Cellcept 1 g/5 ml powder for oral suspension

Patient Information Leaflet

Introduction

Package leaflet: Information for the patient

CellCept 1g/5ml powder for oral suspension

mycophenolate mofetil

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

• Keep this leaflet, as 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, and you should not give it to other people, even if they have the same symptoms as you. It may harm them.
• If you experience any side effects, talk to your doctor or pharmacist, even if they are side effects 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 in adults and children:

• Kidney, heart, or liver.

CellCept should be used together with other medicines:

• Cyclosporine and corticosteroids.

2. What you need to know before starting CellCept

WARNING

Mycophenolate causes birth defects and miscarriages. If you are a woman who could 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. 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 below in this section under the headings “Warnings and precautions”, “Contraception”, and “Pregnancy and breastfeeding”.

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 could 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 planning 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 pharmacist before taking CellCept.

Warnings and precautions

Talk to your doctor before starting treatment with CellCept:

• If you are over 65 years of age, 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 any gastrointestinal problems such as stomach ulcers
• If you have a rare inherited metabolic disorder called familial phenylketonuria
• 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 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 a high sun protection factor

Children

Children, especially those under 6 years of age, are more likely than adults to experience certain adverse reactions, including diarrhea, vomiting, infections, lower red blood cell counts, lower white blood cell counts, and an increased risk of lymphoma or skin cancer.

Do not administer this medicine to children under 1 year of age, as safety and efficacy data in this age group are limited and dosage recommendations cannot be made.

If you are unsure about anything related to your child's treatment, speak with your doctor or pharmacist before administering the medicine.

Other medicines and CellCept

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

In particular, inform your doctor or pharmacist 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)
• 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 receive 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.

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.

Taking CellCept with food and drink

Taking food and drink does not affect your treatment with CellCept.

Contraception in women taking CellCept

If you are a woman who could 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

Consult your doctor to determine the most appropriate contraceptive method for you. This will depend on your individual circumstances. The use of two contraceptive methods is recommended, as this reduces 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 missed taking your contraceptive pill.

You cannot become pregnant if you meet any of the following criteria:

• You are post-menopausal, i.e., you are at least 50 years old and your last menstrual period occurred more than one 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 girl 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 precautionary measure, you or your female partner are advised to use a reliable method of contraception during treatment and for up to 90 days after stopping CellCept.

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

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 organ transplant rejection if:

• You plan to become pregnant
• You miss a period or think you may have missed a menstrual 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 birth defects include abnormalities of the ears, eyes, face (cleft lip and palate), fingers, 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 could become pregnant, you must have a negative pregnancy test result before starting treatment and must follow your doctor's advice on contraception. Your doctor may require more than one pregnancy test to confirm 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.

Important information about some of the ingredients of CellCept

• CellCept contains aspartame. If you have a rare metabolic disorder called phenylketonuria, consult your doctor before starting this medicine.
• CellCept contains sorbitol (a type of sugar). If your doctor has advised you that you cannot tolerate or digest certain sugars, consult your doctor before taking this medicine.

CellCept contains methyl parahydroxybenzoate

This medicine contains methyl parahydroxybenzoate (E218), which may cause allergic reactions (possibly delayed).

CellCept contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose; essentially, it is "sodium-free".

3. How to take CellCept

Follow exactly the instructions given by your doctor for taking this medicine. If in doubt, consult your doctor or pharmacist again.

Dosage

The dose you need to take depends on the type of transplant you have received. The usual doses are shown below. Treatment will continue as long as necessary to prevent rejection of the transplanted organ.

Kidney transplant

Adults

• The first dose should be administered within 3 days after the transplant surgery.
• The daily dose is 10 ml of suspension (2 g of the medicine), given in two separate doses.
• Take 5 ml of suspension in the morning and another 5 ml of suspension in the evening.

Children (between 1 and 18 years of age)

• The dose varies depending on the child's size.
• Your doctor will determine the most appropriate dose based on the child’s height and weight (body surface area measured in square meters “m²”). The recommended starting dose is 600 mg/m², administered twice daily. The recommended maintenance dose remains at 600 mg/m² twice daily (maximum total daily dose of 2 g or 10 ml of oral suspension). Dose individualization should be based on clinical assessment by the physician.

Heart transplant

Adults

• The first dose should be administered within 5 days after the transplant surgery.
• The daily dose is 15 ml of suspension (3 g of the medicine), given in two separate doses.
• Take 7.5 ml of suspension in the morning and another 7.5 ml of suspension in the evening.

Children (between 1 and 18 years of age)

• The dose varies depending on the child's size.
• Your child’s doctor will determine the most appropriate dose based on the child’s height and weight (body surface area measured in square meters “m²”). The recommended starting dose is 600 mg/m², administered twice daily. Dose individualization should be based on clinical assessment by the physician. If well tolerated, the dose may be increased to 900 mg/m² twice daily if necessary (maximum total daily dose of 3 g or 15 ml of oral suspension).

Liver transplant

Adults

• The first dose should be administered at least 4 days after the transplant surgery and once you are able to swallow oral medication.
• The daily dose is 15 ml of suspension (3 g of the medicine), given in two separate doses.
• Take 7.5 ml of suspension in the morning and another 7.5 ml of suspension in the evening.

Children (between 1 and 18 years of age)

• The dose varies depending on the child's size.
• Your child’s doctor will determine the most appropriate dose based on the child’s height and weight (body surface area measured in square meters “m²”). The recommended starting dose is 600 mg/m², administered twice daily. Dose individualization should be based on clinical assessment by the physician. If well tolerated, the dose may be increased to 900 mg/m² twice daily if necessary (maximum total daily dose of 3 g or 15 ml of oral suspension).

Reconstitution of the medicine

The medicine is supplied as a powder. This must be mixed with purified water before administration. Your pharmacist will usually reconstitute the medicine for you. If you need to do it yourself, follow the instructions provided in section 7 “Reconstitution of the medicine”.

Taking this medicine

You will need:

• A bottle of reconstituted oral suspension, with the bottle adapter inserted and the bottle cap attached.
• One of the two 5 ml oral dosing syringes (for multiple uses) supplied with the medicine pack.

Do not use if the package is damaged, any components are missing, or if components are damaged.

• Contact your doctor or pharmacist if either of the two oral dosing syringes is missing or damaged (e.g., dosage markings are no longer clearly visible or the syringe becomes difficult to use). They will advise you on how to continue taking or administering the medicine.

Use and clean the oral dosing syringe as described in these instructions to avoid any possible contamination. Wash your hands before and after use.

Avoid contact of the suspension with your skin, inside of the mouth, or nose. Take care to avoid getting the reconstituted medicine into your eyes.

• If this occurs, rinse thoroughly with copious amounts of running water. Be careful to avoid contact of the reconstituted medicine with your skin.
• If contact occurs, wash the area thoroughly with plenty of water and soap.

1. Before each use, shake the closed bottle well for about 5 seconds.
2. Remove the child-resistant cap.
3. Attach the dosing syringe to the bottle adapter and push the plunger fully to the end of the syringe.
4. Insert the tip of the syringe firmly into the opening of the bottle adapter.
5. Turn the entire unit (bottle and syringe) upside down (see illustration below).

1. Slowly pull back the plunger.

   • Pull the plunger until the amount of medicine you wish to withdraw is drawn into the syringe. Stop at the mark indicating your required dose.

2. Return the entire unit upright to the correct position.

   • Holding the body of the syringe, slowly separate the syringe from the bottle adapter. The bottle adapter should remain in the bottle.

3. Administer directly into the mouth and ensure you swallow all the medicine.

   • Do not mix the medicine with any liquid when swallowing.

Close the bottle with the child-resistant cap after each use.

• To prevent choking or vomiting, ensure the body is in an upright position. Place the oral dosing syringe into the mouth with the tip along either cheek, slowly push the plunger to the bottom, and do not forcefully administer toward the back of the throat.

1. Clean the dosing syringe
   • Immediately after administration – disassemble the syringe and rinse both parts under running tap water until all residue is removed. If clean running water is not available, rinse with clean water (e.g., distilled water).

• Do not sterilize the oral dosing syringe or boil it, as this may damage it. Do not use solvent-containing wipes for cleaning.
• Allow to air dry before next use. Do not use cloths or wipes to dry it.
• For storage, keep the syringe dry and away from direct sunlight.
• Do not discard the oral dosing syringe, as it is intended for multiple uses.
• Only after its final use, dispose of the oral dosing syringe according to local requirements.

If you take more CellCept than you should

If you take more CellCept than prescribed, contact your doctor or go to the hospital immediately. Do this also if someone accidentally takes your medicine. Take the medicine packaging with you.

If you forget to take CellCept

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

If you stop taking CellCept

Do not stop taking CellCept unless your doctor tells you to. If you interrupt 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 pharmacist.

4. Possible adverse effects

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

Contact your doctor 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 level of 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 number of white or red blood cells in the blood, infections, and vomiting. Your doctor will perform 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 natural defenses. This is intended to prevent transplant rejection. However, as a result, the body is also less able to fight infections as effectively as under normal conditions. This means you may be more prone to infections than usual. These may include infections affecting the brain, skin, mouth, stomach and intestines, lungs, and urinary system.

Skin and lymphatic cancers

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

General unwanted effects

General adverse effects affecting the whole body may occur. These include severe allergic reactions (such as anaphylaxis, angioedema), fever, extreme fatigue, difficulty sleeping, pain (such as stomach pain, chest pain, joint or muscle pain), headache, flu-like symptoms, and swelling.

Other possible unwanted adverse effects may include:

Skin problems such as:

• acne, cold sores, shingles, skin growths, 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:

• dizziness, 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, rapid heartbeat, widening of blood vessels

Lung problems such as:

• pneumonia, bronchitis
• difficulty breathing, coughing, which may be due to bronchiectasis (a condition in which the 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

Additional adverse reactions in children and adolescents

Children, especially those under 6 years of age, are more likely than adults to experience certain adverse reactions, including diarrhea, vomiting, infections, lower red and white blood cell counts, and an increased risk of lymphoma or skin cancer.

Reporting of adverse effects

If you experience any adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system listed 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 container and on the vial following EXP.
• The shelf life of the reconstituted suspension is two months. Do not use the suspension after this expiry date.
• Oral suspension powder: Do not store above 30 °C.
• Reconstituted suspension: Do not store above 30 °C.
• Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that 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 bottle contains 35 g of mycophenolate mofetil.
• The other components are sorbitol, colloidal anhydrous silica, sodium citrate, soybean lecithin, fruit flavoring mixture, xanthan gum, aspartame* (E951), methyl parahydroxybenzoate (E218), and anhydrous citric acid. Please also refer to section 2 “Important information about some of the components of CellCept”, “CellCept contains methyl parahydroxybenzoate” and “CellCept contains sodium”.

*Contains a quantity of phenylalanine equivalent to 2.78 mg/5 ml of suspension.

Appearance of the product and contents of the pack

• Each 110 g bottle of powder for oral suspension contains 35 g of mycophenolate mofetil. It must be reconstituted with 94 ml of purified water. After reconstitution, the volume of the suspension is 175 ml, providing a useful volume of 160–165 ml. Each 5 ml of reconstituted suspension contains 1 g of mycophenolate mofetil.
• A bottle adapter and 2 oral dispensers are also included.

7. Reconstitution of the medicine

Your pharmacist will usually reconstitute the medicine for you. If you need to do it yourself, follow the instructions described below:

Avoid inhaling the dry powder. Also, avoid contact with your skin, inside of your mouth, or nose.

Take care to avoid getting the reconstituted medicine into your eyes.

• If this occurs, rinse your eyes thoroughly with running water.

Take care to avoid contact of the reconstituted medicine with your skin.

• If this occurs, wash the affected area thoroughly with water and soap.

1. Tap the closed bottle gently several times to loosen the powder.
2. Measure 94 ml of purified water in a graduated cylinder.
3. Add approximately half of the total amount of purified water to the bottle.

• Then shake the closed bottle vigorously for about 1 minute.

1. Add the remaining water.

• Then shake the closed bottle vigorously for another minute.

1. Remove the child-resistant cap and attach the adapter to the neck of the bottle.
2. Then close the bottle securely with the child-resistant cap.

• This will ensure correct placement of the adapter and proper function of the child-resistant cap.

1. Write the expiry date of the reconstituted suspension on the bottle label.

• The shelf life of the reconstituted suspension is 2 months.

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

For further information about this medicine, please contact the local representative of the Marketing Authorization Holder:

Belgium/Belgium/Belgium, Luxembourg/Luxembourg N.V. Roche S.A. Belgium/Belgium/Belgium Tel/Tel: +32 (0) 2 525 82 11	Lithuania UAB “Roche Lietuva” Tel: +370 5 2546799
Czech Republic Roche s. r. o. Tel: +420 - 2 20382111	Hungary Roche (Hungary) Kft. Tel: +36 – 1 279 4500
Denmark Roche Pharmaceuticals A/S Tlf: +45 - 36 39 99 99
Germany Roche Pharma AG Tel: +49 (0) 7624 140	Netherlands Roche Nederland B.V. Tel: +31 (0) 348 438000
Estonia Roche Eesti OÜ Tel: + 372 - 6 177 380	Norway Roche Norge AS Tlf: +47 - 22 78 90 00
Greece, Cyprus Roche (Hellas) A.E. Greece Tel: +30 210 61 66 100	Austria Roche Austria GmbH Tel: +43 (0) 1 27739
Spain Roche Farma S.A. Tel: +34 - 91 324 81 00	Poland Roche Polska Sp.z o.o. Tel: +48 - 22 345 18 88
France Roche Tél: +33 (0)1 47 61 40 00	Portugal Roche Farmacêutica Química, Lda Tel: +351 - 21 425 70 00
Croatia Roche d.o.o. Tel: + 385 1 47 22 333	Romania Roche România S.R.L. Tel: +40 21 206 47 01
Ireland, Malta Roche Products (Ireland) Ltd. Ireland/Ireland Tel: +353 (0) 1 469 0700	Slovenia Roche farmacevtska družba d.o.o. Tel: +386 - 1 360 26 00
Iceland Roche Pharmaceuticals A/S c/o Icepharma hf Tel: +354 540 8000	Slovakia Roche Slovensko, s.r.o. Tel: +421 - 2 52638201
Italy Roche S.p.A. Tel: +39 - 039 2471	Finland Roche Oy Tel/Tel: +358 (0) 10 554 500
	Sweden Roche AB Tel: +46 (0) 8 726 1200
Latvia Roche Latvija SIA Tel: +371 - 6 7039831

Date of the last 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