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Myfenax

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Summary for the public


What is Myfenax?

Myfenax is a medicine containing the active substance mycophenolate mofetil. It is available as capsules (250 mg) and tablets (500 mg).

Myfenax is a ‘generic medicine’. This means that Myfenax is similar to a ‘reference medicine’ already authorised in the European Union (EU) called CellCept.


What is Myfenax used for?

Myfenax is used to prevent the body from rejecting a transplanted kidney, heart or liver. It is used with ciclosporin and corticosteroids (other medicines used to prevent organ rejection).

The medicine can only be obtained with a prescription.


How is Myfenax used?

Myfenax treatment should be initiated and maintained by a qualified transplant specialist.

The way that Myfenax should be given and the dose depend on the type of organ transplant and the patient’s age and size.

For kidney transplants, the recommended dose in adults is 1.0 g twice a day starting within 72 hours after the transplant. In children aged between two and 18 years, the dose of Myfenax is calculated depending on height and weight.

For heart transplants, the recommended adult dose is 1.5 g twice a day, starting within five days following the transplant.

For liver transplants in adults, mycophenolate mofetil should be given as an infusion (drip into a vein) for the first four days after the transplant, before the patient is switched to 1.5 g Myfenax twice a day as soon as it can be tolerated. Myfenax is not recommended for use in children after heart or liver transplants because of a lack of information on its effects in this group.

The dose may need to be adjusted in patients with liver or kidney disease. For more information, see the Summary of Product Characteristics (also part of the EPAR).


How does Myfenax work?

The active substance in Myfenax, mycophenolate mofetil, is an immunosuppressive medicine. In the body, it is converted into mycophenolic acid, which blocks an enzyme called ‘inosine monophosphate dehydrogenase’. This enzyme is important for the formation of DNA in cells, particularly in the lymphocytes (a type of white blood cell which is involved in the rejection of organ transplants). By preventing the production of new DNA, Myfenax reduces the rate at which the lymphocytes multiply. This makes them less effective at recognising and attacking the transplanted organ, lowering the risk of the organ being rejected.


How has Myfenax been studied?

Because Myfenax is a generic medicine, studies have been limited to tests to demonstrate that it is bioequivalent to the reference medicine (they produce the same levels of the active substance in the body).


What are the benefit and risk of Myfenax?

Because Myfenax is a generic medicine and is bioequivalent to the reference medicine, its benefit and risk are taken as being the same as those of the reference medicine.


Why has Myfenax been approved?

The Committee for Medicinal Products for Human Use (CHMP) concluded that, in accordance with EU requirements, Myfenax has been shown to have comparable quality and to be bioequivalent to Cellcept. Therefore, the CHMP’s view was that, as for CellCept, the benefit outweighs the identified risk. The Committee recommended that Myfenax be given marketing authorisation.


Other information about Myfenax

The European Commission granted a marketing authorisation valid throughout the EU for Myfenax to Teva Pharma B.V. on 21 February 2008.

Authorisation details
Name: Myfenax
EMEA Product number: EMEA/H/C/000884
Active substance: mycophenolate mofetil
INN or common name: mycophenolate mofetil
Therapeutic area: Graft Rejection
ATC Code: L04AA06
Generic: A generic medicine is a medicine which is similar to a medicine that has already been authorised (the 'reference medicine'). A generic medicine contains the same quantity of active substance(s) as the reference medicine. Generic and reference medicines are used at the same dose to treat the same disease, and they are equally safe and effective.
Marketing Authorisation Holder: Teva Pharma B.V.
Revision: 8
Date of issue of Market Authorisation valid throughout the European Union: 21/02/2008
Contact address:
TEVA Pharma B.V.
Computerweg 10
NL-3542 DR Utrecht
The Netherlands



Product Characteristics

ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS


1.
NAME OF THE MEDICINAL PRODUCT
Myfenax 250 mg hard capsules
2.
QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains 250 mg mycophenolate mofetil.
Excipient
For a full list of excipients, see section 6.1
3.
PHARMACEUTICAL FORM
Hard capsule (capsule)
The capsule: body is caramel opaque, printed with ‘250’ axially in black ink
The capsule cap is light blue opaque printed ‘M’ axially in black ink.
4.
CLINICAL PARTICULARS
4.1 Therapeutic indications
Myfenax is indicated in combination with ciclosporin and corticosteroids for the prophylaxis of acute
transplant rejection in patients receiving allogeneic renal, cardiac or hepatic transplants.
4.2 Posology and method of administration
Treatment with Myfenax should be initiated and maintained by appropriately qualified transplant
specialists.
Use in renal transplant:
Adults : oral Myfenax 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).
Children and adolescents: the recommended dose of mycophenolate mofetil is 600 mg/m 2
administered orally twice daily (up to a maximum of 2 g daily). Myfenax capsules should only be
prescribed to patients with a body surface area of at least 1.25 m 2 . Patients with a body surface are of
1.25 to 1.5 m 2 may be prescribed Myfenax 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 2 may be prescribed Myfenax capsules 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.
Children (< 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 Myfenax 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).
2
Children and adolescents : no data are available for paediatric cardiac transplant patients, therefore use
in this patients group is not recommended until further data to support this is available.
Use in hepatic transplant :
Adults : intravenous mycophenolate mofetil should be administered for the first 4 days following
hepatic transplant, with oral Myfenax 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).
Children and adolescents : no data are available for paediatric hepatic transplant patients, therefore use
in this patients group is not recommended until further data to support this is available.
Use in elderly ( 65 years)
The recommended dose of 1g 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.
Use in renal impairment
In renal transplant patients with severe chronic renal impairment (glomerular filtration rate < 25
ml x min -1 x 1.73 m -2 ), 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.
Use in 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
Myfenax is not required. There is no basis for Myfenax dose adjustment following cardiac transplant
rejection. No pharmacokinetic data are available during hepatic transplant rejection.
4.3 Contraindications
Hypersensitivity reactions to the active substance, to mycophenolic acid or any of the excipients.
Myfenax is contraindicated in women who are breast-feeding (see section 4.6).
4.4 Special warnings and precautions for use
Patients receiving immunosuppressive regimens involving combinations of medicinal products,
including Myfenax, 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 ultra violet (UV) light should be limited by wearing
protective clothing and using a sunscreen with a high protection factor.
Patients receiving Myfenax should be instructed to report immediately any evidence of infection,
unexpected bruising, bleeding or any other manifestation of bone marrow depression.
3
Patients treated with immunosuppressants, including Myfenax, are at increased risk for opportunistic
infections (bacterial, fungal, viral and protozoal), fatal infections and sepsis (see section 4.8). Among
the opportunistic infections are BK virus associated nephropathy and JC virus associated progressive
multifocal leukoencephalopathy (PML). 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.
Patients receiving Myfenax should be monitored for neutropenia, which may be related to Myfenax
itself, concomitant medicinal products, viral infections, or some combination of these causes. Patients
taking Myfenax 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 3 /μl) it may be appropriate to interrupt or discontinue Myfenax.
Cases of pure red cell aplasia (PRCA) have been reported in patients treated with mycophenolate
mofetil in combination with other immunosuppressants. The mechanism for mycophenolate mofetil
induced PRCA is unknown. PRCA may resolve with dose reduction or cessation of Myfenax therapy.
Changes to Myfenax 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 should be advised that during treatment with Myfenax, 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.
Because mycophenolate mofetil has been associated with an increased incidence of digestive system
adverse events, including infrequent cases of gastrointestinal tract ulceration, haemorrhage and
perforation, Myfenax should be administered with caution in patients with active serious digestive
system disease.
Myfenax is an inosine monophosphate dehydrogenase (IMPDH) inhibitor. On theoretical grounds,
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.
It is recommended that Myfenax should not be administered concomitantly with azathioprine because
such concomitant administration has not been studied.
In view of the significant reduction in the AUC (area under the curve) of MPA by cholestyramine,
caution should be used in the concomitant administration of Myfenax with medicinal products that
interfere with enterohepatic recirculation because of the potential to reduce the efficacy of Myfenax.
The risk-benefit ratio of mycophenolate mofetil in combination with tacrolimus or sirolimus has not
been established (see also section 4.5).
4.5 Interaction with other medicinal products and other forms of interaction
Interaction studies have only been performed in adults.
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.
4
Antacids with magnesium and aluminium hydroxides : absorption of mycophenolate mofetil was
decreased when administered with antacids.
Cholestyramine : following single dose administration 1.5 g of mycophenolate mofetil to normal
healthy subjects pre-treated with 4 g three times a day (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 Myfenax.
Medicinal products that interfere with enterohepatic circulation : caution should be used with medicinal
products that interfere with enterohepatic circulation because of their potential to reduce the efficacy
of Myfenax.
Ciclosporin A : ciclosporin A (CsA) pharmacokinetics were unaffected by mycophenolate mofetil.
In contrast, if concomitant ciclosporin treatment is stopped, an increase in MPA AUC of around 30%
should be expected.
Ganciclovir : based on the results of a single dose administration study of recommended doses of oral
mycophenolate mofetil and intravenous ganciclovir and the known effects of renal impairment on the
pharmacokinetics of mycophenolate mofetil (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 mycophenolate mofetil dose adjustment is not required. In patients with renal
impairment in which Myfenax and ganciclovir or its prodrugs, e.g. valganciclovir, are co-administered
the dose recommendations for ganciclovir should be observed and patients monitored carefully.
Oral contraceptives : the pharmacokinetics and pharmacodynamics of oral contraceptives were
unaffected by co-administration of mycophenolate mofetil (see also section 5.2).
Rifampicin : in patients not also taking ciclosporin, concomitant administration of Mycophenolate
mofetil 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 Myfenax doses accordingly to maintain
clinical efficacy when rifampicin is administered concomitantly.
Sirolimus : in renal transplant patients, concomitant administration of mycophenolate mofetil and CsA
resulted in reduced MPA exposures by 30-50% compared with patients receiving the combination of
sirolimus and similar doses of Myfenax (see also section 4.4).
Sevelamer : decrease in MPA C max and AUC by 30% and 25%, respectively, were observed when
mycophenolate mofetil was concomitantly administered with sevelamer without any clinical
consequences (i.e. graft rejection). It is recommended, however, to administer Myfenax at least one
hour before or three hours after sevelamer intake to minimise the impact on the absorption of MPA.
There is no data on mycophenolate mofetil with phosphate binders other than sevelamer.
Trimethoprim/sulfamethoxazole : no effect on the bioavailability of MPA was observed.
Norfloxacin and metronidazole : in healthy volunteers, no significant interaction was observed when
mycophenolate mofetil was concomitantly administered with norfloxacin and metronidazole
separately. However, norfloxacin and metronidazole combined reduced the MPA exposure by
approximately 30 % following a single dose of mycophenolate mofetil.
Ciprofloxacin and 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 their discontinuation. The
change in predose level may not accurately represent changes in overall MPA exposure. Therefore, a
change in the dose of Myfenax should not normally be necessary in the absence of clinical evidence of
5
graft dysfunction. However, close clinical monitoring should be performed during the combination
and shortly after antibiotic treatment.
Tacrolimus : in liver transplant recipients initiated on mycophenolate mofetil and tacrolimus, the AUC
and Cmax of MPA, the active metabolite of mycophenolate mofetil, were not significantly affected by
trough tacrolimus level. In renal transplant patients, the tacrolimus concentration did not appear to be
altered by mycophenolate mofetil. However, in hepatic transplant patients, there was an increase of
approximately 20 % in tacrolimus AUC when multiple doses of mycophenolate mofetil (1.5 g taken
twice [BID] a day, morning and evening]) were administered to patients taking tacrolimus (see also
section 4.4).
Other interactions : 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.
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).
4.6 Pregnancy and lactation
It is recommended that Myfenax therapy should not be initiated until a negative pregnancy test has
been obtained. Effective contraception must be used before beginning Myfenax therapy, during
therapy, and for six weeks following discontinuation of therapy (see section 4.5). Patients should be
instructed to consult their physician immediately should pregnancy occur.
The use of Myfenax is not recommended during pregnancy and should be reserved for cases where no
more suitable alternative treatment is available. Myfenax should be used in pregnant women only if
the potential benefit outweighs the potential risk to the foetus. There is limited data from the use of
mycophenolate mofetil in pregnant women. However, congenital malformations including ear
malformations, i.e. abnormally formed or absent external/middle ear have been reported in children of
patients exposed to mycophenolate mofetil in combination with other immunosuppressants during
pregnancy. Cases of spontaneous abortions have been reported in patients exposed to mycophenolate
mofetil .
Studies in animals have shown reproductive toxicity (see section 5.3).
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, Myfenax is contraindicated in breast-feeding
mothers (see section 4.3).
4.7 Effects on ability to drive and use machines
No studies on the effects on the ability to drive and use machines have been performed. The
pharmacodynamics profile and the reported adverse reactions indicate that an effect is unlikely.
4.8 Undesirable effects
The following undesirable effects cover adverse reactions from clinical trials :
The principal adverse reactions associated with the administration of mycophenolate mofetil in
combination with ciclosporin and corticosteroids include diarrhoea, leucopenia, sepsis and vomiting
and there is evidence of a higher frequency of certain types of infections (see section 4.4).
Malignancies :
Patients receiving immunosuppressive regimens involving combinations of medicinal products,
including mycophenolate mofetil, are at increased risk of developing lymphomas and other
6
malignancies, particularly of the skin (see section 4.4). Lymphoproliferative disease or lymphoma
developed in 0.6% of patients receiving mycophenolate mofetil (2 g or 3 g daily) in combination with
other immunosuppressants in controlled clinical trials of renal (2 g data), cardiac and hepatic
transplant patients followed for at least 1 year. Non-melanoma skin carcinomas occurred in 3.6% of
patients; other types of malignancy occurred in 1.1% of patients. Three-year safety data in renal and
cardiac transplant patients did not reveal any unexpected changes in incidence of malignancy
compared to the 1-year data. Hepatic transplant patients were followed for at least 1 year, but less than
3 years.
Opportunistic infections :
All transplant patients are at increased risk of opportunistic infections; the risk increased with total
immunosuppressive load (see section 4.4). The most common opportunistic infections in patients
receiving mycophenolate mofetil (2 g or 3 g daily) with other immunosuppressants in controlled
clinical trials of renal (2 g data), cardiac and hepatic transplant patients followed for at least 1 year
were candida mucocutaneous, cytomegalovirus (CMV) viraemia/syndrome and Herpes simplex. The
proportion of patients with CMV viraemia/syndrome was 13.5%.
Children and adolescents :
The type and frequency of adverse reactions in a clinical study, which recruited 92 paediatric patients
aged 2 to 18 years who where given 600 mg/m 2 mycophenolate mofetil orally twice daily, were
generally similar to those observed in adult patients given 1 g mycophenolate mofetil twice daily.
However, the following treatment-related adverse events were more frequent in the paediatric
population, particularly in children under 6 years of age, when compared to adults: diarrhoea, sepsis,
leucopenia, anaemia and infection.
Elderly patients (≥ 65 years) :
Elderly patients (≥ 65 years) may generally be at increased risk of adverse reactions due to
immunosuppression. Elderly patients receiving Myfenax as part of a combination immunosuppressive
regimen, may be at increased risk of certain infections (including cytomegalovirus tissue invasive
disease) and possibly gastrointestinal haemorrhage and pulmonary oedema, compared to younger
individuals.
Other adverse reactions :
Adverse reactions, probably or possibly related to mycophenolate mofetil, reported in ≥ 1/10 and in ≥
1/100 to < 1/10 of patients treated with mycophenolate mofetil in the controlled clinical trials of renal
(2 g data), cardiac and hepatic transplant patients are listed in the following table.
Within the system organ classes, undesirable effects are listed under headings of frequency, using the
following categories: 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); very rare (≤1/10,000), not known (cannot be estimated from the
available data).Within each frequency grouping, undesirable effects are presented in order of
decreasing seriousness.
Adverse reactions, probably or possibly related to mycophenolate mofetil, reported in patients
treated with mycophenolate mofetil in renal, cardiac and hepatic clinical trials when used in
combination with ciclosporin and corticosteroids
System organ
class
Frequency
Adverse drug reactions
Investigations
Very common -
7
 
Cardiac disorders
Common Hepatic enzyme increased, blood creatinine
increased, blood lactate dehydrogenase increased,
blood urea increased, blood alkaline phosphatase
increased, weight decreased
Very common -
Blood and
lymphatic system
disorders
Common Tachycardia
Very common Leukopenia, thrombocytopenia, anaemia
Common
Pancytopenia, leukocytosis
Nervous system
disorders
Very common -
Common Convulsion, hypertonia, tremor, somnolence,
myasthenic syndrome, dizziness, headache,
paraesthesia, dysgeusia
Very common -
Respiratory,
thoracic and
mediastinal
disorders
Common
Pleural effusion, dyspnoea, cough
Gastrointestinal
disorders
Very common Vomiting, abdominal pain, diarrhoea, nausea
Common Gastrointestinal haemorrhage, peritonitis, ileus,
colitis, gastric ulcer, duodenal ulcer, gastritis,
oesophagitis, stomatitis, constipation, dyspepsia,
flatulence, eructation
Very common -
Renal and urinary
disorders
Common
Renal impairment
Skin and
subcutaneous
tissue disorders
Very common -
Common
Skin hypertrophy, rash, acne, alopecia
Musculoskeletal
and connective
tissue disorders
Very common -
Common
Arthralgia
Metabolism and
nutrition disorders
Very common -
Common Acidosis, hyperkalaemia, hypokalaemia,
hyperglycaemia, hypomagnesaemia, hypocalcaemia,
hypercholesterolaemia, hyperlipidaemia,
hypophosphataemia, hyperuricaemia, gout, anorexia
Very common Sepsis, gastrointestinal candidiasis, urinary tract
infection, herpes simplex, herpes zoster
Infections and
infestations
Neoplasms
benign, malignant
and unspecified
(incl cysts and
polyps)
Common Pneumonia, influenza, respiratory tract infection,
respiratory moniliasis, gastrointestinal infection,
candidiasis, gastroenteritis, infection, bronchitis,
pharyngitis, sinusitis, fungal skin infection, skin
candida, vaginal candidiasis, rhinitis
Very common -
Common
Skin cancer, benign neoplasm of skin
Vascular
disorders
Very common -
Common
Hypotension, hypertension, vasodilatation
General disorders
Very common -
8
 
and
administration site
conditions
Common
Oedema, pyrexia, chills, pain, malaise, asthenia
Hepatobiliary
disorders
Very common -
Common Hepatitis, jaundice, hyperbilirubinaemia
Very common -
Psychiatric
disorders
Common
Agitation, confusional state, depression, anxiety,
thinking abnormal, insomnia
Note: 501 (2 g mycophenolate mofetil daily), 289 (3 g mycophenolate mofetil daily) and 277 (2 g intravenous / 3 g oral mycophenolate
mofetil daily) patients were treated in Phase III studies for the prevention of rejection in renal, cardiac and hepatic transplantation,
respectively.
The following undesirable effects cover adverse reactions from post-marketing experience : the types
of adverse reactions reported during post-marketing with mycophenolate mofetil are similar to those
seen in the controlled renal, cardiac and hepatic transplant studies. Additional adverse reactions
reported during post-marketing are described below with the frequencies reported within brackets if
known.
Gastrointestinal: gingival hyperplasia (≥1/100 to <1/10), colitis including cytomegalovirus colitis,
(common), pancreatitis, (common) and intestinal villous atrophy.
Disorders related to immunosuppression : serious life-threatening infections including meningitis,
endocarditis, tuberculosis and atypical mycobacterial infection. Cases of BK virus associated
nephropathy, as well as cases of JC virus associated progressive multifocal leucoencephalopathy
(PML), have been reported in patients treated with immunosuppressants, including Myfenax.
Agranulocytosis (uncommon) and neutropenia have been reported; therefore regular monitoring of
patients taking Myfenax is advised (see section 4.4). There have been reports of aplastic anaemia and
bone marrow depression in patients treated with mycophenolate mofetil, some of which have been
fatal.
Blood and lymphatic system disorder:
Cases of pure red cell aplasia (PRCA) have been reported in patients treated with mycophenolate
mofetil (see section 4.4).
Isolated cases of abnormal neutrophil morphology, including the acquired Pelger-Huet anomaly, have
been observed in patients treated with mycophenolate mofetil. These changes are not associated with
impaired neutrophil function. These changes may suggest a ‘left shift’ in the maturity of neutrophils in
haematological investigations, which may be mistakenly interpreted as a sign of infection in
immunosuppressed patients such as those that receive Myfenax.
Hypersensitivity: hypersensitivity reactions, including angioneurotic oedema and anaphylactic
reaction have been reported.
Congenital disorders : see further details in section 4.6.
Respiratory, thoracic and mediastinal disorders:
There have been isolated reports of interstitial lung disease and pulmonary fibrosis in patients treated
with mycophenolate mofetil in combination with other immunosuppressants, some of which have been
fatal.
4.9 Overdose
Reports of overdoses with mycophenolate mofetil have been received from clinical trials and during
post-marketing experience. In many of these cases, no adverse events were reported. In those overdose
cases in which adverse events were reported, the events fall within the known safety profile of the
medicinal product.
9
 
It is expected that an overdose of mycophenolate mofetil could possibly result in oversuppression of
the immune system and increase susceptibility to infections and bone marrow suppression (see section
4.4). If neutropenia develops, dosing with Myfenax should be interrupted or the dose reduced (see
section 4.4).
Haemodialysis would not be expected to remove clinically significant amounts of MPA or MPAG.
Bile acid sequestrants, such as cholestyramine, can remove MPA by decreasing the enterohepatic re-
circulation of the drug (see section 5.2).
5.
PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: immunosuppressive agents ATC code: LO4A A06
Mycophenolate mofetil is the 2-morpholinoethyl ester of mycophenolic acid (MPA). MPA is a potent,
selective, uncompetitive and reversible inhibitor of inosine monophosphate dehydrogenase, and
therefore inhibits the de novo pathway of guanosine nucleotide synthesis without incorporation into
DNA. Because T- and B-lymphocytes are critically dependent for their proliferation on de novo
synthesis of purines whereas other cell types can utilise salvage pathways, MPA has more potent
cytostatic effects on lymphocytes than on other cells.
5.2 Pharmacokinetic properties
Following oral administration, mycophenolate mofetil undergoes rapid and extensive absorption and
complete presystemic metabolism to the active metabolite, MPA. As evidenced by suppression of
acute rejection following renal transplantation, the immunosuppressant activity of mycophenolate
mofetil is correlated with MPA concentration. The mean bioavailability of oral mycophenolate
mofetil, based on MPA AUC, is 94% relative to intravenous mycophenolate mofetil. Food had no
effect on the extent of absorption (MPA AUC) of mycophenolate mofetil when administered at doses
of 1.5 g BID to renal transplant patients. However, MPA C max was decreased by 40% in the presence
of food. Mycophenolate mofetil is not measurable systemically in plasma following oral
administration. MPA at clinically relevant concentrations, is 97% bound to plasma albumin.
As a result of enterohepatic recirculation, secondary increases in plasma MPA concentration are
usually observed at approximately 6 – 12 hours post-dose. A reduction in the AUC of MPA of
approximately 40% is associated with the co-administration of cholestyramine (4 g TID), indicating
that there is a significant amount of enterohepatic recirculation.
MPA is metabolised principally by glucuronyl transferase to form the phenolic glucuronide of MPA
(MPAG), which is not pharmacologically active.
A negligible amount of substance is excreted as MPA (< 1% of dose) in the urine. Orally administered
radiolabelled mycophenolate mofetil results in complete recovery of the administered dose; with 93%
of the administered dose recovered in the urine and 6% recovered in the faeces. Most (about 87%) of
the administered dose is excreted in the urine as MPAG.
At clinically encountered concentrations, MPA and MPAG are not removed by haemodialysis.
However, at high MPAG plasma concentrations (> 100μg/ml), small amounts of MPAG are removed.
In the early post-transplant period (< 40 days post-transplant), renal, cardiac and hepatic transplant
patients had mean MPA AUCs approximately 30% lower and C max approximately 40% lower
compared to the late post-transplant period (3 - 6 months post-transplant).
10
Renal impairment :
In a single dose study (6 subjects/group), mean plasma MPA AUC observed in subjects with severe
chronic renal impairment (glomerular filtration rate < 25 ml x min -1 x 1.73 m -2 ) were 28-75% higher
relative to the means observed in normal healthy subjects or subjects with lesser degrees of renal
impairment. However, the mean single dose MPAG AUC was 3-6-fold higher in subjects with severe
renal impairment than in subjects with mild renal impairment or normal healthy subjects, consistent
with the known renal elimination of MPAG. Multiple dosing of mycophenolate mofetil in patients
with severe chronic renal impairment has not been studied. No data are available for cardiac or hepatic
transplant patients with severe chronic renal impairment.
Delayed renal graft function :
In patients with delayed renal graft function post-transplant, mean MPA AUC (0-12h) was comparable
to that seen in post-transplant patients without delayed graft function. Mean plasma MPAG AUC (0-
12h) was 2-3-fold higher than in post-transplant patients without delayed graft function. There may be
a transient increase in the free fraction and concentration of plasma MPA in patients with delayed
renal graft function. Dose adjustment of Myfenax does not appear to be necessary.
Hepatic impairment :
In volunteers with alcoholic cirrhosis, hepatic MPA glucuronidation processes were relatively
unaffected by hepatic parenchymal disease. Effects of hepatic disease on this process probably depend
on the particular disease. However, hepatic disease with predominantly biliary damage, such as
primary biliary cirrhosis, may show a different effect.
Children and adolescents :
Pharmacokinetic parameters were evaluated in 49 paediatric renal transplant patients given 600 mg/m 2
mycophenolate mofetil orally twice daily. This dose achieved MPA AUC values similar to those seen
in adult renal transplant patients receiving mycophenolate mofetil at a dose of 1 g BID in the early and
late post-transplant period. MPA AUC values across age groups were similar in the early and late
post-transplant period.
Elderly patients (≥ 65 years) :
Pharmacokinetic behaviour of mycophenolate mofetil in the elderly has not been formally evaluated.
Oral contraceptives :
The pharmacokinetics of oral contraceptives were unaffected by co administration of mycophenolate
mofetil (see also section 4.5). A study of the co administration of mycophenolate mofetil (1 g BID)
and combined oral contraceptives containing ethinylestradiol (0.02 mg to 0.04 mg) and levonorgestrel
(0.05 mg to 0.15 mg), desogestrel (0.15 mg) or gestodene (0.05 mg to 0.10 mg) conducted in 18 non-
transplant women (not taking other immunosuppressants) over 3 consecutive menstrual cycles showed
no clinically relevant influence of mycophenolate mofetil on the ovulation suppressing action of the
oral contraceptives. Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH)
and progesterone were not significantly affected.
5.3 Preclinical safety data
In experimental models, mycophenolate mofetil was not tumourigenic. The highest dose tested in the
animal carcinogenicity studies resulted in approximately 2-3 times the systemic exposure (AUC or
C max ) observed in renal transplant patients as the recommended clinical dose of 2 g/day and 1.3-2
times the systemic exposure (AUC or C max ) observed in cardiac transplant patients at the
recommended clinical dose of 3 g/day.
Two genotoxicity assays ( in vitro mouse lymphoma assay and in vivo mouse bone marrow
micronucleus test) showed a potential of mycophenolate mofetil to cause chromosomal aberrations.
These effects can be related to the pharmacodynamics mode of action, i.e. inhibition of nucleotide
synthesis in sensitive cells. Other in vitro tests for detection of gene mutation did not demonstrate
genotoxic activity.
11
Mycophenolate mofetil had no effect on fertility of male rats at oral doses up to 20 mg x kg -1 x day -1 . The
systemic exposure at this dose represents 2-3 times the clinical exposure at the recommended clinical
dose of 2 g/day in renal transplant patients and 1.3-2 times the clinical exposure at the recommended
clinical dose of 3 g/day in cardiac transplant patients. In a female fertility and reproduction study
conducted in rats, oral doses of 4.5 mg kg -1 day -1 caused malformations (including anophthalmia,
agnathia and hydrocephaly) in the first generation offspring in the absence of maternal toxicity. The
systemic exposure at this dose was approximately 0.5 times the clinical exposure at the recommended
clinical dose of 2 g/day for renal transplant patients and approximately 0.3 times the clinical exposure
at the recommended clinical dose of 3 g/day for cardiac transplant patients. No effects on fertility or
reproductive parameters were evident in the dams or in the subsequent generation.
In teratology studies in rats and rabbits, foetal resorptions and malformations occurred in rats at 6
mg x kg -1 x day -1 (including anophthalmia, agnathia, and hydrocephaly) and in rabbits at 90 mg x kg -1 x day -1
(including cardiovascular and renal anomalies, such as ectopia cordis and ectopic kidneys, and
diaphragmatic and umbilical hernia), in the absence of maternal toxicity. The systemic exposure at
these levels are approximately equivalent to or less than 0.5 times the clinical exposure at the
recommended clinical dose of 2 g/day for renal transplant patients and approximately 0.3 times the
clinical exposure at the recommended clinical dose of 3 g/day for cardiac transplant patients.
Refer to section 4.6.
The haematopoietic and lymphoid systems were the primary organs affected in toxicology studies
conducted with mycophenolate mofetil in the rat, mouse, dog and monkey. These effects occurred at
systemic exposure levels that are equivalent to or less than the clinical exposure at the recommended
dose of 2 g/day for renal transplant recipients. Gastrointestinal effects were observed in the dog at
systemic exposure levels equivalent to or less than the clinical exposure at the recommended doses.
Gastrointestinal and renal effects consistent with dehydration were also observed in the monkey at the
highest dose (systemic exposure levels equivalent to or greater than clinical exposure). The nonclinical
toxicity profile of mycophenolate mofetil appears to be consistent with adverse events observed in
human clinical trials which now provide safety data of more relevance to the patient population (see
section 4.8).
6.
PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Capsule content:
Pregelatinised starch (maize)
Povidone K-30
Croscarmellose sodium
Magnesium stearate
Capsule shell:
Cap:
Indigo carmine (E132)
Titanium dioxide (E171)
Gelatin
Body:
Red iron oxide (E172)
Yellow iron oxide (E172)
Titanium dioxide (E171)
Gelatin
Black ink containing: shellac, black iron oxide (E172), propylene glycol and potassium hydroxide.
12
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
2 years.
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5 Nature and contents of container
Transparent PVC/PVdC – aluminium blisters in pack sizes of 100 or 300 or 100 x 1 capsules per
carton.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
Because mycophenolate mofetil has demonstrated teratogenic effects in rats and rabbit, Myfenax
capsules should not be opened or crushed. Inhalation or direct contact with skin or mucous membranes
of the powder contained in the capsules should be avoided. If such contact occurs, soap and water
should be used to wash thoroughly and the eyes should be rinsed with plain water.
Any unused product or waste material should be disposed of in accordance with local requirements.
7.
MARKETING AUTHORISATION HOLDER
Teva Pharma B.V.
Computerweg 10
3542 DR Utrecht
The Netherlands
8.
MARKETING AUTHORISATION NUMBER(S)
EU/1/07/438/001 (100 capsules)
EU/1/07/438/002 (300 capsules)
EU/1/07/438/006 (100 x 1 capsules)
9.
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation: 21 February 2008
10. DATE OF REVISION OF THE TEXT
Detailed information on this medicinal product is available on the website of the European Medicines
Agency (EMEA) http://www.emea.europa.eu
13
1.
NAME OF THE MEDICINAL PRODUCT
Myfenax 500 mg film-coated tablets
2.
QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 500 mg mycophenolate mofetil
For a full list of excipients, see section 6.1
3.
PHARMACEUTICAL FORM
Film-coated tablet (tablet)
Pale purple, oval shaped film-coated tablet, debossed with "M500" on one side and plain on the other
side.
4.
CLINICAL PARTICULARS
4.1 Therapeutic indications
Myfenax is indicated in combination with ciclosporin and corticosteroids for the prophylaxis of acute
transplant rejection in patients receiving allogeneic renal, cardiac or hepatic transplants.
4.2 Posology and method of administration
Treatment with Myfenax should be initiated and maintained by appropriately qualified transplant
specialists.
Use in renal transplant:
Adults : oral Myfenax 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).
Children and adolescents : the recommended dose of mycophenolate mofetil is 600 mg/m 2
administered orally twice daily (up to a maximum of 2 g daily). Myfenax tablets should only be
prescribed to patients with a body surface area greater than 1.5 m 2 , 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.
Children (< 2 years) : there are limited safety and efficacy data in children below the age of 2 years.
These are insufficient to make dose recommendations and therefore use in this age group is not
recommended.
Use in cardiac transplant :
Adults : oral Myfenax 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).
Children and adolescents : no data are available for paediatric cardiac transplant patients, therefore use
in this patients group is not recommended until further data to support this is available.
Use in hepatic transplant :
14
Adults : intravenous mycophenolate mofetil should be administered for the first 4 days following
hepatic transplant, with oral Myfenax 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).
Children and adolescents : no data are available for paediatric hepatic transplant patients, therefore use
in this patients group is not recommended until further data to support this is available.
Use in elderly ( 65 years )
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.
Use in renal impairment
In renal transplant patients with severe chronic renal impairment (glomerular filtration rate < 25 ml
min -1 x 1.73 m -2 ), 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.
Use in 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; dose reduction or interruption of
Myfenax is not required. There is no basis for Myfenax dose adjustment following cardiac transplant
rejection. No pharmacokinetic data are available during hepatic transplant rejection.
4.3 Contraindications
Hypersensitivity reactions to the active substance, to mycophenolic acid or any of the excipients.
Myfenax is contraindicated in women who are breast-feeding (see section 4.6).
4.4 Special warnings and precautions for use
Patients receiving immunosuppressive regimens involving combinations of medicinal products,
including Myfenax, 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 ultra-violet (UV) light should be limited by wearing
protective clothing and using a sunscreen with a high protection factor.
Patients receiving Myfenax should be instructed to report immediately any evidence of infection,
unexpected bruising, bleeding or any other manifestation of bone marrow depression.
Patients treated with immunosuppressants, including Myfenax, are at increased risk for opportunistic
infections (bacterial, fungal, viral and protozoal), fatal infections and sepsis (see section 4.8). Among
the opportunistic infections are BK virus associated nephropathy and JC virus associated progressive
multifocal leukoencephalopathy (PML). These infections are often related to a high total
15
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.
Patients receiving Myfenax should be monitored for neutropenia, which may be related to Myfenax
itself, concomitant medicinal products, viral infections, or some combination of these causes. Patients
taking Myfenax 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 3 /μl) it may be appropriate to interrupt or discontinue Myfenax.
Cases of pure red cell aplasia (PRCA) have been reported in patients treated with mycophenolate
mofetil in combination with other immunosuppressants. The mechanism for mycophenolate mofetil
induced PRCA is unknown. PRCA may resolve with dose reduction or cessation of Myfenax therapy.
Changes to Myfenax 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 should be advised that during treatment with Myfenax, 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.
Because mycophenolate mofetil has been associated with an increased incidence of digestive system
adverse events, including infrequent cases of gastrointestinal tract ulceration, haemorrhage and
perforation, Myfenax should be administered with caution in patients with active serious digestive
system disease.
Myfenax is an inosine monophosphate dehydrogenase (IMPDH) inhibitor. On theoretical grounds,
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.
It is recommended that Myfenax should not be administered concomitantly with azathioprine because
such concomitant administration has not been studied.
In view of the significant reduction in the area under the curve (AUC) of MPA by cholestyramine,
caution should be used in the concomitant administration of Myfenax with medicinal products that
interfere with enterohepatic recirculation because of the potential to reduce the efficacy of Myfenax.
The risk-benefit ratio of mycophenolate mofetil in combination with tacrolimus or sirolimus has not
been established (see also section 4.5).
4.5 Interaction with other medicinal products and other forms of interaction
Interaction studies have only been performed in adults.
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 with magnesium and aluminium hydroxides : absorption of mycophenolate mofetil was
decreased when administered with antacids.
Cholestyramine : following single dose administration 1.5 g of mycophenolate mofetil to normal
healthy subjects pre-treated with 4 g three times a day (TID) of cholestyramine for 4 days, there was a
16
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 Myfenax.
Medicinal products that interfere with enterohepatic circulation : caution should be used with medicinal
products that interfere with enterohepatic circulation because of their potential to reduce the efficacy
of mycophenolate mofetil.
Ciclosporin A : ciclosporin A (CsA) pharmacokinetics were unaffected by mycophenolate mofetil.
In contrast, if concomitant ciclosporin treatment is stopped, an increase in MPA AUC of around 30%
should be expected.
Ganciclovir : based on the results of a single dose administration study of recommended doses of oral
mycophenolate mofetil and intravenous ganciclovir and the known effects of renal impairment on the
pharmacokinetics of mycophenolate mofetil (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 Myfenax dose adjustment is not required. In patients with renal impairment in which
mycophenolate mofetil and ganciclovir or its prodrugs, e.g. valganciclovir, are co-administered the
dose recommendations for ganciclovir should be observed and patients monitored carefully.
Oral contraceptives : the pharmacokinetics and pharmacodynamics of oral contraceptives were
unaffected by co administration of mycophenolate mofetil (see also section 5.2).
Rifampicin : in patients not also taking ciclosporin, concomitant administration of mycophenolate
mofetil 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 Myfenax doses accordingly to maintain
clinical efficacy when rifampicin is administered concomitantly.
Sirolimus : in renal transplant patients, concomitant administration of mycophenolate mofetil and CsA
resulted in reduced MPA exposures by 30-50% compared with patients receiving the combination of
sirolimus and similar doses of mycophenolate mofetil (see also section 4.4).
Sevelamer : decrease in MPA C max and AUC 0-12 by 30% and 25%, respectively, were observed when
mycophenolate mofetil was concomitantly administered with sevelamer without any clinical
consequences (i.e. graft rejection). It is recommended, however, to administer Myfenax at least one
hour before or three hours after sevelamer intake to minimise the impact on the absorption of MPA.
There is no data on mycophenolate mofetil with phosphate binders other than sevelamer.
Trimethoprim/sulfamethoxazole : no effect on the bioavailability of MPA was observed.
Norfloxacin and metronidazole : in healthy volunteers, no significant interaction was observed when
mycophenolate mofetil was concomitantly administered with norfloxacin and metronidazole
separately. However, norfloxacin and metronidazole combined reduced the MPA exposure by
approximately 30 % following a single dose of mycophenolate mofetil.
Ciprofloxacin and 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 their discontinuation. The
change in predose level may not accurately represent changes in overall MPA exposure. Therefore, a
change in the dose of Myfenax 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.
Tacrolimus : in liver transplant recipients initiated on mycophenolate mofetil and tacrolimus, the AUC
and Cmax of MPA, the active metabolite of mycophenolate mofetil, were not significantly affected by
17
trough tacrolimus level. In renal transplant patients, the tacrolimus concentration did not appear to be
altered by mycophenolate mofetil. However, in hepatic transplant patients, there was an increase of
approximately 20 % in tacrolimus AUC when multiple doses of mycophenolate mofetil (1.5 g taken
twice a day, morning and evening[BID) were administered to patients taking tacrolimus (see also
section 4.4).
Other interactions : 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.
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).
4.6 Pregnancy and lactation
It is recommended that Myfenax therapy should not be initiated until a negative pregnancy test has
been obtained. Effective contraception must be used before beginning Myfenax therapy, during
therapy, and for six weeks following discontinuation of therapy (see section 4.5). Patients should be
instructed to consult their physician immediately should pregnancy occur.
The use of Myfenax is not recommended during pregnancy and should be reserved for cases where no
more suitable alternative treatment is available. Myfenax should be used in pregnant women only if
the potential benefit outweighs the potential risk to the foetus. There is limited data from the use of
mycophenolate mofetil in pregnant women. However, congenital malformations including ear
malformations, i.e. abnormally formed or absent external/middle ear have been reported in children of
patients exposed to mycophenolate mofetil in combination with other immunosuppressants during
pregnancy. Cases of spontaneous abortions have been reported in patients exposed to mycophenolate
mofetil .
Studies in animals have shown reproductive toxicity (see section 5.3).
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, Myfenax is contraindicated in breast-feeding
mothers (see section 4.3).
4.7 Effects on ability to drive and use machines
No studies on the effects on the ability to drive and use machines have been performed. The
pharmacodynamics profile and the reported adverse reactions indicate that an effect is unlikely.
4.8 Undesirable effects
The following undesirable effects cover adverse reactions from clinical trials :
The principal adverse reactions associated with the administration of mycophenolate mofetil in
combination with ciclosporin and corticosteroids include diarrhoea, leucopenia, sepsis and vomiting
and there is evidence of a higher frequency of certain types of infections (see section 4.4).
Malignancies :
Patients receiving immunosuppressive regimens involving combinations of medicinal products,
including mycophenolate mofetil, are at increased risk of developing lymphomas and other
malignancies, particularly of the skin (see section 4.4). Lymphoproliferative disease or lymphoma
developed in 0.6% of patients receiving mycophenolate mofetil (2 g or 3 g daily) in combination with
other immunosuppressants in controlled clinical trials of renal (2 g data), cardiac and hepatic
transplant patients followed for at least 1 year. Non-melanoma skin carcinomas occurred in 3.6% of
patients; other types of malignancy occurred in 1.1% of patients. Three-year safety data in renal and
18
cardiac transplant patients did not reveal any unexpected changes in incidence of malignancy
compared to the 1-year data. Hepatic transplant patients were followed for at least 1 year, but less than
3 years.
Opportunistic infections :
All transplant patients are at increased risk of opportunistic infections; the risk increased with total
immunosuppressive load (see section 4.4). The most common opportunistic infections in patients
receiving mycophenolate mofetil (2 g or 3 g daily) with other immunosuppressants in controlled
clinical trials of renal (2 g data), cardiac and hepatic transplant patients followed for at least 1 year
were candida mucocutaneous, cytomegalovirus (CMV) viraemia/syndrome and Herpes simplex. The
proportion of patients with CMV viraemia/syndrome was 13.5%.
Children and adolescents :
The type and frequency of adverse reactions in a clinical study, which recruited 92 paediatric patients
aged 2 to 18 years who where given 600 mg/m 2 mycophenolate mofetil orally twice daily, were
generally similar to those observed in adult patients given 1 g mycophenolate mofetil twice daily.
However, the following treatment-related adverse events were more frequent in the paediatric
population, particularly in children under 6 years of age, when compared to adults: diarrhoea, sepsis,
leucopenia, anaemia and infection.
Elderly patients (≥ 65 years) :
Elderly patients (≥ 65 years) may generally be at increased risk of adverse reactions due to
immunosuppression. Elderly patients receiving Myfenax as part of a combination immunosuppressive
regimen, may be at increased risk of certain infections (including cytomegalovirus tissue invasive
disease) and possibly gastrointestinal haemorrhage and pulmonary oedema, compared to younger
individuals.
Other adverse reactions:
Adverse reactions, probably or possibly related to mycophenolate mofetil, reported in ≥ 1/10 and in ≥
1/100 to < 1/10 of patients treated with mycophenolate mofetil in the controlled clinical trials of renal
(2 g data), cardiac and hepatic transplant patients are listed in the following table.
Within the system organ classes, undesirable effects are listed under headings of frequency, using the
following categories: 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); very rare (≤1/10,000), not known (cannot be estimated from the
available data).Within each frequency grouping, undesirable effects are presented in order of
decreasing seriousness
19
Adverse reactions, probably or possibly related to mycophenolate mofetil, reported in patients
treated with mycophenolate mofetil in renal, cardiac and hepatic clinical trials when used in
combination with ciclosporin and corticosteroids
System organ
class
Frequency
Adverse drug reactions
Investigations
Very common -
Cardiac disorders
Common Hepatic enzyme increased, blood creatinine
increased, blood lactate dehydrogenase increased,
blood urea increased, blood alkaline phosphatase
increased, weight decreased
Very common -
Blood and
lymphatic system
disorders
Common Tachycardia
Very common Leukopenia, thrombocytopenia, anaemia
Common
Pancytopenia, leukocytosis
Nervous system
disorders
Very common -
Common Convulsion, hypertonia, tremor, somnolence,
myasthenic syndrome, dizziness, headache,
paraesthesia, dysgeusia
Very common -
Respiratory,
thoracic and
mediastinal
disorders
Common
Pleural effusion, dyspnoea, cough
Gastrointestinal
disorders
Very common Vomiting, abdominal pain, diarrhoea, nausea
Common Gastrointestinal haemorrhage, peritonitis, ileus,
colitis, gastric ulcer, duodenal ulcer, gastritis,
oesophagitis, stomatitis, constipation, dyspepsia,
flatulence, eructation
Very common -
Renal and urinary
disorders
Common Renal impairment
Very common -
Skin and
subcutaneous
tissue disorders
Common
Skin hypertrophy, rash, acne, alopecia
Musculoskeletal
and connective
tissue disorders
Very common -
Common
Arthralgia
20
 
System organ
class
Frequency
Adverse drug reactions
Metabolism and
nutrition disorders
Very common -
Common Acidosis, hyperkalaemia, hypokalaemia,
hyperglycaemia, hypomagnesaemia, hypocalcaemia,
hypercholesterolaemia, hyperlipidaemia,
hypophosphataemia, hyperuricaemia, gout, anorexia
Very common Sepsis, gastrointestinal candidiasis, urinary tract
infection, herpes simplex, herpes zoster
Infections and
infestations
Neoplasms
benign, malignant
and unspecified
(incl cysts and
polyps)
Common Pneumonia, influenza, respiratory tract infection,
respiratory moniliasis, gastrointestinal infection,
candidiasis, gastroenteritis, infection, bronchitis,
pharyngitis, sinusitis, fungal skin infection, skin
candida, vaginal candidiasis, rhinitis
Very common -
Common
Skin cancer, benign neoplasm of skin
Vascular
disorders
Very common -
Common Hypotension, hypertension, vasodilatation
Very common -
General disorders
and
administration site
conditions
Common
Oedema, pyrexia, chills, pain, malaise, asthenia
Hepatobiliary
disorders
Very common -
Common Hepatitis, jaundice, hyperbilirubinaemia
Very common -
Psychiatric
disorders
Common
Agitation, confusional state, depression, anxiety,
thinking abnormal, insomnia
Note: 501 (2 g mycophenolate mofetil daily), 289 (3 g mycophenolate mofetil daily) and 277 (2 g intravenous / 3 g oral mycophenolate
mofetil daily) patients were treated in Phase III studies for the prevention of rejection in renal, cardiac and hepatic transplantation,
respectively.
The following undesirable effects cover adverse reactions from post-marketing experience :
21
 
the types of adverse reactions reported during post-marketing with mycophenolate mofetil are similar
to those seen in the controlled renal, cardiac and hepatic transplant studies. Additional adverse
reactions reported during post-marketing are described below with the frequencies reported within
brackets if known.
Gastrointestinal: gingival hyperplasia (≥1/100 to <1/10), colitis including cytomegalovirus colitis,
(common), pancreatitis, (common) and intestinal villous atrophy.
Disorders related to immunosuppression : serious life-threatening infections including meningitis,
endocarditis, tuberculosis and atypical mycobacterial infection. Cases of BK virus associated
nephropathy, as well as cases of JC virus associated progressive multifocal leucoencephalopathy
(PML), have been reported in patients treated with immunosuppressants, including Myfenax.
Agranulocytosis (uncommon) and neutropenia have been reported; therefore regular monitoring of
patients taking Myfenax is advised (see section 4.4).There have been reports of aplastic anaemia and
bone marrow depression in patients treated with mycophenolate mofetil, some of which have been
fatal.
Blood and lymphatic system disorder:
Cases of pure red cell aplasia (PRCA) have been reported in patients treated with mycophenolate
mofetil (see section 4.4).
Isolated cases of abnormal neutrophil morphology, including the acquired Pelger-Huet anomaly, have
been observed in patients treated with mycophenolate mofetil. These changes are not associated with
impaired neutrophil function. These changes may suggest a ‘left shift’ in the maturity of neutrophils in
haematological investigations, which may be mistakenly interpreted as a sign of infection in
immunosuppressed patients such as those that receive Myfenax.
Hypersensitivity: hypersensitivity reactions, including angioneurotic oedema and anaphylactic
reaction have been reported.
Congenital disorders : see further details in section 4.6.
Respiratory, thoracic and mediastinal disorders:
There have been isolated reports of interstitial lung disease and pulmonary fibrosis in patients treated
with mycophenolate mofetil in combination with other immunosuppressants, some of which have been
fatal.
4.9 Overdose
Reports of overdoses with mycophenolate mofetil have been received from clinical trials and during
post-marketing experience. In many of these cases, no adverse events were reported. In those overdose
cases in which adverse events were reported, the events fall within the known safety profile of the
medicinal product.
It is expected that an overdose of mycophenolate mofetil could possibly result in oversuppression of
the immune system and increase susceptibility to infections and bone marrow suppression (see section
4.4). If neutropenia develops, dosing with Myfenax should be interrupted or the dose reduced (see
section 4.4).
Haemodialysis would not be expected to remove clinically significant amounts of MPA or MPAG.
Bile acid sequestrants, such as cholestyramine, can remove MPA by decreasing the enterohepatic re-
circulation of the drug (see section 5.2).
5.
PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
22
Pharmacotherapeutic group: immunosuppressive agents ATC code: LO4A A06
Mycophenolate mofetil is the 2-morpholinoethyl ester of mycophenolic acid (MPA). MPA is a potent,
selective, uncompetitive and reversible inhibitor of inosine monophosphate dehydrogenase, and
therefore inhibits the de novo pathway of guanosine nucleotide synthesis without incorporation into
DNA. Because T- and B-lymphocytes are critically dependent for their proliferation on de novo
synthesis of purines whereas other cell types can utilise salvage pathways, MPA has more potent
cytostatic effects on lymphocytes than on other cells.
5.2 Pharmacokinetic properties
Following oral administration, mycophenolate mofetil undergoes rapid and extensive absorption and
complete presystemic metabolism to the active metabolite, MPA. As evidenced by suppression of
acute rejection following renal transplantation, the immunosuppressant activity of mycophenolate
mofetil is correlated with MPA concentration. The mean bioavailability of oral mycophenolate
mofetil, based on MPA AUC, is 94% relative to intravenous mycophenolate mofetil. Food had no
effect on the extent of absorption (MPA AUC) of mycophenolate mofetil when administered at doses
of 1.5 g BID to renal transplant patients. However, MPA C max was decreased by 40% in the presence
of food. Mycophenolate mofetil is not measurable systemically in plasma following oral
administration. MPA at clinically relevant concentrations, is 97% bound to plasma albumin.
As a result of enterohepatic recirculation, secondary increases in plasma MPA concentration are
usually observed at approximately 6 – 12 hours post-dose. A reduction in the AUC of MPA of
approximately 40% is associated with the co-administration of cholestyramine (4 g TID), indicating
that these is a significant amount of enterohepatic recirculation.
MPA is metabolised principally by glucuronyl transferase to form the phenolic glucuronide of MPA
(MPAG), which is not pharmacologically active.
A negligible amount of substance is excreted as MPA (< 1% of dose) in the urine. Orally administered
radiolabelled mycophenolate mofetil results in complete recovery of the administered dose; with 93%
of the administered dose recovered in the urine and 6% recovered in the faeces. Most (about 87%) of
the administered dose is excreted in the urine as MPAG.
At clinically encountered concentrations, MPA and MPAG are not removed by haemodialysis.
However, at high MPAG plasma concentrations (> 100μg/ml), small amounts of PAG are removed.
In the early post-transplant period (< 40 days post-transplant), renal, cardiac and hepatic transplants
patients had mean MPA AUCs approximately 30% lower and C max approximately 40% lower
compared to the late post-transplant period (3 – 6 months post-transplant).
Renal impairment :
In a single dose study (6 subjects/group), mean plasma MPA AUC observed in subjects with severe
chronic renal impairment (glomerular filtration rate < 25 ml x min -1 x 1.73 m -2 ) were 28 – 75% higher
relative to the means observed in normal healthy subjects or subjects with lesser degrees of renal
impairment. However, the mean single dose MPAG AUC was 3 – 6 -fold higher in subjects with
severe renal impairment than in subjects with mild renal impairment or normal healthy subjects,
consistent with the known renal elimination of MPAG. Multiple dosing of mycophenolate mofetil in
patients with severe chronic renal impairment has not been studied. No data are available for cardiac
or hepatic transplant patients with severe chronic renal impairment.
Delayed renal graft function :
In patients with delayed renal graft function post-transplant, mean MPA AUC (0-12h) was comparable
to that seen in post-transplant patients without delayed graft function. Mean plasma MPAG AUC (0-
12h) was 2 – 3-fold higher than in post-transplant patients without delayed graft function. There may
23
be a transient increase in the free fraction and concentration of plasma MPA in patients with delayed
renal graft function. Dose adjustment of Myfenax does not appear to be necessary.
Hepatic impairment :
In volunteers with alcoholic cirrhosis, hepatic MPA glucuronidation processes were relatively
unaffected by hepatic parenchymal disease. Effects of hepatic disease on this process probably depend
on the particular disease. However, hepatic disease with predominantly biliary damage, such as
primary biliary cirrhosis, may show a different effect.
Children and adolescents :
Pharmacokinetic parameters were evaluated in 49 paediatric renal transplant patients given 600 mg/m 2
mycophenolate mofetil orally twice daily. This dose achieved MPA AUC values similar to those seen
in adult renal transplant patients receiving mycophenolate mofetil at a dose of 1 g BID in the early and
late post-transplant period. MPA AUC values across age groups were similar in the early and late
post-transplant period.
Elderly patients (≥ 65 years) :
Pharmacokinetic behaviour of mycophenolate mofetil in the elderly has not been formally evaluated.
Oral contraceptives :
The pharmacokinetics of oral contraceptives were unaffected by co administration of mycophenolate
mofetil (see also section 4.5). A study of the co administration of mycophenolate mofetil (1 g BID)
and combined oral contraceptives containing ethinylestradiol (0.02 mg to 0.04 mg) and levonorgestrel
(0.05 mg to 0.15 mg), desogestrel (0.15 mg) or gestodene (0.05 mg to 0.10 mg) conducted in 18 non-
transplant women (not taking other immunosuppressants) over 3 consecutive menstrual cycles showed
no clinically relevant influence of mycophenolate mofetil on the ovulation suppressing action of the
oral contraceptives. Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH)
and progesterone were not significantly affected.
5.3 Preclinical safety data
In experimental models, mycophenolate mofetil was not tumourigenic. The highest dose tested in the
animal carcinogenicity studies resulted in approximately 2 – 3 times the systemic exposure (AUC or
C max ) observed in renal transplant patients as the recommended clinical dose of 2 g/day and 1.3 – 2
times the systemic exposure (AUC or C max ) observed in cardiac transplant patients at the
recommended clinical dose of 3 g/day.
Two genotoxicity assays ( in vitro mouse lymphoma assay and in vivo mouse bone marrow
micronucleus test) showed a potential of mycophenolate mofetil to cause chromosomal aberrations.
These effects can be related to the pharmacodynamics mode of action, i.e. inhibition of nucleotide
synthesis in sensitive cells. Other in vitro tests for detection of gene mutation did not demonstrate
genotoxic activity.
Mycophenolate mofetil had no effect on fertility of male rats at oral doses up to 20 mg x kg -1 x day -1 . The
systemic exposure at this dose represents 2 - 3 times the clinical exposure at the recommended clinical
dose of 2 g/day in renal transplant patients and 1.3 – 2 times the clinical exposure at the recommended
clinical dose of 3 g/day in cardiac transplant patients. In a female fertility and reproduction study
conducted in rats, oral doses of 4.5 mg x kg -1 x day -1 caused malformations (including anophthalmia,
agnathia and hydrocephaly) in the first generation offspring in the absence of maternal toxicity. The
systemic exposure at this dose was approximately 0.5 times the clinical exposure at the recommended
clinical dose of 2 g/day for renal transplant patients and approximately 0.3 times the clinical exposure
at the recommended clinical dose of 3 g/day for cardiac transplant patients. No effects on fertility or
reproductive parameters were evident in the dams or in the subsequent generation.
In teratology studies in rats and rabbits, foetal resorptions and malformations occurred in rats at 6
mg x kg 1 x day -1 (including anophthalmia, agnathia, and hydrocephaly) and in rabbits at 90 mg x kg -1 x day -1
24
(including cardiovascular and renal anomalies, such as ectopia cordis and ectopic kidneys, and
diaphragmatic and umbilical hernia), in the absence of maternal toxicity. The systemic exposure at
these levels are approximately equivalent to or less than 0.5 times the clinical exposure at the
recommended clinical dose of 2 g/day for renal transplant patients and approximately 0.3 times the
clinical exposure at the recommended clinical dose of 3 g/day for cardiac transplant patients.
Refer to section 4.6.
The haematopoietic and lymphoid systems were the primary organs affected in toxicology studies
conducted with mycophenolate mofetil in the rat, mouse, dog and monkey. These effects occurred at
systemic exposure levels that are equivalent to or less than the clinical exposure at the recommended
dose of 2 g/day for renal transplant recipients. Gastrointestinal effects were observed in the dog at
systemic exposure levels equivalent to or less than the clinical exposure at the recommended doses.
Gastrointestinal and renal effects consistent with dehydration were also observed in the monkey at the
highest dose (systemic exposure levels equivalent to or greater than clinical exposure). The nonclinical
toxicity profile of mycophenolate mofetil appears to be consistent with adverse events observed in
human clinical trials which now provide safety data of more relevance to the patient population (see
section 4.8).
6.
PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Tablet core :
Microcrystalline cellulose
Povidone K-30
Magnesium stearate
Croscarmellose sodium
Tablet coat :
Hypromellose (HPMC 2910)
Titanium dioxide (E171)
Macrogol (PEG 400)
Talc
Indigo carmine aluminium lake (E132)
Iron oxide black (E172)
Iron oxide red (E172)
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
2 years.
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5 Nature and contents of container
Transparent PVC/PVdC-aluminium blisters in pack sizes of 50 or 150 or 50 x 1 tablets per carton. Not
all pack sizes may be marketed.
25
6.6 Special precautions for disposal
Because mycophenolate mofetil has demonstrated teratogenic effects in rats and rabbit, Myfenax film-
coated tablets should not be crushed.
Any unused product or waste material should be disposed of in accordance with local requirements.
7. MARKETING AUTHORISATION HOLDER
Teva Pharma B.V.
Computerweg 10,
3542 DR Utrecht
The Netherlands
8.
MARKETING AUTHORISATION NUMBER(S)
EU/1/07/438/003 (50 tablets)
EU/1/07/438/004 (150 tablets)
EU/1/07/438/005 (50 x 1 tablets)
9.
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation: 21 February 2008
10. DATE OF REVISION OF THE TEXT
Detailed information on this medicinal product is available on the website of the European Medicines
Agency (EMEA) http://www.emea.europa.eu
26
ANNEX II
A.
MANUFACTURING AUTHORISATION HOLDER(S)
RESPONSIBLE FOR BATCH RELEASE
B.
CONDITIONS OF THE MARKETING AUTHORISATION
27
A. MANUFACTURING AUTHORISATION HOLDER(S) RESPONSIBLE FOR BATCH
RELEASE
Name and address of the manufacturer responsible for batch release
Teva Pharmaceutical Works Private Limited Company
Pallagi út 13.
Debrecen H-4042
Hungary
TEVA Pharmaceutical Works Private Limited Company
H-2100 Gödöllő
Táncsics Mihály út 82
Hungary
TEVA UK Ltd
Brampton Road
Hampden Park
Eastbourne
East Sussex
BN22 9AG
United Kingdom
Pharmachemie B.V.
Swensweg 5
2031 GA Haarlem
The Netherlands
TEVA Santé SA
Rue Bellocier
89107 Sens
France
The printed package leaflet of the medicinal product must state the name and address of the
manufacturer responsible for the release of the concerned batch.
B. CONDITIONS OF THE MARKETING AUTHORISATION
CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE IMPOSED ON
THE MARKETING AUTHORISATION HOLDER
Medicinal product subject to restricted medical prescription.
CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND
EFFECTIVE USE OF THE MEDICINAL PRODUCT
Not applicable.
OTHER CONDITIONS
Pharmacovigilance system
The MAH must ensure that the system of pharmacovigilance, presented in Module 1.8.1. of the
Marketing Authorisation, is in place and functioning before and whilst the product is on the market.
Risk Management Plan
28
No description of Risk Management Plan has been provided by the applicant. Since the application
concerns a generic with a reference medicinal product for which no safety concern requiring additional
risk minimisation activities has been identified this approach is considered acceptable.
PSURs
The PSUR submission schedule for both strengths should follow the PSUR schedule for the reference
products.
29
ANNEX III
LABELLING AND PACKAGE LEAFLET
30
A.LABELLING
31
 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OUTER CARTON
1.
NAME OF THE MEDICINAL PRODUCT
Myfenax 250mg hard capsules
Mycophenolate mofetil
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each capsule contains 250 mg mycophenolate mofetil
3.
LIST OF EXCIPIENTS
4.
PHARMACEUTICAL FORM AND CONTENTS
100 capsules
300 capsules
100 x 1 capsules
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Oral use.
Read the package leaflet before use
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
Myfenax capsules should be handled with care.
Do not open or crush the capsules and breathe the powder inside the capsules or allow it to touch your
skin.
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
32
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Any unused product or waste material should be disposed of in accordance with local requirements.
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER
Teva Pharma B.V.
Computerweg 10
3542 DR Utrecht
The Netherlands
12. MARKETING AUTHORISATION NUMBER(S)
EU/1/07/438/001 (100 capsules)
EU/1/07/438/002 (300 capsules)
EU/1/07/438/006 (100 x 1 capsules)
13. BATCH NUMBER
Batch
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Myfenax 250 mg Capsules
33
 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS
BLISTER FOIL
1.
NAME OF THE MEDICINAL PRODUCT
Myfenax 250mg hard capsules
Mycophenolate mofetil
2.
NAME OF THE MARKETING AUTHORISATION HOLDER
Teva Pharma B.V.
3.
EXPIRY DATE
EXP
4.
BATCH NUMBER
Lot
5.
OTHER
34
 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OUTER CARTON
1.
NAME OF THE MEDICINAL PRODUCT
Myfenax 500mg film-coated tablets
Mycophenolate mofetil
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each tablet contains 500 mg mycophenolate mofetil
3.
LIST OF EXCIPIENTS
4.
PHARMACEUTICAL FORM AND CONTENTS
50 tablets
150 tablets
50 x 1 tablets
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Oral use.
Read the package leaflet before use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
Myfenax film-coated tablets should be handled with care.
Do not crush the tablets.
8.
EXPIRY DATE
EXP:
9.
SPECIAL STORAGE CONDITIONS
35
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Any unused product or waste material should be disposed of in accordance with local requirements.
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER
Teva Pharma B.V.
Computerweg 10
3542 DR Utrecht
The Netherlands
12. MARKETING AUTHORISATION NUMBER(S)
EU/1/07/438/003 (50 tablets)
EU/1/07/438/004 (150 tablets)
EU/1/07/438/005 (50 x 1 tablets)
13. BATCH NUMBER
Batch
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Myfenax 500 mg Film-coated Tablets
36
 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS
BLISTER FOIL
1.
NAME OF THE MEDICINAL PRODUCT
Myfenax 500 mg film-coated tablets
Mycophenolate mofetil
2.
NAME OF THE MARKETING AUTHORISATION HOLDER
Teva Pharma B.V.
3.
EXPIRY DATE
EXP
4.
BATCH NUMBER
Lot
5.
OTHER
37
 
B.PACKAGE LEAFLET
38
PACKAGE LEAFLET: INFORMATION FOR THE USER
Myfenax 250 mg hard capsules
Mycophenolate mofetil
Read all of this leaflet carefully before you start taking this medicine.
-
If you have any further questions, ask your doctor or pharmacist.
-
This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even
if their symptoms are the same as yours.
-
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,
please tell your doctor or pharmacist.
In this leaflet :
1. What Myfenax is and what it is used for
2. Before you take Myfenax
3. How to take Myfenax
4. Possible side effects
5. How to store Myfenax
6. Further information
1. WHAT MYFENAX IS AND WHAT IT IS USED FOR
Myfenax is a medicine that is used to suppress immune activity.
Myfenax is used to prevent your body rejecting a transplanted kidney, heart or liver. It is used in
combination with other medicines with a similar function (i.e. ciclosporin and corticosteroids).
2. BEFORE YOU TAKE MYFENAX
Do not take Myfenax
- if you are allergic (hypersensitive) to mycophenolate mofetil, mycophenolic acid or any of the
other ingredients of Myfenax.
- if you are breast-feeding.
Take special care with Myfenax
You should inform your doctor immediately:
- if you experience any evidence of infection (e.g. fever, sore throat), unexpected bruising and/or
bleeding.
- if you have or ever have had any problems with your digestive system, e.g. stomach ulcers.
- if you are planning to become pregnant, or if you fall pregnant while taking Myfenax.
Myfenax reduces your body’s defence mechanism. Because of this, there is an increased risk of skin
cancer. Therefore you should limit your exposure to sunlight and ultra violet (UV) light by wearing
appropriate protective clothing and using a sunscreen with a high protection factor.
Taking other medicines
Please inform your doctor or pharmacist if you are taking or have recently taken any other medicines,
even those not prescribed.
If you answer yes to any of the following questions talk to your doctor before you start to take
Myfenax:
39
-
Keep this leaflet. You may need to read it again.
- Are you taking any medicines containing: azathioprine or other immunosuppressive agents (which
are sometimes given to patients after a transplant operation), cholestyramine (used to treat patients
with high blood cholesterol), rifampicin (antibiotic), antacids, phosphate binders (used in patients
with chronic renal kidney failure to reduce the absorption of phosphate) or any other medicines
(including those you can buy without a prescription) that your doctor does not know about?
- Do you need to receive vaccines (live vaccines)? Your doctor will have to advise you what is
indicated for you.
Taking Myfenax with food and drink
Taking food and drink has no influence on your treatment with Myfenax.
Pregnancy and breast-feeding
Use of Myfenax during pregnancy may cause miscarriage or damage to your unborn baby (abnormal
development of ears for example).
If you plan to become pregnant, discuss with your doctor alternative medicines to best prevent
rejection of your transplanted organ. In certain situations, you and your doctor may decide that the
benefit of taking Myfenax for your health is more important than the possible risks to your unborn
baby.
If you become pregnant while taking Myfenax, do not stop taking it, but tell your doctor about your
pregnancy as soon as possible.
Do not take Myfenax if you are:
- Breast-feeding
- Pregnant (unless your doctor clearly tells you)
Tell your doctor straight away if:
- You think you may be pregnant
- You are breast-feeding
- You plan to start a family in the near future
You must always use an effective method of birth control:
- Before you start taking Myfenax
- During the entire treatment with Myfenax
- For 6 weeks after you stop taking Myfenax
You should talk to your doctor about the most suitable method for birth control for you based on your
individual situation.
Women who are capable of becoming pregnant must have a negative pregnancy test BEFORE starting
treatment with Myfenax.
You are a woman who is not capable of becoming pregnant if any of the following applies to you:
- You are post-menopausal, i.e. at least 50 years old and your last period was more than a year ago
(if your periods have stopped because you have treatment for cancer, then there is still a chance
you could become pregnant).
- Your fallopian tubes and both ovaries have been removed (bilateral salpingo-oophorectomy).
- Your uterus has been surgically removed (hysterectomy).
- You have premature failure of the ovaries, confirmed by a specialist gynaecologist.
- You have been diagnosed with one of the following rare conditions that some patients are born
with that make pregnancy impossible: the XY genotype, Turner`s syndrome or uterine agenesis.
- You are a child/teenager who has not started having periods, and cannot become pregnant.
Driving and using machines
Myfenax has not been shown to impair your ability to drive or operate machines.
40
3. HOW TO TAKE MYFENAX
Always take Myfenax exactly as your doctor has told you. You should check with your doctor or
pharmacist if you are not sure. The usual way to take Myfenax is as follows:
Kidney Transplant
Adults:
The first dose will be given within 72 hours after the transplant operation. The recommended daily
dose is 8 capsules (2 g of the active ingredient) taken as 2 separate doses. This means taking 4
capsules in the morning then 4 capsules in the evening.
Children and adolescents:
The dose given will vary depending on the size of the child. Your doctor will decide the most
appropriate dose based on body surface area (height and weight). The recommended dose is 600
mg/m 2 taken twice a day.
Heart Transplant
Adults:
The first dose will be given within 5 days following the transplant operation. The recommended daily
dose is 12 capsules (3 g of the active ingredient) taken as 2 separate doses. This means taking 6
capsules in the morning then 6 capsules in the evening.
Children and adolescents:
No data are available to recommend the use of Myfenax in children and adolescents who have
received a heart transplant.
Liver Transplant
Adults:
The first dose of oral Myfenax will be given to you at least 4 days after the transplant operation and
when you are able to swallow oral medicines. The recommended daily dose is 12 capsules (3 g of the
active ingredient) taken as 2 separate doses. This means taking 6 capsules in the morning then 6
capsules in the evening.
Children and adolescents:
No data are available to recommend the use of Myfenax in children and adolescents who have
received a liver transplant.
Method and route of administration
Swallow your capsules whole with a glass of water. Do not break or crush them and do not take any
capsules that have broken open or split. Avoid contact with any powder that spills out from damaged
capsules. If a capsule breaks open accidentally, wash any powder from your skin with soap and water.
If any powder gets into your eyes or mouth, rinse thoroughly with plenty of plain, fresh water.
Treatment will continue for you as long as you need immunosuppression to prevent your body from
rejecting your transplanted organ.
If you take more Myfenax than you should
It is important not to take too many capsules. Contact your nearest hospital Accident and Emergency
department or a doctor for advice if you have swallowed more capsules than you have been told to
take or if you think a child has swallowed any.
41
If you forget to take Myfenax
If you forget to take your medicine at any time, take it as soon as you remember, then continue to take
it at the usual times.
Do not take a double dose to make up for a forgotten dose.
If you stop taking Myfenax
Do not stop taking Myfenax because you feel better. It is important to take the medicine for as long as
the doctor has told you to. Stopping your treatment with Myfenax may increase the chance of rejection
of your transplanted organ. Do not stop taking your medicine unless your doctor tells you to.
If you have any further questions on the use of this product, ask your doctor or pharmacist.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, Myfenax can have side effects, although not everybody gets them.
Very common side effects likely to affect more than 1 in 10 people:
Diarrhoea, vomiting, feeling sick
Decrease in normal amounts of different blood cells, which can result in increased risk of
infections, bruising, bleeding, breathlessness and weakness
Bacterial, fungal and viral infections of the digestive and urinary tract, cold sores and shingles
Common side effects likely to affect less than 1 in 10, but more than 1 in 100 people:
Changes in different laboratory parameters, including increase in liver enzymes, renal parameters
such as creatinine, potassium, blood sugar, blood lipids, cholesterol, phosphates, magnesium,
calcium and uric acid
Kidney problems with increased levels of urea
Disorders of the digestive system such as constipation, indigestion, flatulence, belching, swelling
of the gums, inflammation of the mouth, oesophagus, stomach, intestine, liver or pancreas and
gastrointestinal bleeding
Convulsions, increased tension in the muscles, shaking and muscle weakness, joint pain
Sleeplessness dizziness and headache, tingling or numbness, change of the sense of taste, loss of
appetite, weight loss
Inflammation and infections of the respiratory and gastrointestinal tract, sore throat, inflammation
of the sinuses, runny and itchy nose
Skin cancer or non cancerous growth of the skin and fungal infections of the skin and vagina
Changes in blood pressure, faster heart beat, dilation of blood vessels
Fluid retention in the body, fever, discomfort, lethargy and weakness
Inflammation of the liver, yellowing of the skin and whites of the eyes
Uncommon side effects likely to affect less than 1 in 100 but more than 1 in 1000 people
Proliferation of the lymphatic tissue, including malignant tumours
Inflammation or infections of the heart and its valves and of the membrane that covers the brain
and spinal cord
Other side effects that have been reported where frequency has not been established
Hypersensitivity (allergic) reactions
Do not stop taking your medicine unless you have discussed this with your doctor first.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please
tell your doctor or pharmacist.
5.
HOW TO STORE MYFENAX
42
Keep out of the reach and sight of children.
Do not use Myfenax after the expiry date as stated on the blister and carton. The expiry date refers to
the last day of that month.
This medicine does not require any special storage conditions.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. These measures will help to protect the environment.
6.
FURTHER INFORMATION
What Myfenax contains:
-
The active substance is mycophenolate mofetil. Each capsule contains 250 mg mycophenolate
mofetil
-
The other ingredients are:
Capsule content:
Pregelatinised maize starch
Povidone K-30
Croscarmellose sodium
Magnesium stearate
Capsule shells:
Cap:
Indigo carmine (E132)
Titanium dioxide (E171)
Gelatin
Body:
Red iron oxide (E172)
Yellow iron oxide (E172)
Titanium dioxide (E171)
Gelatin
Black ink containing: shellac, black iron oxide (E172), propylene glycol and potassium hydroxide
What Myfenax looks like and contents of the pack
Hard capsules:
Body: caramel opaque, printed ‘250’ axially in black ink.
Cap: light blue opaque printed ‘M’ axially in black ink.
Myfenax 250 mg hard capsules are available in PVC/PVdC – aluminium blisters in pack sizes of 100
or 300 or 100 x 1 capsules per carton.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturers
Marketing Authorisation Holder
Teva Pharma B.V.
Computerweg 10
3542 DR Utrecht
The Netherlands
43
Manufacturers
Teva Pharmaceutical Works Private Limited Company
Pallagi út 13.
Debrecen H-4042
Hungary
TEVA Pharmaceutical Works Private Limited Company
H-2100 Gödöllő
Táncsics Mihály út 82
Hungary
TEVA UK Ltd
Brampton Road
Hampden Park
Eastbourne, East Sussex
BN22 9AG UK
Pharmachemie B.V.
Swensweg 5
2031 GA Haarlem
The Netherlands
TEVA Santé SA
Rue Bellocier
89107 Sens
France
44
For any information about this medicinal product, please contact the local representative of the
Marketing Authorisation Holder:
België/Belgique/Belgien
Teva Pharma Belgium N.V./S.A./AG
Tel/Tél: (32) 38.20.73.73
Luxembourg/Luxemburg
Teva Pharma Belgium N.V./S.A./AG
Tel/Tél: (32) 38.20.73.73
България
Teва Фармасютикълс България ЕООД
Телефон: +359 2 489 95 82
Magyarország
Teva Magyarország Zrt.,
Tel: +36 1 288 6400
Česká republika
Teva Pharmaceuticals CR, s.r.o
Telephone: +(420) 606 763 892
Malta
Teva Ελλάς Α.Ε.
Τηλ: +30 210 72 79 099
Danmark
Teva Denmark A/S
Tlf: +45 44 98 55 11
Nederland
Teva Nederland B.V.
Tel: +31 (0) 800 0228400
Deutschland
Teva GmbH
Tel: (49) 351 834 0
Norge
Teva Sweden AB
Telephone: (46) 42 12 11 00
Eesti
Teva Eesti
esindus UAB Sicor Biotech Eesti filial
Tel: +372 611 2409
Österreich
Teva GmbH
Tel: (49) 351 834 0
Ελλάδα
Teva Ελλάς Α.Ε.
Τηλ: +30 210 72 79 099
Polska
Teva Pharmaceuticals Polska Sp. z o.o
Telephone: +(48) 22 345 93 00
España
Teva Pharma, S.L.U.
Telephone: +(34) 91 387 32 80
Portugal
Teva Pharma - Produtos Farmacêuticos, Lda.
Telephone: (351) 214 235 910
France
Teva Santé
Telephone: (33) 1 55 91 7800
România
Teva Pharmaceuticals S.R.L
Telephone: +4021 230 65 24
Ireland
Teva Pharmaceuticals Ireland
Telephone: (353) 42 9395892.
Slovenija
Teva UK Limited
Telephone: (44) 1323 501 111.
Ísland
Teva UK Limited
Telephone: (44) 1323 501 111.
Slovenská republika
TEVA Pharmaceuticals Slovakia s.r.o.
Telephone: +(421) 2 5726 7911
Italia
Teva Italia S.r.l.
Telephone: (39) 0289179805
Suomi/Finland
Teva Sweden AB
Telephone: (46) 42 12 11 00
Κύπρος
Teva Ελλάς Α.Ε.
Τηλ: +30 210 72 79 099
Sverige
Teva Sweden AB
Telephone: (46) 42 12 11 00
45
Latvija
UAB “Sicor Biotech” Latvian Affiliate
Telephone: +371 67784980.
United Kingdom
Teva UK Limited
Telephone: (44) 1323 501 111.
Lietuva
UAB “Sicor Biotech”
Telephone: +370 5 266 02 03
This leaflet was last approved in {MM/YYYY}.
Detailed information on this medicinal product is available on the website of the European Medicines
Agency (EMEA) hhtp://www.emea.europa.eu
46
PACKAGE LEAFLET: INFORMATION FOR THE USER
Myfenax 500mg film-coated tablets
Mycophenolate mofetil
Read all of this leaflet carefully before you start taking this medicine.
-
Keep this leaflet. You may need to read it again.
-
If you have any further questions, ask your doctor or pharmacist.
-
This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even
if their symptoms are the same as yours.
-
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,
please tell your doctor or pharmacist.
In this leaflet :
1.
What Myfenax is and what it is used for
2.
Before you take Myfenax
3.
How to take Myfenax
5.
How to store Myfenax
6.
Further information
1. WHAT MYFENAX IS AND WHAT IT IS USED FOR
Myfenax is a medicine that is used to suppress immune activity.
Myfenax is used to prevent your body rejecting a transplanted kidney, heart or liver. It is used in
combination with other medicines with a similar function (i.e. ciclosporin and corticosteroids).
2. BEFORE YOU TAKE MYFENAX
Do not take Myfenax
-
if you are allergic (hypersensitive) to mycophenolate mofetil, mycophenolic acid or any of the
other ingredients of Myfenax.
if you are breast-feeding.
Take special care with Myfenax
You should inform your doctor immediately:
- if you experience any evidence of infection (e.g. fever, sore throat), unexpected bruising and/or
bleeding.
- if you have or ever have had any problems with your digestive system, e.g. stomach ulcers.
- if you are planning to become pregnant, or if you fall pregnant while taking Myfenax.
Myfenax reduces your body’s defence mechanism. Because of this, there is an increased risk of skin
cancer. Therefore you should limit your exposure to sunlight and ultra violet (UV) light by wearing
appropriate protective clothing and using a sunscreen with a high protection factor.
Taking other medicines
Please inform your doctor or pharmacist if you are taking or have recently taken any other medicines,
even those not prescribed.
47
4.
Possible side effects
If you answer yes to any of the following questions talk to your doctor before you start to take
Myfenax:
- Are you taking any medicines containing: azathioprine or other immunosuppressive agents (which
are sometimes given to patients after a transplant operation), cholestyramine (used to treat patients
with high blood cholesterol), rifampicin (antibiotic), antacids, phosphate binders (used in patients
with chronic kidney failure to reduce the absorption of phosphate), or any other medicines
(including those you can buy without a prescription) that your doctor does not know about?
- Do you need to receive vaccines (live vaccines)? Your doctor will have to advise you what is
indicated for you
Taking Myfenax with food and drink
Taking food and drink has no influence on your treatment with Myfenax.
Pregnancy and breast-feeding
Use of Myfenax during pregnancy may cause miscarriage or damage to your unborn baby (abnormal
development of ears for example).
If you plan to become pregnant, discuss with your doctor alternative medicines to best prevent
rejection of your transplanted organ. In certain situations, you and your doctor may decide that the
benefit of taking Myfenax for your health is more important than the possible risks to your unborn
baby.
If you become pregnant while taking Myfenax, do not stop taking it, but tell your doctor about your
pregnancy as soon as possible.
Do not take Myfenax if you are:
- Breast-feeding
- Pregnant (unless your doctor clearly tells you)
Tell your doctor straight away if:
- You think you may be pregnant
- You are breast-feeding
- You plan to start a family in the near future
You must always use an effective method of birth control:
- Before you start taking Myfenax
- During the entire treatment with Myfenax
- For 6 weeks after you stop taking Myfenax
You should talk to your doctor about the most suitable method for birth control for you based on your
individual situation.
Women who are capable of becoming pregnant must have a negative pregnancy test BEFORE starting
treatment with Myfenax.
You are a woman who is not capable of becoming pregnant if any of the following applies to you:
- You are post-menopausal, i.e. at least 50 years old and your last period was more than a year ago
(if your periods have stopped because you have treatment for cancer, then there is still a chance
you could become pregnant).
- Your fallopian tubes and both ovaries have been removed (bilateral salpingo-oophorectomy).
- Your uterus has been surgically removed (hysterectomy).
- You have premature failure of the ovaries, confirmed by a specialist gynaecologist.
- You have been diagnosed with one of the following rare conditions that some patients are born
with that make pregnancy impossible: the XY genotype, Turner`s syndrome or uterine agenesis.
- You are a child/teenager who has not started having periods, and cannot become pregnant.
48
Driving and using machines
Myfenax has not been shown to impair your ability to drive or operate machines.
3. HOW TO TAKE MYFENAX
Always take Myfenax exactly as your doctor has told you. You should check with your doctor or
pharmacist if you are not sure. The usual way to take Myfenax is as follows:
Kidney Transplant
Adults:
The first dose will be given within 72 hours after the transplant operation. The recommended daily
dose is 4 tablets (2 g of the active ingredient) taken as 2 separate doses. This means taking 2 tablets in
the morning then 2 tablets in the evening.
Children and adolescents:
The dose given will vary depending on the size of the child. Your doctor will decide the most
appropriate dose based on body surface area (height and weight). The recommended dose is 600
mg/m 2 taken twice a day.
Heart Transplant
Adults:
The first dose will be given within 5 days following the transplant operation. The recommended daily
dose is 6 tablets (3 g of the active ingredient) taken as 2 separate doses. This means taking 3 tablets in
the morning then 3 tablets in the evening.
Children and adolescents:
No data are available to recommend the use of Myfenax in children and adolescents who have
received a heart transplant.
Liver Transplant
Adults:
The first dose of oral Myfenax will be given to you at least 4 days after the transplant operation and
when you are able to swallow oral medicines. The recommended daily dose is 6 tablets (3 g of the
active ingredient) taken as 2 separate doses. This means taking 3 tablets in the morning then 3 tablets
in the evening.
Children and adolescents:
No data are available to recommend the use of Myfenax in children and adolescents who have
received a liver transplant.
Method and route of administration
Swallow your tablets whole with a glass of water. Do not break or crush them.
Treatment will continue for you as long as you need immunosuppression to prevent your body from
rejecting your transplanted organ.
If you take more Myfenax than you should
It is important not to take too many tablets. Contact your nearest hospital Accident and Emergency
department or a doctor for advice if you have swallowed more tablets than you have been told to take
or if you think a child has swallowed any.
If you forget to take Myfenax
49
If you forget to take your medicine at any time, take it as soon as you remember, then continue to take
it at the usual times.
Do not take a double dose to make up for a forgotten dose.
If you stop taking Myfenax
Do not stop taking Myfenax because you feel better. It is important to take the medicine for as long as
the doctor has told you to. Stopping your treatment with Myfenax may increase the chance of rejection
of your transplanted organ. Do not stop taking your medicine unless your doctor tells you to.
If you have any further questions on the use of this product, ask your doctor or pharmacist.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, Myfenax can have side effects, although not everybody gets them.
Very common side effects likely to affect more than 1 in 10 people:
Diarrhoea, vomiting, feeling sick
Decrease in normal amounts of different blood cells, which can result in increased risk of
infections, bruising, bleeding, breathlessness and weakness
Bacterial, fungal and viral infections of the digestive and urinary tract, cold sores and shingles
Common side effects likely to affect less than 1 in 10, but more than 1 in 100 people:
Changes in different laboratory parameters, including increase in liver enzymes, renal parameters
such as creatinine, potassium, blood sugar, blood lipids, cholesterol, phosphates, magnesium,
calcium and uric acid
Kidney problems with increased levels of urea
Disorders of the digestive system such as constipation, indigestion, flatulence, belching, swelling
of the gums, inflammation of the mouth, oesophagus, stomach, intestine, liver or pancreas and
gastrointestinal bleeding
Convulsions, increased tension in the muscles, shaking and muscle weakness, joint pain
Sleeplessness dizziness and headache, tingling or numbness, change of the sense of taste, loss of
appetite, weight loss
Inflammation and infections of the respiratory and gastrointestinal tract, sore throat, inflammation
of the sinuses, runny and itchy nose
Skin cancer or non cancerous growth of the skin and fungal infections of the skin and vagina
Changes in blood pressure, faster heart beat, dilation of blood vessels
Fluid retention in the body, fever, discomfort, lethargy and weakness
Inflammation of the liver, yellowing of the skin and whites of the eyes
Uncommon side effects likely to affect less than 1 in 100 but more than 1 in 1000 people
Proliferation of the lymphatic tissue, including malignant tumours
Inflammation or infections of the heart and its valves and of the membrane that covers the brain
and spinal cord
Other side effects that have been reported where frequency has not been established
Hypersensitivity (allergic) reactions
Do not stop taking your medicine unless you have discussed this with your doctor first.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please
tell your doctor or pharmacist
5.
HOW TO STORE MYFENAX
Keep out of the reach and sight of children.
50
Do not use Myfenax after the expiry date as stated on the blister and carton. The expiry date refers to
the last day of that month.
This medicine does not require any special storage conditions.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. These measures will help to protect the environment.
6.
FURTHER INFORMATION
What Myfenax contains:
The active substance is 500 mg mycophenolate mofetil.
The other ingredients are:
Tablet core:
Microcrystalline cellulose
Povidone K-30
Magnesium stearate
Croscarmellose sodium
Tablet coat:
Hypromellose (HPMC 2910)
Titanium dioxide (E171)
Macrogol (PEG 400)
Talc
Indigo carmine aluminium lake (E132)
Iron oxide black (E172)
Iron oxide red (E172)
What Myfenax looks like and contents of the pack
Film-coated tablets:
Pale purple, oval shaped film-coated tablet, debossed with "M500" on one side and plain on the other
side.
Myfenax 500 mg film-coated tablets is available in PVC/PVdC – aluminium blisters in pack sizes of
50 or 150 or 50 x 1 tablets per carton.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Teva Pharma B.V.
Computerweg 10
3542 DR Utrecht
The Netherlands
Manufacturers
Teva Pharmaceutical Works Private Limited Company
Pallagi út 13.
Debrecen H-4042
Hungary
51
Teva Pharmaceutical Works Private Limited Company
H-2100 Gödöllő, Táncsics Mihály ut 82
Hungary
Teva UK Ltd
Brampton Road
Hampden Park
Eastbourne, East Sussex
BN22 9AG, UK
Pharmachemie B.V.
Swensweg 5
2031 GA Haarlem
The Netherlands
TEVA Santé SA
Rue Bellocier
89107 Sens
France
For any information about this medicinal product, please contact the local representative of the
Marketing Authorisation Holder:
België/Belgique/Belgien
Teva Pharma Belgium N.V./S.A./AG
Tel/Tél: (32) 38.20.73.73
Luxembourg/Luxemburg
Teva Pharma Belgium N.V./S.A./AG
Tel/Tél: (32) 38.20.73.73
България
Teва Фармасютикълс България ЕООД
Телефон: +359 2 489 95 82
Magyarország
Teva Magyarország Zrt.,
Tel: +36 1 288 6400
Česká republika
Teva Pharmaceuticals CR, s.r.o
Telephone: +(420) 606 763 892
Malta
Teva Ελλάς Α.Ε.
Τηλ: +30 210 72 79 099
Danmark
Teva Denmark A/S
Tlf: +45 44 98 55 11
Nederland
Teva Nederland B.V.
Tel: +31 (0) 800 0228400
Deutschland
Teva GmbH
Tel: (49) 351 834 0
Norge
Teva Sweden AB
Telephone: (46) 42 12 11 00
Eesti
Teva Eesti
esindus UAB Sicor Biotech Eesti filial
Tel: +372 611 2409
Österreich
Teva GmbH
Tel: (49) 351 834 0
Ελλάδα
Teva Ελλάς Α.Ε.
Τηλ: +30 210 72 79 099
Polska
Teva Pharmaceuticals Polska Sp. z o.o
Telephone: +(48) 22 345 93 00
España
Teva Pharma, S.L.U.
Telephone: +(34) 91 387 32 80
Portugal
Teva Pharma - Produtos Farmacêuticos, Lda.
Telephone: (351) 214 235 910
52
France
Teva Santé
Telephone: (33) 1 55 91 7800
România
Teva Pharmaceuticals S.R.L
Telephone: +4021 230 65 24
Ireland
Teva Pharmaceuticals Ireland
Telephone: (353) 42 9395892.
Slovenija
Teva UK Limited
Telephone: (44) 1323 501 111.
Ísland
Teva UK Limited
Telephone: (44) 1323 501 111.
Slovenská republika
TEVA Pharmaceuticals Slovakia s.r.o.
Telephone: +(421) 2 5726 7911
Italia
Teva Italia S.r.l.
Telephone: (39) 0289179805
Suomi/Finland
Teva Sweden AB
Telephone: (46) 42 12 11 00
Κύπρος
Teva Ελλάς Α.Ε.
Τηλ: +30 210 72 79 099
Sverige
Teva Sweden AB
Telephone: (46) 42 12 11 00
Latvija
UAB “Sicor Biotech” Latvian Affiliate
Telephone: +371 67784980.
United Kingdom
Teva UK Limited
Telephone: (44) 1323 501 111.
Lietuva
UAB “Sicor Biotech”
Telephone: +370 5 266 02 03
This leaflet was last approved in {MM/YYYY}.
Detailed information on this medicinal product is available on the website of the European Medicines
Agency (EMEA) http://www.emea.europa.eu .
53


Source: European Medicines Agency



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