Mycophenolate Mofetil Information
Mycophenolate mofetil () Description
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 a molecular 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 µg/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 () tablet contains 500 mg of Mycophenolate mofetil () . In addition, each tablet contains the following inactive ingredients: croscarmellose sodium, magnesium stearate, microcrystalline cellulose, povidone, talc, hypromellose, hydroxypropyl cellulose, polyethylene glycol, titanium dioxide, iron oxide black, and iron oxide red.
Mycophenolate mofetil () Clinical Pharmacology
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 both mitogenic 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.
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.
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) 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
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 : and ).
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 µg/mL), hemodialysis removes only small amounts of MPAG.
The pharmacokinetic parameters of MPA and MPAG have been evaluated in 55 pediatric patients (ranging from 1 year to 18 years of age) receiving Mycophenolate mofetil () oral suspension at a dose of 600 mg/m bid (up to a maximum of 1 g bid) after allogeneic renal transplantation. The pharmacokinetic data for MPA is provided in Table 3:
The Mycophenolate mofetil () oral suspension dose of 600 mg/m bid (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 Mycophenolate mofetil () 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.
Mycophenolate mofetil () Contraindications
Allergic reactions to Mycophenolate mofetil () have been observed; therefore, Mycophenolate mofetil () is contraindicated in patients with a hypersensitivity to Mycophenolate mofetil () , mycophenolic acid or any component of the drug product. Mycophenolate mofetil () intravenous is contraindicated in patients who are allergic to Polysorbate 80 (TWEEN).
Mycophenolate mofetil () Warnings
(see boxed WARNING)
Patients receiving immunosuppressive regimens involving combinations of drugs, including Mycophenolate mofetil () , as part of an immunosuppressive regimen are at increased risk of developing lymphomas and other malignancies, particularly of the skin (see The risk appears to be related to the intensity and duration of immunosuppression rather than to the use of any specific agent.
As usual for patients with increased 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.
Lymphoproliferative disease or lymphoma developed in 0.4% to 1% of patients receiving Mycophenolate mofetil () (2 g or 3 g) with other immunosuppressive agents in controlled clinical trials of renal, cardiac, and hepatic transplant patients (see
In pediatric patients, no other malignancies besides lymphoproliferative disorder (2/148 patients) have been observed (see
Immunosuppressed patients are at increased risk for opportunistic infections, including activation of latent viral infections. These include cases of progressive multifocal leukoencephalopathy (PML) and BK virus-associated nephropathy (BKVAN) which have been observed in patients receiving immuno suppress ants, including Mycophenolate mofetil () .
Cases of progressive multifocal leukoencephalopathy (PML), sometimes fatal, have been reported in patients treated with Mycophenolate mofetil () . Hemiparesis, apathy, confusion, cognitive deficiencies and ataxia were the most frequent clinical features observed. The reported cases generally had risk factors for PML, including treatment with immunosuppressant therapies and impairment of immune function. In immunosuppressed patients, physicians should consider PML in the differential diagnosis in patients reporting neurological symptoms and consultation with a neurologist should be considered as clinically indicated. Consideration should be given to reducing the amount of immunosuppression in patients who develop PML. In transplant patients, physicians should also consider the risk that reduced immunosuppression represents to the graft.
BKVAN is associated with serious outcomes, including deteriorating renal function and renal graft loss (see Patient monitoring may help detect patients at risk for BK virus-associated nephropathy. Reduction in immunosuppression should be considered for patients who develop evidence of BK virus-associated nephropathy.
Women of childbearing potential should have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 1 week prior to beginning therapy. Mycophenolate mofetil () therapy should not be initiated until a negative pregnancy test report is obtained.
Women of childbearing potential (including pubertal girls and peri-menopausal women) taking Mycophenolate mofetil () must receive contraceptive counseling and use effective contraception. The patient should begin using her two chosen methods of contraception 4 weeks prior to starting Mycophenolate mofetil () therapy, unless abstinence is the chosen method. She should continue contraceptive use during therapy and for 6 weeks after stopping Mycophenolate mofetil () . Patients should be aware that Mycophenolate mofetil () reduces blood levels of the hormones in the oral contraceptive pill and could theoretically reduce its effectiveness (see and
Severe neutropenia [absolute neutrophil count (ANC)
Patients receiving Mycophenolate mofetil () should be instructed to report immediately any evidence of infection, unexpected bruising, bleeding or any other manifestation of bone marrow depression.
Cases of pure red cell aplasia (PRCA) have been reported in patients treated with CellCept in combination with other immunosuppressive agents. The mechanism for Mycophenolate mofetil () induced PRCA is unknown; the relative contribution of other immunosuppressants and their combinations in an immunosuppression regimen are also unknown. In some cases, PRCA was found to be reversible with dose reduction or cessation of Mycophenolate mofetil () therapy. In transplant patients, however, reduced immunosuppression may place the graft at risk.
CAUTION: Mycophenolate mofetil () INTRAVENOUS SOLUTION SHOULD NEVER BE ADMINISTERED BY RAPID OR BOLUS INTRAVENOUS INJECTION.
Mycophenolate mofetil () Precautions
Gastrointestinal bleeding (requiring hospitalization) has been observed in approximately 3% of renal, in 1.7% of cardiac, and in 5.4% of hepatic transplant patients treated with Mycophenolate mofetil () 3 g daily. In pediatric renal transplant patients, 5/148 cases of gastrointestinal bleeding (requiring hospitalization) were observed.
Gastrointestinal perforations have rarely been observed. Most patients receiving Mycophenolate mofetil () were also receiving other drugs known to be associated with these complications. Patients with active peptic ulcer disease were excluded from enrollment in studies with Mycophenolate mofetil () . Because Mycophenolate mofetil () has been associated with an increased incidence of digestive system adverse events, including infrequent cases of gastrointestinal tract ulceration, hemorrhage, and perforation, Mycophenolate mofetil () should be administered with caution in patients with active serious digestive system disease.
Subjects with severe chronic renal impairment (GFR
No data are available for cardiac or hepatic transplant patients with severe chronic renal impairment. Mycophenolate mofetil () may be used for cardiac or hepatic transplant patients with severe chronic renal impairment if the potential benefits outweigh the potential risks.
In patients with delayed renal graft function posttransplant, mean MPA AUC was comparable, but MPAG AUC was 2-fold to 3-fold higher, compared to that seen in posttransplant patients without delayed renal graft function. In the three controlled studies of prevention of renal rejection, there were 298 of 1483 patients (20%) with delayed graft function. Although patients with delayed graft function have a higher incidence of certain adverse events (anemia, thrombocytopenia, hyperkalemia) than patients without delayed graft function, these events were not more frequent in patients receiving Mycophenolate mofetil () than azathioprine or placebo. No dose adjustment is recommended for these patients; however, they should be carefully observed (see and
In cardiac transplant patients, the overall incidence of opportunistic infections was approximately 10% higher in patients treated with Mycophenolate mofetil () than in those receiving azathioprine therapy, but this difference was not associated with excess mortality due to infection/sepsis among patients treated with Mycophenolate mofetil () (see
There were more herpes virus (H. simplex, H. zoster, and cytomegalovirus) infections in cardiac transplant patients treated with Mycophenolate mofetil () compared to those treated with azathioprine (see
It is recommended that Mycophenolate mofetil () not be administered concomitantly with azathioprine because both have the potential to cause bone marrow suppression and such concomitant administration has not been studied clinically.
In view of the significant reduction in the AUC of MPA by cholestyramine, caution should be used in the concomitant administration of Mycophenolate mofetil () with drugs that interfere with enterohepatic recirculation because of the potential to reduce the efficacy of Mycophenolate mofetil () (see
On theoretical grounds, because Mycophenolate mofetil () is an IMPDH (inosine monophosphate dehydrogenase) inhibitor, it should be avoided in patients with rare hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) such as Lesch-Nyhan and Kelley-Seegmiller syndrome.
During treatment with Mycophenolate mofetil () , the use of live attenuated vaccines should be avoided and patients should be advised that vaccinations may be less effective (see
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 10 stable renal transplant patients. The mean (±SD) AUC(0-12h) and C 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 () .
In renal transplant patients, mean MPA exposure (AUC) was approximately 30-50% greater when Mycophenolate mofetil () is administered without cyclosporine compared with when Mycophenolate mofetil () is coadministered with cyclosporine. This interaction is due to cyclosporine inhibition of multidrug-resistance-associated protein 2 (MRP-2) transporter in the biliary tract, thereby preventing the excretion of MPAG into the bile that would lead to enterohepatic recirculation of MPA. This information should be taken into consideration when MMF is used without cyclosporine.
The measured value for renal clearance of MPAG indicates removal occurs by renal tubular secretion as well as glomerular filtration. Consistent with this, coadministration of probenecid, a known inhibitor of tubular secretion, with Mycophenolate mofetil () in monkeys results in a 3-fold increase in plasma MPAG AUC and a 2-fold increase in plasma MPA AUC. Thus, other drugs known to undergo renal tubular secretion may compete with MPAG and thereby raise plasma concentrations of MPAG or the other drug undergoing tubular secretion.
Drugs that alter the gastrointestinal flora may interact with Mycophenolate mofetil () by disrupting enterohepatic recirculation. Interference of MPAG hydrolysis may lead to less MPA available for absorption.
In a 104-week oral carcinogenicity study in mice, Mycophenolate mofetil () in daily doses up to 180 mg/kg was not tumorigenic. The highest dose tested was 0.5 times the recommended clinical dose (2 g/day) in renal transplant patients and 0.3 times the recommended clinical dose (3 g/day) in cardiac transplant patients when corrected for differences in body surface area (BSA). In a 104-week oral carcinogenicity study in rats, Mycophenolate mofetil () in daily doses up to 15 mg/kg was not tumorigenic. The highest dose was 0.08 times the recommended clinical dose in renal transplant patients and 0.05 times the recommended clinical dose in cardiac transplant patients when corrected for BSA. While these animal doses were lower than those given to patients, they were maximal in those species and were considered adequate to evaluate the potential for human risk (see
The genotoxic potential of Mycophenolate mofetil () was determined in five assays. Mycophenolate mofetil () was genotoxic in the mouse lymphoma/thymidine kinase assay and the mouse micronucleus assay. Mycophenolate mofetil () was not genotoxic in the bacterial mutation assay, the yeast mitotic gene conversion assay or the Chinese hamster ovary cell chromosomal aberration assay.
Mycophenolate mofetil () had no effect on fertility of male rats at oral doses up to 20 mg/kg/day. This dose represents 0.1 times the recommended clinical dose in renal transplant patients and 0.07 times the recommended clinical dose in cardiac transplant patients when corrected for BSA. In a female fertility and reproduction study conducted in rats, oral doses of 4.5 mg/kg/day caused malformations (principally of the head and eyes) in the first generation offspring in the absence of maternal toxicity. This dose was 0.02 times the recommended clinical dose in renal transplant patients and 0.01 times the recommended clinical dose in cardiac transplant patients when corrected for BSA. No effects on fertility or reproductive parameters were evident in the dams or in the subsequent generation.
Based on pharmacokinetic and safety data in pediatric patients after renal transplantation, the recommended dose of Mycophenolate mofetil () oral suspension is 600 mg/mbid (up to a maximum of 1 g bid). Also see ,
Safety and effectiveness in pediatric patients receiving allogeneic cardiac or hepatic transplants have not been established.
Mycophenolate mofetil () Adverse Reactions
The principal adverse reactions associated with the administration of Mycophenolate mofetil () include diarrhea, leukopenia, sepsis, vomiting, and there is evidence of a higher frequency of certain types of infections eg, opportunistic infection (see and The adverse event profile associated with the administration of Mycophenolate mofetil () intravenous has been shown to be similar to that observed after administration of oral dosage forms of Mycophenolate mofetil () .
Elderly patients (≥ 65 years), particularly those who are receiving Mycophenolate mofetil () 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 (see
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 Mycophenolate mofetil () 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 Mycophenolate mofetil () had an overall better safety profile than did patients receiving 3 g/day of Mycophenolate mofetil () .
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 Mycophenolate mofetil () compared to patients treated with azathioprine. The incidence of sepsis was comparable in Mycophenolate mofetil () and in azathioprine-treated patients in cardiac and hepatic studies.
In the digestive system, diarrhea was increased in renal and cardiac transplant patients receiving Mycophenolate mofetil () compared to patients receiving azathioprine, but was comparable in hepatic transplant patients treated with Mycophenolate mofetil () or azathioprine.
Patients receiving Mycophenolate mofetil () alone or as part of an immunosuppressive regimen are at increased risk of developing lymphomas and other malignancies, particularly of the skin (see . 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 Mycophenolate mofetil () (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 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
All transplant patients are at increased risk of opportunistic infections. The risk increases with total immunosuppressive load (see and 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 Mycophenolate mofetil () 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 Mycophenolate mofetil () (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 (see ).
In cardiac transplant patients, the overall incidence of opportunistic infections was approximately 10% higher in patients treated with Mycophenolate mofetil () than in those receiving azathioprine, but this difference was not associated with excess mortality due to infection/sepsis among patients treated with Mycophenolate mofetil () .
The following adverse events were reported with 3% to
The adverse event profile of Mycophenolate mofetil () intravenous was determined from a single, double-blind, controlled comparative study of the safety of 2 g/day of intravenous and oral Mycophenolate mofetil () in renal transplant patients in the immediate posttransplant period (administered for the first 5 days). The potential venous irritation of Mycophenolate mofetil () intravenous was evaluated by comparing the adverse events attributable to peripheral venous infusion of Mycophenolate mofetil () 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 Mycophenolate mofetil () intravenous.
In the active controlled study in hepatic transplant patients, 2 g/day of Mycophenolate mofetil () intravenous were administered in the immediate posttransplant period (up to 14 days). The safety profile of intravenous Mycophenolate mofetil () was similar to that of intravenous azathioprine.
Mycophenolate mofetil () Overdosage
The experience with overdose of Mycophenolate mofetil () in humans is very limited. The events received from reports of overdose fall within the known safety profile of the drug. The highest dose administered to renal transplant patients in clinical trials has been 4 g/day. In limited experience with cardiac and hepatic transplant patients in clinical trials, the highest doses used were 4 g/day or 5 g/day. At doses of 4 g/day or 5 g/day, there appears to be a higher rate, compared to the use of 3 g/day or less, of gastrointestinal intolerance (nausea, vomiting, and/or diarrhea), and occasional hematologic abnormalities, principally neutropenia, leading to a need to reduce or discontinue dosing.
In acute oral toxicity studies, no deaths occurred in adult mice at doses up to 4000 mg/kg or in adult monkeys at doses up to 1000 mg/kg; these were the highest doses of Mycophenolate mofetil () tested in these species. These doses represent 11 times the recommended clinical dose in renal transplant patients and approximately 7 times the recommended clinical dose in cardiac transplant patients when corrected for BSA. In adult rats, deaths occurred after single-oral doses of 500 mg/kg of Mycophenolate mofetil () . The dose represents approximately 3 times the recommended clinical dose in cardiac transplant patients when corrected for BSA.
MPA and MPAG are usually not removed by hemodialysis. However, at high MPAG plasma concentrations (>100 µg/mL), small amounts of MPAG are removed. By increasing excretion of the drug, MPA can be removed by bile acid sequestrants, such as cholestyramine (see
Mycophenolate mofetil () Dosage And Administration
In renal transplant patients with severe chronic renal impairment (GFR
No data are available for cardiac or hepatic transplant patients with severe chronic renal impairment. Mycophenolate mofetil () 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
Mycophenolate mofetil () How Supplied
Mycophenolate mofetil () tablets are available as follows:
500 mg, lavender colored, film-coated biconvex tablets with ‘SZ’ on one side and ‘327’ on the other side.
NDC 0781-5175-01, bottle of 100 tablets
NDC 0781-5175-05, bottle of 500 tablets
NDC 0781-5175-10, bottle of 1000 tablets
Mycophenolate mofetil () Storage
Store at 20º to 25°C (68º to 77°F) [see USP Controlled Room Temperature]. Protect from moisture. Dispense in a tight, light-resistant container as defined in the USP with a child resistant cap.
Manufactured in India by Sandoz Private Ltd.
for Sandoz Inc., Princeton, NJ 08540
Rev. 12/2009
Mycophenolate mofetil ()
Mycophenolate mofetil ()
