CellCept 500 mg powder for concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

CellCept 500mg powder for concentrate for solution for infusion

mycophenolate mofetil

Read the entire leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or nurse.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it could harm them.
• If you experience any adverse reactions, consult your doctor or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet contents:

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

1. What CellCept is and what it is used for

CellCept contains mycophenolate mofetil:

• It belongs to a group of medicines called "immunosuppressants".

CellCept is used to prevent the body from rejecting a transplanted organ:

• Kidney or liver.

CellCept must be used together with other medicines:

• Cyclosporine and corticosteroids.

2. What you need to know before using CellCept

WARNING

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

Your doctor will explain and provide you with written information, particularly about the effects of mycophenolate on unborn babies. Please read this information carefully and follow the instructions.

If you do not fully understand these instructions, please consult your doctor again for further explanation before taking mycophenolate.

See more information in this section under the headings “Warnings and precautions”, “Contraception”, “Pregnancy and breastfeeding”.

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 result before the first prescription, as mycophenolate may cause birth defects and miscarriages.
• If you are pregnant or plan to become pregnant, or think you might be pregnant.
• If you are not using effective contraception (see Contraception, Pregnancy, and Breastfeeding)
• If you are breastfeeding.

Do not take this medicine if any of the above apply to you. If you are unsure, consult 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 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 develop unexpected bruising or bleeding.
• If you have or have had gastrointestinal problems such as stomach ulcers.
• If you plan to become pregnant or 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 apply to you (or if you are unsure), consult your doctor or nurse immediately before starting treatment with CellCept.

Effect of sunlight

CellCept reduces your body's defenses. For this reason, there is an increased risk of developing skin cancer. Limit your exposure to sunlight and UV light by:

• Wearing appropriate protective clothing that also covers your head, neck, arms, and legs.
• Using a sunscreen with high protection factor.

Children

Do not give this medicine to children, as the safety and efficacy of use in pediatric patients have not been established.

Other medicines and CellCept

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

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

• Azathioprine or other medicines that suppress the immune system – given after transplant surgery.
• 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 renal 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 a vaccine (live organism vaccine) during treatment with CellCept, consult your doctor or pharmacist first. Your doctor will advise you on which vaccines are suitable for you.

You must not donate blood during treatment with CellCept and for at least 6 weeks after stopping treatment. Men must 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 an effective method of contraception:

• Before starting CellCept.
• Throughout treatment with CellCept.
• For up to 6 weeks after stopping CellCept.

Talk to your doctor to determine the most appropriate contraceptive method for you, which will depend on your personal situation. Using two contraceptive methods is recommended, as this reduces the risk of unintended pregnancy. Contact your doctor as soon as possible if you think your contraceptive method may not have been effective or if you missed taking your contraceptive pill.

You cannot become pregnant if any of the following apply to you:

• You are post-menopausal, i.e., you are at least 50 years old and your last menstrual period was over a year ago (if your periods have stopped due to cancer treatment, you may still be able to become pregnant).
• You have had both fallopian tubes and both ovaries surgically removed (bilateral salpingo-oophorectomy).
• You have had your uterus surgically removed (hysterectomy).
• Your ovaries do not function (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 child or adolescent who has not yet started menstruating.

Contraception in men taking CellCept

Available evidence does not indicate an increased risk of birth defects or miscarriage if the father takes mycophenolate. However, the risk cannot be completely ruled out. As a precaution, you or your female partner should use a reliable method of contraception during treatment and for 90 days after stopping CellCept.

If you are planning to have a child, discuss potential risks and alternative treatments with your doctor.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you might be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine. Your doctor will discuss the risks and alternative treatments available to prevent rejection of the transplanted organ if:

• You plan to become pregnant.
• You have a missed period or think you may have missed a period, have unusual menstrual bleeding, or suspect you might be pregnant.
• You have had sexual intercourse without using effective contraception.

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 rate of miscarriages (50%) and serious harm to the unborn baby (23–27%). Reported malformations include abnormalities of the ears, eyes, face (cleft lip and palate), finger development, heart, esophagus (the tube connecting the throat to the stomach), kidneys, and nervous system (e.g., 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 result before starting treatment and must follow your doctor's contraception advice. Your doctor may require more than one pregnancy test to ensure you are not pregnant before starting treatment.

Breastfeeding

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

Driving and using machines

The effect of CellCept on the ability to drive and use machines is moderate. If you feel drowsy, dizzy, or confused, talk to your doctor or nurse and do not drive or operate tools or machinery until you feel better.

CellCept contains polysorbate

This medicine contains 25 mg of polysorbate 80 per 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 capsule; essentially, it is “sodium-free”.

3. How to use CellCept

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

Dose you should receive

The dose you should receive depends on the type of transplant you have had. The usual doses are shown below. Treatment will continue for as long as 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 two separate doses.
• You will receive 1 g 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.
• You will receive the medicine for at least 4 days.
• The recommended daily dose is 2 g of the medicine given in two separate doses.
• You will receive 1 g in the morning and 1 g in the evening.
• When you are able to swallow, you will be given the medicine orally.

Reconstitution of the medicine

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

If you receive more CellCept than you should

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

If you miss a dose of CellCept

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

If you stop CellCept treatment

Do not stop using 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 about the use of this medicine, ask your doctor or nurse.

4. Possible adverse effects

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

Contact your doctor or nurse immediately if you notice any of the following serious adverse effects, as you may require urgent medical treatment:

• if you have signs of infection such as fever or sore throat
• if you develop bruising or bleeding unexpectedly
• rash, itching, hives, difficulty breathing or shortness of breath, wheezing, coughing, dizziness, lightheadedness, changes in consciousness, hypotension, with or without mild generalized itching, skin redness, or swelling of the face or throat (symptoms of a severe allergic reaction).

Common problems

Some of the more common problems include diarrhea, decreased numbers of white or red blood cells in the blood, infection, and vomiting. Your doctor will carry out regular blood tests to monitor for any changes in:

• blood cell counts or signs of infection

Fighting infections

Treatment with CellCept reduces the body's defenses. This is intended to prevent transplant rejection. For this reason, the body is also less able to fight infections effectively under normal conditions. This means you may get more infections than usual. These may include infections affecting the brain, skin, mouth, stomach and intestines, lungs, and urinary system.

Skin and lymphatic cancer

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

General adverse effects

General adverse effects affecting the whole body may occur. 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 possible adverse effects may include:

Skin problems such as:

• acne, cold sores, skin overgrowth, shingles (herpes zoster), hair loss, skin rash, itching.

Urinary problems such as:

• blood in the urine.

Digestive system and mouth problems such as:

• swollen gums and mouth ulcers,
• inflammation of the pancreas, colon, or stomach,
• gastrointestinal disorders including bleeding,
• liver disorders,
• diarrhea, constipation, feeling unwell (nausea), indigestion, loss of appetite, flatulence.

Nervous system problems such as:

• drowsiness or numbness,
• tremor, muscle spasms, seizures,
• feelings of anxiety or depression, changes in mood or thought.

Heart and blood vessel problems such as:

• changes in blood pressure, blood clots, rapid heartbeat,
• pain, redness, and swelling of blood vessels at the infusion site.

Lung problems such as:

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

Other problems such as:

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

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect 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 help provide 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 expiry date stated on the pack 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 and packaging you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of CellCept

• The active substance 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 polysorbate” and “CellCept contains sodium”).

Presentation of the product and contents of the pack

• CellCept is presented as a white to off-white powder in 20 ml Type I clear glass vials with grey butyl rubber stoppers and aluminium seals with easy-open plastic caps.
• The reconstituted solution is slightly yellowish.
• It is available in packs of 4 vials.

1. Reconstitution of the medicinal product

Method of administration and route of administration

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

The contents of each vial of CellCept 500 mg powder for concentrate for solution for infusion should be reconstituted with 14 ml of 5% intravenous glucose solution. Further dilution with 5% intravenous glucose solution is required to achieve a final concentration of 6 mg/ml. This means that to prepare a dose of 1 g of mycophenolate mofetil, the contents of 2 reconstituted vials (approx. 2 x 15 ml) should be further diluted in 140 ml of 5% intravenous glucose solution. If the infusion solution is not prepared immediately before administration, administration must be initiated within 3 hours after reconstitution and dilution of the medicinal product.

Take care to avoid contact of the reconstituted medicine with the eyes.

• If this occurs, rinse the eyes thoroughly with running water.
• Take care to avoid contact of the reconstituted medicine with the skin.
• If contact occurs, wash the area thoroughly 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 ensure administration over a period of 2 hours.

The intravenous solution of CellCept must never be administered as a 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.

Further information on this medicinal product is available upon request by contacting the local representative of the Marketing Authorization Holder:

Date of the most recent review of this leaflet

Other sources of information

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