Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/828
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| rdf:type | |
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CellCept (Capsule)
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| dailymed-instance:dosage |
Renal Transplantation:<br/>Adults: A dose of 1 g administered orally or intravenously
(over NO LESS THAN 2 HOURS) twice a day (daily dose of 2 g) is recommended
for use in renal transplant patients. Although a dose of 1.5 g administered
twice daily (daily dose of 3 g) was used in clinical trials and was
shown to be safe and effective, no efficacy advantage could be established
for renal transplant patients. Patients receiving 2 g/day of CellCept
demonstrated an overall better safety profile than did patients receiving
3 g/day of CellCept.<br/>Pediatrics (3 months to 18
years of age): The recommended dose of CellCept oral suspension
is 600 mg/madministered twice daily (up to a maximum
daily dose of 2 g/10 mL oral suspension). Patients with a body surface
area of 1.25 mto 1.5 mmay be dosed with
CellCept capsules at a dose of 750 mg twice daily (1.5 g daily dose).
Patients with a body surface area>1.5 mmay be dosed
with CellCept capsules or tablets at a dose of 1 g twice daily (2
g daily dose).<br/>Cardiac Transplantation:<br/>Adults: A dose of 1.5 g bid administered intravenously (over
NO LESS THAN 2 HOURS) or 1.5 g bid oral (daily dose of 3 g) is recommended
for use in adult cardiac transplant patients.<br/>Hepatic Transplantation:<br/>Adults: A dose of 1 g bid administered intravenously (over
NO LESS THAN 2 HOURS) or 1.5 g bid oral (daily dose of 3 g) is recommended
for use in adult hepatic transplant patients.<br/>CellCept Capsules, Tablets,
and Oral Suspension: The initial oral dose of CellCept should be given
as soon as possible following renal, cardiac or hepatic transplantation.
Food had no effect on MPA AUC, but has been shown to decrease MPA
Cby 40%. Therefore, it is recommended that CellCept
be administered on an empty stomach. However, in stable renal transplant
patients, CellCept may be administered with food if necessary.<br/>Note:: If required, CellCept Oral Suspension can be administered
via a nasogastric tube with a minimum size of 8 French (minimum 1.7
mm interior diameter).<br/>Patients With Hepatic Impairment: No dose adjustments are recommended for renal patients
with severe hepatic parenchymal disease. However, it is not known
whether dose adjustments are needed for hepatic disease with other
etiologies . No data are available for cardiac
transplant patients with severe hepatic parenchymal disease.<br/>Geriatrics: The recommended oral dose of 1 g bid for renal transplant
patients, 1.5 g bid for cardiac transplant patients, and 1 g bid administered
intravenously or 1.5 g bid administered orally in hepatic transplant
patients is appropriate for elderly patients (see PRECAUTIONS:
Geriatric Use).<br/>Preparation of Oral Suspension: It is recommended that CellCept Oral Suspension be
constituted by the pharmacist prior to dispensing to the patient. CellCept Oral Suspension should not be mixed with any
other medication. Mycophenolate mofetil has
demonstrated teratogenic effects in rats and rabbits. There are no
adequate and well-controlled studies in pregnant women (see WARNINGS, PRECAUTIONS, ADVERSE REACTIONS,
and HANDLING AND DISPOSAL). Care should be taken
to avoid inhalation or direct contact with skin or mucous membranes
of the dry powder or the constituted suspension. If such contact occurs,
wash thoroughly with soap and water; rinse eyes with water. Dispense with patient instruction sheet and oral
dispensers. It is recommended to write the date of expiration of the
constituted suspension on the bottle label. (The shelf-life of the
constituted suspension is 60 days.) After constitution
the oral suspension contains 200 mg/mL mycophenolate mofetil. Store
constituted suspension at 25��C (77��F); excursions permitted
to 15��to 30��C (59��to 86��F). Storage in a refrigerator
at 2��to 8��C (36��to 46��F) is acceptable. Do not
freeze. Discard any unused portion 60 days after constitution.<br/>CellCept Intravenous:<br/>Adults: CellCept Intravenous is an alternative dosage form
to CellCept capsules, tablets and oral suspension recommended for
patients unable to take oral CellCept. CellCept Intravenous should
be administered within 24 hours following transplantation. CellCept
Intravenous can be administered for up to 14 days; patients should
be switched to oral CellCept as soon as they can tolerate oral medication. CellCept Intravenous must be reconstituted and diluted
to a concentration of 6 mg/mL using 5% Dextrose Injection USP. CellCept
Intravenous is incompatible with other intravenous infusion solutions.
Following reconstitution, CellCept Intravenous must be administered
by slow intravenous infusion over a period of NO LESS THAN 2 HOURS
by either peripheral or central vein. CAUTION:
CELLCEPT INTRAVENOUS SOLUTION SHOULD NEVER BE ADMINISTERED BY RAPID
OR BOLUS INTRAVENOUS INJECTION .<br/>Preparation of Infusion Solution
(6 mg/mL): Caution should be exercised in the handling and preparation
of solutions of CellCept Intravenous. Avoid direct contact of the
prepared solution of CellCept Intravenous with skin or mucous membranes.
If such contact occurs, wash thoroughly with soap and water; rinse
eyes with plain water . CellCept Intravenous does not contain an
antibacterial preservative; therefore, reconstitution and dilution
of the product must be performed under aseptic conditions. Additionally,
this product is sealed under vacuum and should retain a vacuum throughout
its shelf life. If a lack of vacuum in the vial is noted while adding
diluent, the vial should not be used. CellCept
Intravenous infusion solution must be prepared in two steps: the first
step is a reconstitution step with 5% Dextrose Injection USP, and
the second step is a dilution step with 5% Dextrose Injection USP.
A detailed description of the preparation is given below: Step 1 Step 2 If the infusion solution is not prepared immediately
prior to administration, the commencement of administration of the
infusion solution should be within 4 hours from reconstitution and
dilution of the drug product. Keep solutions at 25��C (77��F);
excursions permitted to 15��to 30��C (59��to 86��F). CellCept Intravenous should not be mixed or administered
concurrently via the same infusion catheter with other intravenous
drugs or infusion admixtures.<br/>Dosage Adjustments: In renal transplant patients with severe chronic
renal impairment (GFR<25 mL/min/1.73 m) outside the
immediate posttransplant period, doses of CellCept greater than 1
g administered twice a day should be avoided. These patients should
also be carefully observed. No dose adjustments are needed in renal
transplant patients experiencing delayed graft function postoperatively
. No data are available for cardiac or hepatic
transplant patients with severe chronic renal impairment. CellCept
may be used for cardiac or hepatic transplant patients with severe
chronic renal impairment if the potential benefits outweigh the potential
risks. If neutropenia develops (ANC<1.3��10/��L), dosing with CellCept should be interrupted
or the dose reduced, appropriate diagnostic tests performed, and the
patient managed appropriately .
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| dailymed-instance:descripti... |
CellCept (mycophenolate mofetil) is the 2-morpholinoethyl
ester of mycophenolic acid (MPA), an immunosuppressive agent; inosine
monophosphate dehydrogenase (IMPDH) inhibitor. The chemical name for mycophenolate mofetil (MMF) is 2-morpholinoethyl
(E)-6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate.
It has an empirical formula of CHNO, a molecular weight of 433.50, and the following structural
formula: Mycophenolate mofetil is a white to
off-white crystalline powder. It is slightly soluble in water (43��g/mL at pH 7.4); the solubility increases in acidic medium (4.27
mg/mL at pH 3.6). It is freely soluble in acetone, soluble in methanol,
and sparingly soluble in ethanol. The apparent partition coefficient
in 1-octanol/water (pH 7.4) buffer solution is 238. The pKa values
for mycophenolate mofetil are 5.6 for the morpholino group and 8.5
for the phenolic group. Mycophenolate mofetil
hydrochloride has a solubility of 65.8 mg/mL in 5% Dextrose Injection
USP (D5W). The pH of the reconstituted solution is 2.4 to 4.1. CellCept is available for oral administration as capsules
containing 250 mg of mycophenolate mofetil, tablets containing 500
mg of mycophenolate mofetil, and as a powder for oral suspension,
which when constituted contains 200 mg/mL mycophenolate mofetil. Inactive ingredients in CellCept 250 mg capsules include
croscarmellose sodium, magnesium stearate, povidone (K-90) and pregelatinized
starch. The capsule shells contain black iron oxide, FD&C blue
#2, gelatin, red iron oxide, silicon dioxide, sodium lauryl sulfate,
titanium dioxide, and yellow iron oxide. Inactive
ingredients in CellCept 500 mg tablets include black iron oxide, croscarmellose
sodium, FD&C blue #2 aluminum lake, hydroxypropyl cellulose, hydroxypropyl
methylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene
glycol 400, povidone (K-90), red iron oxide, talc, and titanium dioxide;
may also contain ammonium hydroxide, ethyl alcohol, methyl alcohol,
n-butyl alcohol, propylene glycol, and shellac. Inactive ingredients in CellCept Oral Suspension include aspartame,
citric acid anhydrous, colloidal silicon dioxide, methylparaben, mixed
fruit flavor, sodium citrate dihydrate, sorbitol, soybean lecithin,
and xanthan gum. CellCept Intravenous is the
hydrochloride salt of mycophenolate mofetil. The chemical name for
the hydrochloride salt of mycophenolate mofetil is 2-morpholinoethyl
(E)-6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate
hydrochloride. It has an empirical formula of CHNOHCl and a molecular weight of 469.96. CellCept Intravenous is available as a sterile white to
off-white lyophilized powder in vials containing mycophenolate mofetil
hydrochloride for administration by intravenous infusion only. Each
vial of CellCept Intravenous contains the equivalent of 500 mg mycophenolate
mofetil as the hydrochloride salt. The inactive ingredients are polysorbate
80, 25 mg, and citric acid, 5 mg. Sodium hydroxide may have been used
in the manufacture of CellCept Intravenous to adjust the pH. Reconstitution
and dilution with 5% Dextrose Injection USP yields a slightly yellow
solution of mycophenolate mofetil, 6 mg/mL. (For detailed method of
preparation, see DOSAGE AND ADMINISTRATION).
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| dailymed-instance:clinicalP... |
Mechanism of Action: Mycophenolate mofetil has been demonstrated in experimental
animal models to prolong the survival of allogeneic transplants (kidney,
heart, liver, intestine, limb, small bowel, pancreatic islets, and
bone marrow). Mycophenolate mofetil has also
been shown to reverse ongoing acute rejection in the canine renal
and rat cardiac allograft models. Mycophenolate mofetil also inhibited
proliferative arteriopathy in experimental models of aortic and cardiac
allografts in rats, as well as in primate cardiac xenografts. Mycophenolate
mofetil was used alone or in combination with other immunosuppressive
agents in these studies. Mycophenolate mofetil has been demonstrated
to inhibit immunologically mediated inflammatory responses in animal
models and to inhibit tumor development and prolong survival in murine
tumor transplant models. Mycophenolate mofetil
is rapidly absorbed following oral administration and hydrolyzed to
form MPA, which is the active metabolite. MPA is a potent, selective,
uncompetitive, and reversible inhibitor of inosine monophosphate dehydrogenase
(IMPDH), 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 utilize salvage pathways,
MPA has potent cytostatic effects on lymphocytes. MPA inhibits proliferative
responses of T- and B-lymphocytes to bothmitogenic and allospecific
stimulation. Addition of guanosine or deoxyguanosine reverses the
cytostatic effects of MPA on lymphocytes. MPA also suppresses antibody
formation by B-lymphocytes. MPA prevents the glycosylation of lymphocyte
and monocyte glycoproteins that are involved in intercellular adhesion
to endothelial cells and may inhibit recruitment of leukocytes into
sites of inflammation and graft rejection. Mycophenolate mofetil did
not inhibit early events in the activation of human peripheral blood
mononuclear cells, such as the production of interleukin-1 (IL-1)
and interleukin-2 (IL-2), but did block the coupling of these events
to DNA synthesis and proliferation.<br/>Pharmacokinetics: Following oral and intravenous administration, mycophenolate
mofetil undergoes rapid and complete metabolism to MPA, the active
metabolite. Oral absorption of the drug is rapid and essentially complete.
MPA is metabolized to form the phenolic glucuronide of MPA (MPAG)
which is not pharmacologically active. The parent drug, mycophenolate
mofetil, can be measured systemically during the intravenous infusion;
however, shortly (about 5 minutes) after the infusion is stopped or
after oral administration, MMF concentration is below the limit of
quantitation (0.4��g/mL).<br/>Absorption: In 12 healthy volunteers, the mean absolute bioavailability
of oral mycophenolate mofetil relative to intravenous mycophenolatemofetil (based on MPA AUC) was 94%. The area under the plasma-concentration
time curve (AUC) for MPA appears to increase in a dose-proportional
fashion in renal transplant patients receiving multiple doses of mycophenolate
mofetil up to a daily dose of 3 g (see Table
1). Food (27 g fat, 650 calories)
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 Cwas decreased by 40% in the
presence of food .<br/>Distribution: The mean (��SD) apparent volume of distribution
of MPA in 12 healthy volunteers is approximately 3.6 (��1.5) and
4.0 (��1.2) L/kg following intravenous and oral administration,
respectively. MPA, at clinically relevant concentrations, is 97% bound
to plasma albumin. MPAG is 82% bound to plasma albumin at MPAG concentration
ranges that are normally seen in stable renal transplant patients;
however, at higher MPAG concentrations (observed in patients with
renal impairment or delayed renal graft function), the binding of
MPA may be reduced as a result of competition between MPAG and MPA
for protein binding. Mean blood to plasma ratioof radioactivity concentrations
was approximately 0.6 indicating that MPA and MPAG do not extensively
distribute into the cellular fractions of blood. In vitro studies to evaluate the effect of other agents on the binding
of MPA to human serum albumin (HSA) or plasma proteins showed that
salicylate (at 25 mg/dL with HSA) and MPAG (at���460��g/mL
with plasma proteins) increased the free fraction of MPA. At concentrations
that exceeded what is encountered clinically, cyclosporine, digoxin,
naproxen, prednisone, propranolol, tacrolimus, theophylline, tolbutamide,
and warfarin did not increase the free fraction of MPA. MPA at concentrations
as high as 100��g/mL had little effect on the binding of warfarin,
digoxin or propranolol, but decreased the binding of theophylline
from 53% to 45% and phenytoin from 90% to 87%.<br/>Metabolism: Following oral and intravenous dosing, mycophenolate
mofetil undergoes complete metabolism to MPA, the active metabolite.
Metabolism to MPA occurs presystemically after oral dosing. MPA is
metabolized principally by glucuronyl transferase to form the phenolic
glucuronide of MPA (MPAG) which is not pharmacologically active. In
vivo, MPAG is converted to MPA via enterohepatic recirculation. The
following metabolites of the 2-hydroxyethyl-morpholino moiety are
also recovered in the urine following oral administration of mycophenolate
mofetil to healthy subjects: N-(2-carboxymethyl)-morpholine, N-(2-hydroxyethyl)-morpholine,
and the N-oxide of N-(2-hydroxyethyl)-morpholine. Secondary peaks in the plasma MPA concentration-time profile are
usually observed 6 to 12 hours postdose. The coadministration of cholestyramine
(4 g tid) resulted in approximately a 40% decrease in the MPA AUC
(largely as a consequence of lower concentrations in the terminal
portion of the profile). These observations suggest that enterohepatic
recirculation contributes to MPA plasma concentrations. Increased plasma concentrations of mycophenolate mofetil
metabolites (MPA 50% increase and MPAG about a 3-fold to 6-fold increase)
are observed in patients with renal insufficiency (see CLINICAL PHARMACOLOGY:
Special Populations).<br/>Excretion: Negligible amount of drug is excreted as MPA (<1%
of dose) in the urine. Orally administered radiolabeled mycophenolate
mofetil resulted in complete recovery of the administered dose, with
93% of the administered dose recovered in the urine and 6% recovered
in feces. Most (about 87%) of the administered dose is excreted in
the urine as MPAG. At clinically encountered concentrations, MPA and
MPAG are usually not removed by hemodialysis. However, at high MPAG
plasma concentrations (>100��g/mL), small amounts of MPAG are
removed. Bile acid sequestrants, such as cholestyramine, reduce MPA
AUC by interfering with enterohepatic circulation of the drug . Mean (��SD) apparent half-life
and plasma clearance of MPA are 17.9 (��6.5) hours and 193 (��48)
mL/min following oral administration and 16.6 (��5.8) hours and
177 (��31) mL/min following intravenous administration, respectively.<br/>Pharmacokinetics in Healthy
Volunteers, Renal, Cardiac, and Hepatic Transplant Patients: Shown below are the mean (��SD) pharmacokinetic
parameters for MPA following the administration of mycophenolate mofetil
given as single doses to healthy volunteers and multiple doses to
renal, cardiac, and hepatic transplant patients. In the early posttransplant
period (<40 days posttransplant), renal, cardiac, and hepatic transplant
patients had mean MPA AUCs approximately 20% to 41% lower and mean
Capproximately 32% to 44% lower compared to the late
transplant period (3 to 6 months posttransplant). Mean MPA AUC values following administration of 1 g bid intravenous
mycophenolate mofetil over 2 hours to renal transplant patients for
5 days were about 24% higher than those observed after oral administration
of a similar dose in the immediate posttransplant phase. In hepatic
transplant patients, administration of 1 g bid intravenous CellCept
followed by1.5 g bid oral CellCept resulted in mean MPA AUC values
similar to those found in renal transplant patients administered 1
g CellCept bid. Two 500 mg tablets have been shown to be bioequivalent
to four 250 mg capsules. Five mL of the 200 mg/mL constituted oral
suspension have been shown to be bioequivalent to four 250 mg capsules.<br/>Special Populations: Shown below are the mean (��SD) pharmacokinetic
parameters for MPA following the administration of oral mycophenolate
mofetil given as single doses to non-transplant subjects with renal
or hepatic impairment.<br/>Renal Insufficiency: In a single-dose study, MMF was administered as capsule
or intravenous infusion over 40 minutes. Plasma MPA AUC observed after
oral dosing to volunteers with severe chronic renal impairment [glomerular
filtration rate (GFR)<25 mL/min/1.73 m] was about
75% higher relative to that observed in healthy volunteers (GFR>80
mL/min/1.73 m). In addition, the single-dose plasma MPAG
AUC was 3-fold to 6-fold higher in volunteers with severe renal impairment
than in volunteers with mild renal impairment or healthy volunteers,
consistent with the known renal elimination of MPAG. No data are available
on the safety of long-term exposure to this level of MPAG. Plasma MPA AUC observed after single-dose (1 g) intravenous
dosing to volunteers (n=4) with severe chronic renal impairment (GFR<25
mL/min/1.73 m) was 62.4��g���h/mL (��19.3).
Multiple dosing of mycophenolate mofetil in patients with severe chronic
renal impairment has not been studied . In patients with delayed renal graft function posttransplant, mean
MPA AUC(0���12h) was comparable to that seen in posttransplant
patients without delayed renal graft function. There is a potential
for a transient increase in the free fraction and concentration of
plasma MPA in patients with delayed renal graft function. However,
dose adjustment does not appear to be necessary in patients with delayed
renal graft function. Mean plasma MPAG AUC(0���12h) was 2-fold
to 3-fold higher than in posttransplant patients without delayed renal
graft function (see PRECAUTIONS: General and DOSAGE
AND ADMINISTRATION). In
8 patients with primary graft non-function following renal transplantation,
plasma concentrations of MPAG accumulated about 6-fold to 8-fold after
multiple dosing for 28 days. Accumulation of MPA was about 1-fold
to 2-fold. The pharmacokinetics of mycophenolate
mofetil are not altered by hemodialysis. Hemodialysis usually does
not remove MPA or MPAG. At high concentrations of MPAG (>100��g/mL),
hemodialysis removes only small amounts of MPAG.<br/>Hepatic Insufficiency: In a single-dose (1 g oral) study of 18 volunteers
with alcoholic cirrhosis and 6 healthy volunteers, hepatic MPA glucuronidation
processes appeared to be relatively unaffected by hepatic parenchymal
disease when pharmacokinetic parameters of healthy volunteers and
alcoholic cirrhosis patients within this study were compared. However,
it should be noted that for unexplained reasons, the healthy volunteers
in this study had about a 50% lower AUC as compared to healthy volunteers
in other studies, thus making comparisons between volunteers with
alcoholic cirrhosis and healthy volunteers difficult. Effects of hepatic
disease on this process probably depend on the particular disease.
Hepatic disease with other etiologies, such as primary biliary cirrhosis,
may show a different effect. In a single-dose (1 g intravenous) study
of 6 volunteers with severe hepatic impairment (aminopyrine breath
test less than 0.2% of dose) due to alcoholic cirrhosis, MMF was
rapidly converted to MPA. MPA AUC was 44.1��g���h/mL (��15.5).<br/>Pediatrics: The pharmacokinetic parameters of MPA and MPAG have
been evaluated in 55 pediatric patients (ranging from 1 year to 18
years of age) receiving CellCept oral suspension at a dose of 600
mg/mbid (up to a maximum of 1 g bid) after allogeneic
renal transplantation. The pharmacokinetic data for MPA is provided
in Table 3: The CellCept oral suspension dose of 600 mg/mbid (up to a maximum of 1 g bid) achieved mean MPA AUC values
in pediatric patients similar to those seen in adult renal transplant
patients receiving CellCept capsules at a dose of 1 g bid in the early
posttransplant period. There was wide variability in the data. As
observed in adults, early posttransplant MPA AUC values were approximately
45% to 53% lower than those observed in the later posttransplant period
(>3 months). MPA AUC values were similar in the early and late posttransplant
period across the 1 year to 18 year age range.<br/>Gender: Data obtained from several studies were pooled to
look at any gender-related differences in the pharmacokinetics of
MPA (data were adjusted to 1 g oral dose). Mean (��SD) MPA AUC(0���12h)
for males (n=79) was 32.0 (��14.5) and for females (n=41) was
36.5 (��18.8)��g���h/mL while mean (��SD) MPA Cwas 9.96 (��6.19) in the males and 10.6 (��5.64)��g/mL in the females. These differences are not of clinical significance.<br/>Geriatrics: Pharmacokinetics in the elderly have not been studied.
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| dailymed-instance:activeIng... | |
| dailymed-instance:contraind... |
Allergic reactions to CellCept have been observed;
therefore, CellCept is contraindicated in patients with a hypersensitivity
to mycophenolate mofetil, mycophenolic acid or any component of the
drug product. CellCept Intravenous is contraindicated in patients
who are allergic to Polysorbate 80 (TWEEN).
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| dailymed-instance:supply |
CellCept (mycophenolate mofetil
capsules) 250 mg: Blue-brown, two-piece hard gelatin capsules, printed
in black with "CellCept 250" on the blue cap and "Roche" on the brown
body. Supplied in the following presentations: NDC Number Size NDC 0004-0259-01 Bottle
of 100 NDC 0004-0259-05 Package
containing 12 bottles of 120 NDC 0004-0259-43 Bottle
of 500 Storage Store at
25��C (77��F); excursions permitted to 15��to 30��C
(59��to 86��F).<br/>CellCept (mycophenolate mofetil
tablets) 500 mg: Lavender-colored, caplet-shaped, film-coated tablets
printed in black with "CellCept 500" on one side and "Roche" on the
other. Supplied in the following presentations: NDC Number Size NDC 0004-0260-01 Bottle
of 100 NDC 0004-0260-43 Bottle
of 500 Storage and Dispensing Information Store at 25��C (77��F); excursions permitted to
15��to 30��C (59��to 86��F). Dispense in light-resistant
containers, such as the manufacturer's original containers.<br/>CellCept Oral Suspension (mycophenolate
mofetil for oral suspension): Supplied as a white to off-white powder blend for
constitution to a white to off-white mixed-fruit flavor suspension.
Supplied in the following presentation: NDC Number Size NDC 0004-0261-29 225
mL bottle with bottle adapter and 2 oral dispensers Storage Store dry powder at 25��C (77��F);
excursions permitted to 15��to 30��C (59��to 86��F).
Store constituted suspension at 25��C (77��F); excursions
permitted to 15��to 30��C (59��to 86��F) for up
to 60 days. Storage in a refrigerator at 2��to 8��C (36��to 46��F) is acceptable. Do not freeze.<br/>CellCept Intravenous (mycophenolate
mofetil hydrochloride for injection): Supplied in a 20 mL, sterile vial containing the
equivalent of 500 mg mycophenolate mofetil as the hydrochloride salt
in cartons of 4 vials: NDC Number NDC
0004-0298-09 Storage Store
powder and reconstituted/infusion solutions at 25��C (77��F);
excursions permitted to 15��to 30��C (59��to 86��F).
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| dailymed-instance:genericDr... | |
| dailymed-instance:boxedWarn... |
WARNING: Immunosuppression may lead
to increased susceptibility to infection and possible development
of lymphoma. Only physicians experienced in immunosuppressive therapy
and management of renal, cardiac or hepatic transplant patients should
use CellCept. Patients receiving the drug should be managed in facilities
equipped and staffed with adequate laboratory and supportive medical
resources. The physician responsible for maintenance therapy should
have complete information requisite for the follow-up of the patient. Female users of
childbearing potential must use contraception. Use of CellCept during
pregnancy is associated with increased risk of pregnancy loss and
congenital malformations.
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| dailymed-instance:activeMoi... | |
| dailymed-instance:inactiveI... |
dailymed-ingredient:FD&C_blue_#2,
dailymed-ingredient:black_iron_oxide,
dailymed-ingredient:croscarmellose_sodium,
dailymed-ingredient:gelatin,
dailymed-ingredient:magnesium_stearate,
dailymed-ingredient:povidone_(K-90),
dailymed-ingredient:pregelatinized_starch,
dailymed-ingredient:red_iron_oxide,
dailymed-ingredient:silicon_dioxide,
dailymed-ingredient:sodium_lauryl_sulfate,
dailymed-ingredient:titanium_dioxide,
dailymed-ingredient:yellow_iron_oxide
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| dailymed-instance:possibleD... | |
| dailymed-instance:genericMe... |
Mycophenolate mofetil
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| dailymed-instance:fullName |
CellCept (Capsule)
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| dailymed-instance:adverseRe... |
The principal adverse reactions associated with the
administration of CellCept include diarrhea, leukopenia, sepsis, vomiting,
and there is evidence of a higher frequency of certain types of infections
eg, opportunistic infection (see WARNINGS: Infections and WARNINGS: Progressive Multifocal
Leukoencephalopathy (PML)). The adverse event
profile associated with the administration of CellCept Intravenous
has been shown to be similar to that observed after administration
oforal dosage forms of CellCept.<br/>CellCept Oral: The incidence of adverse events for CellCept was
determined in randomized, comparative, double-blind trials in prevention
of rejection in renal (2 active, 1 placebo-controlled trials), cardiac
(1 active-controlled trial), and hepatic (1 active-controlled trial)
transplant patients.<br/>Geriatrics: Elderly patients (���65 years), particularly
those who are receiving CellCept as part of a combination immunosuppressive
regimen, may be at increased risk of certain infections (including
cytomegalovirus [CMV] tissue invasive disease) and possibly gastrointestinal
hemorrhage and pulmonary edema, compared to younger individuals . Safety data are summarized below
for all active-controlled trials in renal (2 trials), cardiac (1 trial),
and hepatic (1 trial) transplant patients. Approximately 53% of the
renal patients, 65% of the cardiac patients, and 48% of the hepatic
patients have been treated for more than 1 year. Adverse events reported
in���20% of patients in the CellCept treatment groups are presented
below. The placebo-controlled renal transplant study generally
showed fewer adverse events occurring in���20% of patients.
In addition, those that occurred were not only qualitatively similar
to the azathioprine-controlled renal transplant studies, but also
occurred at lower rates, particularly for infection, leukopenia, hypertension,
diarrhea and respiratory infection. The above
data demonstrate that in three controlled trials for prevention of
renal rejection, patients receiving 2 g/day of CellCept had an overall
better safety profile than did patients receiving 3 g/day of CellCept. The above data demonstrate that the types of adverse events
observed in multicenter controlled trials in renal, cardiac, and hepatic
transplant patients are qualitatively similar except for those that
are unique to the specific organ involved. Sepsis,
which was generally CMV viremia, was slightly more common in renal
transplant patients treated with CellCept compared to patients treated
with azathioprine. The incidence of sepsis was comparable in CellCept
and in azathioprine-treated patients in cardiac and hepatic studies. In the digestive system, diarrhea was increased in renal
and cardiac transplant patients receiving CellCept compared to patients
receiving azathioprine, but was comparable in hepatic transplant patients
treated with CellCept or azathioprine. Patients
receiving CellCept alone or as part of an immunosuppressive regimen
are at increased risk of developing lymphomas and other malignancies,
particularly of the skin . The incidence of malignancies among the 1483 patients
treated in controlled trials for the prevention of renal allograft
rejection who were followed for���1 year was similar to the
incidence reported in the literature for renal allograft recipients. Lymphoproliferative disease or lymphoma developed in 0.4%
to 1% of patients receiving CellCept (2 g or 3 g daily) with other
immunosuppressive agents in controlled clinical trials of renal, cardiac,
and hepatic transplant patients followed for at least 1 year (see WARNINGS: Lymphoma
and Malignancy). Non-melanoma skin carcinomas
occurred in 1.6% to 4.2% of patients, other types of malignancy in
0.7% to 2.1% 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. In
pediatric patients, no other malignancies besides lymphoproliferative
disorder (2/148 patients) have been observed. Severe neutropenia (ANC<0.5��10/��L) developed
in up to 2.0% of renal transplant patients, up to 2.8% of cardiac
transplant patients and up to 3.6% of hepatic transplant patients
receiving CellCept 3 g daily (see WARNINGS: Neutropenia, PRECAUTIONS:
Laboratory Tests and DOSAGE AND ADMINISTRATION). All transplant patients are at
increased risk of opportunistic infections. The risk increases with
total immunosuppressive load (see WARNINGS: Infections and WARNINGS: Progressive Multifocal
Leukoencephalopathy (PML)). Table 9 shows the incidence of opportunistic
infections that occurred in the renal, cardiac, and hepatic transplant
populations in the azathioprine-controlled prevention trials: The following other opportunistic infections occurred
with an incidence of less than 4% in CellCept patients in the above
azathioprine-controlled studies: Herpes zoster, visceral disease;
Candida, urinary tract infection, fungemia/disseminated disease, tissue
invasive disease; Cryptococcosis; Aspergillus/Mucor; Pneumocystis
carinii. In the placebo-controlled renal transplant
study, the same pattern of opportunistic infection was observed compared
to the azathioprine-controlled renal studies, with a notably lower
incidence of the following: Herpes simplex and CMV tissue-invasive
disease. In patients receiving CellCept (2 g
or 3 g) in controlled studies for prevention of renal, cardiac or
hepatic rejection, fatal infection/sepsis occurred in approximately
2% of renal and cardiac patients and in 5% of hepatic patients . In cardiac transplant patients,
the overall incidence of opportunistic infections was approximately
10% higher in patients treated with CellCept than in those receiving
azathioprine, but this difference was not associated with excess mortality
due to infection/sepsis among patients treated with CellCept. The following adverse events were reported with 3% to<20% incidence in renal, cardiac, and hepatic transplant patients
treated with CellCept, in combination with cyclosporine and corticosteroids.<br/>Pediatrics: The type and frequency of adverse events in a clinical
study in 100 pediatric patients 3 months to 18 years of age dosed
with CellCept oral suspension 600 mg/mbid (up to 1 g
bid) were generally similar to those observed in adult patients dosed
with CellCept capsules at a dose of 1 g bid with the exception of
abdominal pain, fever, infection, pain, sepsis, diarrhea, vomiting,
pharyngitis, respiratory tract infection, hypertension, leukopenia,
and anemia, which were observed in a higher proportion in pediatric
patients.<br/>CellCept Intravenous: The adverse event profile of CellCept Intravenous
was determined from a single, double-blind, controlled comparative
study of the safety of 2 g/day of intravenous and oral CellCept in
renal transplant patients in the immediate posttransplant period (administered
for the first 5 days). The potential venous irritation of CellCept
Intravenous was evaluated by comparing the adverse events attributable
to peripheral venous infusion of CellCept Intravenous with those observed
in the intravenous placebo group; patients in this group received
active medication by the oral route. Adverse
events attributable to peripheral venous infusion were phlebitis and
thrombosis, both observed at 4% in patients treated with CellCept
Intravenous. In the active controlled study
in hepatic transplant patients, 2 g/day of CellCept Intravenous were
administered in the immediate posttransplant period (up to 14 days).
The safety profile of intravenous CellCept was similar to that of
intravenous azathioprine.<br/>Postmarketing Experience:<br/>Congenital Disorders:: Congenital malformations including ear malformations
have been reported in offspring of patients exposed to mycophenolate
mofetil during pregnancy .<br/>Digestive:: Colitis (sometimes caused by cytomegalovirus), pancreatitis,
isolated cases of intestinal villous atrophy.<br/>Resistance Mechanism Disorders:: Serious life-threatening infections such as meningitis
and infectious endocarditis have been reported occasionally and there
is evidence of a higher frequency of certain types of serious infections
such as tuberculosis and atypical mycobacterial infection. Cases of
progressive multifocal leukoencephalopathy (PML), sometimes fatal,
have been reported in patients treated with CellCept. The reported
cases generally had risk factors for PML, including treatment with
immunosuppressant therapies and impairment of immune function.<br/>Respiratory:: Interstitial lung disorders, including fatal pulmonary
fibrosis, have been reported rarely and should be considered in the
differential diagnosis of pulmonary symptoms ranging from dyspnea
to respiratory failure in posttransplant patients receiving CellCept.
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Renal, Cardiac, and Hepatic
Transplant: CellCept is indicated for the prophylaxis of organ
rejection in patients receiving allogeneic renal, cardiac or hepatic
transplants. CellCept should be used concomitantly with cyclosporine
and corticosteroids. CellCept Intravenous is
an alternative dosage form to CellCept capsules, tablets and oral
suspension. CellCept Intravenous should be administered within 24
hours following transplantation. CellCept Intravenous can be administered
for up to 14 days; patients should be switched to oral CellCept as
soon as they can tolerate oral medication.
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CellCept
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