once in the syringe the medication may be kept at room temperature (not exceeding 25-C) or refrigerated and should be used within 24 hours.

5. Empty the contents of the dosing syringe into only a glass or plastic container holding at least 60 ml of water or orange juice. Stir well for one minute and drink immediately at once. Refill the glass with at least 120 ml of water or orange juice, stir well, and drink immediately. No other liquids, including grapefruit juice, should be used for dilution. The dosing syringe and cap are to be used once and then discarded.

When refrigerated the solution in the bottle may develop a slight haze. If this occurs, simply bring your Rapamune oral solution to room temperature and shake gently. The presence of this haze 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 contact a doctor or go to the nearest hospital emergency department straight away. Always take the labelled medicine bottle 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. After that, continue to take your medicines as usual. Do not take a double dose to make up for a forgotten dose, and always take Rapamune and ciclosporin approximately 4 hours apart. If you miss a dose of Rapamune completely, you should inform your doctor.

If you stop taking Rapamune

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

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

What are possible side effects?

Like all medicines, Rapamune can cause side effects, although not everybody gets them.

Allergic reactions

You should see your doctor immediately if you experience symptoms, such as swollen face, tongue and/or back of the mouth (pharynx) and/or difficulties in breathing (angioedema), or a skin condition whereby the skin can peel off (exfoliative dermatitis). These may be symptoms of a serious allergic reaction.

Kidney damage with low blood cell counts (thrombocytopaenic purpura/haemolytic uraemic syndrome)

When taken with medicines called calcineurin inhibitors (ciclosporin or tacrolimus), Rapamune may increase the risk of kidney damage with low blood platelets and low red blood cell counts, with or without rash (thrombocytopaenic purpura/haemolytic uraemic syndrome). If you experience symptoms, such as bruising or rash, changes in your urine, or changes in behaviour, or any others that are serious, unusual or prolonged, contact your doctor.

Infections

Rapamune reduces your body?s own defence mechanisms to stop your rejecting your transplanted organ. Consequently your body will not be as good as normal at fighting infections. So if you are taking Rapamune, you may therefore catch more infections than usual, such as infections of the skin, mouth, stomach and intestines, lungs and urinary tract (see list below). You should contact your doctor if you experience symptoms that are serious, unusual, or prolonged.

Side effect frequencies

The frequency of side effects listed below is defined using the following convention:

very common (affects more than 1 user in 10)
common (affects 1 to 10 users in 100)
uncommon (affects 1 to 10 users in 1,000)
rare (affects 1 to 10 users in 10,000)
not known (frequency cannot be estimated from the available data)

Very common Fluid collection around the kidney Swelling of the extremities e.g., hands, feet Pain Fever Headache Increased blood pressure Stomach pain, diarrhoea, constipation, nausea Low red blood cells, low blood platelets

Increased fat in the blood cholesterol andor triglycerides, increased blood sugar, low blood potassium, low blood phosphorus, increased lactate dehydrogenase in the blood, increased creatinine in the blood Joint pain Acne Urinary tract infection

Common Slow healing this may include separation of the layers of a surgical wound or stitch line Swelling Infections including life-threatening infections Rapid heart rate Blood clots in the legs Mouth sores Fluid collection in the abdomen Kidney damage with low blood platelets and low red blood cell counts, with or without rash thrombocytopaenic purpurahaemolytic uraemic syndrome A reduced number of infection-fighting cells in the blood white blood cells, low levels of a type of white blood cells called neutrophils Diabetes Abnormal tests of liver function, elevated AST andor ALT liver enzymes Deterioration of bone Pneumonia and other causes of inflammation that may lead to lung damage, fluid around the lung Nose bleeds Skin cancer Rash Kidney infection protein in the urine

Uncommon:
- Fluid collection in the sac around the heart, that in some cases may decrease the heart's ability to pump blood
- Inflammation of the pancreas
- Blood clots in the lung
- Cancer of the lymph tissue (lymphoma/post-transplant lympho-proliferative disorder), combined lowering of red blood cells, white blood cells and blood platelets
- Bleeding from the lung
- Protein in the urine, occasionally severe and associated with side effects, such as swelling

Rare:
- Protein build-up in the air sacs of the lungs that may interfere with breathing
- Too much fluid collecting in the tissues due to irregular lymph function
- Serious allergic reactions (see above paragraph on allergic reactions)

Not known:
- Serious liver damage and scarring in the kidney that may reduce kidney function - There is a general tendency for fluid to collect in various tissues.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

How should it be stored?

Keep out of the reach and sight of children.

Do not use Rapamune after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of that month.

Store in a refrigerator (2-C -8-C).
Keep Rapamune oral solution in its original bottle in order to protect from light.
Once the bottle has been opened, the contents should be kept refrigerated and used within 30 days. If necessary, you may store the bottle at room temperature up to 25-C for a short period of time, but no longer than 24 hours.

Once the dosing syringe has been filled with Rapamune oral solution, it should be kept at room temperature, but not above 25-C, for maximum 24 hours.
Once the contents of the dosing syringe have been diluted with water or orange juice, the preparation should be drunk immediately.

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.

Further information

What Rapamune contains

The active substance is sirolimus. Each ml of Rapamune oral solution contains 1 mg of sirolimus.

The other ingredients are:
Polysorbate 80 (E433) and phosal 50 PG(phosphatidylcholine, propylene glycol, monodiglycerides, ethanol, soya fatty acids, and ascorbyl palmitate).

What Rapamune looks like and contents of the pack

Rapamune oral solution is a pale yellow to yellow solution 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 plastic) and one syringe carry case.

Marketing Authorisation Holder Wyeth Europa Ltd Huntercombe Lane South Taplow, Maidenhead Berkshire, SL6 0PH United Kingdom. Manufacturer Wyeth Medica Ireland Little Connell Newbridge Co. Kildare Ireland. Or

Wyeth Pharmaceuticals
New Lane
Havant
Hampshire PO9 2NG
United Kingdom

For any information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder.

Magyarország Pfizer Kft. Tel 36 1 488 3700 BelgiëBelgiqueBelgien LuxembourgLuxemburg Pfizer S.A. N.V. TélTel 32 02 554 62 11

EestiLatvijaLietuva Slovenija Wyeth Whitehall Export GmbH TeTelTãlr43 1 89 1140 Malta Vivian Corporation Ltd. Tel 35621 344610

eská Republika Pfizer s.r.o. Tel 420-283-004-111 Nederland Wyeth Pharmaceuticals B.V. Tel 31 23 567 2567

Danmark Pfizer ApS Tlf 45 44 201 100 Norge Pfizer AS Tlf 47 67 526 100

Deutschland Pfizer Pharma GmbH Tel 49 030 550055-51000 Österreich Pfizer Corporation Austria Ges.m.b.H. Tel 43 01 521 15-0

Pfizer Hellas A.E. . 30 210 6785 800 Polska Pfizer Polska Sp. z o.o., Tel. 48 22 335 61 00

España Pfizer, S.A. Télf34914909900 Portugal Laboratórios Pfizer, Lda. Tel 351 21 423 55 00

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Ireland Wyeth Pharmaceuticals Tel 353 1 449 3500 Slovenská Republika Pfizer Luxembourg SARL, organizaná zloka Tel 421 2 3355 5500

Ísland Icepharma hf Tel 354 540 8000 SuomiFinland Pfizer Oy PuhTel 358 09 430 040

Italia Wyeth Lederle S.p.A. Tel 39 06 927151 Sverige Pfizer AB Tel 46 08 550 520 00

K Wyeth Hellas Cyprus Branch AEBE T 357 22 817690 United Kingdom Wyeth Pharmaceuticals Tel 44 1628 415330

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