Myclausen

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



2 

1. NAME OF THE MEDICINAL PRODUCT 
 
Myclausen 500 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains 500 mg mycophenolate mofetil. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet 
 
White round film-coated tablets. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Myclausen is indicated in adults, and children and adolescents aged 2 to 18 years 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 Myclausen should be initiated and maintained by appropriately qualified transplant 
specialists. 
 
Posology 
 
Use in renal transplant 

 
Adults 

Oral Myclausen should be initiated within 72 hours following transplantation. The recommended dose 
in renal transplant patients is 1 g administered twice daily (2 g daily dose). 
 
Paediatric population aged 2 to 18 years 

The recommended dose of mycophenolate mofetil is 600 mg/m2
 
administered orally twice daily (up to 

a maximum of 2 g daily). Myclausen film-coated tablets should only be prescribed to patients with a 
body surface area greater than 1.5 m2, at a dose of 1 g twice daily (2 g daily dose). As some adverse 
reactions occur with greater frequency in this age group (see section 4.8) compared with adults, 
temporary dose reduction or interruption may be required; these will need to take into account relevant 
clinical factors including severity of reaction. 
 
Paediatric population < 2 years 

There are limited safety and efficacy data in children below the age of 2 years. These are insufficient 
to make dosage recommendations and therefore use in this age group is not recommended. 
 
Use in cardiac transplant 

 
Adults 
Oral Myclausen 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). 



3 

 
Paediatric population 

No data are available for paediatric cardiac transplant patients. 
 
Use in hepatic transplant 

 
Adults 

Intravenous mycophenolate mofetil should be administered for the first 4 days following hepatic 
transplant, with oral Myclausen initiated as soon after this as it can be tolerated. The recommended 
oral dose in hepatic transplant patients is 1.5 g administered twice daily (3 g daily dose). 
 
Paediatric population 

No data are available for paediatric hepatic transplant patients. 
 
Use in special populations 
 
Elderly 

The recommended dose of 1 g administered twice a day for renal transplant patients and 1.5 g twice a 
day for cardiac or hepatic transplant patients is appropriate for the elderly. 
 
Renal impairment 

In renal transplant patients with severe chronic renal impairment (glomerular filtration 
rate < 25 mL/min/1.73 m2), outside the immediate post-transplant period, doses greater than 1 g 
administered twice a day should be avoided. These patients should also be carefully observed. No dose 
adjustments are needed in patients experiencing delayed renal graft function post-operatively (see 
section 5.2). No data are available for cardiac or hepatic transplant patients with severe chronic renal 
impairment. 
 
Severe hepatic impairment 

No dose adjustments are needed for renal transplant patients with severe hepatic parenchymal disease. 
No data are available for cardiac transplant patients with severe hepatic parenchymal disease. 
 
Treatment during rejection episodes 

Mycophenolic acid (MPA) is the active metabolite of mycophenolate mofetil. Renal transplant 
rejection does not lead to changes in MPA pharmacokinetics; dosage reduction or interruption of 
Myclausen is not required. There is no basis for Myclausen dose adjustment following cardiac 
transplant rejection. No pharmacokinetic data are available during hepatic transplant rejection. 
 
Method of administration 
 
Myclausen is for oral use. The film-coated tablets should be swallowed whole with a glass of water. 
 
Precautions to be taken before handling or administering the medicinal product. 

Because mycophenolate mofetil has demonstrated teratogenic effects in rats and rabbits, Myclausen 
film-coated tablets should not be broken or crushed. 
 
4.3 Contraindications 
 
 Myclausen should not be given to patients with hypersensitivity to mycophenolate mofetil, 

mycophenolic acid or to any of the excipients listed in section 6.1. 
Hypersensitivity reactions to mycophenolate mofetil have been observed (see section 4.8). 

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

effective contraception (see section 4.6). 
 
 Myclausen treatment should not be initiated in women of child bearing potential without 

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



4 

 
 Myclausen should not be used during pregnancy unless there is no suitable alternative treatment 

to prevent transplant rejection (see section 4.6) 
 
 Myclausen should not be given to women who are breast-feeding (see section 4.6). 
 
 
4.4 Special warnings and precautions for use 
 
Neoplasms 
 
Patients receiving immunosuppressive regimens involving combinations of medicinal products, 
including Myclausen, are at increased risk of developing lymphomas and other malignancies, 
particularly of the skin (see section 4.8). The risk appears to be related to the intensity and duration of 
immunosuppression rather than to the use of any specific agent. As general advice to minimise the risk 
for skin cancer, exposure to sunlight and UV light should be limited by wearing protective clothing 
and using a sunscreen with a high protection factor. 
 
 
Infections 
 
Patients treated with immunosuppressants, including Myclausen, are at increased risk for opportunistic 
infections (bacterial, fungal, viral and protozoal), fatal infections and sepsis (see section 4.8). Such 
infections include latent viral reactivation, such as hepatitis B or hepatitis C reactivation and infections 
caused by polyomaviruses (BK virus associated nephropathy, JC virus associated progressive 
multifocal leukoencephalopathy PML). Cases of hepatitis due to reactivation of hepatitis B or hepatitis 
C have been reported in carrier patients treated with immunosuppressants. These infections are often 
related to a high total immunosuppressive burden and may lead to serious or fatal conditions that 
physicians should consider in the differential diagnosis in immunosuppressed patients with 
deteriorating renal function or neurological symptoms. 
 
There have been reports of hypogammaglobulinaemia in association with recurrent infections in 
patients receiving mycophenolate mofetil in combination with other immunosuppressants. In some of 
these cases switching mycophenolate mofetil to an alternative immunosuppressant resulted in serum 
IgG levels returning to normal. Patients on Myclausen who develop recurrent infections should have 
their serum immunoglobulins measured. In cases of sustained, clinically relevant 
hypogammaglobulinaemia, appropriate clinical action should be considered taking into account the 
potent cytostatic effects that mycophenolic acid has on T and B lymphocytes. 
 
There have been published reports of bronchiectasis in adults and children who received 
mycophenolate mofetil in combination with other immunosuppressants. In some of these cases 
switching mycophenolate mofetil to another immunosuppressant resulted in improvement in 
respiratory symptoms. The risk of bronchiectasis may be linked to hypogammaglobulinaemia or to a 
direct effect on the lung. There have also been isolated reports of interstitial lung disease and 
pulmonary fibrosis, some of which were fatal (see section 4.8). It is recommended that patients who 
develop persistent pulmonary symptoms, such as cough and dyspnoea, are investigated. 
 
Blood and immune system 
 
Patients receiving Myclausen should be monitored for neutropenia, which may be related to 
Myclausen itself, concomitant medications, viral infections, or some combination of these causes. 
Patients taking Myclausen 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 103/µl), it may be appropriate to interrupt or 
discontinue Myclausen. 
 
Cases of pure red cell aplasia (PRCA) have been reported in patients treated with mycophenolate 



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mofetil in combination with other immunosuppressants. The mechanism for mycophenolate mofetil 
induced PRCA is unknown. PRCA may resolve with dose reduction or cessation of Myclausen 
therapy. Changes to Myclausen therapy should only be undertaken under appropriate supervision in 
transplant recipients in order to minimise the risk of graft rejection (see section 4.8). 
 
Patients receiving Myclausen should be instructed to report immediately any evidence of infection, 
unexpected bruising, bleeding or any other manifestation of bone marrow depression. 
 
Patients should be advised that during treatment with Myclausen, vaccinations may be less effective, 
and the use of live attenuated vaccines should be avoided (see section 4.5). Influenza vaccination may 
be of value. Prescribers should refer to national guidelines for influenza vaccination. 
 
Gastro-intestinal 
 
Mycophenolate mofetil has been associated with an increased incidence of digestive system adverse 
events, including infrequent cases of gastrointestinal tract ulceration, haemorrhage and perforation, 
Myclausen should be administered with caution in patients with active serious digestive system 
disease. 
 
Mycophenolate mofetil is an IMPDH (inosine monophosphate dehydrogenase) inhibitor. Therefore, it 
should be avoided in patients with rare hereditary deficiency of hypoxanthine-guanine 
phosphoribosyl-transferase (HGPRT) such as Lesch-Nyhan and Kelley-Seegmiller syndrome. 
 
Interactions 
 
Caution should be exercised when switching combination therapy from regimens containing 
immunosuppressants, which interfere with MPA enterohepatic recirculation e.g. ciclosporin to others 
devoid of this effect e.g. sirolimus, belatacept, or vice versa, as this might result in changes of MPA 
exposure. Medicinal products of other classes which interfere with MPA’s enterohepatic cycle e.g. 
cholestyramine should be used with caution due to their potential to reduce the plasma levels and 
efficacy of Myclausen (see also section 4.5). 
 
It is recommended that Myclausen should not be administered concomitantly with azathioprine 
because such concomitant administration has not been studied. 
 
The risk/benefit ratio of mycophenolate mofetil in combination with tacrolimus or sirolimus has not 
been established (see also section 4.5). 
 
Special populations 
 

Elderly patients may be at an increased risk of adverse events such as certain infections (including 
cytomegalovirus tissue invasive disease) and possibly gastrointestinal haemorrhage and pulmonary 
oedema, compared with younger individuals (see section 4.8). 
 
Teratogenic effects 
Mycophenolate is a powerful human teratogen. Spontaneous abortion (rate of 45% to 49%) and 
congenital malformations (estimated rate of 23% to 27%) have been reported following MMF 
exposure during pregnancy. Therefore Myclausen is contraindicated in pregnancy unless there are no 
suitable alternative treatments to prevent transplant rejection. Female patients of childbearing potential 
should be made aware of the risks and follow the recommendations provided in section 4.6. (e.g. 
contraceptive methods, pregnancy testing) prior to, during, and after therapy with Myclausen. 
Physicians should ensure that women taking mycophenolate understand the risk of harm to the baby, 
the need for effective contraception, and the need to immediately consult their physician if there is a 
possibility of pregnancy. 
 
Contraception (see section 4.6) 
Because of robust clinical evidence showing a high risk of abortion and congenital malformations 



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when mycophenolate mofetil is used in pregnancy every effort to avoid pregnancy during treatment 
should be taken. Therefore women with childbearing potential must use at least one form of reliable 
contraception (see section 4.3) before starting Myclausen therapy, during therapy, and for six weeks 
after stopping the therapy; unless abstinence is the chosen method of contraception. Two 
complementary forms of contraception simultaneously are preferred to minimise the potential for 
contraceptive failure and unintended pregnancy. 
 
For contraception advice for men see section 4.6. 
 
Educational materials 
In order to assist patients in avoiding foetal exposure to mycophenolate and to provide additional 
important safety information, the Marketing Authorisation holder will provide educational materials to 
healthcare professionals. The educational materials will reinforce the warnings about the teratogenicity 
of mycophenolate, provide advice on contraception before therapy is started and guidance on the need 
for pregnancy testing. Full patient information about the teratogenic risk and the pregnancy prevention 
measures should be given by the physician to women of childbearing potential and, as appropriate, to 
male patients.  
 
Additional precautions 
Patients should not donate blood during therapy or for at least 6 weeks following discontinuation of 
mycophenolate. Men should not donate semen during therapy or for 90 days following discontinuation 
of mycophenolate. 
 
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially 
‘sodium-free’. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Aciclovir 
Higher aciclovir plasma concentrations were observed when mycophenolate mofetil was administered 
with aciclovir in comparison to the administration of aciclovir alone. The changes in MPAG (the 
phenolic glucuronide of MPA) pharmacokinetics (MPAG increased by 8 %) were minimal and are not 
considered clinically significant. Because MPAG plasma concentrations are increased in the presence 
of renal impairment, as are aciclovir concentrations, the potential exists for mycophenolate mofetil and 
aciclovir, or its prodrugs, e.g. valaciclovir, to compete for tubular secretion and further increases in 
concentrations of both substances may occur. 
 
Antacids and proton pump inhibitors (PPIs) 
Decreased MPA exposure has been observed when antacids, such as magnesium and aluminium 
hydroxides, and PPIs, including lansoprazole and pantoprazole, were administered with 
mycophenolate mofetil. When comparing rates of transplant rejection or rates of graft loss between 
mycophenolate mofetil patients taking PPIs versus mycophenolate mofetil patients not taking PPIs, no 
significant differences were seen. These data support extrapolation of this finding to all antacids 
because the reduction in exposure when mycophenolate mofetil was co- administered with magnesium 
and aluminium hydroxides is considerably less than when mycophenolate mofetil was co-administered 
with PPIs. 
 
Cholestyramine 
Following single dose administration of 1.5 g of mycophenolate mofetil to normal healthy subjects 
pre-treated with 4 g TID of cholestyramine for 4 days, there was a 40 % reduction in the AUC of MPA 
(see section 4.4 and section 5.2). Caution should be used during concomitant administration because 
of the potential to reduce efficacy of Myclausen. 
 
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 Myclausen. 
 



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Ciclosporin A 
Ciclosporin A (CsA) pharmacokinetics are unaffected by mycophenolate mofetil. In contrast, if 
concomitant ciclosporin treatment is stopped, an increase in MPA AUC of around 30 % should be 
expected. CsA interferes with MPA enterohepatic recycling, resulting in reduced MPA exposures by 
30 50 % in renal transplant patients treated with mycophenolate mofetil and CsA compared with 
patients receiving sirolimus or belatacept and similar doses of mycophenolate mofetil (see also 
section 4.4). Conversely, changes of MPA exposure should be expected when switching patients from 
CsA to one of the immunosuppressants which does not interfere with MPA´s enterohepatic cycle. 
 
Telmisartan 
Concomitant administration of telmisartan and mycophenolate mofetil esulted in an approximately 
30 % decrease of MPA concentrations. Telmisartan changes MPA’s elimination by enhancing 
PPAR gamma (peroxisome proliferator-activated receptor gamma) expression, which in turn results in 
an enhanced UGT1A9 expression and activity. When comparing rates of transplant rejection, rates of 
graft loss or adverse event profiles between mycophenolate mofetil patients with and without 
concomitant telmisartan medication, no clinical consequences of the pharmacokinetic medicinal 
product-medicinal product interaction were seen. 
 
Ganciclovir 
Based on the results of a single dose administration study of recommended doses of oral 
mycophenolate and IV ganciclovir and the known effects of renal impairment on the pharmacokinetics 
of 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 Myclausen dose adjustment is not required. In patients with renal impairment in whom 
Myclausen and ganciclovir or its prodrugs, e.g. valganciclovir, are co-administered, the dose 
recommendations for ganciclovir should be observed and patients should be monitored carefully. 
 
Oral contraceptives 
The pharmacokinetics and pharmacodynamics of oral contraceptives were unaffected by 
coadministration 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 (AUC0-12 h) of 18 % to 70 %. It is recommended 
to monitor MPA exposure levels and to adjust Myclausen doses accordingly to maintain clinical 
efficacy when rifampicin is administered concomitantly. 
 
Sevelamer 
Decrease in MPA Cmax and AUC (0-12h) 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 Myclausen at least one 
hour before or three hours after sevelamer intake to minimise the impact on the absorption of MPA. 
There are no data on 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 or 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 



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amoxicillin plus clavulanic acid. This effect tended to diminish with continued antibiotic use and to 
cease within a few days of antibiotic discontinuation. The change in predose level may not accurately 
represent changes in overall MPA exposure. Therefore, a change in the dose of Myclausen 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 hepatic transplant patients initiated on mycophenolate mofetil and tacrolimus, the AUC and Cmax 
of MPA, the active metabolite of mycophenolate mofetil, were not significantly affected by 
coadministration with tacrolimus. In contrast, there was an increase of approximately 20 % in 
tacrolimus AUC when multiple doses of mycophenolate mofetil (1.5 g BID) were administered to 
hepatic transplant patients taking tacrolimus. However, in renal transplant patients, tacrolimus 
concentration did not appear to be altered by mycophenolate mofetil (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). 
 
Paediatric population 
Interaction studies have only been performed in adults. 
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential 
Pregnancy whilst taking mycophenolate must be avoided. Therefore women of childbearing potential 
must use at least one form of reliable contraception (see section 4.3) before starting Myclausen 
therapy, during therapy, and for six weeks after stopping the therapy, unless abstinence is the chosen 
method of contraception. Two complementary forms of contraception simultaneously are preferred. 
 
Pregnancy 
 
Myclausen is contraindicated during pregnancy unless there is no suitable alternative treatment to 
prevent transplant rejection. Treatment should not be initiated without providing a negative pregnancy 
test result to rule out unintended use in pregnancy (see section 4.3). 
 
Female patients of reproductive potential must be made aware of the increased risk of pregnancy loss 
and congenital malformations at the beginning of the treatment and must be counselled regarding 
pregnancy prevention and planning. 
 
Before starting Myclausen treatment, women of child bearing potential should have two negative 
serum or urine pregnancy tests with a sensitivity of at least 25 mIU/mL  in order to exclude unintended 
exposure of the embryo to mycophenolate. It is recommended that the second test should be performed 
8 – 10 days after the first test. For transplants from deceased donors, if it is not possible to perform 
two test 8 – 10 days apart before treatment starts (because of the timing of transplant organ 
availability), a pregnancy test must be performed immediately before starting treatment and a further 
test performed 8 – 10 days later. Pregnancy tests should be repeated as clinically required (e.g. after 
any gap in contraception is reported). Results of all pregnancy tests should be discussed with the 
patient. Patients should be instructed to consult their physician immediately should pregnancy occur. 
 
Mycophenolate is a powerful human teratogen, with an increased risk of spontaneous abortions and 
congenital malformations in case of exposure during pregnancy; 



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 Spontaneous abortions have been reported in 45 to 49% of pregnant women exposed to 
mycophenolate mofetil, compared to a reported rate of between 12 and 33% in solid organ 
transplant patients treated with immunosuppressants other than mycophenolate mofetil. 

 Based on literature reports, malformations occurred in 23 to 27% of live births in women exposed 
to mycophenolate mofetil during pregnancy (compared to 2 to 3 % of live births in the overall 
population and approximately 4 to 5% of live births in solid organ transplant recipients treated 
with immunosuppressants other than mycophenolate mofetil). 

 
Congenital malformations, including reports of multiple malformations, have been observed post-
marketing in children of patients exposed to Myclausen in combination with other 
immunosuppressants during pregnancy. The following malformations were most frequently reported:  
 Abnormalities of the ear (e.g. abnormally formed or absent external ear), external auditory canal 

artesia (middle ear); 
 Facial malformations such as cleft lip, cleft palate, micrognathia and hypertelorism of the orbits; 
 Abnormalities of the eye (e.g. coloboma); 
 Congenital heart disease such as atrial and ventricular septal defects; 
 Malformations of the fingers (e.g. polydactyly, syndactyly); 
 Tracheo-Oesophageal malformations (e.g. oesophageal atresia);  
 Nervous system malformations such as spina bifida;  
 Renal abnormalities. 
 
In addition there have been isolated reports of the following malformations: 
 Microphthalmia; 
 congenital choroid plexus cyst; 
 septum pellucidum agenesis; 
 olfactory nerve agenesis. 
 
Studies in animals have shown reproductive toxicity (see section 5.3).  
 
Breast-feeding 
 
Mycophenolate mofetil has been shown to be excreted in the milk of lactating rats. It is not known 
whether this substance is excreted in human milk. Because of the potential for serious adverse 
reactions to mycophenolate mofetil in breast-fed infants, Myclausen is contraindicated in nursing 
mothers (see section 4.3). 
 
Men 
 
Limited clinical evidence does not indicate an increased risk of malformations or miscarriage 
following paternal exposure to mycophenolate mofetil. 
 
MPA is a powerful teratogen. It is not known if MPA is present in semen. Calculations based on 
animal data show that the maximum amount of MPA that could potentially be transferred to woman is 
so low that it would be unlikely to have an effect. Mycophenolate has been shown to be genotoxic in 
animal studies at concentrations exceeding the human therapeutic exposures by small margins, such 
that the risk of genotoxic effects on sperm cells cannot completely be excluded. 
 
Therefore, the following precautionary measures are recommended: sexually active male patients or 
their female partners are recommended to use reliable contraception during treatment of the male 
patient and for at least 90 days after cessation of mycophenolate mofetil. Male patients of reproductive 
potential should be made aware of and discuss the potential risk of fathering a child with a qualified 
health-care professional. 
 
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 



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pharmacodynamic 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 
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, CMV viraemia/syndrome and Herpes simplex. The proportion of 
patients with CMV viraemia/syndrome was 13.5 %. 
 
Paediatric population 

The type and frequency of adverse reactions in a clinical study, which recruited 92 paediatric patients 
aged 2 to 18 years who were given 600 mg/m2

 
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 

Elderly patients (≥ 65 years) may generally be at increased risk of adverse reactions due to 
immunosuppression. Elderly patients receiving mycophenolate mofetil 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. 
 
Adverse reactions, reported in patients treated with mycophenolate mofetil in renal, cardiac and 
hepatic clinical trials when used in combination with ciclosporin and corticosteroids 
 
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. 



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System organ class Adverse drug reactions 

Infections and infestations Very 
common 

Sepsis, gastrointestinal candidiasis, urinary 
tract infection, herpes simplex, herpes zoster 

Common Pneumonia, influenza, respiratory tract 
infection, respiratory moniliasis, 
gastrointestinal infection, candidiasis, 
gastroenteritis, infection, bronchitis, 
pharyngitis, sinusitis, fungal skin infection, 
skin candida, vaginal candidiasis, rhinitis 

Neoplasms benign, malignant and 
unspecified (incl. cysts and 
polyps) 

Very 
common 

- 

Common Skin cancer, benign neoplasm of skin 

Blood and lymphatic system 
disorders 

Very 
common 

Leucopenia, thrombocytopenia, anaemia 

Common Pancytopenia, leukocytosis 
Metabolism and nutrition 
disorders 

Very 
common 

- 

Common Acidosis, hyperkalaemia, hypokalaemia, 
hyperglycaemia, hypomagnesaemia, 
hypocalcaemia, hypercholesterolaemia, 
hyperlipidaemia, hypophosphataemia, 
hyperuricaemia, gout, anorexia 

Psychiatric disorders Very 
common 

- 

Common Agitation, confusional state, depression, 
anxiety, thinking abnormal, insomnia 

Nervous system disorders Very 
common 

- 

Common Convulsion, hypertonia, tremor, somnolence, 
myasthenic syndrome, dizziness, headache, 
paraesthesia, dysgeusia 

Cardiac disorders Very 
common 

- 

Common Tachycardia 
Vascular disorders Very 

common 
- 

Common Hypotension, hypertension, vasodilatation 
Respiratory, thoracic and 
mediastinal disorders 

Very 
common 

- 

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 

Hepatobiliary disorders Very 
common 

- 

Common Hepatitis, jaundice, hyperbilirubinaemia 
Skin and subcutaneous tissue 
disorders 

Very 
common 

- 

Common Skin hypertrophy, rash, acne, alopecia 



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System organ class Adverse drug reactions 

Musculoskeletal and connective 
tissue disorders 

Very 
common 

- 

Common Arthralgia 
Renal and urinary disorders Very 

common 
- 

Common Renal impairment 
General disorders and 
administration site conditions 

Very 
common 

- 

Common Oedema, pyrexia, chills, pain, malaise, asthenia 
Investigations Very 

common 
- 

Common Hepatic enzyme increased, blood creatinine 
increased, blood lactate dehydrogenase 
increased, blood urea increased, blood alkaline 
phosphatase increased, weight decreased 

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, (≥ 1/100 to < 1/10), 
pancreatitis (≥ 1/100 to < 1/10) and intestinal villous atrophy. 
 
Infections 
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 mycophenolate mofetil. Agranulocytosis (≥ 1/1000 to < 1/100) 
and neutropenia have been reported; therefore, regular monitoring of patients taking Myclausen 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 mycophenolate mofetil. 
 
Hypersensitivity 
Hypersensitivity reactions, including angioneurotic oedema and anaphylactic reaction have been 
reported. 
 
Pregnancy, puerperium and perinatal conditions 

Cases of spontaneous abortions have been reported in patients exposed to mycophenolate mofetil, 
mainly in the first trimester, see section 4.6. 



13 

 
Congenital disorders 
Congenital malformations have been observed post-marketing in children of patients exposed to 
mycophenolate mofetil in combination with other immunosuppressants, see 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. There have also been reports of bronchiectasis in children and adults (frequency not known). 
 
Immune system disorders 

Hypogammaglobulinaemia has been reported in patients receiving mycophenolate mofetil in 
combination with other immunosuppressants (frequency not known). 
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
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 Myclausen 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: immunosuppressants, selective immunosuppressants, ATC code: 
L04AA06 
 
Mechanism of action 
Mycophenolate mofetil is the 2-morpholinoethyl ester of 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 
 
Absorption 
 

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14 

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 IV 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 Cmax was decreased by 40 % in the presence of food. 
Mycophenolate mofetil is not measurable systemically in plasma following oral administration. 
 
Distribution 
 
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 at clinically relevant concentrations is 97 % bound to plasma albumin. 
 
Biotransformation 
 
MPA is metabolised principally by glucuronyl transferase (isoform UGT1A9) to form the inactive 
phenolic glucuronide of MPA (MPAG). In vivo, MPAG is converted back to free MPA via 
enterohepatic recirculation. A minor acylglucuronide (AcMPAG) is also formed. AcMPAG is 
pharmacologically active and is suspected to be responsible for some of mycophenolate mofetil´s side 
effects (diarrhoea, leucopenia). 
 
Elimination 
 
A negligible amount of substance is excreted as MPA (< 1 % of dose) in the urine. Oral administration 
of 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 (> 100 µg/mL), small amounts of MPAG are 
removed. 
By interfering with enterohepatic circulation of the medicinal product, bile acid sequestrants such as 
cholestyramine, reduce MPA AUC (see section 4.9). 
MPA’s disposition depends on several transporters. Organic anion-transporting polypeptides (OATPs) 
and multidrug resistance-associated protein 2 (MRP2) are involved in MPA’s disposition; OATP 
isoforms, MRP2 and breast cancer resistance protein (BCRP) are transporters associated with the 
glucuronides’ biliary excretion. Multidrug resistance protein 1 (MDR1) is also able to transport MPA, 
but its contribution seems to be confined to the absorption process. In the kidney MPA and its 
metabolites potently interact with renal organic anion transporters. 
 
In the early post-transplant period (< 40 days post-transplant), renal, cardiac and hepatic transplant 
patients had mean MPA AUCs approximately 30 % lower and Cmax approximately 40 % lower 
compared to the late post-transplant period (3-6 months post-transplant). 
 
Special populations 
 
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/min/1.73 m2) 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 



15 

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 (0–12 h) was 
comparable to that seen in post-transplant patients without delayed graft function. Mean plasma 
MPAG AUC (0-12 h) 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 Myclausen 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. 
 
Paediatric population 

Pharmacokinetic parameters were evaluated in 49 paediatric renal transplant patients (aged 2 to 18 
years) given 600 mg/m2 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 posttransplant period. MPA AUC values across age groups were 
similar in the early and late posttransplant period. 
 
Elderly 
Pharmacokinetic behaviour of mycophenolate mofetil in the elderly ( 65 years) has not been formally 
evaluated. 
 
Patients taking oral contraceptives 

The pharmacokinetics of oral contraceptives were unaffected by coadministration 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 immunosupressants) 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 LH, 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 
Cmax) observed in renal transplant patients at the recommended clinical dose of 2 g/day and 
1.3-2 times the systemic exposure (AUC or Cmax) 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 pharmacodynamic 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/kg/day. 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/day caused 
malformations (including anophthalmia, agnathia, and hydrocephaly) in the first generation offspring 



16 

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/kg/day (including anophthalmia, agnathia, and hydrocephaly) and in rabbits at 90 mg/kg/day 
(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 is 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 (see 
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 dose. 
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) 
Croscarmellose sodium 
Magnesium stearate 
 
Tablet coating 
Polyvinyl alcohol (partially hydrolysed) 
Titanium dioxide (E 171) 
Macrogol 3000 
Talc 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years. 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
6.5 Nature and contents of container 
 



17 

PVC-aluminium blisters containing 10 film-coated tablets. 
 
Each carton contains either 50 or 150 film-coated tablets. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Passauer Pharma GmbH 
Eiderstedter Weg 3 
14129 Berlin 
Germany 
Tel.: 0049 (0)30 744 60 12 
Fax: 0049 (0)30 744 60 41 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/10/647/001-002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 7 October 2010 
Date of latest renewal: 27 May 2015 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
 
 

http://www.ema.europa.eu/


18 

1. NAME OF THE MEDICINAL PRODUCT 
 
Myclausen 250 mg hard capsules 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each hard capsule contains 250 mg mycophenolate mofetil. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Capsule, hard. 
 
Oblong, white capsules. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Myclausen 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 Myclausen should be initiated and maintained by appropriately qualified transplant 
specialists. 
 
Posology 
 
Use in renal transplant 

 
Adults 

Oral Myclausen should be initiated within 72 hours following transplantation. The recommended dose 
in renal transplant patients is 1 g administered twice daily (2 g daily dose). 
 
Paediatric population aged 2 to 18 years 

The recommended dose of mycophenolate mofetil is 600 mg/m2 administered orally twice daily (up to 
a maximum of 2 g daily). Myclausen capsules should only be prescribed to patients with a body 
surface area of at least 1.25 m2. Patients with a body surface area of 1.25 to 1.5 m2 may be prescribed 
Myclausen capsules at a dose of 750 mg twice daily (1.5 g daily dose). Patients with a body surface 
area greater than 1.5 m2 may be prescribed Myclausen 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. 
 
Paediatric population < 2 years 

There are limited safety and efficacy data in children below the age of 2 years. These are insufficient 
to make dosage recommendations and therefore use in this age group is not recommended. 
 
Use in cardiac transplant 
 
Adults 

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



19 

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

No data are available for paediatric cardiac transplant patients. 
 
Use in hepatic transplant 
 
Adults 

Intravenous mycophenolate mofetil should be administered for the first 4 days following hepatic 
transplant, with oral Myclausen initiated as soon after this as it can be tolerated. The recommended 
oral dose in hepatic transplant patients is 1.5 g administered twice daily (3 g daily dose). 
 
Paediatric population 

No data are available for paediatric hepatic transplant patients. 
 
Use in special populations 

 
Elderly 

The recommended dose of 1 g administered twice a day for renal transplant patients and 1.5 g twice a 
day for cardiac or hepatic transplant patients is appropriate for the elderly. 
 
Renal impairment 

In renal transplant patients with severe chronic renal impairment (glomerular filtration 
rate < 25 mL/min/1.73 m2), outside the immediate post-transplant period, doses greater than 1 g 
administered twice a day should be avoided. These patients should also be carefully observed. No dose 
adjustments are needed in patients experiencing delayed renal graft function post-operatively (see 
section 5.2). No data are available for cardiac or hepatic transplant patients with severe chronic renal 
impairment. 
Severe hepatic impairment 

No dose adjustments are needed for renal transplant patients with severe hepatic parenchymal disease. 
No data are available for cardiac transplant patients with severe hepatic parenchymal disease. 
 
Treatment during rejection episodes 
Mycophenolic acid (MPA) is the active metabolite of mycophenolate mofetil. Renal transplant 
rejection does not lead to changes in MPA pharmacokinetics; dosage reduction or interruption of 
Myclausen is not required. There is no basis for Myclausen dose adjustment following cardiac 
transplant rejection. No pharmacokinetic data are available during hepatic transplant rejection. 
 
Method of administration 
 
Myclausen is for oral use. The hard capsules should be swallowed whole with a glass of water. They 
should not be opened or crushed. 
 
Precautions to be taken before handling or administering the medicinal product. 

Because mycophenolate mofetil has demonstrated teratogenic effects in rats and rabbits, Myclausen 
capsules should not be opened or crushed to avoid inhalation or direct contact with skin or mucous 
membranes of the powder contained in Myclausen capsules. If such contact occurs, wash thoroughly 
with soap and water; rinse eyes with plain water. 
 
4.3 Contraindications 
 
 Myclausen should not be given to patients with hypersensitivity mycophenolate mofetil, 

mycophenolic acid or to any of the excipients listed in section 6.1. 
Hypersensitivity reactions to mycophenolate mofetil have been observed (see section 4.8). 

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

effective contraception (see section 4.6). 



20 

 
 Myclausen treatment should not be initiated in women of child bearing potential without 

providing a pregnancy test result to rule out unintended use in pregnancy (see section 4.6). 
 
 Myclausen should not be used in pregnancy unless there is no suitable alternative treatment to 

prevent transplant rejection (see section 4.6). 
 
 Myclausen should not be given to women who are breastfeeding (see section 4.6).  
 
4.4 Special warnings and precautions for use 
 
Neoplasms 
 
Patients receiving immunosuppressive regimens involving combinations of medicinal products, 
including Myclausen, are at increased risk of developing lymphomas and other malignancies, 
particularly of the skin (see section 4.8). The risk appears to be related to the intensity and duration of 
immunosuppression rather than to the use of any specific agent. As general advice to minimise the risk 
for skin cancer, exposure to sunlight and UV light should be limited by wearing protective clothing 
and using a sunscreen with a high protection factor. 
 
Infections 
 
Patients treated with immunosuppressants, including Myclausen, are at increased risk for opportunistic 
infections (bacterial, fungal, viral and protozoal), fatal infections and sepsis (see section 4.8). Such 
infections include latent viral reactivation, such as hepatitis B or hepatitis C reactivation and infections 
caused by polyomaviruses (BK virus associated nephropathy, JC virus associated progressive 
multifocal leukoencephalopathy PML). Cases of hepatitis due to reactivation of hepatitis B or hepatitis 
C have been reported in carrier patients treated with immunosuppressants. These infections are often 
related to a high total immunosuppressive burden and may lead to serious or fatal conditions that 
physicians should consider in the differential diagnosis in immunosuppressed patients with 
deteriorating renal function or neurological symptoms. 
 
There have been reports of hypogammaglobulinaemia in association with recurrent infections in 
patients receiving mycophenolate mofetil in combination with other immunosuppressants. In some of 
these cases switching mycophenolate mofetil to an alternative immunosuppressant resulted in serum 
IgG levels returning to normal. Patients on Myclausen who develop recurrent infections should have 
their serum immunoglobulins measured. In cases of sustained, clinically relevant 
hypogammaglobulinaemia, appropriate clinical action should be considered taking into account the 
potent cytostatic effects that mycophenolic acid has on T and B lymphocytes. 
 
There have been published reports of bronchiectasis in adults and children who received 
mycophenolate mofetil in combination with other immunosuppressants. In some of these cases 
switching mycophenolate mofetil to another immunosuppressant resulted in improvement in 
respiratory symptoms. The risk of bronchiectasis may be linked to hypogammaglobulinaemia or to a 
direct effect on the lung. There have also been isolated reports of interstitial lung disease and 
pulmonary fibrosis, some of which were fatal (see section 4.8). It is recommended that patients who 
develop persistent pulmonary symptoms, such as cough and dyspnoea, are investigated. 
 
Blood and immune system 
 
Patients receiving Myclausen should be monitored for neutropenia, which may be related to 
Myclausen itself, concomitant medications, viral infections, or some combination of these causes. 
Patients taking Myclausen 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 103/µl), it may be appropriate to interrupt or 
discontinue Myclausen. 
 



21 

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 Myclausen 
therapy. Changes to Myclausen therapy should only be undertaken under appropriate supervision in 
transplant recipients in order to minimise the risk of graft rejection (see section 4.8). 
 
Patients receiving Myclausen should be instructed to report immediately any evidence of infection, 
unexpected bruising, bleeding or any other manifestation of bone marrow depression. 
 
Patients should be advised that during treatment with Myclausen, vaccinations may be less effective 
and the use of live attenuated vaccines should be avoided (see section 4.5). Influenza vaccination may 
be of value. Prescribers should refer to national guidelines for influenza vaccination. 
 
Gastro-intestinal 
 
Mycophenolate mofetil has been associated with an increased incidence of digestive system adverse 
events, including infrequent cases of gastrointestinal tract ulceration, haemorrhage and perforation, 
Myclausen should be administered with caution in patients with active serious digestive system 
disease. 
 
Mycophenolate mofetil is an IMPDH (inosine monophosphate dehydrogenase) inhibitor. Therefore, it 
should be avoided in patients with rare hereditary deficiency of hypoxanthine-guanine 
phosphoribosyl-transferase (HGPRT) such as Lesch-Nyhan and Kelley-Seegmiller syndrome. 
 
Interactions 
 
Caution should be exercised when switching combination therapy from regimens containing 
immunosuppressants, which interfere with MPA enterohepatic recirculation e.g. ciclosporin to others 
devoid of this effect e.g. sirolimus, belatacept, or vice versa, as this might result in changes of MPA 
exposure. Medicinal products of other classes which interfere with MPA’s enterohepatic cycle e.g. 
cholestyramine should be used with caution due to their potential to reduce the plasma levels and 
efficacy of Myclausen (see also section 4.5). 
 
It is recommended that Myclausen should not be administered concomitantly with azathioprine 
because such concomitant administration has not been studied.  
 
The risk/benefit-ratio of mycophenolate mofetil in combination with tacrolimus or sirolimus has not 
been established (see also section 4.5). 
 
Special populations 
 

Elderly patients may be at an increased risk of adverse events such as certain infections (including 
cytomegalovirus tissue invasive disease) and possibly gastrointestinal haemorrhage and pulmonary 
oedema, compared with younger individuals (see section 4.8). 
 
Teratogenic effects 
Mycophenolate is a powerful human teratogen. Spontaneous abortion (rate of 45% to 49%) and 
congenital malformations (estimated rate of 23% to 27%) have been reported following MMF 
exposure during pregnancy. Therefore Myclausen is contraindicated in pregnancy unless there are no 
suitable alternative treatments to prevent transplant rejection. Female patients of childbearing potential 
should be made aware of the risks and follow the recommendations provided in section 4.6. (e.g. 
contraceptive methods, pregnancy testing) prior to, during, and after therapy with Myclausen. 
Physicians should ensure that women taking mycophenolate understand the risk of harm to the baby, 
the need for effective contraception, and the need to immediately consult their physician if there is a 
possibility of pregnancy. 
 
Contraception (see section 4.6) 



22 

Because of robust clinical evidence showing a high risk of abortion and congenital malformations 
when mycophenolate mofetil is used in pregnancy every effort to avoid pregnancy during treatment 
should be taken. Therefore women with childbearing potential must use at least one form of reliable 
contraception (see section 4.3) before starting Myclausen therapy, during therapy, and for six weeks 
after stopping the therapy; unless abstinence is the chosen method of contraception. Two 
complementary forms of contraception simultaneously are preferred to minimise the potential for 
contraceptive failure and unintended pregnancy. 
 
For contraception advice for men see section 4.6. 
 
Educational materials 
In order to assist patients in avoiding foetal exposure to mycophenolate and to provide additional 
important safety information, the Marketing Authorisation holder will provide educational materials to 
healthcare professionals. The educational materials will reinforce the warnings about the teratogenicity 
of mycophenolate, provide advice on contraception before therapy is started and guidance on the need 
for pregnancy testing. Full patient information about the teratogenic risk and the pregnancy prevention 
measures should be given by the physician to women of childbearing potential and, as appropriate, to 
male patients.  
 
Additional precautions 
Patients should not donate blood during therapy or for at least 6 weeks following discontinuation of 
mycophenolate. Men should not donate semen during therapy or for 90 days following discontinuation 
of mycophenolate. 
 
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially 
‘sodium-free’. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Aciclovir 
Higher aciclovir plasma concentrations were observed when mycophenolate mofetil was administered 
with aciclovir in comparison to the administration of aciclovir alone. The changes in MPAG (the 
phenolic glucuronide of MPA) pharmacokinetics (MPAG increased by 8 %) were minimal and are not 
considered clinically significant. Because MPAG plasma concentrations are increased in the presence 
of renal impairment, as are aciclovir concentrations, the potential exists for mycophenolate mofetil and 
aciclovir, or its prodrugs, e.g. valaciclovir, to compete for tubular secretion and further increases in 
concentrations of both substances may occur. 
 
Antacids and proton pump inhibitors (PPIs) 
Decreased MPA exposure has been observed when antacids, such as magnesium and aluminium 
hydroxides, and PPIs, including lansoprazole and pantoprazole, were administered with 
mycophenolate mofetil. When comparing rates of transplant rejection or rates of graft loss between 
mycophenolate mofetil patients taking PPIs versus mycophenolate mofetil patients not taking PPIs, no 
significant differences were seen. These data support extrapolation of this finding to all antacids 
because the reduction in exposure when mycophenolate mofetil was co- administered with magnesium 
and aluminium hydroxides is considerably less than when mycophenolate mofetil was co-administered 
with PPIs. 
 
Cholestyramine 
Following single dose administration of 1.5 g of mycophenolate mofetil to normal healthy subjects 
pre-treated with 4 g TID of cholestyramine for 4 days, there was a 40 % reduction in the AUC of MPA 
(see section 4.4 and section 5.2). Caution should be used during concomitant administration because 
of the potential to reduce efficacy of Myclausen. 
 
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 Myclausen. 



23 

 
Ciclosporin A 
Ciclosporin A (CsA) pharmacokinetics are unaffected by mycophenolate mofetil. In contrast, if 
concomitant ciclosporin treatment is stopped, an increase in MPA AUC of around 30 % should be 
expected. CsA interferes with MPA enterohepatic recycling, resulting in reduced MPA exposures by 
30 50 % in renal transplant patients treated with mycophenolate mofetil and CsA compared with 
patients receiving sirolimus or belatacept and similar doses of mycophenolate mofetil (see also 
section 4.4). Conversely, changes of MPA exposure should be expected when switching patients from 
CsA to one of the immunosuppressants which does not interfere with MPA´s enterohepatic cycle. 
 
Telmisartan 
Concomitant administration of telmisartan and mycophenolate mofetil esulted in an approximately 
30 % decrease of MPA concentrations. Telmisartan changes MPA’s elimination by enhancing 
PPAR gamma (peroxisome proliferator-activated receptor gamma) expression, which in turn results in 
an enhanced UGT1A9 expression and activity. When comparing rates of transplant rejection, rates of 
graft loss or adverse event profiles between mycophenolate mofetil patients with and without 
concomitant telmisartan medication, no clinical consequences of the pharmacokinetic medicinal 
product-medicinal product interaction were seen. 
 
Ganciclovir 
Based on the results of a single dose administration study of recommended doses of oral 
mycophenolate and IV ganciclovir and the known effects of renal impairment on the pharmacokinetics 
of 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 Myclausen dose adjustment is not required. In patients with renal impairment in whom 
Myclausen and ganciclovir or its prodrugs, e.g. valganciclovir, are co-administered, the dose 
recommendations for ganciclovir should be observed and patients should be monitored carefully. 
 
Oral contraceptives 
The pharmacokinetics and pharmacodynamics of oral contraceptives were unaffected by 
coadministration 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 (AUC0-12 h) of 18 % to 70 %. It is recommended 
to monitor MPA exposure levels and to adjust Myclausen doses accordingly to maintain clinical 
efficacy when rifampicin is administered concomitantly. 
 
Sevelamer 
Decrease in MPA Cmax and AUC (0-12h) 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 Myclausen at least one 
hour before or three hours after sevelamer intake to minimise the impact on the absorption of MPA. 
There are no data on 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 or 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 



24 

transplant recipients in the days immediately following commencement of oral ciprofloxacin or 
amoxicillin plus clavulanic acid. This effect tended to diminish with continued antibiotic use and to 
cease within a few days of antibiotic discontinuation. The change in predose level may not accurately 
represent changes in overall MPA exposure. Therefore, a change in the dose of Myclausen 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 hepatic transplant patients initiated on mycophenolate mofetil and tacrolimus, the AUC and Cmax 
of MPA, the active metabolite of mycophenolate mofetil, were not significantly affected by 
coadministration with tacrolimus. In contrast, there was an increase of approximately 20 % in 
tacrolimus AUC when multiple doses of mycophenolate mofetil (1.5 g BID) were administered to 
hepatic transplant patients taking tacrolimus. However, in renal transplant patients, tacrolimus 
concentration did not appear to be altered by mycophenolate mofetil (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). 
 
Paediatric population 
Interaction studies have only been performed in adults. 
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential 
Pregnancy whilst taking mycophenolate must be avoided. Therefore women of childbearing potential 
must use at least one form of reliable contraception (see section 4.3) before starting Myclausen 
therapy, during therapy, and for six weeks after stopping the therapy, unless abstinence is the chosen 
method of contraception. Two complementary forms of contraception simultaneously are preferred. 
 
Pregnancy 
 
Myclausen is contraindicated during pregnancy unless there is no suitable alternative treatment to 
prevent transplant rejection. Treatment should not be initiated without providing a negative pregnancy 
test result to rule out unintended use in pregnancy (see section 4.3). 
 
Female patients of reproductive potential must be made aware of the increased risk of pregnancy loss 
and congenital malformations at the beginning of the treatment and must be counseled regarding 
pregnancy prevention, and planning. 
 
Before starting Myclausen treatment, women of child bearing potential should have two negative 
serum or urine  pregnancy tests with a sensitivity of at least 25 mIU/mL in order to exclude unintended 
exposure of the embryo to mycophenolate. It is recommended that the second test should be performed 
8 – 10 days after the first test. For transplants from deceased donors, if it is not possible to perform 
two test 8 – 10 days apart before treatment starts (because of the timing of transplant organ 
availability), a pregnancy test must be performed immediately before starting treatment and a further 
test performed 8 – 10 days later. Pregnancy tests should be repeated as clinically required (e.g. after 
any gap in contraception is reported). Results of all pregnancy tests should be discussed with the 
patient. Patients should be instructed to consult their physician immediately should pregnancy occur. 
 
Mycophenolate is a powerful human teratogen, with an increased risk of spontaneous abortions and 



25 

congenital malformations in case of exposure during pregnancy; 
 Spontaneous abortions have been reported in 45 to 49% of pregnant women exposed to 

mycophenolate mofetil, compared to a reported rate of between 12 and 33% in solid organ 
transplant patients treated with immunosuppressants other than mycophenolate mofetil. 

 Based on literature reports, malformations occurred in 23 to 27% of live births in women exposed 
to mycophenolate mofetil during pregnancy (compared to 2 to 3 % of live births in the overall 
population and approximately 4 to 5% of live births in solid organ transplant recipients treated 
with immunosuppressants other than mycophenolate mofetil). 

 
Congenital malformations, including reports of multiple malformations, have been observed post-
marketing in children of patients exposed to Myclausen in combination with other 
immunosuppressants during pregnancy. The following malformations were most frequently reported:  
 Abnormalities of the ear (e.g. abnormally formed or absent external ear), external auditory canal 

artesia (middle ear); 
 Facial malformations such as cleft lip, cleft palate, micrognathia and hypertelorism of the orbits; 
 Abnormalities of the eye (e.g. coloboma); 
 Congenital heart disease such as atrial and ventricular septal defects; 
 Malformations of the fingers (e.g. polydactyly, syndactyly); 
 Tracheo-Oesophageal malformations (e.g. oesophageal atresia);  
 Nervous system malformations such as spina bifida;  
 Renal abnormalities. 
 
In addition there have been isolated reports of the following malformations: 
 Microphthalmia; 
 congenital choroid plexus cyst; 
 septum pellucidum agenesis; 
 olfactory nerve agenesis. 
 
Studies in animals have shown reproductive toxicity (see section 5.3).  
 
Breast-feeding 
 
Mycophenolate mofetil has been shown to be excreted in the milk of lactating rats. It is not known 
whether this substance is excreted in human milk. Because of the potential for serious adverse 
reactions to mycophenolate mofetil in breast-fed infants, Myclausen is contraindicated in nursing 
mothers (see section 4.3). 
 
Men 
 
Limited clinical evidence does not indicate an increased risk of malformations or miscarriage 
following paternal exposure to mycophenolate mofetil. 
 
MPA is a powerful teratogen. It is not known if MPA is present in semen. Calculations based on 
animal data show that the maximum amount of MPA that could potentially be transferred to woman is 
so low that it would be unlikely to have an effect. Mycophenolate has been shown to be genotoxic in 
animal studies at concentrations exceeding the human therapeutic exposures by small margins, such 
that the risk of genotoxic effects on sperm cells cannot completely be excluded. 
 
Therefore, the following precautionary measures are recommended: sexually active male patients or 
their female partners are recommended to use reliable contraception during treatment of the male 
patient and for at least 90 days after cessation of mycophenolate mofetil. Male patients of reproductive 
potential should be made aware of and discuss the potential risk of fathering a child with a qualified 
health-care professional. 
 
4.7 Effects on ability to drive and use machines 
 



26 

No studies on the effects on the ability to drive and use machines have been performed. The 
pharmacodynamic 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 
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, CMV viraemia/syndrome and Herpes simplex. The proportion of 
patients with CMV viraemia/syndrome was 13.5 %. 
 
Paediatric population 

The type and frequency of adverse reactions in a clinical study, which recruited 92 paediatric patients 
aged 2 to 18 years who were given 600 mg/m2 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 

Elderly patients (≥ 65 years) may generally be at increased risk of adverse reactions due to 
immunosuppression. Elderly patients receiving mycophenolate mofetil 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. 
 
Adverse reactions, reported in patients treated with mycophenolate mofetil in renal, cardiac and 
hepatic clinical trials when used in combination with ciclosporin and corticosteroids 
 
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 



27 

decreasing seriousness. 
 
System organ class Adverse drug reactions 

Infections and infestations Very 
common 

Sepsis, gastrointestinal candidiasis, urinary 
tract infection, herpes simplex, herpes zoster 

Common Pneumonia, influenza, respiratory tract 
infection, respiratory moniliasis, 
gastrointestinal infection, candidiasis, 
gastroenteritis, infection, bronchitis, 
pharyngitis, sinusitis, fungal skin infection, 
skin candida, vaginal candidiasis, rhinitis 

Neoplasms benign, malignant and 
unspecified (incl. cysts and 
polyps) 

Very 
common 

- 

Common Skin cancer, benign neoplasm of skin 

Blood and lymphatic system 
disorders 

Very 
common 

Leucopenia, thrombocytopenia, anaemia 

Common Pancytopenia, leukocytosis 
Metabolism and nutrition 
disorders 

Very 
common 

- 

Common Acidosis, hyperkalaemia, hypokalaemia, 
hyperglycaemia, hypomagnesaemia, 
hypocalcaemia, hypercholesterolaemia, 
hyperlipidaemia, hypophosphataemia, 
hyperuricaemia, gout, anorexia 

Psychiatric disorders Very 
common 

- 

Common Agitation, confusional state, depression, 
anxiety, thinking abnormal, insomnia 

Nervous system disorders Very 
common 

- 

Common Convulsion, hypertonia, tremor, somnolence, 
myasthenic syndrome, dizziness, headache, 
paraesthesia, dysgeusia 

Cardiac disorders Very 
common 

- 

Common Tachycardia 
Vascular disorders Very 

common 
- 

Common Hypotension, hypertension, vasodilatation 
Respiratory, thoracic and 
mediastinal disorders 

Very 
common 

- 

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 

Hepatobiliary disorders Very 
common 

- 

Common Hepatitis, jaundice, hyperbilirubinaemia 
Skin and subcutaneous tissue 
disorders 

Very 
common 

- 



28 

System organ class Adverse drug reactions 

Common Skin hypertrophy, rash, acne, alopecia 
Musculoskeletal and connective 
tissue disorders 

Very 
common 

- 

Common Arthralgia 
Renal and urinary disorders Very 

common 
- 

Common Renal impairment 
General disorders and 
administration site conditions 

Very 
common 

- 

Common Oedema, pyrexia, chills, pain, malaise, asthenia 
Investigations Very 

common 
- 

Common Hepatic enzyme increased, blood creatinine 
increased, blood lactate dehydrogenase 
increased, blood urea increased, blood alkaline 
phosphatase increased, weight decreased 

 
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, (≥ 1/100 to < 1/10), 
pancreatitis, (≥ 1/100 to < 1/10) and intestinal villous atrophy. 
 
Infections 

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 mycophenolate mofetil. Agranulocytosis (≥ 1/1000 to < 1/100) 
and neutropenia have been reported; therefore, regular monitoring of patients taking Myclausen 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 mycophenolate mofetil. 
 
Hypersensitivity 

Hypersensitivity reactions, including angioneurotic oedema and anaphylactic reaction have been 
reported. 
 
Pregnancy, puerperium and perinatal conditions 



29 

Cases of spontaneous abortions have been reported in patients exposed to mycophenolate mofetil, 
mainly in the first trimester, see section 4.6. 
 
Congenital disorders 
Congenital malformations have been observed post-marketing in children of patients exposed to 
mycophenolate mofetil in combination with other immunosuppressants, see 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. There have also been reports of bronchiectasis in children and adults (frequency not known). 
 
Immune system disorders 

Hypogammaglobulinaemia has been reported in patients receiving mycophenolate mofetil in 
combination with other immunosuppressants (frequency not known). 
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
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 Myclausen 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: immunosuppressants, selective immunosuppressants, ATC code 
L04AA06 
 
Mechanism of action 
Mycophenolate mofetil is the 2-morpholinoethyl ester of 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 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


30 

Absorption 
 
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 IV 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 Cmax was decreased by 40 % in the presence of food. 
Mycophenolate mofetil is not measurable systemically in plasma following oral administration. 
 
Distribution 
 
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 at clinically relevant concentrations is 97 % bound to plasma albumin. 
 
Biotransformation 
 
MPA is metabolised principally by glucuronyl transferase (isoform UGT1A9) to form the inactive 
phenolic glucuronide of MPA (MPAG). In vivo, MPAG is converted back to free MPA via 
enterohepatic recirculation. A minor acylglucuronide (AcMPAG) is also formed. AcMPAG is 
pharmacologically active and is suspected to be responsible for some of mycophenolate mofetil´s side 
effects (diarrhoea, leucopenia). 
 
Elimination 
 
A negligible amount of substance is excreted as MPA (< 1 % of dose) in the urine. Oral administration 
of 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 (> 100 µg/mL), small amounts of MPAG are 
removed. 
By interfering with enterohepatic circulation of the medicinal product, bile acid sequestrants such as 
cholestyramine, reduce MPA AUC (see section 4.9). 
MPA’s disposition depends on several transporters. Organic anion-transporting polypeptides (OATPs) 
and multidrug resistance-associated protein 2 (MRP2) are involved in MPA’s disposition; OATP 
isoforms, MRP2 and breast cancer resistance protein (BCRP) are transporters associated with the 
glucuronides’ biliary excretion. Multidrug resistance protein 1 (MDR1) is also able to transport MPA, 
but its contribution seems to be confined to the absorption process. In the kidney MPA and its 
metabolites potently interact with renal organic anion transporters. 
 
In the early post-transplant period (< 40 days post-transplant), renal, cardiac and hepatic transplant 
patients had mean MPA AUCs approximately 30 % lower and Cmax approximately 40 % lower 
compared to the late post-transplant period (3-6 months post-transplant). 
 
Special populations 
 
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•min-1•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 



31 

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 (0–12 h) was 
comparable to that seen in post-transplant patients without delayed graft function. Mean plasma 
MPAG AUC (0-12 h) 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 Myclausen 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. 
Paediatric population 

Pharmacokinetic parameters were evaluated in 49 paediatric renal transplant patients (aged 2 to 18 
years) given 600 mg/m2 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 posttransplant period. MPA AUC values across age groups were 
similar in the early and late posttransplant period. 
 
Elderly 

Pharmacokinetic behaviour of mycophenolate mofetil in the elderly ( 65 years) has not been formally 
evaluated. 
 
Patients taking oral contraceptives 

The pharmacokinetics of oral contraceptives were unaffected by coadministration 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 immunosupressants) 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 LH, 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 
Cmax) observed in renal transplant patients at the recommended clinical dose of 2 g/day and 
1.3-2 times the systemic exposure (AUC or Cmax) 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 pharmacodynamic 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/kg/day. 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/day caused 



32 

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/kg/day (including anophthalmia, agnathia, and hydrocephaly) and in rabbits at 90 mg/kg/day 
(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 is 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 (see 
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 dose. 
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) 
Croscarmellose sodium 
Povidone (K-30) 
Magnesium stearate 
 
Capsule shells 
Gelatine 
Titanium dioxide (E 171) 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years. 
 
6.4 Special precautions for storage 
 
Store below 30 °C. 
 
6.5 Nature and contents of container 
 
PVC-aluminium blisters containing 10 hard capsules. 



33 

 
Each carton contains either 100 or 300 hard capsules. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Passauer Pharma GmbH 
Eiderstedter Weg 3 
14129 Berlin 
Germany 
Tel.: 0049 (0)30 744 60 12 
Fax: 0049 (0)30 744 60 41 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/10/647/003-004 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 7 October 2010 
Date of latest renewal: 27 May 2015 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
 
 

http://www.ema.europa.eu/


34 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION 

 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 



35 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer responsible for batch release 
 
Passauer Pharma GmbH 
Eiderstedter Weg 3 
14129 Berlin 
Germany 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic Safety Update Reports 
 
The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
 
 Risk Management Plan (RMP) 
 
Not applicable. 
 
 Additional risk minimisation measures  
 
Prior to the use of Myclausen in each Member State (MS) the Marketing Authorisation Holder (MAH) 
must agree about the content and format of the educational programme and a follow-up pregnancy 
questionnaire, including communication media, distribution modalities, and any other aspects of the 
programme, with the National Competent Authority. 
 
The educational programme is aimed at ensuring that the health professionals and patients are aware 
of the teratogenicity and mutagenicity, the need for pregnancy tests before starting therapy with 
mycophenolate mofetil, the contraceptive requirements for both male and female patients and what to 
do in case of pregnancy during treatment with Myclausen.  
 
The MAH shall ensure that in each MS where Myclausen is marketed, all healthcare professionals and 
patients who are expected to prescribe, dispense or use Myclausen are provided with the following 
educational package:  
·         Physician educational material  
·         Patient information pack  
 
The health professional educational material should contain:  
·         The Summary of Product Characteristics  
·         Guide for healthcare professionals  
 
The patient information pack should contain:  



36 

·         The Package Leaflet  
·         Guide for patients  
 
The educational materials should be implemented within four months after completion of this 
procedure and shall contain the following key elements: 
  
Separate guides for healthcare professionals and patients should be provided. For patients, the text 
should be appropriately separated for men and women. The following areas should be covered in these 
guides:  
 
 An introduction in each guide will inform the reader that the purpose of the guide is to tell them 

that a foetal exposure must be avoided and how to minimize the risk of birth defects and 
miscarriage associated with mycophenolate mofetil. It will explain that although this guide is very 
important it does not provide full information on mycophenolate mofetil and that the SmPC 
(healthcare professionals) and package leaflet (patients) supplied with the medicine must also be 
read carefully.  

 
 Background information on mycophenolate mofetil teratogenicity and mutagenicity in humans. 

This section will provide important background information concerning the teratogenicity and 
mutagenicity of mycophenolate mofetil. It will provide details about the nature and magnitude of 
the risk, in line with the information provided in the SmPC. The information provided in this 
section will facilitate a correct understanding of the risk and explain the rationale for the 
following pregnancy prevention measures. Guides should also mention that patients should not to 
give this drug to any other person.  

 
 Counselling of patients: This section will emphasise the importance of a thorough, informative 

and ongoing dialogue between patient and healthcare professional about the pregnancy risks 
associated with mycophenolate mofetil and the relevant minimisation strategies including 
alternative treatment choices, if applicable. The need to plan a pregnancy will be highlighted.  

 
 The need to avoid foetal exposure: Contraceptive requirements for patients of reproductive 

potential prior to, during and after treatment with mycophenolate mofetil. Contraceptive 
requirements for sexually active male patients (including vasectomised men) and female patients 
of childbearing potential will be explained. The need for contraception prior to, during and after 
treatment with mycophenolate mofetil, including details of the duration of time for which 
contraception must be continued after cessation of therapy, will be clearly stated.  

 
In addition, the text relating to women should explain the pregnancy test requirements prior to and 
during therapy with mycophenolate mofetil; including the advice for two negative pregnancy tests 
prior to starting therapy and the importance of the timing of these tests. The need for subsequent 
pregnancy tests during treatment will also be explained.  
 
 Advice that patients should not donate blood during therapy or for at least 6 weeks following 

discontinuation of mycophenolate. Furthermore, men should not donate semen during therapy or 
for 90 days following discontinuation of mycophenolate. 

 
 Advice on action if a pregnancy occurs or is suspected during or shortly after being treated with 

mycophenolate mofetil. Patients will be informed that they should not stop taking mycophenolate 
mofetil but must contact their doctor immediately. It will be explained that the correct course of 
action, based on an assessment of the individual benefit-risk, will be determined on a case by case 
basis through a discussion between the treating physician and the patient. 

 
In addition, a pregnancy follow-up questionnaire including details of exposure during pregnancy, 
including timing and dose; duration of therapy, before and during pregnancy; concomitant drugs; 
known teratogenic risks and full details of congenital malformations should be agreed to with the 
national competent authorities and implemented within four months after completion of this 
procedure. 



37 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 



38 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 



39 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Myclausen 500 mg 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 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Myclausen film-coated tablets should be handled with care. 
Do not break or crush the tablets. 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 



40 

Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Passauer Pharma GmbH 
Eiderstedter Weg 3 
14129 Berlin 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/10/647/001 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Myclausen 500 mg 
 
 



41 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Myclausen 500 mg 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 
 
150 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Myclausen film-coated tablets should be handled with care. 
Do not break or crush the tablets. 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 



42 

Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Passauer Pharma GmbH 
Eiderstedter Weg 3 
14129 Berlin 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/10/647/002 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Myclausen 500 mg 
 
 



43 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS  
 
BLISTER FOIL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Myclausen 500 mg film-coated tablets 
Mycophenolate mofetil 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Passauer Pharma GmbH 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 



44 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Myclausen 250 mg 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 hard capsules 
300 hard capsules 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Myclausen 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 
 
Store below 30 °C. 
 
 



45 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Passauer Pharma GmbH 
Eiderstedter Weg 3 
14129 Berlin 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/10/647/003 (100 hard capsules) 
EU/1/10/647/004 (300 hard capsules) 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Myclausen 250 mg 
 
 



46 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER FOIL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Myclausen 250 mg hard capsules 
Mycophenolate mofetil 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Passauer Pharma GmbH 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 



47 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 



48 

Package leaflet: Information for the user 
 

Myclausen 500 mg film-coated tablets 
Mycophenolate mofetil 

 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
- 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 only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.  
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Myclausen is and what it is used for  
2. What you need to know before you take Myclausen  
3. How to take Myclausen  
4. Possible side effects  
5. How to store Myclausen  
6. Contents of the pack and other information 
 
 
1. What Myclausen is and what it is used for 
 
The full name of your medicine is Myclausen 500 mg film-coated tablets. 
In this leaflet the shorter name Myclausen is used. 
 
Myclausen contains mycophenolate mofetil. 
• This belongs to a group of medicines called “immunosuppressants”. 
Myclausen is used to prevent your body rejecting a transplanted organ. 
• A kidney, heart or liver. 
Myclausen should be used together with other medicines: 
• Ciclosporin and corticosteroids. 
 
 
2. What you need to know before you take Myclausen 
 
WARNING 
Mycophenolate causes birth defects and miscarriage. If you are a woman who could become pregnant, 
you must provide a negative pregnancy test before starting treatment and must follow the 
contraception advice given to you by your doctor. 
 
Your doctor will speak to you and give you written information, particularly on the effects of 
mycophenolate on unborn babies. Read the information carefully and follow the instructions. 
If you do not fully understand these instructions, please ask your doctor to explain them again before 
you take mycophenolate. See also further information in this section under “Warnings and 
precautions” and “Pregnancy and breast-feeding”. 
 
Do not take Myclausen 
• If you are allergic (hypersensitive) to mycophenolate mofetil, mycophenolic acid or any of the 

other ingredients in this medicine (listed in section 6). 
• If you are a woman who could be pregnant and you have not provided a negative pregnancy test 

before your first prescription, as mycophenolate causes birth defects and miscarriage. 
• If you are pregnant or planning to become pregnant or think you may be pregnant 
• If you are not using effective contraception (see Pregnancy, contraception and breast-feeding). 



49 

• If you are breast-feeding. 
 
 
Do not take this medicine if any of the above applies to you. If you are not sure, talk to your doctor or 
pharmacist before taking Myclausen. 
 
Warnings and precautions 
Talk to your doctor straight away before taking Myclausen 
• If you have a sign of infection such as a fever or sore throat 
• If you have any unexpected bruising or bleeding 
• If you have ever had a problem with your digestive system such as a stomach ulcer 
• If you are planning to become pregnant or if you get pregnant while taking Myclausen. 
 
If any of the above apply to you (or you are not sure), talk to your doctor straight away before taking 
Myclausen. 
 
The effect of sunlight 
Myclausen reduces your body’s defences. As a result, there is an increased risk of skin cancer. Limit 
the amount of sunlight and UV light you get. Do this by: 
• wearing protective clothing which also covers your head, neck, arms and legs 
• using a sunscreen with a high protection factor. 
 
Other medicines and Myclausen 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. This includes medicines obtained without a prescription, including herbal medicines. This 
is because Myclausen can affect the way some other medicines work. Also other medicines can affect 
the way Myclausen works. 
 
In particular, tell your doctor or pharmacist if you are taking any of the following medicines before 
you start Myclausen: 
• azathioprine or other medicines which suppress your immune system (given after a transplant 

operation) 
• cholestyramine (used to treat high cholesterol) 
• rifampicin (an antibiotic used to prevent and treat infections such as tuberculosis) 
• antacids or proton pump inhibitors (used for acid problems in your stomach such as indigestion) 
• phosphate binders (used by people with chronic kidney failure to reduce how much phosphate 

gets absorbed into their blood). 
 
Vaccines 
If you need to have a vaccine (a live vaccine) while taking Myclausen, talk to your doctor or 
pharmacist first. Your doctor will have to advise you on what vaccines you can have. 
 
You must not donate blood during treatment with Myclausen and for at least 6 weeks after stopping 
treatment. Men must not donate semen during treatment with Myclausen and for at least 90 days after 
stopping treatment. 
 
Myclausen with food and drink 
Taking food and drink has no effect on your treatment with Myclausen. 
 
Pregnancy, contraception and breast-feeding 
 
Contraception in women taking Myclausen 
If you are a woman who could become pregnant you must use an effective methods of contraception 
with Myclausen. This includes: 
• Before you start taking Myclausen 
• During your entire treatment with Myclausen 
• For 6 weeks after you stop taking Myclausen. 



50 

Talk to your doctor about the most suitable contraception for you. This will depend on your individual 
situation. Two forms of contraception are preferable as this will reduce the risk of unintended 
pregnancy. Contact your doctor as soon as possible, if you think your contraception may not 
have been effective or if you have forgotten to take your contraceptive pill. 
 
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 had treatment for cancer, then there is still a 
chance you could become pregnant) 

• Your fallopian tubes and both ovaries have been removed by surgery (bilateral salpingo-
oophorectomy) 

• Your womb (uterus) has been removed by surgery (hysterectomy) 
• Your ovaries no longer work (premature ovarian failure, which has been confirmed by a 

specialist gynaecologist) 
• You were born with one of the following rare conditions that make pregnancy impossible: the 

XY genotype, Turner’s syndrome or uterine agenesis 
• You are a child or teenager who has not started having periods. 
 
Contraception in men taking Myclausen 
The available evidence does not indicate an increased risk of malformations or miscarriage if the 
father takes mycophenolate. However, a risk cannot be completely excluded. As a precautionyou or 
your female partner are recommended to use reliable contraception during treatment and for 90 days 
after you stop taking Myclausen.  
 
If you are planning to have a child, talk to your doctor about the potential risks. 
 
Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. Your doctor will talk to you about 
the risks in case of pregnancy and the alternatives you can take to prevent rejection of your transplant 
organ if: 
• You plan to become pregnant. 
• You miss or think you have missed a period, or you have unusual menstrual bleeding, or suspect 

you are pregnant. 
• You have sex without using an effective method of contraception. 
If you do become pregnant during the treatment with mycophenolate, you must inform your doctor 
immediately. However, keep taking Myclausen until you see him or her. 
 
Pregnancy 
Mycophenolate causes a very high frequency of miscarriage (50%) and of severe birth defects (23 - 
27%) in the unborn baby. Birth defects which have been reported include anomalies of ears, of eyes, 
of face (cleft lip/palate), of development of fingers, of heart, oesophagus (tube that connects the throat 
with the stomach), kidneys and nervous system (for example spina bifida (where the bones of the 
spine are not properly developed)).Your baby may be affected by one or more of these. 
 
If you are a woman who could become pregnant, you must provide a negative pregnancy test before 
starting treatment and must follow the contraception advice given to you by your doctor. Your doctor 
may request more than one test to ensure you are not pregnant before starting treatment. 
 
Breast-feeding 
Do not take Myclausen if you are breast-feeding. This is because small amounts of the medicine can 
pass into the mother’s milk. 
 
Driving and using machines 
Myclausen is not likely to affect you being able to drive or use any tools or machines. 
 
Myclausen contains sodium 



51 

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially 
‘sodium-free’ 
 
 
3. How to take Myclausen 
 
Always take Myclausen exactly as your doctor has told you. You should check with your doctor or 
pharmacist if you are not sure. 
 
How much to take 
The amount you take depends on the type of transplant you have had. The usual doses are shown 
below. Treatment will continue for as long as you need to prevent you from rejecting your transplant 
organ. 
 
Kidney transplant 
Adults 
• The first dose will be given within 3 days after the transplant operation. 
• The daily dose is 4 tablets (2 g of the medicine) taken as 2 separate doses. 
• Take 2 tablets in the morning then 2 tablets in the evening. 
 
Children aged 2 to 18 years 
• The dose given will vary depending on the size of the child. 
• Your doctor will decide the most appropriate dose based on your child’s height and weight 

(body surface area – measured as square metres or ‘m2’). The recommended dose is 600 mg per 
m2 taken twice a day. 

 
Heart transplant 
Adults 
• The first dose is given within 5 days of the transplant operation. 
• The daily dose is 6 tablets (3 g of the medicine) taken as 2 separate doses. 
• Take 3 tablets in the morning then 3 tablets in the evening. 
 
Children 
• There is no information for the use of Myclausen in children with a heart transplant. 
 
Liver transplant 
Adults 
• The first dose of oral Myclausen will be given to you at least 4 days after the transplant 

operation and when you are able to swallow oral medications. 
• The daily dose is 6 tablets (3 g of the medicine) taken as 2 separate doses. 
• Take 3 tablets in the morning and then 3 tablets in the evening. 
 
Children 
• There is no information for the use of Myclausen in children with a liver transplant. 
 
How to take Myclausen 
• Swallow your tablets whole with a glass of water. 
• Do not break or crush them. 
 
If you take more Myclausen than you should 
If you take more Myclausen than you should, talk to a doctor or go to a hospital straight away. Also do 
this if someone else accidentally takes your medicine. Take the medicine pack with you. 
 
If you forget to take Myclausen 
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. 
 



52 

If you stop taking Myclausen 
Do not stop taking Myclausen unless your doctor tells you to. If you stop your treatment you may 
increase the chance of rejection of your transplanted organ. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Talk to a doctor straight away if you notice any of the following serious side effects – you 
may need urgent medical treatment: 
• you have a sign of infection such as a fever or sore throat 
• you have any unexpected bruising or bleeding 
• you have a rash, swelling of your face, lips, tongue or throat, with difficulty breathing - you may 

be having a serious allergic reaction to the medicine (such as anaphylaxis, angioeodema). 
 
Usual problems 
Some of the more usual problems are diarrhoea, fewer white cells or red cells in your blood, infection 
and vomiting. Your doctor will do regular blood tests to check for any changes in 
• the number of your blood cells 
• the amount in your blood of things like sugar, fat or cholesterol. 
Children may be more likely than adults to have some side effects. This includes diarrhoea, infections, 
fewer white cells and fewer red cells in the blood. 
 
Fighting infections 
Myclausen reduces your body’s defences. This is to stop you rejecting your transplant. As a result, 
your body will not be as good as normal at fighting infections. This means you may catch more 
infections than usual. This includes infections of the brain, skin, mouth, stomach and gut, lungs and 
urinary system. 
 
Lymph and skin cancer 
As can happen in patients taking this type of medicine (immune-suppressants), a very small number of 
Myclausen patients have developed cancer of the lymphoid tissues and skin. 
 
General unwanted effects 
You may get general side effects affecting your body as a whole. This include serious allergic 
reactions (such as anaphylaxis, angioeodema), fever, feeling very tired, difficulty in sleeping, pains 
(such as stomach, chest, joint or muscle, pain on passing urine), headache, flu symptoms and swelling. 
 
Other unwanted effects may include: 
 
Skin problems such as: 
• acne, cold sores, shingles, skin growth, hair loss, rash, itching. 
 
Urinary problems such as: 
• kidney problems or the urgent need to pass water (urine). 
 
Digestive system and mouth problems such as: 
• swelling of the gums and mouth ulcers 
• inflammation of the pancreas, colon or stomach 
• gut problems including bleeding, liver problems 
• constipation, feeling sick (nausea), indigestion, loss of appetite, flatulence. 
 
Nervous system problems such as: 
• feeling dizzy, drowsy or numb 



53 

• tremor, muscle spasms, convulsions 
• feeling anxious or depressed, changes in your mood or thoughts. 
 
Heart and blood vessel problems such as: 
• change in blood pressure, unusual heartbeat, widening of blood vessels. 
 
Lung problems such as: 
• pneumonia, bronchitis 
• shortness of breath, cough, which can be due to bronchiectasis (a condition in which the lung 

airways are abnormally dilated) or pulmonary fibrosis (scarring of the lung). Talk to your doctor 
if you develop a persistent cough or breathlessness 

• fluid on the lungs or inside the chest 
• sinus problems. 
 
Other problems such as: 
• weight loss, gout, high blood sugar, bleeding, bruising. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store Myclausen 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the blister and carton after EXP. The 
expiry date refers to the last day of that month. 
 
This medicine does not require any special storage conditions. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Myclausen contains 
 
The active substance is mycophenolate mofetil. 
Each tablet contains 500 mg mycophenolate mofetil 
 
The other ingredients are: 
 
Tablet core: 
Microcrystalline cellulose, povidone (K-30), croscarmellose sodium, magnesium stearate 
 
Tablet coat: 
Polyvinyl alcohol (partially hydrolysed), titanium dioxide (E 171) macrogol 3000,talc 
 
What Myclausen looks like and contents of the pack 
 
White round film-coated tablets. 
Myclausen 500 mg film-coated tablets are available in PVC-aluminium blisters containing 10 tablets. 
Each carton contains either 50 or 150 tablets. 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


54 

 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder 
Passauer Pharma GmbH 
Eiderstedter Weg 3 
14129 Berlin 
Germany 
 
Manufacturer 
Passauer Pharma GmbH 
Eiderstedter Weg 3 
14129 Berlin 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 

België/Belgique/Belgien 
Passauer Pharma GmbH, 
Duitsland/Allemagne/Deutschland 
Tél/Tel: +49(0)3074460-12 

Lietuva 
Passauer Pharma GmbH, 
Vokietija 
Tel: +49(0)3074460-12 

България 
Passauer Pharma GmbH, 
Германия 
Тел: +49(0)3074460-12 

Luxembourg/Luxemburg 
Passauer Pharma GmbH, 
Allemagne/Deutschland 
Tél/Tel: +49(0)3074460-12 

Česká republika 
Pharmagen CZ, s.r.o. 
Česká republika 
Tel: +420 721 137 749 

Magyarország 
Passauer Pharma GmbH, 
Németország 
Tel: +49(0)3074460-12 

Danmark 
Passauer Pharma GmbH, 
Tyskland 
Tlf: +49(0)3074460-12 

Malta 
Passauer Pharma GmbH, 
Il-Ġermanja 
Tel: +49(0)3074460-12 

Deutschland 
Passauer Pharma GmbH, 
Deutschland 
Tel: +49(0)3074460-12 

Nederland 
Passauer Pharma GmbH, 
Duitsland 
Tel: +49(0)3074460-12 

Eesti 
Passauer Pharma GmbH, 
Saksamaa 
Tel: +49(0)3074460-12 

Norge 
Passauer Pharma GmbH, 
Tyskland 
Tlf: +49(0)3074460-12 

Ελλάδα 
YAS Pharma L.P.  
Λεωφ. Κηφισίας 120 & Φλοίας 10 
151 25 Μαρούσι,  
Αθήνα - Ελλάδα  
Τηλ: + 30 210-6194190 

Österreich 
Passauer Pharma GmbH, 
Deutschland 
Tel: +49(0)3074460-12 



55 

España 
Passauer Pharma GmbH, 
Alemania 
Tel: +49(0)3074460-12 

Polska 
Passauer Pharma GmbH, 
Niemcy 
Tel: +49(0)3074460-12 

France 
Passauer Pharma GmbH, 
Allemagne 
Tél: +49(0)3074460-12 

Portugal 
Passauer Pharma GmbH, 
Alemanha 
Tel: +49(0)3074460-12 

Hrvatska 
Passauer Pharma GmbH, 
Njemačka 
Tel: +49(0)3074460-12 

România 
Passauer Pharma GmbH, 
Germania 
Tel: +49(0)3074460-12 

Ireland 
Passauer Pharma GmbH, 
Germany 
Tel: +49(0)3074460-12 

Slovenija 
Passauer Pharma GmbH, 
Nemčija 
Tel: +49(0)3074460-12 

Ísland 
Passauer Pharma GmbH, 
Þýskaland 
Sími: +49(0)3074460-12 

Slovenská republika 
Passauer Pharma GmbH, 
Nemecko 
Tel: +49(0)3074460-12 

Italia 
Passauer Pharma GmbH, 
Germania 
Tel: +49(0)3074460-12 

Suomi/Finland 
Passauer Pharma GmbH, 
Saksa 
Puh/Tel: +49(0)3074460-12 

Κύπρος 
ISANGEN PHARMA CYPRUS LTD 
Guricon House, Ηνωμένων Εθνών 48, 2ος & 
3ος όροφος 
6042, Λάρνακα, Κύπρος 
Τηλ.: +357-24-638833 
 

Sverige 
Passauer Pharma GmbH, 
Tyskland 
Tel: +49(0)3074460-12 

Latvija 
Passauer Pharma GmbH, 
Vācija 
Tel: +49(0)3074460-12 

United Kingdom 
Passauer Pharma GmbH, 
Germany 
Tel: +49(0)3074460-12 

 
This leaflet was last revised in {MM/YYYY} 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 

http://www.ema.europa.eu/


56 

Package leaflet: Information for the user 
 

Myclausen 250 mg hard capsules 
Mycophenolate mofetil 

 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
• 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 only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1 What Myclausen is and what it is used for 
2 What you need to know before you take Myclausen 
3 How to take Myclausen 
4 Possible side effects 
5 How to store Myclausen 
6 Contents of the pack and other information 
 
 
1. What Myclausen is and what it is used for 
 
The full name of your medicine is Myclausen 250 mg hard capsules. 
In this leaflet the shorter name Myclausen is used. 
 
Myclausen contains mycophenolate mofetil. 
• This belongs to a group of medicines called “immunosuppressants”. 
Myclausen is used to prevent your body rejecting a transplanted organ. 
• A kidney, heart or liver. 
Myclausen should be used together with other medicines: 
• Ciclosporin and corticosteroids. 
 
 
2. What you need to know before you take Myclausen 
 
WARNING 
Mycophenolate causes birth defects and miscarriage. If you are a woman who could become pregnant, 
you must provide a negative pregnancy test before starting treatment and must follow the 
contraception advice given to you by your doctor. 
 
Your doctor will speak to you and give you written information, particularly on the effects of 
mycophenolate on unborn babies. Read the information carefully and follow the instructions. 
If you do not fully understand these instructions, please ask your doctor to explain them again before 
you take mycophenolate. See also further information in this section under “Warnings and 
precautions” and “Pregnancy and breast-feeding”. 
 
Do not take Myclausen 
• If you are allergic (hypersensitive) to mycophenolate mofetil, mycophenolic acid or any of the 

other ingredients in this medicine (listed in section 6). 
• If you are a woman who could be pregnant and you have not provided a negative pregnancy test 

before your first prescription, as mycophenolate causes birth defects and miscarriage. 
• If you are pregnant or planning to become pregnant or think you may be pregnant 
• If you are not using effective contraception (see Pregnancy, contraception and breast-feeding). 



57 

• If you are breast-feeding. 
 
Do not take this medicine if any of the above applies to you. If you are not sure, talk to your doctor or 
pharmacist before taking Myclausen. 
 
Warnings and precautions 
Talk to your doctor straight away before taking Myclausen: 
• If you have a sign of infection such as a fever or sore throat 
• If you have any unexpected bruising or bleeding 
• If you have ever had a problem with your digestive system such as a stomach ulcer 
• If you are planning to become pregnant or if you get pregnant while taking Myclausen. 
 
If any of the above apply to you (or you are not sure), talk to your doctor straight away before taking 
Myclausen. 
 
The effect of sunlight 
Myclausen reduces your body’s defences. As a result, there is an increased risk of skin cancer. Limit 
the amount of sunlight and UV light you get. Do this by: 
• wearing protective clothing which also covers your head, neck, arms and legs 
• using a sunscreen with a high protection factor. 
 
Other medicines and Myclausen 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. This includes medicines obtained without a prescription, including herbal medicines. This 
is because Myclausen can affect the way some other medicines work. Also other medicines can affect 
the way Myclausen works. 
 
In particular, tell your doctor or pharmacist if you are taking any of the following medicines before 
you start Myclausen: 
• azathioprine or other medicines which suppress your immune system (given after a transplant 

operation) 
• cholestyramine (used to treat high cholesterol) 
• rifampicin (an antibiotic used to prevent and treat infections such as tuberculosis) 
• antacids or proton pump inhibitors (used for acid problems in your stomach such as indigestion) 
• phosphate binders (used by people with chronic kidney failure to reduce how much phosphate 

gets absorbed into their blood). 
 
Vaccines 
If you need to have a vaccine (a live vaccine) while taking Myclausen, talk to your doctor or 
pharmacist first. Your doctor will have to advise you on what vaccines you can have. 
 
You must not donate blood during treatment with Myclausen and for at least 6 weeks after stopping 
treatment. Men must not donate semen during treatment with Myclausen and for at least 90 days after 
stopping treatment. 
 
Myclausen with food and drink 
Taking food and drink has no effect on your treatment with Myclausen. 
 
Pregnancy, contraception and breast-feeding 
 
Contraception in women taking Myclausen 
If you are a woman who could become pregnant you must use an effective methods of contraception 
with Myclausen. This includes: 
• Before you start taking Myclausen 
• During your entire treatment with Myclausen 
• For 6 weeks after you stop taking Myclausen. 
Talk to your doctor about the most suitable contraception for you. This will depend on your individual 



58 

situation. Two forms of contraception are preferable as this will reduce the risk of unintended 
pregnancy. Contact your doctor as soon as possible, if you think your contraception may not 
have been effective or if you have forgotten to take your contraceptive pill. 
 
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 had treatment for cancer, then there is still a 
chance you could become pregnant) 

• Your fallopian tubes and both ovaries have been removed by surgery (bilateral salpingo-
oophorectomy) 

• Your womb (uterus) has been removed by surgery (hysterectomy) 
• Your ovaries no longer work (premature ovarian failure, which has been confirmed by a 

specialist gynaecologist) 
• You were born with one of the following rare conditions that make pregnancy impossible: the 

XY genotype, Turner’s syndrome or uterine agenesis 
• You are a child or teenager who has not started having periods. 
 
Contraception in men taking Myclausen 
The available evidence does not indicate an increased risk of malformations or miscarriage if the 
father takes mycophenolate. However, a risk cannot be completely excluded. As a precaution you or 
your female partner  are recommended to use reliable contraception during treatment and for 90 days 
after you stop taking Myclausen. 
 
If you are planning to have a child, talk to your doctor about the potential risks. 
 
Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. Your doctor will talk to you about 
the risks in case of pregnancy and the alternatives you can take to prevent rejection of your transplant 
organ if: 
• You plan to become pregnant. 
• You miss or think you have missed a period, or you have unusual menstrual bleeding, or suspect 

you are pregnant. 
• You have sex without using an effective method of contraception. 
If you do become pregnant during the treatment with mycophenolate, you must inform your doctor 
immediately. However, keep taking Myclausen until you see him or her. 
 
Pregnancy 
Mycophenolate causes a very high frequency of miscarriage (50%) and of severe birth defects (23 - 
27%) in the unborn baby. Birth defects which have been reported include anomalies of ears, of eyes, 
of face (cleft lip/palate), of development of fingers, of heart, oesophagus (tube that connects the throat 
with the stomach), kidneys and nervous system (for example spina bifida (where the bones of the 
spine are not properly developed)).Your baby may be affected by one or more of these. 
 
If you are a woman who could become pregnant, you must provide a negative pregnancy test before 
starting treatment and must follow the contraception advice given to you by your doctor. Your doctor 
may request more than one test to ensure you are not pregnant before starting treatment. 
 
Breast-feeding 
Do not take Myclausen if you are breast-feeding. This is because small amounts of the medicine can 
pass into the mother’s milk. 
 
Driving and using machines 
Myclausen is not likely to affect you being able to drive or use any tools or machines. 
 
Myclausen contains sodium 
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially 



59 

‘sodium-free’ 
 
 
3. How to take Myclausen 
 
Always take Myclausen exactly as your doctor has told you. You should check with your doctor or 
pharmacist if you are not sure. 
 
How much to take 
The amount you take depends on the type of transplant you have had. The usual doses are shown 
below. Treatment will continue for as long as you need to prevent you from rejecting your transplant 
organ. 
 
Kidney transplant 
Adults 
• The first dose will be given within 3 days after the transplant operation. 
• The daily dose is 8 capsules (2 g of the medicine) taken as 2 separate doses. 
• Take 4 capsules in the morning then 4 capsules in the evening. 
 
Children aged 2 to 18 years 
• The dose given will vary depending on the size of the child. 
• Your doctor will decide the most appropriate dose based on your child’s height and weight 

(body surface area - measured as square metres or ‘m2’). The recommended dose is 600 mg per 
m2 taken twice a day. 

 
Heart transplant 
Adults 
• The first dose is given within 5 days of the transplant operation. 
• The daily dose is 12 capsules (3 g of the medicine) taken as 2 separate doses. 
• Take 6 capsules in the morning then 6 capsules in the evening. 
 
Children 
• There is no information for the use of Myclausen in children with a heart transplant. 
 
Liver transplant 
Adults 
• The first dose of oral Myclausen will be given to you at least 4 days after the transplant 

operation and when you are able to swallow oral medications. 
• The daily dose is 12 capsules (3 g of the medicine) taken as 2 separate doses. 
• Take 6 capsules in the morning and then 6 capsules in the evening. 
 
Children 
• There is no information for the use of Myclausen in children with a liver transplant. 
 
How to take Myclausen 
• Swallow your capsules whole with a glass of water. 
• Do not open or crush them. 
• Do not take any capsules that have broken open or split. 
 
Take care not to let any powder from inside a broken capsule get into your eyes or mouth 
• If this happens, rinse with plenty of water. 
 
Take care not to let any powder from inside a broken capsule get onto your skin. 
• If this happens, wash the area thoroughly with soap and water. 
 
If you take more Myclausen than you should 
If you take more Myclausen than you should, talk to a doctor or go to a hospital straight away. Also do 



60 

this if someone else accidentally takes your medicine. Take the medicine pack with you. 
 
If you forget to take Myclausen 
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 Myclausen 
Do not stop taking Myclausen unless your doctor tells you to. If you stop your treatment you may 
increase the chance of rejection of your transplanted organ. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Talk to a doctor straight away if you notice any of the following serious side effects – you 
may need urgent medical treatment: 
• you have a sign of infection such as a fever or sore throat 
• you have any unexpected bruising or bleeding 
• you have a rash, swelling of your face, lips, tongue or throat, with difficulty breathing - you may 

be having a serious allergic reaction to the medicine (such as anaphylaxis, angioeodema). 
 
Usual problems 
Some of the more usual problems are diarrhoea, fewer white cells or red cells in your blood, infection 
and vomiting. Your doctor will do regular blood tests to check for any changes in 
• the number of your blood cells 
• the amount in your blood of things like sugar, fat or cholesterol. 
Children may be more likely than adults to have some side effects. This includes diarrhoea, infections, 
fewer white cells and fewer red cells in the blood. 
 
Fighting infections 
Myclausen reduces your body’s defences. This is to stop you rejecting your transplant. As a result, 
your body will not be as good as normal at fighting infections. This means you may catch more 
infections than usual. This includes infections of the brain, skin, mouth, stomach and gut, lungs and 
urinary system. 
 
Lymph and skin cancer 
As can happen in patients taking this type of medicine (immune-suppressants), a very small number of 
Myclausen patients have developed cancer of the lymphoid tissues and skin. 
 
General unwanted effects 
You may get general side effects affecting your body as a whole. This include serious allergic 
reactions (such as anaphylaxis, angioeodema), fever, feeling very tired, difficulty in sleeping, pains 
(such as stomach, chest, joint or muscle, pain on passing urine), headache, flu symptoms and swelling. 
 
Other unwanted effects may include: 
 
Skin problems such as 
• acne, cold sores, shingles, skin growth, hair loss, rash, itching. 
 
Urinary problems such as: 
• kidney problems or the urgent need to pass water (urine). 
 
Digestive system and mouth problems such as: 
• swelling of the gums and mouth ulcers 



61 

• inflammation of the pancreas, colon or stomach 
• gut problems including bleeding, liver problems 
• constipation, feeling sick (nausea), indigestion, loss of appetite, flatulence. 
 
Nervous system problems such as: 
• feeling dizzy, drowsy or numb 
• tremor, muscle spasms, convulsions 
• feeling anxious or depressed, changes in your mood or thoughts. 
 
Heart and blood vessel problems such as: 
• change in blood pressure, unusual heartbeat, widening of blood vessels. 
 
Lung problems such as: 
• pneumonia, bronchitis 
• shortness of breath, cough, which can be due to bronchiectasis (a condition in which the lung 

airways are abnormally dilated) or pulmonary fibrosis (scarring of the lung). Talk to your doctor 
if you develop a persistent cough or breathlessness 

• fluid on the lungs or inside the chest 
• sinus problems. 
 
Other problems such as: 
• weight loss, gout, high blood sugar, bleeding, bruising. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store Myclausen 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the blister and carton after EXP. The 
expiry date refers to the last day of that month. 
 
Store below 30 °C. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Myclausen contains 
 
The active substance is mycophenolate mofetil. Each capsule contains 250 mg. 
The other ingredients are: 
Capsule content: 
pre-gelatinised starch (maize), croscarmellose sodium, povidone (K-30), magnesium stearate 
 
Capsule shells: 
gelatine, titanium dioxide (E 171) 
 
What Myclausen looks like and contents of the pack 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


62 

White oblong capsules. 
Myclausen 250 mg capsules is available PVC-aluminium blister containing 10 capsules. Each carton 
contains either 100 or 300 capsules. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder 
Passauer Pharma GmbH 
Eiderstedter Weg 3 
14129 Berlin 
Germany 
 
Manufacturer 
Passauer Pharma GmbH 
Eiderstedter Weg 3 
14129 Berlin 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 

België/Belgique/Belgien 
Passauer Pharma GmbH, 
Duitsland/Allemagne/Deutschland 
Tél/Tel: +49(0)3074460-12 

Lietuva 
Passauer Pharma GmbH, 
Vokietija 
Tel: +49(0)3074460-12 

България 
Passauer Pharma GmbH, 
Германия 
Тел: +49(0)3074460-12 

Luxembourg/Luxemburg 
Passauer Pharma GmbH, 
Allemagne/Deutschland 
Tél/Tel: +49(0)3074460-12 

Česká republika 
Pharmagen CZ, s.r.o. 
Česká republika 
Tel: +420 721 137 749 

Magyarország 
Passauer Pharma GmbH, 
Németország 
Tel: +49(0)3074460-12 

Danmark 
Passauer Pharma GmbH, 
Tyskland 
Tlf: +49(0)3074460-12 

Malta 
Passauer Pharma GmbH, 
Il-Ġermanja 
Tel: +49(0)3074460-12 

Deutschland 
Passauer Pharma GmbH, 
Deutschland 
Tel: +49(0)3074460-12 

Nederland 
Passauer Pharma GmbH, 
Duitsland 
Tel: +49(0)3074460-12 

Eesti 
Passauer Pharma GmbH, 
Saksamaa 
Tel: +49(0)3074460-12 

Norge 
Passauer Pharma GmbH, 
Tyskland 
Tlf: +49(0)3074460-12 



63 

Ελλάδα 
YAS Pharma L.P.  
Λεωφ. Κηφισίας 120 & Φλοίας 10 
151 25 Μαρούσι,  
Αθήνα - Ελλάδα  
Τηλ: + 30 210-6194190 

Österreich 
Passauer Pharma GmbH, 
Deutschland 
Tel: +49(0)3074460-12 

España 
Passauer Pharma GmbH, 
Alemania 
Tel: +49(0)3074460-12 

Polska 
Passauer Pharma GmbH, 
Niemcy 
Tel: +49(0)3074460-12 

France 
Passauer Pharma GmbH, 
Allemagne 
Tél: +49(0)3074460-12 

Portugal 
Passauer Pharma GmbH, 
Alemanha 
Tel: +49(0)3074460-12 

Hrvatska 
Passauer Pharma GmbH, 
Njemačka 
Tel: +49(0)3074460-12 

România 
Passauer Pharma GmbH, 
Germania 
Tel: +49(0)3074460-12 

Ireland 
Passauer Pharma GmbH, 
Germany 
Tel: +49(0)3074460-12 

Slovenija 
Passauer Pharma GmbH, 
Nemčija 
Tel: +49(0)3074460-12 

Ísland 
Passauer Pharma GmbH, 
Þýskaland 
Sími: +49(0)3074460-12 

Slovenská republika 
Passauer Pharma GmbH, 
Nemecko 
Tel: +49(0)3074460-12 

Italia 
Passauer Pharma GmbH, 
Germania 
Tel: +49(0)3074460-12 

Suomi/Finland 
Passauer Pharma GmbH, 
Saksa 
Puh/Tel: +49(0)3074460-12 

Κύπρος 
ISANGEN PHARMA CYPRUS LTD 
Guricon House, Ηνωμένων Εθνών 48, 2ος & 
3ος όροφος 
6042, Λάρνακα, Κύπρος 
Τηλ.: +357-24-638833 
 

Sverige 
Passauer Pharma GmbH, 
Tyskland 
Tel: +49(0)3074460-12 

Latvija 
Passauer Pharma GmbH, 
Vācija 
Tel: +49(0)3074460-12 

United Kingdom 
Passauer Pharma GmbH, 
Germany 
Tel: +49(0)3074460-12 

 
This leaflet was last revised in {MM/YYYY} 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 

http://www.ema.europa.eu/


64 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX IV 
SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE 

TERMS OF THE MARKETING AUTHORISATION(S) 
 
 
 
 
 
 



65 

Scientific conclusions 
Taking into account the PRAC Assessment Report on the PSUR(s) for mycophenolate 
mofetil, mycophenolic acid, the scientific conclusions of CHMP are as follows:  
Following a review of all available information regarding pregnancies following paternal 
exposure to mycophenolate mofetil or mycophenolic acid, including a review of all non-
clinical data and information on transmission of mycophenolic acid via the semen, the PRAC 
concluded that the data does not highlight any patterns or an increase in congenital 
malformations or spontaneous abortions. The PRAC therefore recommended to amend the 
product information, to update information on teratogenic effects and pregnancy as well as the 
contraception recommendations for male patients. Additional amendments have been made 
regarding use of contraception in women and pregnancy testing, to clarify the requirements. 
 

The CHMP agrees with the scientific conclusions made by the PRAC. 
 
Grounds for the variation to the terms of the marketing authorisation(s) 
On the basis of the scientific conclusions for mycophenolate mofetil, mycophenolic acid the 
CHMP is of the opinion that the benefit-risk balance of the medicinal product(s) containing 
mycophenolate mofetil, mycophenolic acid is unchanged subject to the proposed changes to 
the product information 
The CHMP recommends that the terms of the marketing authorisation(s) should be varied. 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODU
	A. LABELLING
	B. PACKAGE LEAFLET