CELLCEPT 250 MG

Israel - English - Ministry of Health

Buy It Now

Active ingredient:
MYCOPHENOLATE MOFETIL
Available from:
ROCHE PHARMACEUTICALS (ISRAEL) LTD
ATC code:
L04AA06
Pharmaceutical form:
CAPSULES
Composition:
MYCOPHENOLATE MOFETIL 250 MG
Administration route:
PER OS
Prescription type:
Required
Manufactured by:
HOFFMANN LA ROCHE, SWITZERLAND
Therapeutic group:
MYCOPHENOLIC ACID
Therapeutic area:
MYCOPHENOLIC ACID
Therapeutic indications:
Prophylaxis of rejection in renal allograft recepients, and in patients reciving allogenic cardiac transplants. Cellcept should be used concomitantly with cyclosporin and corticosteroids.Allogenic hepatic transplant.
Authorization number:
111 34 29434 00
Authorization date:
2013-06-30

Documents in other languages

Patient Information leaflet Patient Information leaflet - Arabic

18-01-2021

Patient Information leaflet Patient Information leaflet - Hebrew

03-03-2020

CellCept PL version 7

PATIENT PACKAGE INSERT IN ACCORDANCE WITH THE

PHARMACISTS’ REGULATIONS (PREPARATIONS) – 198

This medicine is dispensed with a doctor’s prescription only

CellCept

®

250 mg

Capsules

CellCept

®

500 mg

Tablets

Composition:

Each capsule contains:

Each film-coated tablet contains:

Mycophenolate mofetil

250 mg

Mycophenolate mofetil

500 mg

* For information on the inactive

ingredients, see section 6 “Further

Information”.

Read this leaflet carefully in its entirety

before using the medicine. This leaflet

contains concise information about the

medicine. If you have further questions,

refer to the doctor or pharmacist.

Keep this leaflet. You may need to

read it again.

This medicine has been prescribed for the treatment of your

ailment only. Do not pass it on to others. It may harm them,

even if it seems to you that their medical condition is similar.

If you get any side effects, refer to your doctor or pharmacist.

This includes any possible side effects not listed in this

leaflet )see section 4 “Side Effects”(.

IMPORTANT INFORMATION FOR YOUR REVIEW

Warning: mycophenolate causes miscarriages and birth

defects. Do not begin treatment with CellCept in women of

child-bearing age, who do not have a negative pregnancy

test before starting treatment.

Follow the contraception instructions given to you by the

attending doctor. Before taking the preparation, consult

doctor

again

fully

understand

instructions. For further information, see section “Special

warnings regarding use of this medicine” and “Pregnancy,

contraception

breast-feeding”

section.

The medicine belongs to a group of medicines that suppress

the immune system and is provided as capsules at a dose of

250 mg or as film-coated tablets at a dose of 500 mg.

Adherence to the doctor’s instructions )dosage, instructions

for use and duration of treatment( increases the chance

of the treatment success. In any case, do not stop the

treatment without consulting the attending doctor. Please

review sections 2 and 4 for detailed safety information.

1.

WHAT IS THE MEDICINE INTENDED FOR?

CellCept

used,

combination

with

cyclosporine

corticosteroids, to prevent rejection of a transplanted organ in

kidney, heart or liver transplant recipients.

Therapeutic group

Immunosuppressants.

2.

BEFORE USING THE MEDICINE

Do not use the medicine if:

sensitive

)allergic(

mycophenolate

mofetil,

mycophenolic

acid,

other

ingredients

contained in the medicine )for the list of inactive ingredients,

section

“Further

Information”(.

You are a woman of child-bearing age and you have not

provided a negative pregnancy test before receiving your

first prescription of CellCept, as mycophenolate causes

miscarriages and birth defects.

You are pregnant, planning to become pregnant or think you

are pregnant.

You are a woman of child-bearing age and you do not use

effective contraceptive methods )for further information, see

section “Pregnancy, contraception and breast-feeding”(.

You are breast-feeding.

If any of the above conditions applies to you, do not take the

medicine. If you are not sure, refer to your attending doctor

or pharmacist before taking CellCept.

Special warnings regarding use of this medicine

Do not start treatment with CellCept and refer to the

attending

doctor

immediately

if:

you have a sign of an infection, such as: a fever or sore throat

you have unexpected bruising or bleeding

you are suffering, or have suffered in the past, from problems

with the digestive system )such as: a stomach ulcer(

you are planning to become pregnant or if you become

pregnant during treatment with the medicine.

If any of the above conditions applies to you )or if you are not

sure(, refer to the attending doctor immediately, before taking

the medicine.

The effect of sunlight on the treatment

CellCept reduces your body’s defense mechanisms. As a

result, there is an increased risk of developing skin cancer.

Limit your exposure to sunlight and to UV radiation by:

Wearing protective clothing, which also covers your head,

neck, arms and legs.

Using sunscreens with a high protection factor.

CellCept and other medicines

If you are taking, or have recently taken, other medicines,

including

non-prescription

medicines

and

nutritional

supplements, tell the doctor or pharmacist.

It is important to do so, as CellCept may affect the way some

other medicines work, and other medicines can affect the way

CellCept works. In particular, tell the doctor or pharmacist

if you are taking any of the following medicines before you

start treatment with CellCept:

Azathioprine or other medicines which suppress the immune

system and are given after a transplant operation.

Cholestyramine - a medicine used to treat high cholesterol.

Rifampicin - an antibiotic intended to prevent and treat

infections

such

tuberculosis

)TB(.

Antacids, or proton pump inhibitors )PPIs( – preparations

used

treat

problems

with

excessive

acidity

your

stomach

such

indigestion.

Phosphate binders - given to patients with chronic kidney

failure, to reduce the amount of phosphate that is absorbed

into the blood.

Antibiotics - used to treat bacterial infections.

Isavuconazole - used to treat fungal infections.

Telmisartan - used to treat high blood pressure.

Vaccinations

If you need to have a vaccine )a live-attenuated vaccine( while

taking CellCept, first refer to your doctor or pharmacist. The

attending doctor will have to advise you on what vaccines you

can have.

You must not donate blood during treatment with CellCept

and for at least 6 weeks after stopping treatment.

Use of the medicine and food

Food and drink have no effect on your treatment with CellCept.

Pregnancy, contraception and breast-feeding

Contraception in women taking CellCept:

Women of child-bearing age who were prescribed CellCept,

must use an effective method of contraception:

Before starting treatment with CellCept

During the entire treatment with CellCept

For 6 weeks after stopping treatment with CellCept

Consult the attending doctor about the most suitable methods

of contraception for you. These contraception methods will

be determined depending on your condition. Two forms of

contraception are preferable as this will reduce the risk of

unintended

pregnancy.

Contact your doctor as soon as possible, if you think your

contraception may not have been effective or if you have

forgotten to take your contraceptive pill.

If you meet any of the following criteria, you are not capable

of becoming pregnant:

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 because you have

had treatment for cancer, there is still a chance you

could 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

longer

work

)premature

ovarian

failure, which has been confirmed by a specialist

gynaecologist(

You were born with one of the following rare conditions

that make pregnancy impossible: the XY genotype,

Turner syndrome or lack of development of the uterus

)Uterine

agenesis(

You are a child or teenager who has not started having

periods

Contraception in men taking CellCept

available

data

indicate

increased

risk

malformations

miscarriage

father

takes

mycophenolate.

However,

risk

cannot

completely

excluded.

If you are planning a pregnancy with your partner, talk to your

doctor about the potential risks and alternative therapies.

Pregnancy and breast-feeding:

If you are pregnant, breast-feeding, planning a pregnancy

or think you are pregnant, consult the attending doctor or

pharmacist before taking the preparation.

The doctor will talk to you about the risks of pregnancy and the

alternative treatments which can be taken to prevent rejection

of your transplant organ in the following cases:

You plan to become pregnant

You miss or think you have missed a period, or you have

unusual menstrual bleeding, or suspect you are pregnant

without

using

effective

method

contraception

Inform your doctor immediately if you become pregnant during

the treatment with CellCept. However, keep taking CellCept

until you meet with the doctor.

Pregnancy:

Mycophenolate causes a very high frequency of miscarriage

)50%( and of severe birth defects )23%-27%(.

Birth defects which have been reported include: anomalies

of ears, of eyes, of face )cleft lip/palate(, of development of

fingers, of heart, esophagus )the tube that connects the throat

with the stomach(, kidneys and nervous system )for example

spina bifida - where the bones of the spine are not properly

developed(. Your baby may be affected by one or more of the

defects appearing above.

Do not begin treatment with CellCept in women of child-

bearing age, without providing a negative pregnancy test

before starting treatment. Follow the contraception instructions

given to you by the attending doctor. The doctor may request

an additional pregnancy test to ensure you are not pregnant

before starting treatment.

Breast-feeding:

Do not take CellCept if you are breast-feeding, since small

amounts of the medicine can pass into the mother’s milk.

Driving and using machines

Cellcept has a moderate effect on your ability to drive and

use tools and machines. If you feel drowsy, numb, or confused

talk to your doctor or nurse and do not drive or use tools and

machines until you feel better.

This medicine contains less than 1 millimole of sodium )23 mg(

per capsule/tablet so it is considered ‘sodium free’.

.

HOW SHOULD YOU USE THE MEDICINE?

Always use according to the doctor’s instructions.

Check with the doctor or pharmacist if you are not sure.

Usual dosage

The dosage and treatment regimen will be determined by the

doctor only.

The dosage depends on the type of transplant you have had.

The usual dosages are listed below.

The treatment will continue for as long as there is a need to

prevent your body from rejecting your transplant organ.

Do not exceed the recommended dose.

Kidney transplant

Adults:

The first dose is given within 3 days of the transplant

operation.

The daily dosage is 2 g of CellCept, divided into two

separate doses: 1 g in the morning and 1 g in the evening.

Children )aged 2 to 18 years(:

The dosage depends on the size of the child.

The attending doctor will determine the most appropriate

dosage based on your child’s height and weight.

Heart transplant

Adults:

The first dose is given within 5 days of the transplant

operation.

The daily dosage is 3 g of CellCept, divided into two separate

doses: 1.5 g in the morning and 1.5 g in the evening.

Children:

There is no information regarding use of CellCept in children

after a heart transplant.

Liver transplant

Adults:

The first dose of CellCept will be given to you at least 4

days after the transplant operation and when you are able

to swallow medicines.

The daily dosage is 3 g of CellCept, divided into two separate

doses: 1.5 g in the morning and 1.5 g in the evening

Children:

There is no information regarding use of CellCept in children

after a liver transplant.

Instructions for use of the medicine

Swallow the capsules/tablets whole with a glass of water.

Do not break or crush the capsules/tablets.

Capsules: Do not open or split the capsules. Do not take

capsules that have been opened or split.

Avoid contact between powder that has spilled out of damaged

capsules and the skin, eyes and mouth. If a capsule has been

accidentally opened/broken, wash the residue of the powder

from the skin with water and soap. If powder gets into your

eyes/mouth, wash thoroughly with a lot of water.

If you accidentally took a higher dosage or if a child, or

anyone else, has accidentally swallowed the medicine, refer

immediately to a doctor or proceed to a hospital emergency

room and bring the package of the medicine with you.

If you forgot to take this medicine at the required time,

take a dose as soon as you remember and continue to take

the medicine at the usual times. Do not take a double dose to

make up for a missed dose.

Adhere to the treatment regimen as recommended by the

doctor.

If you stop taking the medicine

Do not stop treatment with CellCept, unless your doctor has

instructed you to do so. If you stop your treatment you may

increase the risk of rejection of the transplanted organ.

Even if there is an improvement in your health, do not stop

treatment with the medicine without consulting the doctor.

have

further

questions

regarding

this

medicine,

doctor

pharmacist.

Do not take medicines in the dark! Check the label and the

dose each time you take medicine. Wear glasses if you need

them.

4.

SIDE EFFECTS

As with any medicine, use of CellCept may cause side effects

in some users. Do not be alarmed by the list of side effects.

You may not suffer from any of them.

Refer to the doctor immediately if you notice any of the

following severe side effects - you may need urgent

medical

treatment:

you have a sign of an infection, such as a fever or sore throat

you suffer from unexpected bruising or bleeding

you suffer from a rash, swelling of the face, lips, tongue

or throat, with difficulty in breathing - you may be having

serious

allergic

reaction

medicine

)such

anaphylaxis, angioedema(.

Common side effects

Some of the more common side effects are: diarrhoea, fewer

white cells or red cells in the blood, infection and vomiting.

The attending doctor will perform regular blood tests to identify

changes in:

the number of your blood cells or signs of infections.

Children may be more likely than adults to suffer from the

following side effects: diarrhoea, infections, fewer white cells

and fewer red cells in the blood.

Protection from infections

CellCept

reduces

your

body’s

defense

mechanisms,

prevent you from rejecting the transplanted organ. As a result,

your body’s ability to fight infections will not be as good as it

normally is. Therefore, you may catch more infections than

usual, including: infections of the brain, skin, mouth, stomach,

gut, lungs and urinary system.

Lymph and skin cancer

As can happen in patients taking these types of medicines

)immune-suppressants(, a very small number of patients who

took CellCept developed cancer of the lymphoid tissues and

skin.

Additional side effects:

You may suffer from generalized side effects that affect the

entire body, including: serious allergic reactions )such as:

anaphylaxis, angioedema(, fever, extreme fatigue, difficulty

sleeping, pains )such as: abdominal pain, chest pain, joint or

muscle pain(, headache, flu symptoms and swelling.

Other side effects can include:

Skin problems, such as: acne, cold sores, shingles, skin

growths, hair loss, rash and itching.

Urinary system problems, such as: blood in the urine.

Digestive system and mouth problems, such as:

swelling of the gums and mouth ulcers

inflammation of the pancreas, colon or stomach

gastrointestinal disorders including bleeding

liver disorders

diarrhoea, constipation, feeling sick )nausea(, indigestion, loss

of appetite, flatulence )gas in the digestive tract(

Nervous system problems, such as:

dizziness, drowsiness or numbness

tremor, muscle spasms, convulsions

feeling anxious or depressed, changes in mood or thoughts

Heart and blood system problems, such as:

changes in blood pressure, accelerated heart rate, widening of

blood vessels

Lung problems, such as:

pneumonia, bronchitis

shortness

breath,

cough,

which

bronchiectasis )a condition in which the lung airways are

abnormally dilated( or pulmonary fibrosis )scarring of the

lungs(. Consult with the doctor if you develop a persistent

cough or shortness of breath

fluid in the lungs or inside the chest

sinus problems

Other problems, such as: weight loss, gout, high blood sugar

level, bleeding and bruising.

If a side effect occurs, if one of the side effects mentioned

above

worsens,

suffer

from

side

effect

mentioned in this leaflet, consult with the doctor immediately.

Reporting side effects

Side effects can be reported to the Ministry of Health by clicking

on the link “Reporting side effects following drug treatment”

found on the Ministry of Health homepage )www.health.gov.il)

that directs you to the online form for reporting side effects, or

by entering the link:

https://sideeffects.health.gov.il

5.

HOW SHOULD THE MEDICINE BE STORED?

Avoid poisoning! This medicine, and any other medicine,

should be kept in a safe place out of the reach and sight of

children and/or infants in order to avoid poisoning. Do not

induce vomiting unless explicitly instructed to do so by the

doctor.

Do not use the medicine after the expiry date )exp. date( that

appears on the package. The expiry date refers to the last

day of that month.

Storage conditions: Store below 25°C, in a cool and dry

place. Store in the original package to protect from light and

moisture.

The medicine should not be disposed of via wastewater or

household waste. Consult the pharmacist how to dispose of

medicines no longer required. Taking these measures will

help you protect the environment.

.

FURTHER INFORMATION

In addition to the active ingredient, the medicine also contains:

Capsules 250 mg:

Capsules:

Starch

pregelatinized,

Croscarmellose

sodium,

Polyvidone

K90,

Magnesium

stearate.

Capsule shells:

Body:

Titanium dioxide )E171(, Iron oxide yellow )E172(, Iron oxide

red )E172(, Gelatin, Printing ink.

Cap:

Titanium dioxide )E171(, Indigo carmine FD&C blue 2 )E132(,

Gelatin, Printing ink.

Tablets 500 mg:

Tablets: Microcrystalline cellulose, Croscarmellose sodium,

Polyvidone K90, Magnesium stearate.

Tablet

Coating:

Hypromellose,

Hydroxypropyl

cellulose,

Titanium

dioxide

)E171(,

Macrogol

400,

Indigo

carmine

aluminium

lake

)E132(,

Iron

oxide

)E172(.

What does the medicine look like and what are the

contents of the package?

CellCept capsules are elongated capsules, one side is blue-

colored and the other side is brown-colored. “CellCept 250” is

imprinted in black on the blue side of the capsule, and “Roche”

is imprinted in black on the brown side. The capsules are

available in packages of 100 )in blister packs of 10(.

CellCept tablets are elongated )caplet-shaped(, film-coated,

lavender colored tablets. “CellCept 500” is imprinted on one

side of the tablet and “Roche” is imprinted on the other side.

The tablets are available in packages of 50 )in blister packs

of 10(.

License

holder

and

address:

Roche

Pharmaceuticals

)Israel(

Ltd.,

P.O.B.

6391,

Hasharon

4524079.

Manufacturer

and

address:

Hoffmann-La

Roche

Ltd.,

Basel, Switzerland.

This leaflet was checked and approved by the Ministry of

Health in: March 2017, and was last revised in December 2019

according to Ministry of Health guidelines.

Registration number of the medicine in the National Drug

Registry of the Ministry of Health:

CellCept 250 mg capsules: 111.34.29434

CellCept 500 mg tablets: 111.35.29435

CellCept PI version 7

CellCept

®

MYCOPHENOLATE MOFETIL

Capsules 250 mg and Tablets 500 mg

1.

NAME OF THE MEDICINAL PRODUCT

CellCept 250 mg capsules.

CellCept 500 mg film coated tablets.

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each capsule contains 250 mg mycophenolate mofetil.

Each tablet contains 500 mg mycophenolate mofetil.

Excipient(s) with known effect

Sodium less than 1 mmol (23 mg) per dose

For the full list of excipients, see section 6.1.

3.

PHARMACEUTICAL FORM

CellCept 250 mg capsules:

Capsules, hard oblong, blue/brown, branded with black "CellCept 250" on the capsule cap and

"Roche" name on the capsule body.

CellCept 500 mg film coated tablets:

Lavender coloured caplet-shaped tablet, engraved with "CellCept 500" on one side and “ROCHE"

name on the other.

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

Prophylaxis of rejection in renal allograft recepients, and in patients receiving allogenic cardiac

transplants.

Cellcept should be used concomitantly with cyclosporin and corticosteroids.

Allogenic hepatic transplant.

4.2

Posology and method of administration

Treatment with CellCept should be initiated and maintained by appropriately qualified transplant

specialists.

Posology

Use in renal transplant

Adults

Oral CellCept should be initiated within 72 hours following transplantation. The recommended dose in

renal transplant patients is 1 g administered twice daily (2 g daily dose).

Paediatric population aged 2 to 18 years

The recommended dose of mycophenolate mofetil is 600 mg/m

administered orally twice daily (up to

a maximum of 2 g daily).

CellCept 250 mg capsules should only be prescribed to patients with a body surface area of at least

1.25 m

. Patients with a body surface area of 1.25 to 1.5 m

may be prescribed CellCept capsules at a

dose of 750 mg twice daily (1.5 g daily dose). Patients with a body surface area greater than 1.5 m

may be prescribed CellCept capsules at a dose of 1 g twice daily (2 g daily dose).

CellCept 500 mg tablets should only be prescribed to patients with a body surface area greater than 1.5

, at a dose of 1 g twice daily (2 g daily dose).

As some adverse reactions occur with greater frequency in this age group (see section 4.8) compared

with adults, temporary dose reduction or interruption may be required; these will need to take into

account relevant clinical factors including severity of reaction.

Paediatric population < 2 years

There are limited safety and efficacy data in children below the age of 2 years. These are insufficient

to make dosage recommendations and therefore use in this age group is not recommended.

Use in cardiac transplant

Adults

Oral CellCept should be initiated within 5 days following transplantation. The recommended dose in

cardiac transplant patients is 1.5 g administered twice daily (3 g daily dose).

Paediatric population

No data are available for paediatric cardiac transplant patients.

Use in hepatic transplant

Adults

IV CellCept should be administered for the first 4 days following hepatic transplant, with oral

CellCept initiated as soon after this as it can be tolerated. The recommended oral dose in hepatic

transplant patients is 1.5 g administered twice daily (3 g daily dose).

Paediatric population

No data are available for paediatric hepatic transplant patients.

Use in special populations

Elderly

The recommended dose of 1 g administered twice a day for renal transplant patients and 1.5 g twice a

day for cardiac or hepatic transplant patients is appropriate for the elderly.

Renal impairment

In renal transplant patients with severe chronic renal impairment (glomerular filtration rate

< 25 mL/min/1.73 m

), outside the immediate post-transplant period, doses greater than 1 g

administered twice a day should be avoided. These patients should also be carefully observed. No dose

adjustments are needed in patients experiencing delayed renal graft function post-operatively (see

section 5.2). No data are available for cardiac or hepatic transplant patients with severe chronic renal

impairment.

Severe hepatic impairment

No dose adjustments are needed for renal transplant patients with severe hepatic parenchymal disease.

No data are available for cardiac transplant patients with severe hepatic parenchymal disease.

Treatment during rejection episodes

Mycophenolic acid (MPA) is the active metabolite of mycophenolate mofetil. Renal transplant

rejection does not lead to changes in MPA pharmacokinetics; dosage reduction or interruption of

CellCept is not required. There is no basis for CellCept dose adjustment following cardiac transplant

rejection. No pharmacokinetic data are available during hepatic transplant rejection.

Paediatric population

No data are available for treatment of first or refractory rejection in paediatric transplant patients.

Method of administration

Oral administration

Precautions to be taken before handling or administering the medicinal product.

Because mycophenolate mofetil has demonstrated teratogenic effects in rats and rabbits, CellCept

capsules should not be opened or crushed to avoid inhalation or direct contact with skin or mucous

membranes of the powder contained in CellCept capsules. If such contact occurs, wash thoroughly

with soap and water; rinse eyes with plain water.

CellCept tablets should not be crushed.

4.3

Contraindications

CellCept should not be given to patients with hypersensitivity to mycophenolate mofetil,

mycophenolic acid or to any of the excipients listed in section 6.1. Hypersensitivity reactions to

CellCept have been observed (see section 4.8).

CellCept should not be given to women of childbearing potential who are not using highly

effective contraception (see section 4.6).

CellCept treatment should not be initiated in women of childbearing potential without providing

a pregnancy test result to rule out unintended use in pregnancy (see section 4.6).

CellCept should not be used in pregnancy unless there is no suitable alternative treatment to

prevent transplant rejection (see section 4.6).

CellCept should not be given to women who are breastfeeding (see section 4.6).

4.4

Special warnings and precautions for use

Neoplasms

Patients receiving immunosuppressive regimens involving combinations of medicinal products,

including CellCept, are at increased risk of developing lymphomas and other malignancies,

particularly of the skin (see section 4.8). The risk appears to be related to the intensity and duration of

immunosuppression rather than to the use of any specific agent.

As general advice to minimise the risk for skin cancer, exposure to sunlight and UV light should be

limited by wearing protective clothing and using a sunscreen with a high protection factor.

Infections

Patients treated with immunosuppressants, including CellCept, are at increased risk for opportunistic

infections (bacterial, fungal, viral and protozoal), fatal infections and sepsis (see section 4.8). Such

infections include latent viral reactivation, such as hepatitis B or hepatitis C reactivation and infections

caused by polyomaviruses (BK virus associated nephropathy, JC virus associated progressive

multifocal leukoencephalopathy PML). Cases of hepatitis due to reactivation of hepatitis B or hepatitis

C have been reported in carrier patients treated with immunosuppressants. These infections are often

related to a high total immunosuppressive burden and may lead to serious or fatal conditions that

physicians should consider in the differential diagnosis in immunosuppressed patients with

deteriorating renal function or neurological symptoms.

There have been reports of hypogammaglobulinaemia in association with recurrent infections in

patients receiving CellCept in combination with other immunosuppressants. In some of these cases

switching CellCept to an alternative immunosuppressant resulted in serum IgG levels returning to

normal. Patients on CellCept who develop recurrent infections should have their serum

immunoglobulins measured. In cases of sustained, clinically relevant hypogammaglobulinaemia,

appropriate clinical action should be considered taking into account the potent cytostatic effects that

mycophenolic acid has on T- and B-lymphocytes.

There have been published reports of bronchiectasis in adults and children who received CellCept in

combination with other immunosuppressants. In some of these cases switching CellCept to another

immunosuppressant resulted in improvement in respiratory symptoms. The risk of bronchiectasis may

be linked to hypogammaglobulinaemia or to a direct effect on the lung. There have also been isolated

reports of interstitial lung disease and pulmonary fibrosis, some of which were fatal (see section 4.8).

It is recommended that patients who develop persistent pulmonary symptoms, such as cough and

dyspnoea, are investigated.

Blood and immune system

Patients receiving CellCept should be monitored for neutropenia, which may be related to CellCept

itself, concomitant medications, viral infections, or some combination of these causes. Patients taking

CellCept should have complete blood counts weekly during the first month, twice monthly for the

second and third months of treatment, then monthly through the first year. If neutropenia develops

(absolute neutrophil count < 1.3 x 10

/µl), it may be appropriate to interrupt or discontinue CellCept.

Cases of pure red cell aplasia (PRCA) have been reported in patients treated with CellCept in

combination with other immunosuppressants. The mechanism for mycophenolate mofetil induced

PRCA is unknown. PRCA may resolve with dose reduction or cessation of CellCept therapy. Changes

to CellCept therapy should only be undertaken under appropriate supervision in transplant recipients

in order to minimise the risk of graft rejection (see section 4.8).

Patients receiving CellCept should be instructed to report immediately any evidence of infection,

unexpected bruising, bleeding or any other manifestation of bone marrow failure.

Patients should be advised that during treatment with CellCept, vaccinations may be less effective and

the use of live attenuated vaccines should be avoided (see section 4.5). Influenza vaccination may be

of value. Prescribers should refer to national guidelines for influenza vaccination.

Gastro-intestinal

CellCept has been associated with an increased incidence of digestive system adverse events,

including infrequent cases of gastrointestinal tract ulceration, haemorrhage and perforation. CellCept

should be administered with caution in patients with active serious digestive system disease.

CellCept is an IMPDH (inosine monophosphate dehydrogenase) inhibitor. Therefore, it should be

avoided in patients with rare hereditary deficiency of hypoxanthine-guanine phosphoribosyl-

transferase (HGPRT) such as Lesch-Nyhan and Kelley-Seegmiller syndrome.

Interactions

Caution should be exercised when switching combination therapy from regimens containing

immunosuppressants, which interfere with MPA enterohepatic recirculation, e.g. ciclosporin, to others

devoid of this effect, e.g. tacrolimus, sirolimus, belatacept, or vice versa, as this might result in

changes of MPA exposure. Drugs which interfere with MPA’s enterohepatic cycle (e.g.

cholestyramine, antibiotics) should be used with caution due to their potential to reduce the plasma

levels and efficacy of CellCept (see also section 4.5). Therapeutic drug monitoring of MPA may be

appropriate when switching combination therapy (e.g. from ciclosporin to tacrolimus or vice versa) or

to ensure adequate immunosuppression in patients with high immunological risk (e.g. risk of rejection,

treatment with antibiotics, addition or removal of an interacting medication).

It is recommended that CellCept should not be administered concomitantly with azathioprine because

such concomitant administration has not been studied.

The risk/benefit ratio of mycophenolate mofetil in combination with sirolimus has not been

established (see also section 4.5).

Special populations

Elderly patients may be at an increased risk of adverse events such as certain infections (including

cytomegalovirus tissue invasive disease) and possibly gastrointestinal haemorrhage and pulmonary

oedema, compared with younger individuals (see section 4.8).

Teratogenic effects

Mycophenolate is a powerful human teratogen. Spontaneous abortion (rate of 45% to 49%) and

congenital malformations (estimated rate of 23% to 27%) have been reported following MMF

exposure during pregnancy. Therefore, CellCept is contraindicated in pregnancy unless there are no

suitable alternative treatments to prevent transplant rejection. Female patients of childbearing potential

should be made aware of the risks and follow the recommendations provided in section 4.6 (e.g.

contraceptive methods, pregnancy testing) prior to, during, and after therapy with CellCept. Physicians

should ensure that women taking mycophenolate understand the risk of harm to the baby, the need for

effective contraception, and the need to immediately consult their physician if there is a possibility of

pregnancy.

Contraception (see section 4.6)

Because of robust clinical evidence showing a high risk of abortion and congenital malformations

when mycophenolate mofetil is used in pregnancy every effort to avoid pregnancy during treatment

should be taken. Therefore, women with childbearing potential must use at least one form of reliable

contraception (see section 4.3) before starting CellCept therapy, during therapy, and for six weeks

after stopping the therapy; unless abstinence is the chosen method of contraception. Two

complementary forms of contraception simultaneously are preferred to minimise the potential for

contraceptive failure and unintended pregnancy.

For contraception advice for men see section 4.6.

Additional precautions

Patients should not donate blood during therapy or for at least 6 weeks following discontinuation of

mycophenolate.

4.5

Interaction with other medicinal products and other forms of interaction

Aciclovir

Higher aciclovir plasma concentrations were observed when mycophenolate mofetil was administered

with aciclovir in comparison to the administration of aciclovir alone. The changes in MPAG (the

phenolic glucuronide of MPA) pharmacokinetics (MPAG increased by 8%) were minimal and are not

considered clinically significant. Because MPAG plasma concentrations are increased in the presence

of renal impairment, as are aciclovir concentrations, the potential exists for mycophenolate mofetil and

aciclovir, or its prodrugs, e.g. valaciclovir, to compete for tubular secretion and further increases in

concentrations of both substances may occur.

Antacids and proton pump inhibitors (PPIs)

Decreased MPA exposure has been observed when antacids, such as magnesium and aluminium

hydroxides, and PPIs, including lansoprazole and pantoprazole, were administered with CellCept.

When comparing rates of transplant rejection or rates of graft loss between CellCept patients taking

PPIs vs. CellCept patients not taking PPIs, no significant differences were seen. This data support

extrapolation of this finding to all antacids because the reduction in exposure when CellCept was co-

administered with magnesium and aluminium hydroxides is considerably less than when CellCept was

co-administered with PPIs.

Medicinal products that interfere with enterohepatic recirculation (e.g. cholestyramine, ciclosporin A,

antibiotics)

Caution should be used with medicinal products that interfere with enterohepatic recirculation because

of their potential to reduce the efficacy of CellCept.

Cholestyramine

Following single dose administration of 1.5 g of mycophenolate mofetil to normal healthy subjects

pre-treated with 4 g TID of cholestyramine for 4 days, there was a 40% reduction in the AUC of MPA

(see section 4.4 and section 5.2). Caution should be used during concomitant administration because

of the potential to reduce efficacy of CellCept.

Ciclosporin A

Ciclosporin A (CsA) pharmacokinetics are unaffected by mycophenolate mofetil.

In contrast, if concomitant CsA treatment is stopped, an increase in MPA AUC of around 30% should

be expected. CsA interferes with MPA enterohepatic recycling, resulting in reduced MPA exposures

by 30-50% in renal transplant patients treated with CellCept and CsA compared with patients

receiving sirolimus or belatacept and similar doses of CellCept (see also section 4.4). Conversely,

changes of MPA exposure should be expected when switching patients from CsA to one of the

immunosuppressants which does not interfere with MPA´s enterohepatic cycle.

Antibiotics eliminating

-glucuronidase-producing bacteria in the intestine (e.g. aminoglycoside,

cephalosporin, fluoroquinolone, and penicillin classes of antibiotics) may interfere with MPAG/MPA

enterohepatic recirculation thus leading to reduced systemic MPA exposure. Information concerning

the following antibiotics is available:

Ciprofloxacin or amoxicillin plus clavulanic acid

Reductions in pre-dose (trough) MPA concentrations of about 50% have been reported in renal

transplant recipients in the days immediately following commencement of oral ciprofloxacin or

amoxicillin plus clavulanic acid. This effect tended to diminish with continued antibiotic use and to

cease within a few days of antibiotic discontinuation. The change in predose level may not accurately

represent changes in overall MPA exposure. Therefore, a change in the dose of CellCept should not

normally be necessary in the absence of clinical evidence of graft dysfunction. However, close clinical

monitoring should be performed during the combination and shortly after antibiotic treatment.

Norfloxacin and metronidazole

In healthy volunteers, no significant interaction was observed when CellCept was concomitantly

administered with norfloxacin or metronidazole separately. However, norfloxacin and metronidazole

combined reduced the MPA exposure by approximately 30% following a single dose of CellCept.

Trimethoprim/sulfamethoxazole

No effect on the bioavailability of MPA was observed.

Medicinal products that affect glucuronidation (e.g. isavuconazole, telmisartan)

Concomitant administration of drugs affecting glucuronidation of MPA may change MPA exposure.

Caution is therefore recommended when administering these drugs concomitantly with CellCept.

Isavuconazole

An increase of MPA AUC

0-∞

by 35% was observed with concomitant administration of isavuconazole.

Telmisartan

Concomitant administration of telmisartan and CellCept resulted in an approximately 30% decrease of

MPA concentrations. Telmisartan changes MPA’s elimination by enhancing PPAR gamma

(peroxisome proliferator-activated receptor gamma) expression, which in turn results in an enhanced

UGT1A9 expression and activity. When comparing rates of transplant rejection, rates of graft loss or

adverse event profiles between CellCept patients with and without concomitant telmisartan

medication, no clinical consequences of the pharmacokinetic drug-drug interaction were seen.

Ganciclovir

Based on the results of a single dose administration study of recommended doses of oral

mycophenolate and IV ganciclovir and the known effects of renal impairment on the pharmacokinetics

of CellCept (see section 4.2) and ganciclovir, it is anticipated that co-administration of these agents

(which compete for mechanisms of renal tubular secretion) will result in increases in MPAG and

ganciclovir concentration. No substantial alteration of MPA pharmacokinetics is anticipated and

CellCept dose adjustment is not required. In patients with renal impairment in whom CellCept and

ganciclovir or its prodrugs, e.g. valganciclovir, are co-administered, the dose recommendations for

ganciclovir should be observed and patients should be monitored carefully.

Oral contraceptives

The pharmacokinetics and pharmacodynamics of oral contraceptives were unaffected by co-

administration of CellCept (see also section 5.2).

Rifampicin

In patients not also taking ciclosporin, concomitant administration of CellCept and rifampicin resulted

in a decrease in MPA exposure (AUC

0-12h

) of 18% to 70%. It is recommended to monitor MPA

exposure levels and to adjust CellCept doses accordingly to maintain clinical efficacy when rifampicin

is administered concomitantly.

Sevelamer

Decrease in MPA C

and AUC

0-12h

by 30% and 25%, respectively, were observed when CellCept

was concomitantly administered with sevelamer without any clinical consequences (i.e. graft

rejection). It is recommended, however, to administer CellCept at least one hour before or three hours

after sevelamer intake to minimise the impact on the absorption of MPA. There are no data on

CellCept with phosphate binders other than sevelamer.

Tacrolimus

In hepatic transplant patients initiated on CellCept and tacrolimus, the AUC and C

of MPA, the

active metabolite of CellCept, were not significantly affected by co-administration with tacrolimus. In

contrast, there was an increase of approximately 20% in tacrolimus AUC when multiple doses of

CellCept (1.5 g BID) were administered to hepatic transplant patients taking tacrolimus. However, in

renal transplant patients, tacrolimus concentration did not appear to be altered by CellCept (see also

section 4.4).

Live vaccines

Live vaccines should not be given to patients with an impaired immune response. The antibody

response to other vaccines may be diminished (see also section 4.4).

Paediatric population

Interaction studies have only been performed in adults.

Potential interaction

Co-administration of probenecid with mycophenolate mofetil in monkeys raises plasma AUC of

MPAG by 3-fold. Thus, other substances known to undergo renal tubular secretion may compete with

MPAG, and thereby raise plasma concentrations of MPAG or the other substance undergoing tubular

secretion.

4.6

Pregnancy and lactation

Women of childbearing potential

Pregnancy whilst taking mycophenolate must be avoided. Therefore, women of childbearing potential

must use at least one form of reliable contraception (see section 4.3) before starting CellCept therapy,

during therapy, and for six weeks after stopping the therapy, unless abstinence is the chosen method of

contraception. Two complementary forms of contraception simultaneously are preferred.

Pregnancy

CellCept is contraindicated during pregnancy unless there is no suitable alternative treatment to

prevent transplant rejection. Treatment should not be initiated without providing a negative pregnancy

test result to rule out unintended use in pregnancy.

Female patients of reproductive potential must be made aware of the increased risk of pregnancy loss

and congenital malformations at the beginning of the treatment and must be counseled regarding

pregnancy prevention and planning.

Before starting CellCept treatment, women of childbearing potential should have two negative serum

or urine pregnancy tests with a sensitivity of at least 25 mIU/mL in order to exclude unintended

exposure of the embryo to mycophenolate. It is recommended that the second test should be performed

8 – 10 days after the first test. For transplants from deceased donors, if it is not possible to perform

two tests 8-10 days apart before treatment starts (because of the timing of transplant organ

availability), a pregnancy test must be performed immediately before starting treatment and a further

test performed 8-10 days later. Pregnancy tests should be repeated as clinically required (e.g. after any

gap in contraception is reported). Results of all pregnancy tests should be discussed with the patient.

Patients should be instructed to consult their physician immediately should pregnancy occur.

Mycophenolate is a powerful human teratogen, with an increased risk of spontaneous abortions and

congenital malformations in case of exposure during pregnancy;

Spontaneous abortions have been reported in 45 to 49% of pregnant women exposed to

mycophenolate mofetil, compared to a reported rate of between 12 and 33% in solid organ

transplant patients treated with immunosuppressants other than mycophenolate mofetil.

Based on literature reports, malformations occurred in 23 to 27% of live births in women

exposed to mycophenolate mofetil during pregnancy (compared to 2 to 3 % of live births in the

overall population and approximately 4 to 5% of live births in solid organ transplant recipients

treated with immunosuppressants other than mycophenolate mofetil).

Congenital malformations, including reports of multiple malformations, have been observed post-

marketing in children of patients exposed to CellCept in combination with other immunosuppressants

during pregnancy. The following malformations were most frequently reported:

Abnormalities of the ear (e.g. abnormally formed or absent externalear), external auditory canal

atresia (middle ear);

Facial malformations such as cleft lip, cleft palate, micrognathia and hypertelorism of the orbits;

Abnormalities of the eye (e.g. coloboma);

Congenital heart disease such as atrial and ventricular septal defects;

Malformations of the fingers (e.g. polydactyly, syndactyly);

Tracheo-Oesophageal malformations (e.g. oesophageal atresia);

Nervous system malformations such as spina bifida;

Renal abnormalities.

In addition, there have been isolated reports of the following malformations:

Microphthalmia;

congenital choroid plexus cyst;

septum pellucidum agenesis;

olfactory nerve agenesis.

Studies in animals have shown reproductive toxicity (see section 5.3).

Breast-feeding

Mycophenolate mofetil has been shown to be excreted in the milk of lactating rats. It is not known

whether this substance is excreted in human milk. Because of the potential for serious adverse

reactions to mycophenolate mofetil in breast-fed infants, CellCept is contraindicated in nursing

mothers (see section 4.3).

Limited clinical evidence does not indicate an increased risk of malformations or miscarriage

following paternal exposure to mycophenolate mofetil.

MPA is a powerful teratogen. It is not known if MPA is present in semen. Calculations based on

animal data show that the maximum amount of MPA that could potentially be transferred to woman is

so low that it would be unlikely to have an effect. Mycophenolate has been shown to be genotoxic in

animal studies at concentrations exceeding the human therapeutic exposures only by small margins,

such that the risk of genotoxic effects on sperm cells cannot completely be excluded.

4.7

Effects on ability to drive and use machines

CellCept has a moderate influence on the ability to drive and use machines.

Cellcept may cause somnolence, confusion, dizziness, tremor or hypotension, and therefore patients are

advised to use caution when driving or using machines.

4.8

Undesirable effects

Summary of safety profile

An estimated total of 1557 patients received CellCept during five clinical trials in the prevention of

acute organ rejection. Of these, 991 were included in the three renal studies, 277 were included in one

hepatic study, and 289 were included in one cardiac study. Azathioprine was the comparator used in

the hepatic and cardiac studies and in two of the renal studies whilst the other renal study was placebo-

controlled. Patients in all study arms also received cyclosporine and corticosteroids. The types of

adverse reactions reported during post-marketing with CellCept are similar to those seen in the

controlled renal, cardiac and hepatic transplant studies

Diarrhoea, leucopenia, sepsis and vomiting were among the most common and/or serious adverse drug

reactions associated with the administration of CellCept in combination with ciclosporin and

corticosteroids. There is also evidence of a higher frequency of certain types of infections (see section

4.4).

Tabulated list of adverse reactions

The adverse drug reactions (ADRs) from clinical trials and post marketing experience are listed in

Table 1, by MedDRA system organ class (SOC) along with their frequencies. The corresponding

frequency category for each adverse drug reaction is based on the following convention: very common

(≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000)

and very rare (<1/10,000). Due to the large differences observed in the frequency of certain ADRs

across the different transplant indications, the frequency is presented separately for renal, hepatic and

cardiac transplant patients.

Table 1 Summary of adverse drug reactions occurring in patients treated with CellCept reported

from clinical trials and post marketing experience

CellCept

רבמבונ

2018

ת/חקור ,ה/רקי ה/אפור ,ה/רקי

לע םכעידוהל תשקבמ מ"עב (לארשי) הקיטבצמרפ שור תרבח ןוכדע

ןולעב

ןכרצל

אפורל ןולעבו לש

.הלעמ םירישכתה

.הרמחה םיווהמ רשא םינוכדעו םייתוהמ םינוכדע קר םיניוצמ וז העדוהב

וותהה

י

תו

מושרה תו

ל

רישכת םי

:לארשיב

Prophylaxis of rejection in renal allograft recepients, and in patients receiving

allogenic cardiac transplants.

Cellcept should be used concomitantly with cyclosporin and corticosteroids.

Allogenic hepatic transplant

:רבסה

יתחת וק םע טסקט

והש טסקט ןייצמ .ןולעל ףס

הצוח וק םע טסקט

.ןולעה ןמ רסוהש טסקט ןייצמ

ל ןולעב ןייעל שי ףסונ עדימל ןכרצ

ןולעבו

רשואש יפכ אפור

.תואירבה דרשמ י"ע

ולעה םינ

כדועמה םינ

חלשנ

לבקל ןתינו ,תואירבה דרשמ רתאבש תופורתה רגאמב םוסרפל

ספדומ םי

לע

ד.ת ,מ"עב (לארשי) הקיטבצמרפ שור :םושירה לעבל היינפ ידי

6391

דוה , ןורשה

4524079

ןופלט

09-9737777

:טנרטניאב ונתבותכ .

www.roche.co.il

ירפצ רואתב

גגח

רדא יליל

םושיר תקלחמ

הנוממ תחקור

CellCept

®

500 mg

CellCept

®

250 mg

טפסלס

500

ג"מ

טפסלס

250

ג"מ

Mycophenolate mofetil

Mycophenolate mofetil

Film coated tablets

Capsules

CellCept

אפורל ןולעב םייתוהמ םינוכדע

ףיעסב

Special warnings and precautions for use 4.4

,

ןכדוע :אבה עדימה

Interactions

Caution should be exercised when switching combination therapy from regimens containing

immunosuppressants, which interfere with MPA enterohepatic recirculation, e.g. ciclosporin, to

others devoid of this effect, e.g. tacrolimus, sirolimus, belatacept, or vice versa, as this might

result in changes of MPA exposure. Drugs which interfere with MPA’s enterohepatic cycle (e.g.

cholestyramine, antibiotics) should be used with caution due to their potential to reduce the

plasma levels and efficacy of CellCept (see also section 4.5). Therapeutic drug monitoring of

MPA may be appropriate when switching combination therapy (e.g. from ciclosporin to

tacrolimus or vice versa) or to ensure adequate immunosuppression in patients with high

immunological risk (e.g. risk of rejection, treatment with antibiotics).

It is recommended that CellCept should not be administered concomitantly with azathioprine

because such concomitant administration has not been studied.

The risk/benefit ratio of mycophenolate mofetil in combination with tacrolimus or sirolimus has

not been established (see also section 4.5).

ףיעסב

4.6 Pregnancy and lactation

,

ןכדוע :אבה עדימה

Limited clinical evidence does not indicate an increased risk of malformations or miscarriage

following paternal exposure to mycophenolate mofetil.

MPA is a powerful teratogen. It is not known if MPA is present in semen. Calculations based on

animal data show that the maximum amount of MPA that could potentially be transferred to

woman is so low that it would be unlikely to have an effect. Mycophenolate has been shown to

be genotoxic in animal studies at concentrations exceeding the human therapeutic exposures

only by small margins, such that the risk of genotoxic effects on sperm cells cannot completely

be excluded.

ןולעב םייתוהמ םינוכדע ןכרצל

ףיעסב

2

הפורתב שומישה ינפל .

,

ןכדוע

:אבה עדימה

...

ה תעינמ

י

ןויר

טפסלס םילטונה םירבגב

דחי .טאלונפוקימ לטונ באה םא תולפה וא םימגפל ןוכיסב היילע לע םיעיבצמ אל םינימזה םינותנה .ןוכיסל תורשפאה תא ןיטולחל לולשל ןתינ אל ,תאז םע

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