CellCept 500mg. 50 capsules
CellCept 500mg. 50 capsules
QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains 500 mg mycophenolate mofetil (mycophenolate mofetil).
For a full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
CellCept capsules: oblong, blue / brown, black "CellCept 500" on the cover
the capsule and the company logo on the body.
4. CLINICAL DATA
4.1 Therapeutic indications
CellCept is indicated in combination with cyclosporin and corticosteroids for the prophylaxis of acute
rejection of tranpslantata in patients receiving allogeneic renal, cardiac or
4.2 Posology and method of administration
CellCept therapy should be initiated and maintained by appropriately
qualification in the field of transplantation.
Use in renal transplantation:
Adults: oral CellCept should be initiated within 72 hours after
transplantation. The recommended dose in renal transplant patients is 1 g,
administered twice daily (2 g daily dose).
Children and adolescents (aged 2 to 18 years): the recommended dose of mycophenolate mofetil
Administered orally twice daily (up to a maximum of 2 g daily). CellCept
capsules should only be prescribed to patients with a body surface area greater than 1,25 m2
Patients with a body surface area of 1.25 to 1,5 m2
may be prescribed CellCept capsules at a dose
750 mg twice daily (1,5 g daily dose). Patients with a body surface area greater than 1,5 m2
may be prescribed CellCept capsules at a dose of 1 g twice daily (2 g daily dose). so
some adverse reactions occurred more frequently in this age group (see section 4.8)
compared with adults, may need temporary dose reduction or interruption of
treatment; these will need to take into account relevant clinical factors
including the severity of the reaction.
Children (<2 years): data on safety and efficacy in children under 2 years
age limited. These are insufficient to make dosage recommendations and therefore
use in this age group is not recommended.
Use in cardiac transplant:
Adults: oral CellCept should be initiated within 5 days after
transplantation. The recommended dose in cardiac transplant patients is 1,5 g,
administered twice daily (3 g daily dose).
Children: no data are available for cardiac transplant in children.
Use in hepatic transplant:
Adults: IV CellCept should be initiated within the first 4 days after
liver transplantation, and oral CellCept should start
as soon as possible after the patient can bear it. The recommended oral
dose in hepatic transplant patients is 1,5 g, administered twice daily (3 g
Children: no data are available for liver transplantation in children.
Use in elderly patients (? 65 years): the recommended dose of 1 g,
administered twice daily in patients with renal transplant and 1,5 g twice daily
in patients with a heart transplant or liver are suitable for the elderly
Use in renal impairment: in renal transplant patients with severe chronic
renal impairment (glomerular filtration rate <25 ml • min-1 • 1,73 m-2), outside the period
immediately after transplantation to avoid doses greater than 1 g, administered
twice daily. These patients should also be carefully monitored. It is not necessary
Dose adjustment in patients with delayed postoperative renal function
graft (see section 5.2). There are no data in patients with heart or liver
transplantation, and severe chronic renal impairment.
Use in severe hepatic impairment: no dose adjustments are needed in
renal transplant patients with severe hepatic parenchymal disease of the liver. no
data in patients with heart transplantation and severe parenchymal liver disease
Treatment during rejection episodes: MPA (mycophenolic acid) is the active
metabolite of mycophenolate mofetil. Renal transplant rejection does not lead to
changes in MPA pharmacokinetics; not require dose reduction or
cessation of CellCept. There is no reason to adjust the dose of CellCept after
cardiac transplant rejection. No pharmacokinetic data in rejecting
Observed hypersensitivity reactions to CellCept (see section 4.8). Therefore
CellCept is contraindicated in patients with hypersensitivity to mycophenolate mofetil
or mycophenolic acid.
CellCept is contraindicated in women who are breastfeeding (see section 4.6).
For information on use in pregnancy and contraceptive requirements see. Section 4.6.
4.4 Special warnings and precautions for use
Patients receiving immunosuppressive regimens involving combinations of medicinal
products including CellCept, are at increased risk of lymphomas and 4
other malignancies, particularly of the skin (see section 4.8). The risk appears to be related
rather the intensity and duration of immunosuppression rather than to use
of a specific product. As general advice to minimize the risk of cancer
skin should limit exposure to sunlight and UV light by wearing
protective clothing and using a sunscreen with a high protection factor.
Patients receiving CellCept, should be instructed to report immediately any
evidence of infection, unexpected bruising, bleeding or any other manifestation of
bone marrow suppression.
Patients treated with immunosuppressants, including CellCept, are at increased risk of
opportunistic infections (bacterial, fungal, viral and protozoal) infections with lethal
output and sepsis (see section 4.8). Such infections are reactivation of latent viral
infections such as hepatitis B or hepatitis C infections caused by polyomaviruses
(nephropathy associated with the BK virus, progressive multifocal leukoencephalopathy (PML)
JC virus associated). Reported cases of hepatitis due to hepatitis B reactivation
and hepatitis C patients, carriers, which are treated with immunosuppressive drugs. these infections
are often associated with 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
Patients receiving CellCept, should be monitored for neutropenia, which
can be related to the actual CellCept, concomitant medications, viral
infections, or a combination of these reasons. Complete blood count of patients treated with
CellCept, should be performed weekly during the first month, twice monthly for the second and
the third month of treatment, then monthly through the first year. If an
neutropenia (absolute neutrophil count <1,3 x 103
/ ?l), you may need to
interrupt or discontinue treatment with CellCept.
Cases of pure red blood cells (PRCA) in patients
treated with CellCept in combination with other immunosuppressants. The mechanism of PRCA
mycophenolate mofetil induced is unknown. PRCA may resolve with reduction
dose or discontinuation of treatment with CellCept. Changes in therapy with CellCept
should only be undertaken under appropriate supervision in transplant recipients
to minimize the risk of graft rejection (see section 4.8).
Patients should be advised that during treatment with CellCept vaccinations may
to be less effective and the use of live attenuated vaccines should be avoided
(see section 4.5). Influenza vaccination may be useful. Prescribers should
refer to national guidelines for influenza vaccination.
Because CellCept has been associated with an increased incidence of adverse events
digestive system, including infrequent cases of ulceration
gastrointestinal tract bleeding and perforation, CellCept should be used with caution
in patients with serious active disease of the digestive system.
CellCept is an inhibitor of IMPDH (inosine monophosphate dehydrogenase). Therefore, the
theoretically, its use should be avoided in patients with rare hereditary
deficiency of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT), Syndrome
of Lesch-Nyhan and Kelley-Seegmiller.
It is recommended that CellCept not be administered concomitantly with azathioprine because
concomitant administration has not been studied.
In view of the significant reduction in the AUC of MPA by cholestyramine, caution should be exercised
the concomitant administration of CellCept with drugs that interfere
enterohepatic recirculation because of the potential to reduce the efficacy of CellCept.
The risk: not established benefit of mycophenolate mofetil in combination with tacrolimus
or sirolimus (see also section 4.5).
4.5 Interaction with other medicinal products and other forms of interaction
Interaction studies have only been performed in adults.
Acyclovir: were observed at higher levels of the plasma concentrations of acyclovir when
mycophenolate mofetil was administered with aciclovir in comparison of single
acyclovir. Changes in the pharmacokinetics of MPA (the phenolic glucuronide of MPA)
(MPAG increased by 8%) were minimal and not considered clinically significant. as
plasma concentrations of MPAG and aciclovir concentrations are increased in
renal impairment, potential exists for mycophenolate mofetil and aciclovir, or its
precursors, e. valaciclovir, to compete for tubular secretion and thus
further to increase the concentrations of both drugs.
Antacids and proton pump inhibitors (PPIs): Decreased exposure
mycophenolic acid (MPA), antacids such as magnesium and aluminum hydroxide, and
PPIs, including lansoprazole and pantoprazole, apply with CellCept. Not observed
significant differences in the comparison of the incidence of graft rejection, or frequency of
graft loss among patients receiving CellCept, taking PPIs and patients on CellCept,
not taking PPIs. These data support the extrapolation of these results on
all antacids as reducing exposure during co-administration of
CellCept with magnesium and aluminum hydroxide is substantially less than the
concomitant administration of CellCept with IPA.
Cholestyramine: following single dose administration of 1,5 g of mycophenolate mofetil to healthy subjects
pre-treated with 4 g cholestyramine, three times daily for 4 days,
reduction in the AUC of MPA by 40% (see section 4.4 and section 5.2). In both
administration should be careful because of the potential to reduce the efficacy of
Medicinal products that interfere with enterohepatic circulation: caution should be exercised when
use of medicinal products that interfere with enterohepatic circulation because
potential to reduce the efficacy of CellCept.
Cyclosporin A: pharmacokinetics of cyclosporin A (CsA) were unaffected by mycophenolate
On the contrary, if discontinued concurrent therapy with cyclosporine, should be expected
increase in MPA AUC of around 30%.
Ganciclovir: based on the results of a study with a single dose
mycophenolate and IV ganciclovir and the known
effects of renal impairment on the pharmacokinetics of CellCept (see section 4.2)
ganciclovir, it is anticipated that co-administration of these agents (which compete
the mechanism of renal tubular secretion) will result in increased concentrations of
MPAG and ganciclovir. No substantial alteration of MPA pharmacokinetics and not
adjustment of the dose of CellCept. In patients with renal impairment where
CellCept and ganciclovir or its prodrugs, eg. valganciclovir apply
simultaneously, you should follow the dosage recommendations of ganciclovir and patients
should be monitored carefully.
Oral contraceptives: the pharmacokinetics and pharmacodynamics of oral
contraceptives were unaffected by coadministration of CellCept (see also section
Rifampicin: Concomitant administration of CellCept and rifampicin resulted in reduced
MPA exposure (AUC0-12h) of 18% to 70% in patients not taking
cyclosporine. It is recommended to monitor the levels of MPA exposure and hence
adjust CellCept doses to maintain clinical efficacy in both
administration of rifampicin.
Sirolimus: in renal transplant patients, concomitant administration of CellCept
and CsA resulted in reduced MPA exposures by 30-50% compared with patients
receiving the combination of sirolimus and similar doses of CellCept (see also section 4.4).
Sevelamer: decrease in Cmax and AUC0-12 of MPA by 30% and 25% in
CellCept was concomitantly administered with sevelamer without any clinical consequences (ie
graft rejection). Is recommended, however, to administer CellCept at least one hour
before or three hours after sevelamer intake to minimize the impact on
absorption of MPA. No data on CellCept with other phosphate binders,
Trimethoprim / sulfamethoxazole: no effect on the bioavailability of MPA.
Norfloxacin and metronidazole: in healthy volunteers, no significant
interaction when CellCept was concomitantly administered with norfloxacin and
metronidazole. But the combination of norfloxacin and metronidazole reduces exposure
IFC by about 30% after a single dose of CellCept.
Ciprofloxacin and amoxycillin plus clavulanic acid: Reductions
lowest concentrations of MPA by 50% in renal transplant recipients in the days
immediately after the commencement of oral ciprofloxacin or amoxicillin plus
clavulanic acid. There is a tendency to reduce this effect in
prolonged use of antibiotics and within a few days after the termination
them. Changes to the lowest level may not accurately represent changes in overall exposure
MPA. Therefore, a change in the dose of CellCept should not normally be necessary for
lack of clinical evidence of graft dysfunction. Must be done, however,
close clinical monitoring during treatment combination and shortly after
Tacrolimus: in hepatic transplant recipients initiated treatment with
CellCept and tacrolimus, AUC and Cmax of MPA, the active metabolite of CellCept, were not
significantly affected by coadministration with tacrolimus. In contrast, there is
an increase of approximately 20% in tacrolimus AUC when multiple doses of
CellCept (1,5 g twice daily) in patients receiving tacrolimus. In patients with renal
Transplantation, however, the concentration of tacrolimus appears to not be altered by CellCept (see
also section 4.4).
Other interactions: co-administration of probenecid with mycophenolate mofetil
in monkeys led to a threefold increase in the plasma AUC of MPAG. Thus
other drugs which are known to undergo renal tubular secretion, can be
compete with MPAG and thereby raise plasma concentrations of MPAG or the other
drugs eliminated by renal tubular secretion.
Live vaccines: live vaccines should not be administered to patients with impaired immune response.
Antibody response to other vaccines may be diminished (see also section 4.4).
4.6 Pregnancy and lactation
It is recommended that CellCept therapy should not be initiated until a negative test
pregnancy. Effective contraception must be used before beginning treatment with
CellCept, during treatment and for six weeks following discontinuation
(see section 4.5). Patients should be instructed to immediately consult
your doctor if pregnancy occurs.
The use of CellCept during pregnancy is not recommended except when there is no
a suitable alternative treatment. CellCept should be used in pregnant women only
if the potential benefit outweighs the potential risk to the fetus. There is limited data
use of CellCept in pregnant women. There are, however, congenital malformations
including ear malformations, ie abnormally formed or absent external / middle
ear, in children of patients that during pregnancy were exposed to CellCept
combination with other immunosuppressants. Cases of miscarriage in patients
exposed to CellCept. Studies in animals have shown reproductive
toxicity (see section 5.3).
It has been shown that mycophenolate mofetil is excreted in the milk of lactating rats. not
known whether the drug is excreted in human milk. Because of the potential
serious adverse reactions in nursing infants from mycophenolate mofetil, the use of
CellCept is contraindicated in nursing mothers (see section 4.3).
4.7 Effects on ability to drive and use machines
No studies on the effects on ability to drive and use machines.
Pharmacodynamic profile and the reported adverse reactions indicate that an effect is