| Cellcept |
 |
| |
SIDE EFFECTS
The principal adverse reactions associated with the administration
of CellCept include diarrhea, leukopenia, sepsis and vomiting,
and there is evidence of a higher frequency of certain types
of infections. The adverse event profile associated with
the administration of CellCept Intravenous has been shown
to be similar to that observed after administration of oral
dosage forms of CellCept.
CellCept (oral)
The incidence of adverse events for CellCept was determined
in three randomized, comparative, double-blind trials in
prevention of rejection in renal transplant patients, and
in one randomized, comparative, double-blind trial in cardiac
transplant patients.
Elderly patients, particularly those who are receiving CellCept
as part of a combination immunosuppressive regimen, may
be at increased risk of certain infections (including CMV
tissue invasive disease) and possibly gastrointestinal hemorrhage
and pulmonary edema, compared to younger individuals (see
PRECAUTIONS).
Safety data are summarized below for all renal transplant
patients in the double-blind prevention studies; approximately
53% of these patients have been treated for more than 1
year. Adverse events that were reported in ³10% of
patients in either CellCept treatment group are presented
below for the two active-controlled studies combined (USA
and Europe/Canada/Australia) and for the one European placebo-controlled
study. Because of the lower overall reporting of events
in the European placebo-controlled study, these data were
not combined with the other two active-controlled prevention
trials, but are instead presented separately.
| Adverse
Events in Controlled Studies in Prevention of Renal
Allograft Rejection |
| |
USA Study Combined with Europe/ Canada/ Australia
Study |
CellCept
2 g/day
(n= 336)
% |
CellCept
3 g/day
(n= 330)
% |
Azathioprine
1 to 2 mg/ kg/ day or
100 to 150 mg/ day
(n= 326)
% |
| Body as a Whole |
| Pain |
33.0 |
31.2 |
32.2 |
| Abdominal pain |
24.7 |
27.6 |
23.0 |
| Fever |
21.4 |
23.3 |
23.3 |
| Headache |
21.1 |
16.1 |
21.2 |
| Infection |
18.2 |
20.9 |
19.9 |
| Sepsis |
17.6 |
19.7 |
15.6 |
| Asthenia |
13.7 |
16.1 |
19.9 |
| Chest pain |
13.4 |
13.3 |
14.7 |
| Back pain |
11.6 |
12.1 |
14.1 |
|
Hemic and Lymphatic |
| Anemia |
25.6 |
25.8 |
23.6 |
| Leukopenia |
23.2 |
34.5 |
24.8 |
| Thrombocytopenia |
10.1 |
8.2 |
13.2 |
| Hypochromic anemia |
7.4 |
11.5 |
9.2 |
| Leukocytosis |
7.
1 |
10.9 |
7.4 |
|
Urogenital |
| Urinary tract infection |
37.
2 |
37.
0 |
33.
7 |
| Hematuria |
14.0 |
12.1 |
11.3 |
| Kidney tubular necrosis |
6.3 |
10.0 |
5.
8 |
|
Cardiovascular |
| Hypertension |
32.4 |
28.2 |
32.2 |
|
Metabolic and Nutritional |
| Peripheral edema |
28.6 |
27.0 |
28.2 |
| Hypercholesteremia |
12.8 |
8.
5 |
11.3 |
| Hypophosphatemia |
12.5 |
15.8 |
11.7 |
| Edema |
12.2 |
11.8 |
13.5 |
| Hypokalemia |
10.1 |
10.0 |
8.
3 |
| Hyperkalemia |
8.9 |
10.3 |
16.9 |
| Hyperglycemia |
8.6 |
12.4 |
15.0 |
|
Digestive |
| Diarrhea |
31.0 |
36.1 |
20.9 |
| Constipation |
22.9 |
18.5 |
22.4 |
| Nausea |
19.9 |
23.6 |
24.5 |
| Dyspepsia |
17.6 |
13.6 |
13.8 |
| Vomiting |
12.
5 |
13.
6 |
9.
2 |
| Nausea and vomiting |
10.
4 |
9.
7 |
10.
7 |
| Oral moniliasis |
10.
1 |
12.
1 |
11.
3 |
|
Respiratory |
| Infection |
22.0 |
23.9 |
19.6 |
| Dyspnea |
15.5 |
17.3 |
16.6 |
| Cough increased |
15.
5 |
13.
3 |
15.
0 |
| Pharyngitis |
9.
5 |
11.
2 |
8.
0 |
|
Skin and Appendages |
| Acne |
10.1 |
9.
7 |
6.4 |
| Rash |
7.7 |
6.
4 |
10.4 |
|
Nervous System |
| Tremor |
11.0 |
11.8 |
12.3 |
| Insomnia |
8.9 |
11.8 |
10.4 |
| Dizziness |
5.7 |
11.2 |
11.0 |
| |
Europe Study |
CellCept
2 g/day
(n= 165)
% |
CellCept
3 g/day
(n= 160)
% |
Placebo
(n= 166)
% |
| Body
as a Whole |
| Sepsis |
21.8 |
17.5 |
13.9 |
| Infection |
12.7 |
15.6 |
13.3 |
| Abdominal pain |
12.1 |
11.9 |
11.4 |
|
Hemic and Lymphatic |
| Leukopenia |
11.5 |
16.3 |
4.
2 |
|
Urogenital |
| Urinary tract infection |
45.
5 |
44.
4 |
37.
3 |
| Urinary tract disorder |
6.7 |
10.6 |
4.
2 |
|
Cardiovascular |
| Hypertension |
17.6 |
16.9 |
19.3 |
|
Digestive |
| Diarrhea |
16.4 |
18.8 |
13.9 |
|
Respiratory |
| Infection |
15.8 |
13.1 |
9. 0 |
| Bronchitis |
8.5 |
11. 9 |
8. 4 |
| Pneumonia |
3. 6 |
10.6 |
10.8 |
In the randomized, double-blind, comparative trial in cardiac
transplant recipients, approximately 65% of patients have
been treated for more than 1 year. Adverse events reported
in ³ 10% of patients in the group treated with CellCept
are provided below
| Adverse Events
in the Controlled Studies in Prevention of Cardiac
Allograft Rejection |
| |
CellCept
3 g/day
(n= 289)
% |
Azathioprine
1.5 to 3 mg/kg/day
(n= 289)
% |
| Body as a Whole |
| Pain |
75.8 |
74.7 |
| Abdominal
pain |
33.9 |
33.2 |
| Fever |
47.4 |
46.4 |
| Headache |
54.3 |
51.9 |
| Infection |
25.6 |
19.4 |
| Sepsis |
18.7 |
18.7 |
| Asthenia |
43.3 |
36.3 |
| Chest
pain |
26.3 |
26.0 |
| Back
pain |
34.6 |
28.4 |
| Accidental
injury |
19.0 |
14.9 |
| Chills |
11.4 |
11.4 |
|
Hemic and Lymphatic |
| Anemia |
42.9 |
43.9 |
| Leukopenia |
30.4 |
39.1 |
| Thrombocytopenia |
23.5 |
27.0 |
| Hypochromic
anemia |
24.6 |
23.5 |
| Leukocytosis |
40.5 |
35.6 |
| Ecchymosis |
16.6 |
8.0 |
|
Urogenital |
| Urinary
tract infection |
13.1 |
11.8 |
| Kidney
function abnormal |
21.8 |
26.3 |
| Oliguria |
14.2 |
12.8 |
|
Cardiovascular |
| Hypertension |
77.5 |
72.3 |
| Hypotension |
32.5 |
36.0 |
| Cardiovascular
disorder |
25.6 |
24.2 |
| Tachycardia |
20.1 |
18.0 |
| Arrhythmia |
19.0 |
18.7 |
| Bradycardia |
17.3 |
17.3 |
| Pericardial
effusion |
15.9 |
13.5 |
| Heart
failure |
11.8 |
8.7 |
|
Metabolic and Nutritional |
| Peripheral
edema |
64.0 |
53.3 |
| Hypercholesteremia |
41.2 |
38.4 |
| Edema |
26.6 |
25.6 |
| Hypokalemia |
31.8 |
25.6 |
| Hyperkalemia |
14.5 |
19.7 |
| Hyperglycemia |
46.7 |
52.6 |
| Creatinine
increased |
39.4 |
36.0 |
| BUN increased |
34.6 |
32.5 |
| Lactic
dehydrogenase increased |
23.2 |
17.0 |
| Bilirubinemia |
18.0 |
21.8 |
| Hypervolemia |
16.6 |
22.8 |
| Generalized
edema |
18.0 |
20.1 |
| Hyperuricemia |
16.3 |
17.6 |
| SGOT
increased |
17.3 |
15.6 |
| Hypomagnesemia |
18.3 |
12.8 |
| Acidosis |
14.2 |
16.6 |
| Weight
gain |
15.6 |
15.2 |
| SGPT
increased |
15.6 |
12.5 |
| Hyponatremia |
11.4 |
11.8 |
| Hyperlipemia |
10.7 |
9.3 |
|
Digestive |
| Diarrhea |
45.3 |
34.3 |
| Constipation |
41.2 |
37.7 |
| Nausea |
54.0 |
54.3 |
| Dyspepsia |
18.7 |
19.4 |
| Vomiting |
33.9 |
28.4 |
| Nausea
and vomiting |
11.1 |
7.6 |
| Oral
moniliasis |
11.4 |
11.8 |
| Flatulence |
13.8 |
15.6 |
|
Respiratory |
| Infection |
37.0 |
35.3 |
| Dyspnea |
36.7 |
36.3 |
| Cough
increased |
31.1 |
25.6 |
| Pharyngitis |
18.3 |
13.5 |
| Lung
disorder |
30.1 |
29.1 |
| Sinusitis |
26.0 |
19.0 |
| Rhinitis |
19.0 |
15.6 |
| Pleural
effusion |
17.0 |
13.8 |
| Asthma |
11.1 |
11.4 |
| Pneumonia |
10.7 |
10.4 |
|
Skin and Appendages |
| Acne |
12.1 |
9. 3 |
| Rash |
22.1 |
18.0 |
| Skin
disorder |
12.5 |
8. 7 |
|
Nervous System |
| Tremor |
24.2 |
23.9 |
| Insomnia |
40.8 |
37.7 |
| Dizziness |
28.7 |
27.7 |
| Anxiety |
28.4 |
23.9 |
| Paresthesia |
20.8 |
18.0 |
| Hypertonia |
15.6 |
14.5 |
| Depression |
15.6 |
12.5 |
| Agitation |
13.1 |
12.8 |
| Somnolence |
11.1 |
10.4 |
| Confusion |
13.5 |
7.6 |
| Nervousness |
11.4 |
9.0 |
|
Musculoskeletal System |
| Leg Cramps |
16.6 |
15.6 |
| Myasthenia |
12.5 |
9.7 |
| Myalgia |
12.5 |
9.3 |
|
Special Senses |
| Amblyopia |
14.9 |
6.6 |
| Endocrine System |
12.1 |
12.8 |
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. Sepsis, which
was generally CMV viremia, was slightly more common in those
renal patients treated with CellCept, with an incidence
of 18% to 22%, compared to 16% in patients receiving azathioprine
and 14% in patients receiving placebo. In the controlled
cardiac transplant study, there was no difference in the
incidence of sepsis (18.7%) between patients treated with
CellCept and control patients. In the digestive system,
diarrhea was increased in renal and cardiac patients receiving
CellCept, with an incidence of up to 36%, compared to 21%
for patients receiving azathioprine and 14% for patients
receiving placebo in the renal transplant studies. In the
controlled cardiac transplant study, an incidence of diarrhea
up to 45.3% in the patients treated with CellCept was reported
compared to 34.3% for patients receiving azathioprine. The
types of adverse events in the cardiac transplant patients
studied in the multicenter controlled trial were qualitatively
similar to those observed in renal transplant patients.
The incidence of malignancies among the 1483 patients treated
in controlled trials for the prevention of renal allograft
rejection who were followed for ³1 year was similar
to the incidence reported in the literature for renal allograft
recipients. Lymphoproliferative disease or lymphoma developed
in approximately 1% of patients receiving CellCept (2 g
or 3 g) with other immunosuppressive agents in controlled
clinical trials of renal and cardiac transplant patients
(see WARNINGS).
The following table summarizes the incidence of malignancies
observed in the controlled renal and cardiac trials.
| Malignancies
Observed in Renal and Cardiac Transplant Trials |
| |
Renal
Trials |
Cardiac
Trial |
| |
CellCept
2 g/day |
CellCept
3 g/day |
Placebo |
Azathioprine
1 to 2
mg/kg/day or
100 to 150
mg/day |
CellCept
3 g/day |
Azathioprine
1.5 to 3
mg/kg/day |
| |
(n= 501) |
(n= 490) |
(n= 166) |
(n= 326) |
(n= 289) |
(n= 289) |
Lymphoma/
lymphoproliferative
disease |
0.6% |
1.0% |
0.0% |
0.3% |
0.7% |
2.1% |
Non- melanoma skin
carcinoma |
4.0% |
1.6% |
0.0% |
2.4% |
4.2% |
2.8% |
| Other malignancy |
0.8% |
1.4% |
1.8% |
1.8% |
2.1% |
2.1% |
Up to 2.0% of patients receiving CellCept 3 g daily for
prevention of renal rejection developed severe neutropenia
[absolute neutrophil count (ANC) <0.5 × 10³/µL].
Up to 2.8% of cardiac transplant patients receiving CellCept
3 g daily developed severe neutropenia (see WARNINGS , PRECAUTIONS
: Laboratory Tests and DOSAGE AND ADMINISTRATION).
The following tables show the incidence of opportunistic
infections that occurred in the renal and cardiac transplant
populations in the controlled prevention trials:
| Opportunistic
Infections in Prevention of Renal Rejection Trials |
| |
USA
Study Combined with
Europe/ Canada/ Australia Study |
CellCept
2 g/day |
CellCept
3 g/day |
Azathioprine
1 to 2 mg/kg/day or
100 to 150 mg/day |
(n=
336)
% |
(n=
330)
% |
(n= 326)
% |
| Herpes
simplex |
16.7 |
20.0 |
19.0 |
CMV
viremia/syndrome |
13.4 |
12.4 |
13.8 |
| tissue
invasive disease |
8.3 |
11.5 |
6.1 |
| Herpes
zoster |
6.0 |
7.6 |
5.8 |
Candida
fungemia/disseminated |
0.6 |
0.6 |
0.3 |
| tissue
invasive disease |
0.6 |
0.6 |
0.3 |
| Aspergillus/Mucor
invasive disease |
0.3 |
0.9 |
0.3 |
| Pneumocystis
carinii |
0.3 |
0.0 |
1.2 |
| |
Europe
Study |
CellCept
2 g/day |
CellCept
3 g/day |
Placebo |
(n=
165)
% |
(n= 160)
% |
(n= 166)
% |
| Herpes
simplex |
15.2 |
12.5 |
6.0 |
CMV
viremia/syndrome |
15.2 |
15.0 |
13.3 |
| tissue
invasive disease |
3.6 |
7.5 |
2.4 |
| Herpes
zoster |
6.7 |
6.9 |
2.4 |
Candida
fungemia/disseminated |
0.0 |
0.6 |
0.0 |
| tissue
invasive disease |
0.0 |
0.6 |
0.0 |
| Pneumocystis
carinii |
0.0 |
0.0 |
2.4 |
| Opportunistic
Infections in Prevention of Cardiac Rejection Trial
|
| |
CellCept
3 g/ day
(n=289)
% |
Azathioprine
1.5 to 3 mg/ kg/ day
(n= 289)
% |
| Herpes
simplex |
20.8 |
14.5 |
| CMV
|
|
|
| viremia/
syndrome |
12.1 |
10.0 |
| tissue
invasive disease |
11.4 |
8.7 |
| CMV infection
|
2.8
|
2.8 |
|
CMV urine |
2.4 |
2.8 |
| CMV nasal
secretions |
0.3 |
0.0 |
|
CMV saliva |
0.3 |
0.0 |
| Herpes
zoster |
10.7
|
5.9 |
| Herpes
zoster cutaneous disease |
10.0 |
5.5
|
|
Herpes zoster visceral disease |
0.7 |
0.3 |
| Candida
|
18.7
|
17.6
|
| mucocutaneous
|
18.0
|
17.3
|
|
urnary tract infection |
0.7
|
1.0
|
| fungemia/
disseminated disease |
0.7
|
0.3
|
| invasive tissue disease |
0.0 |
0.3 |
| Cryptococcosis |
0.7 |
0.3 |
| Aspergillus/ Mucor |
2.1 |
2.1 |
| Aspergillus pulmonary or
sinus invasive |
0.7 |
1.4 |
| Aspergillus disseminated
or metastatic |
0.3 |
1.0 |
| cutaneous |
0.7 |
0.0 |
| Aspergillus sputum |
0.3 |
0.3 |
| Pneumocystis carinii |
0.0 |
1.7 |
| Listeriosis
|
0.0 |
0.7 |
In controlled studies for prevention of renal or cardiac
rejection, similar rates of fatal infection/sepsis (<2%)
occurred in patients receiving CellCept (2 g or 3 g) (see
WARNINGS). 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, not mentioned in any of the
tables above, were reported with ³3% incidence in both
renal and cardiac transplant patients treated with CellCept,
in combination with cyclosporine and corticosteroids.
Body as a Whole: abdomen
enlarged, chills occurring with fever, cyst, face edema,
flu syndrome, hemorrhage, pelvic pain, malaise
Urogenital: dysuria, impotence,
urinary frequency
Cardiovascular:
angina pectoris, atrial fibrillation, palpitation, peripheral
vascular disorder, postural hypotension
Metabolic
and Nutritional: alkaline phosphatase increased,
dehydration, hypervolemia, hypocalcemia, hypoglycemia, hypoproteinemia
Digestive: anorexia, esophagitis,
gastritis, gastroenteritis, gingivitis, gum hyperplasia,
infection, liver function tests abnormal, rectal disorder
Respiratory: lung edema
Skin and Appendages: fungal
dermatitis, pruritus, skin benign neoplasm, skin hypertrophy,
skin ulcer, sweating
Endocrine:
diabetes mellitus
Musculoskeletal:
arthralgia, joint disorder
Special
Senses: conjunctivitis
The following adverse events, not mentioned in any of the
tables above were reported with ³3% incidence in renal
transplant patients only treated with CellCept, in combination
with other immunosuppressive agents:
Body
as a Whole: accidental injury, hernia
Hemic and Lymphatic: ecchymosis,
polycythemia
Urogenital: albuminuria,
hydronephrosis, pain, pyelonephritis, urinary tract disorder
Cardiovascular: cardiovascular
disorder, hypotension, tachycardia, thrombosis, vasodilatation
Metabolic and Nutritional: acidosis,
creatinine increased, gamma glutamyl transpeptidase increased,
hypercalcemia, hyperlipemia, hyperuricemia, lactic dehydrogenase
increased, SGOT increased, SGPT increased, weight gain
Digestive: flatulence, gastrointestinal
hemorrhage, gastrointestinal moniliasis, hepatitis, ileus,
mouth ulceration
Respiratory:
asthma, lung disorder, pleural effusion, rhinitis, sinusitis
Skin and Appendages: alopecia,
hirsutism, rash, skin disorder
Nervous: anxiety, depression,
hypertonia, paresthesia, somnolence
Endocrine: parathyroid disorder
Musculoskeletal: leg cramps, myalgia,
myasthenia
Special Senses: amblyopia, cataract
(not specified)
The following adverse events, not mentioned in any of the
tables above, were reported with ³3% incidence in cardiac
transplant patients treated with CellCept, in combination
with other immunosuppressive agents:
Body as a Whole: neck pain, cellulitis
Hemic and Lymphatic: prothrombin
increased, thromboplastin decreased, petechia
Urogenital: nocturia, kidney failure,
urine abnormality, hematuria, urinary incontinence, prostatic
disorder, urinary retention
Cardiovascular: ventricular extrasystole,
congestive heart failure, supraventricular tachycardia,
ventricular tachycardia, atrial flutter, pulmonary hypertension,
heart arrest, venous pressure increased, syncope, supraventricular
extrasystoles, extrasystoles, pallor, vasospasm
Metabolic and Nutritional: hypoxia,
hypophosphatemia, gout, abnormal healing, alkalosis, weight
loss, hypochloremia, thirst, respiratory acidosis
Digestive: gastrointestinal disorder,
melena, liver damage, dysphagia, jaundice, stomatitis
Respiratory: atelectasis, hiccup,
pneumothorax, sputum increased, respiratory disorder, epistaxis,
apnea, voice alteration, pain, hemoptysis, neoplasm
Skin and Appendages: hemorrhage,
skin carcinoma
Nervous: emotional lability, neuropathy,
convulsion, hallucinations, thinking abnormal, vertigo
Endocrine: Cushing's syndrome,
hypothyroidism
Special Senses: ear pain, deafness,
ear disorder, tinnitus, abnormal vision, lacrimation disorder,
eye hemorrhage
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 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 IV 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.
Postmarketing Experience
Digestive: colitis (sometimes
caused by cytomegalovirus), pancreatitis
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.
DRUG INTERACTIONS
Drug interaction studies with mycophenolate mofetil have
been conducted with acyclovir, antacids, cholestyramine,
cyclosporine, ganciclovir, oral contraceptives, and trimethoprim/sulfamethoxazole.
Drug interaction studies have not been conducted with other
drugs that may be commonly administered to renal or cardiac
transplant patients. CellCept has not been administered
concomitantly with azathioprine.
Acyclovir: Coadministration of
mycophenolate mofetil (1 g) and acyclovir (800 mg) to twelve
healthy volunteers resulted in no significant change in
MPA AUC and Cmax . However, MPAG and acyclovir plasma AUCs
were increased 10.6% and 21.9%, respectively. Because MPAG
plasma concentrations are increased in the presence of renal
impairment, as are acyclovir concentrations, the potential
exists for the two drugs to compete for tubular secretion,
further increasing the concentrations of both drugs.
Antacids With Magnesium and Aluminum Hydroxides:
Absorption of a single dose of mycophenolate
mofetil (2 g) was decreased when administered to ten rheumatoid
arthritis patients also taking Maalox® TC (10 mL qid).
The Cmax and AUC0-24 for MPA were 33% and 17% lower, respectively,
than when mycophenolate mofetil was administered alone under
fasting conditions. CellCept may be administered to patients
who are also taking antacids containing magnesium and aluminum
hydroxides; however, it is recommended that CellCept and
the antacid not be administered simultaneously.
Cholestyramine: Following single-dose
administration of 1.5 g mycophenolate mofetil to twelve
healthy volunteers pretreated with 4 g tid of cholestyramine
for 4 days, MPA AUC decreased approximately 40%. This decrease
is consistent with interruption of enterohepatic recirculation
which may be due to binding of recirculating MPAG with cholestyramine
in the intestine. Some degree of enterohepatic recirculation
is also anticipated following IV administration of CellCept.
Therefore, CellCept is not recommended to be given with
cholestyramine or other agents that may interfere with enterohepatic
recirculation.
Cyclosporine: Cyclosporine (Sandimmune®)
pharmacokinetics (at doses of 275 to 415 mg/day) were unaffected
by single and multiple doses of 1.5 g bid of mycophenolate
mofetil in ten stable renal transplant patients. The mean
(± SD) AUC0-12 and Cmax of cyclosporine after 14
days of multiple doses of mycophenolate mofetil were 3290
(± 822) ng·h/ mL and 753 (± 161) ng/mL,
respectively, compared to 3245 (± 1088) ng·h/mL
and 700 (± 246) ng/mL, respectively, 1 week before
administration of mycophenolate mofetil. The effect of cyclosporine
on mycophenolate mofetil pharmacokinetics could not be evaluated
in this study; however, plasma concentrations of MPA were
similar to that for healthy volunteers.
Ganciclovir: Following single-dose
administration to twelve stable renal transplant patients,
no pharmacokinetic interaction was observed between mycophenolate
mofetil (1.5 g) and IV ganciclovir (5 mg/kg). Mean (±
SD) ganciclovir AUC and Cmax (n=10) were 54.3 (±
19.0) µg·h/mL and 11.5 (± 1.8) µg/mL,
respectively, after coadministration of the two drugs, compared
to 51.0 (± 17.0) µg·h/mL and 10.6 (±
2.0) µg/mL, respectively, after administration of
IV ganciclovir alone. The mean (± SD) AUC and Cmax
of MPA (n=12) after coadministration were 80.9 (±
21.6) µg·h/mL and 27.8 (± 13.9) µg/mL,
respectively, compared to values of 80.3 (± 16.4)
µg·h/mL and 30.9 (± 11.2) µg/mL,
respectively, after administration of mycophenolate mofetil
alone. Because MPAG plasma concentrations are increased
in the presence of renal impairment, as are ganciclovir
concentrations, the two drugs will compete for tubular secretion
and thus further increases in concentrations of both drugs
may occur. In patients with renal impairment in which MMF
and ganciclovir are coadministered, patients should be monitored
carefully.
Oral Contraceptives: A study of
coadministration of CellCept (1 g bid) and combined oral
contraceptives containing ethinylestradiol (0.02 to 0.04
mg) and levonorgestrel (0.05 to 0.20 mg), desogestrel (0.15
mg) or gestodene (0.05 to 0.10 mg) was conducted in 18 women
with psoriasis over 3 consecutive menstrual cycles. Mean
AUC(0-24) was similar for ethmylestradiol and 3-keto desogestrel;
however, mean levonorgestrel AUC(0-24) significantly decreased
by about 15%. There was large inter-patient variability
(% CV in the range of 60-70%) in the data, especially for
ethinylestradiol. Mean serum level of LH, FSH and progesterone
were not significantly affected. CellCept may not have any
influence on the ovulation-suppressing action of the studied
oral contraceptives. However, it is recommended that oral
contraceptives are coadministered with CellCept with caution
and additional birth control methods be considered (see
PRECAUTIONS: Pregnancy).
Trimethoprim/sulfamethoxazole:
Following single-dose administration of mycophenolate mofetil
(1.5 g) to twelve healthy male volunteers on day 8 of a
10 day course of BactrimTM DS (trimethoprim 160 mg/sulfamethoxazole
800 mg) administered bid, no effect on the bioavailability
of MPA was observed. The mean (± SD) AUC an | | |
