CELLCEPT 500 MG POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION

2. What you need to know before you start taking CellCept

WARNING

Mycophenolate causes birth defects and miscarriages. If you are a woman who can become pregnant, you must have a negative pregnancy test before starting treatment and must follow the advice on contraception given by your doctor.

Your doctor will discuss and give you written information, in particular about the effects of mycophenolate on unborn babies. Read this information carefully and follow the instructions.

If you do not understand these instructions completely, please ask your doctor to explain them to you again before taking mycophenolate.

See more information in this section under the headings “Warnings and precautions” and “Pregnancy and breast-feeding”.

Do not take CellCept:

• If you are allergic to mycophenolate mofetil, mycophenolic acid, polysorbate 80 or any of the other ingredients of this medicine (listed in section 6).
• If you are a woman who can become pregnant and have not had a negative pregnancy test before the first prescription, since mycophenolate can cause birth defects and miscarriages.
• If you are pregnant or plan to become pregnant or think you may be pregnant.
• If you are not using effective contraception (see Pregnancy, contraception and breast-feeding)
• If you are breast-feeding.

Do not take this medicine if any of the above applies to you. If you are not sure, ask your doctor or nurse before taking CellCept.

Warnings and precautions

Talk to your doctor or nurse before starting treatment with CellCept:

• If you are over 65 years old, as you may have a higher risk of developing side effects such as certain viral infections, gastrointestinal bleeding and pulmonary oedema compared to younger patients
• If you have any signs of infection such as fever or sore throat
• If you get bruising or bleeding unexpectedly
• If you have or have had any problems with your digestive system such as stomach ulcers
• If you plan to become pregnant or have become pregnant while you or your partner are taking CellCept
• If you have a hereditary enzyme deficiency such as Lesch-Nyhan syndrome and Kelley-Seegmiller syndrome

If any of the above applies to you (or you are not sure), ask your doctor or nurse immediately before starting treatment with CellCept.

Effect of sunlight

CellCept reduces your body's defences. For this reason, there is a higher risk of getting skin cancer. Limit the amount of sunlight and UV light you absorb by:

• wearing protective clothing that also covers your head, neck, arms and legs
• using a sunscreen with a high protection factor

Children

Do not give this medicine to children, as the safety and efficacy of administration to paediatric patients has not been established.

Other medicines and CellCept

Tell your doctor or nurse if you are taking or have recently taken any other medicines. This includes medicines obtained without a prescription, such as herbal medicines. This is because CellCept may affect the way other medicines work. Also, other medicines may affect the way CellCept works.

In particular, tell your doctor or nurse if you are taking any of the following medicines before starting CellCept:

• azathioprine or another medicine that suppresses the immune system – which was given after the transplant operation
• cholestyramine – used to treat high cholesterol levels
• rifampicin – an antibiotic used to prevent and treat infections such as tuberculosis (TB)
• phosphate binders – used in patients with chronic kidney failure to reduce phosphate absorption into the blood
• antibiotics – used to treat bacterial infections
• isavuconazole – used to treat fungal infections
• telmisartan – used to treat high blood pressure

Vaccines

If you need to have a vaccine (live organism vaccine) during treatment with CellCept, consult your doctor or pharmacist first. Your doctor will advise which vaccines you can have.

Do not donate blood during treatment with CellCept and for at least 6 weeks after stopping treatment. Men should not donate semen during treatment with CellCept and for at least 90 days after stopping treatment.

Contraception in women taking CellCept

If you are a woman who can become pregnant, you must use a reliable method of contraception. This includes:

• before starting CellCept
• during treatment with CellCept
• for 6 weeks after stopping CellCept

Talk to your doctor about the most suitable contraceptive method for you. This will depend on your personal situation. It is recommended to use two methods of contraception as this will reduce the risk of unplanned pregnancy. Talk to your doctor as soon as possible if you think your contraceptive method may not have been effective or if you have forgotten to take your contraceptive pill.

You cannot become pregnant if:

• You are post-menopausal, i.e. you are over 50 years old and your last period was more than a year ago (if your periods have stopped due to cancer treatment, you may still be able to become pregnant)
• Your fallopian tubes and both ovaries have been removed by surgery (bilateral salpingo-oophorectomy)
• Your uterus has been removed by surgery (hysterectomy)
• Your ovaries do not work (premature ovarian failure that has been confirmed by a specialist gynaecologist)
• You were born with one of the following rare conditions that make pregnancy impossible: XY genotype, Turner syndrome or uterine agenesis
• You are a girl or adolescent who has not started having periods

Contraception in men taking CellCept

Available evidence does not indicate an increased risk of malformations or miscarriage if the father takes mycophenolate. However, the risk cannot be completely excluded. As a precaution, it is recommended that you or your female partner use a reliable method of contraception during treatment and for 90 days after stopping CellCept.

If you are planning to have a child, talk to your doctor about the potential risks and alternative treatments.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. Your doctor will discuss with you the potential risks and alternative treatments that can be used to prevent rejection of the transplanted organ if:

• You plan to become pregnant.
• You have missed a period or have unusual menstrual bleeding or suspect you are pregnant.
• You have had unprotected sex.

If you become pregnant during treatment with mycophenolate, you must inform your doctor immediately. However, keep taking CellCept until you see your doctor.

Pregnancy

Mycophenolate causes a very high frequency of miscarriages (50%) and severe harm to the unborn baby (23-27%). Among the birth defects that have been reported are ear, eye, facial (cleft lip and palate), finger, heart, oesophagus (tube connecting the throat to the stomach), kidney and nervous system defects (such as spina bifida, where the bones of the spine do not develop properly). Your baby may be affected by one or more of these.

If you are a woman who can become pregnant, you must have a negative pregnancy test before starting treatment and must follow the advice on contraception given by your doctor. Your doctor may ask for more than one pregnancy test to make sure you are not pregnant before starting treatment.

Breast-feeding

Do not take CellCept if you are breast-feeding. This is because small amounts of the medicine may pass into breast milk.

Driving and using machines

CellCept has a moderate influence on the ability to drive and use machines. If you feel drowsy, sleepy or confused, talk to your doctor or nurse and do not drive or use tools or machines until you feel better.

CellCept contains polysorbate

This medicine contains 25 mg of polysorbate 80 in each vial. Polysorbates may cause allergic reactions. Talk to your doctor if you have any known allergies.

CellCept contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per vial; this is essentially “sodium-free”.

3. How to use CellCept

CellCept is usually given by a doctor or nurse in a hospital. It is given as an intravenous infusion by drip.

Amount to be given

The amount to be given depends on the type of transplant you have. The usual doses are shown below. Treatment will continue until it is necessary to prevent rejection of the transplanted organ.

Kidney transplant

Adults

• The first dose should be given within 24 hours after the transplant operation.
• The daily dose is 2 g of the medicine given in 2 separate doses.
• 1 g will be given in the morning and 1 g in the evening.

Liver transplant

Adults

• The first dose should be given as soon as possible after the transplant operation.
• The medicine will be given for at least 4 days.
• The recommended daily dose is 2 g of the medicine given in 2 separate doses.
• 1 g will be given in the morning and 1 g in the evening.
• When you are able to swallow, the medicine will be given by mouth.

Reconstitution of the medicinal product

The medicine is presented as a powder. This needs to be mixed with glucose before it is given. Your doctor or nurse will reconstitute the medicine and give it to you. They will follow the instructions included in section 7 “Reconstitution of the medicinal product”.

If you are given too much CellCept

If you think you have been given too much medicine, talk to your doctor or nurse immediately.

If you miss a dose of CellCept

If you miss a dose of the medicine, it will be given as soon as possible. Your treatment will then continue at the usual times.

If you stop treatment with CellCept

Do not stop taking CellCept unless your doctor tells you to. If you stop treatment, you may increase the risk of rejection of the transplanted organ.

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

4. Possible side effects

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

Talk to your doctor or nurse immediately if you notice any of the following serious side effects, as you may need urgent medical treatment:

• if you have signs of infection such as fever or sore throat
• if you get bruising or bleeding unexpectedly
• if you get a rash, swelling of the face, lips, tongue or throat with difficulty breathing. You may be having a serious allergic reaction to the medicine (such as anaphylaxis, angioedema).

Common problems

Some of the most common problems are diarrhoea, reduction in the number of white blood cells or red blood cells in the blood, infection and vomiting. Your doctor will regularly do blood tests to check for any changes in:

• the number of blood cells or signs of infection

Fighting infections

Treatment with CellCept reduces your body's defences. This is to prevent rejection of the transplant. For this reason, your body will not be able to fight infections as effectively as under normal conditions. This means you may get more infections than usual. These include infections affecting the brain, skin, mouth, stomach and gut, lungs and urinary system.

Skin and lymph cancer

As with patients taking this type of medicine (immunosuppressants), a very small number of patients treated with CellCept have developed lymphoid and skin cancer.

General unwanted effects

You may get general unwanted effects that affect your whole body. These include serious allergic reactions (such as anaphylaxis, angioedema), fever, feeling very tired, difficulty sleeping, pain (such as stomach pain, chest pain, joint or muscle pain), headache, flu-like symptoms and swelling.

Other unwanted effects may be:

Skin problemssuch as:

• acne, cold sores, skin growth, shingles, hair loss, skin rash, itching.

Urinary problemssuch as:

• blood in the urine.

Problems with the digestive system and mouthsuch as:

• swollen gums and mouth ulcers,
• inflammation of the pancreas, colon or stomach,
• gastrointestinal disorders that include bleeding,
• liver disorders,
• diarrhoea, constipation, feeling sick (nausea), indigestion, loss of appetite, wind.

Nervous system problemssuch as:

• feeling drowsy or numb,
• tremor, muscle spasms, fits (seizures),
• feeling anxious or depressed, changes in mood or thinking.

Heart and blood vessel problemssuch as:

• changes in blood pressure, blood clots, fast heart rate,
• pain, redness and swelling of the blood vessels at the site of infusion.

Lung problemssuch as:

• pneumonia, bronchitis,
• difficulty breathing, cough, which may be due to bronchiectasis (a condition in which the airways are abnormally widened) or pulmonary fibrosis (scarring of the lung). Talk to your doctor if you develop persistent cough or if you are short of breath,
• fluid in the lungs or inside the chest,
• problems with the sinuses.

Other problemssuch as:

• weight loss, gout, high blood sugar levels, bleeding, bruising.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storing CellCept

• 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 carton and vial after EXP.
• Powder for concentrate for solution for infusion: do not store above 30°C.
• Reconstituted solution and diluted solution: store between 15°C and 30°C.
• 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 protect the environment.

6. Container Content and Additional Information

CellCept Composition

• The active ingredient is mycophenolate mofetil.
• Each vial contains 500 mg of mycophenolate mofetil.

The other components are: polysorbate 80, citric acid, hydrochloric acid, sodium chloride (see section 2 "CellCept contains sodium").

Product Appearance and Container Content

• CellCept is presented as a white to off-white powder in 20 ml type I glass vials with a gray butyl rubber stopper and an aluminum seal with easy-to-open plastic caps.

• The reconstituted solution is slightly yellowish.
• It is available in packs of 4 vials.

1. Reconstitution of the Medication

Method of Use and Administration Route

CellCept 500 mg powder for concentrate for solution for infusion does not contain antibacterial preservatives; therefore, the reconstitution and dilution of the product must be carried out under aseptic conditions.

The content of each vial of CellCept 500 mg powder for concentrate for solution for infusion must be reconstituted with 14 ml of 5% glucose intravenous infusion solution. A subsequent dilution with 5% glucose intravenous infusion solution is necessary to achieve a final concentration of 6 mg/ml. This means that to prepare a dose of 1 g of mycophenolate mofetil, the content of 2 reconstituted vials (approx. 2 x 15 ml) must be diluted subsequently in 140 ml of 5% glucose intravenous infusion solution. If the infusion solution is not prepared immediately before administration, the start of administration of the infusion solution must be carried out within 3 hours following the reconstitution and dilution of the medication.

Be careful not to let the reconstituted medication get into your eyes.

• If this happens, rinse your eyes with running water.

Be careful not to let the reconstituted medication come into contact with your skin.

• If this happens, wash the area with plenty of water and soap.

CellCept 500 mg powder for concentrate for solution for infusion must be administered as an intravenous infusion. The infusion rate must be controlled to cover a 2-hour administration period.

The intravenous solution of CellCept must never be administered by rapid intravenous injection or bolus.

Marketing Authorization Holder

Roche Registration GmbH

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

Manufacturer

Roche Pharma AG, Emil-Barell-Strasse 1, 79639 Grenzach-Wyhlen, Germany.

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

Date of the Last Revision of this Prospectus

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