CELLCEPT 250 mg CAPSULES

2. What you need to know before you take CellCept

WARNING

Mycophenolate causes congenital malformations and spontaneous abortions. 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 explain and give you written information, in particular about the effects of mycophenolate on unborn babies. Read the information carefully and follow the instructions.

If you do not understand these instructions completely, please consult your doctor again so that they can explain them to you once more before you take 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 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 may cause congenital malformations and spontaneous abortions.
• If you are pregnant or plan to become pregnant or think you may be pregnant.
• If you are not using effective contraception (see Contraception, pregnancy 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, consult your doctor or pharmacist before taking CellCept.

Warnings and precautions

Consult your doctor before starting treatment with CellCept:

• If you are over 65 years old, as you may have a higher risk of developing adverse reactions such as certain viral infections, gastrointestinal bleeding and pulmonary edema 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 ever had a problem with your digestive system such as a stomach ulcer.
• If you are planning 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 or Kelley-Seegmiller syndrome.

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

Effect of sunlight

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

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

Children

Children, especially those under 6 years of age, are more likely than adults to have certain adverse reactions, including diarrhea, vomiting, infections, low red blood cell count and low white blood cell count, and the possibility of lymphoma or skin cancer.

The capsules are only suitable for children who can swallow solid medication without the risk of choking. Therefore, the medicine should only be given according to the doctor's prescription.

If you are not sure about something regarding your child's treatment, talk to your doctor or pharmacist before taking it.

Other medicines and CellCept

Tell your doctor or pharmacist 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 pharmacist if you are taking any of the following medicines before starting CellCept:

• azathioprine or another medicine that suppresses the immune system – which was given to you after the transplant operation.
• cholestyramine – used to treat high cholesterol levels.
• rifampicin – an antibiotic used to prevent and treat infections such as tuberculosis (TB).
• antacids, or proton pump inhibitors – used for stomach acid problems such as indigestion.
• phosphate binders – used in patients with chronic kidney failure to reduce phosphate absorption in 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 be vaccinated (live organism vaccine) during treatment with CellCept, consult your doctor or pharmacist first. Your doctor will advise you on 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.

Taking CellCept with food and drinks

Taking food and drinks has no effect on your treatment with CellCept.

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 the entire treatment with CellCept.
• Until 6 weeks after stopping CellCept.

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

You cannot become pregnant if:

• You are post-menopausal, i.e. you are at least 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 surgically removed (bilateral salpingo-oophorectomy).
• Your uterus has been surgically removed (hysterectomy).
• Your ovaries do not work (premature ovarian failure confirmed by a specialist gynecologist).
• 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 spontaneous abortion 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, consult 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 become pregnant, consult your doctor or pharmacist before using this medicine. Your doctor will discuss the risks and alternative treatments that you can take to prevent organ rejection if:

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

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

Pregnancy

Mycophenolate causes a very high frequency of spontaneous abortions (50%) and severe damage to the unborn baby (23-27%). Among the malformations that have been reported are ear, eye, facial (cleft lip and palate), finger, heart, esophagus (tube connecting the throat to the stomach), kidney and nervous system (e.g. spina bifida, where the bones of the spine do not develop properly) anomalies. 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 you to have more than one pregnancy test to ensure that 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

The influence of CellCept on the ability to drive and use machines is moderate.

If you feel drowsy, dazed or confused, talk to your doctor or nurse and do not drive or use tools or machines until you feel better.

CellCept contains sodium

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

3. How to take CellCept

Follow exactly the instructions of your doctor. In case of doubt, consult your doctor or pharmacist again.

How much to take

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

Kidney transplant

Adults

• The first dose should be given within 3 days after the transplant operation.
• The daily dose is 8 capsules (2 g of the medicine), given in 2 divided doses.
• Take 4 capsules in the morning and 4 capsules in the evening.

Children

• The capsules are only suitable for children who can swallow solid medication without the risk of choking. Therefore, the medicine should only be given according to the doctor's prescription. If you are not sure, talk to your doctor or pharmacist before taking it.
• The dose varies depending on the child's size.
• Your child's doctor will decide what dose is most suitable, taking into account the child's height and weight (body surface area measured in square meters “m2”). The recommended starting dose is 600 mg/m2, given twice daily. The maintenance dose should be kept at 600 mg/m2 twice daily (maximum total daily dose of 2 g). The dose should be individualized based on the doctor's clinical evaluation.

Heart transplant

Adults

• The first dose should be given within 5 days after the transplant operation.
• The daily dose is 12 capsules (3 g of the medicine), given in 2 divided doses.
• Take 6 capsules in the morning and 6 capsules in the evening.

Children

• The capsules are only suitable for children who can swallow solid medication without the risk of choking. Therefore, the medicine should only be given according to the doctor's prescription. If you are not sure, talk to your doctor or pharmacist before taking it.
• The dose varies depending on the child's size.
• Your child's doctor will decide what dose is most suitable, taking into account the child's height and weight (body surface area measured in square meters “m2”). The recommended starting dose is 600 mg/m2, given twice daily. The dose should be individualized based on the doctor's clinical evaluation. If well tolerated, the dose may be increased to 900 mg/m2 twice daily if necessary (maximum total daily dose of 3 g).

Liver transplant

Adults

• The first dose should be given at least 4 days after the transplant operation and when you are able to take oral medication.
• The daily dose is 12 capsules (3 g of the medicine), given in 2 divided doses.
• Take 6 capsules in the morning and 6 capsules in the evening.

Children:

• The capsules are only suitable for children who can swallow solid medication without the risk of choking. Therefore, the medicine should only be given according to the doctor's prescription. If you are not sure, talk to your doctor or pharmacist before taking it.
• The dose varies depending on the child's size.
• Your child's doctor will decide what dose is most suitable, taking into account the child's height and weight (body surface area measured in square meters “m2”). The recommended starting dose is 600 mg/m2, given twice daily. The dose should be individualized based on the doctor's clinical evaluation. If well tolerated, the dose may be increased to 900 mg/m2 twice daily if necessary (maximum total daily dose of 3 g).

Taking this medicine

Swallow the capsules whole with a glass of water.

• Do not break or crush them.
• Do not take any capsule that has been broken or opened.

Be careful not to get the powder from a broken capsule in your eyes or mouth.

• If this happens, rinse them with plenty of running water.

Be careful not to get the powder from a broken capsule in contact with your skin.

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

If you take more CellCept than you should

If you take more CellCept than you should, consult your doctor or go to the hospital immediately.

Do this also if someone accidentally takes your medicine. Take the medicine pack with you.

If you forget to take CellCept

If you forget to take your medicine, take it as soon as you remember. Then continue taking it at the usual times. Do not take a double dose to make up for forgotten doses.

If you stop taking CellCept

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

If you have any other 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 all people suffer from them.

Consult your doctor immediately if you notice any of the following serious adverse effects, as you may need urgent medical treatment:

Common Problems

Some of the most common problems are diarrhea, decrease in the number of white or red blood cells in the blood, infection, and vomiting. Your doctor will perform regular blood tests to monitor any changes in:

• the number of blood cells or signs of infection

Fighting Infections

Treatment with CellCept reduces the body's defenses. This is to prevent transplant rejection. For this reason, the body cannot fight infections as effectively as under normal conditions. This means you may get more infections than usual. These include infections that affect the brain, skin, mouth, stomach, and intestines, 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 cancer of lymphoid tissues and skin.

General Undesired Effects

General adverse effects may occur that affect your entire body. These include severe 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 undesired adverse effects may be:

Skin Problemssuch as:

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

Urinary Problemssuch as:

• blood in the urine.

Problems of 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,
• diarrhea, constipation, feeling unwell (nausea), indigestion, loss of appetite, flatulence.

Nervous System Problemssuch as:

• feeling dizzy, drowsy, or numb,
• tremors, muscle spasms, convulsions,
• feeling anxious or depressed, mood or thought changes.

Cardiac and Blood Vessel Problemssuch as:

• changes in blood pressure, rapid heartbeat, and dilation of blood vessels.

Lung Problemssuch as:

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

Other Problemssuch as:

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

Additional Adverse Reactions in Children and Adolescents

Children, especially those under 6 years of age, are more likely than adults to have some adverse reactions, including diarrhea, vomiting, infections, fewer red and white blood cells in the blood, and the possibility of lymphoma or skin cancer.

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of CellCept

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiration date stated on the packaging after EXP.
• Do not store above 25°C.
• Store in the outer packaging to protect from moisture.
• Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Package Contents and Additional Information

Composition of CellCept

• The active ingredient is mycophenolate mofetil
• Each capsule contains 250 mg of mycophenolate mofetil.
• The other ingredients are:
• CellCept capsules: pregelatinized corn starch, sodium croscarmellose, povidone (K-90), magnesium stearate (see section 2 "CellCept contains sodium").
• Capsule shell: gelatin, carmine indigo (E132), yellow iron oxide (E172), red iron oxide (E172), titanium dioxide (E171), black iron oxide (E172), potassium hydroxide, shellac.

Appearance of the Product and Package Contents

• The CellCept capsules are oblong, with one side blue and the other brown. They have "CellCept 250" printed in black on the cap of the capsule and "Roche" printed in black on the body of the capsule.
• Available packages are 100 and 300 capsules (both in blisters of 10) or in a multiple package containing 300 (3 packages of 100) capsules. Only some package sizes may be marketed.

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 medicine by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet

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