mycophenolate mofetil 500 MG Oral Tablet
Generic Name: MYCOPHENOLATE MOFETIL
Brand Name: Mycophenolate mofetil
- Substance Name(s):
- MYCOPHENOLATE MOFETIL
WARNINGS
(see boxed WARNING) Embryofetal Toxicity Mycophenolate mofetil (MMF) can cause fetal harm when administered to a pregnant female.
Use of MMF during pregnancy is associated with an increased risk of first trimester pregnancy loss and an increased risk of congenital malformations, especially external ear and other facial abnormalities including cleft lip and palate, and anomalies of the distal limbs, heart, esophagus, kidney and nervous system (see PRECAUTIONS: Pregnancy ).
Pregnancy Exposure Prevention and Planning Females of reproductive potential must be made aware of the increased risk of first trimester pregnancy loss and congenital malformations and must be counseled regarding pregnancy prevention and planning.
For recommended pregnancy testing and contraception methods (see PRECAUTIONS: Pregnancy Exposure Prevention and Planning ).
Lymphoma and Malignancy 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 ADVERSE REACTIONS ).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 ADVERSE REACTIONS ).
In pediatric patients, no other malignancies besides lymphoproliferative disorder (2/148 patients) have been observed (see ADVERSE REACTIONS ).
Combination with Other Immunosuppressive Agents Mycophenolate mofetil has been administered in combination with the following agents in clinical trials: antithymocyte globulin (ATGAM ®), OKT3 (Orthoclone OKT ® 3), cyclosporine (Sandimmune ®, Neoral ®) and corticosteroids.
The efficacy and safety of the use of mycophenolate mofetil in combination with other immunosuppressive agents have not been determined.
Serious Infections Patients receiving immunosuppressants, including mycophenolate mofetil, are at increased risk of developing bacterial, fungal, protozoal and new or reactivated viral infections, including opportunistic infections.
These infections may lead to serious, including fatal outcomes.
Because of the danger of oversuppression of the immune system which can increase susceptibility to infection, combination immunosuppressant therapy should be used with caution (see ADVERSE REACTIONS ).
New or Reactivated Viral Infections Polyomavirus associated nephropathy (PVAN), JC virus associated progressive multifocal leukoencephalopathy (PML), cytomegalovirus (CMV) infections, reactivation of hepatitis B (HBV) or hepatitis C (HCV) have been reported in patients treated with immunosuppressants, including mycophenolate mofetil.
Reduction in immunosuppression should be considered for patients who develop evidence of new or reactivated viral infections.
Physicians should also consider the risk that reduced immunosuppression represents to the functioning allograft.
PVAN, especially due to BK virus infection, is associated with serious outcomes, including deteriorating renal function and renal graft loss (see ADVERSE REACTIONS: Postmarketing Experience ).
Patient monitoring may help detect patients at risk for PVAN.
PML, which is sometimes fatal, commonly presents with hemiparesis, apathy, confusion, cognitive deficiencies, and ataxia.
Risk factors for PML include treatment with immunosuppressant therapies and impairment of immune function (see ADVERSE REACTIONS: Postmarketing Experience ).
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.
The risk of CMV viremia and CMV disease is highest among transplant recipients seronegative for CMV at time of transplant who receive a graft from a CMV seropositive donor.
Therapeutic approaches to limiting CMV disease exist and should be routinely provided.
Patient monitoring may help detect patients at risk for CMV disease.
Viral reactivation has been reported in patients infected with HBV or HCV.
Monitoring infected patients for clinical and laboratory signs of active HBV or HCV infection is recommended.
Neutropenia Severe neutropenia [absolute neutrophil count (ANC) < 0.5 x 10 3/µL] developed in up to 2% of renal, up to 2.8% of cardiac, and up to 3.6% of hepatic transplant patients receiving mycophenolate mofetil 3 g daily (see ADVERSE REACTIONS ).
Patients receiving mycophenolate mofetil should be monitored for neutropenia (see PRECAUTIONS: Laboratory Tests ).The development of neutropenia may be related to mycophenolate mofetil itself, concomitant medications, viral infections, or some combination of these causes.
If neutropenia develops (ANC < 1.3 x 10 3/µL), dosing with mycophenolate mofetil should be interrupted or the dose reduced, appropriate diagnostic tests performed, and the patient managed appropriately (see DOSAGE AND ADMINISTRATION ).Neutropenia has been observed most frequently in the period from 31 to 180 days posttransplant in patients treated for prevention of renal, cardiac, and hepatic rejection.
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.
Pure Red Cell Aplasia (PRCA) 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 MUST NOT BE ADMINISTERED BY RAPID OR BOLUS INTRAVENOUS INJECTION.
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 C 23H 31NO 7, 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 mcg/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 tablets are available for oral administration, as tablets 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.
structural formula
CLINICAL STUDIES
Adults The safety and efficacy of mycophenolate mofetil in combination with corticosteroids and cyclosporine for the prevention of organ rejection were assessed in randomized, double-blind, multicenter trials in renal (3 trials), in cardiac (1 trial), and in hepatic (1 trial) adult transplant patients.
Renal Transplant Adults The three renal studies compared two dose levels of oral mycophenolate mofetil (1 g bid and 1.5 g bid) with azathioprine (2 studies) or placebo (1 study) when administered in combination with cyclosporine (Sandimmune ®) and corticosteroids to prevent acute rejection episodes.
One study also included antithymocyte globulin (ATGAM ®) induction therapy.
These studies are described by geographic location of the investigational sites.
One study was conducted in the USA at 14 sites, one study was conducted in Europe at 20 sites, and one study was conducted in Europe, Canada, and Australia at a total of 21 sites.
The primary efficacy endpoint was the proportion of patients in each treatment group who experienced treatment failure within the first 6 months after transplantation (defined as biopsy-proven acute rejection on treatment or the occurrence of death, graft loss or early termination from the study for any reason without prior biopsy-proven rejection).
Mycophenolate mofetil, when administered with antithymocyte globulin (ATGAM ®) induction (one study) and with cyclosporine and corticosteroids (all three studies), was compared to the following three therapeutic regimens: (1) antithymocyte globulin (ATGAM ®) induction/azathioprine/cyclosporine/corticosteroids, (2) azathioprine/cyclosporine/corticosteroids, and (3) cyclosporine/corticosteroids.
Mycophenolate mofetil, in combination with corticosteroids and cyclosporine reduced (statistically significant at 0.05 level) the incidence of treatment failure within the first 6 months following transplantation.
Table 4 and Table 5 summarize the results of these studies.
These tables show (1) the proportion of patients experiencing treatment failure, (2) the proportion of patients who experienced biopsy-proven acute rejection on treatment, and (3) early termination, for any reason other than graft loss or death, without a prior biopsy-proven acute rejection episode.
Patients who prematurely discontinued treatment were followed for the occurrence of death or graft loss, and the cumulative incidence of graft loss and patient death are summarized separately.
Patients who prematurely discontinued treatment were not followed for the occurrence of acute rejection after termination.
More patients receiving mycophenolate mofetil discontinued without prior biopsy-proven rejection, death or graft loss than discontinued in the control groups, with the highest rate in the mycophenolate mofetil 3 g/day group.
Therefore, the acute rejection rates may be underestimates, particularly in the mycophenolate mofetil 3 g/day group.
Table 4 Renal Transplant Studies Incidence of Treatment Failure (Biopsy-proven Rejection or Early Termination for Any Reason) USA Study Antithymocyte globulin induction/MMF or azathioprine/cyclosporine/corticosteroids.
(N=499 patients) Mycophenolate mofetil 2 g/day (n=167 patients) Mycophenolate mofetil 3 g/day (n=166 patients) Azathioprine 1 to 2 mg/kg/day (n=166 patients) All treatment failures 31.1% 31.3% 47.6% Early termination without prior acute rejection Does not include death and graft loss as reason for early termination.
9.6% 12.7% 6% Biopsy-proven rejection episode on treatment 19.8% 17.5% 38% Europe/Canada/ Australia Study MMF or azathioprine/cyclosporine/corticosteroids.
(N=503 patients) Mycophenolate mofetil 2 g/day (n=173 patients) Mycophenolate mofetil 3 g/day (n=164 patients) Azathioprine 100 to 150 mg/kg/day (n=166 patients) All treatment failures 38.2% 34.8% 50% Early termination without prior acute rejection 13.9% 15.2% 10.2% Biopsy-proven rejection episode on treatment 19.7% 15.9% 35.5% Europe Study MMF or placebo/cyclosporine/corticosteroids.
(N=491 patients) Mycophenolate mofetil 2 g/day (n=165 patients) Mycophenolate mofetil 3 g/day (n=160 patients) Placebo (n=166 patients) All treatment failures 30.3% 38.8% 56% Early termination without prior acute rejection 11.5% 22.5% 7.2% Biopsy-proven rejection episode on treatment 17% 13.8% 46.4% The cumulative incidence of 12-month graft loss or patient death is presented below.
No advantage of mycophenolate mofetil with respect to graft loss or patient death was established.
Numerically, patients receiving mycophenolate mofetil 2 g/day and 3 g/day experienced a better outcome than controls in all three studies; patients receiving mycophenolate mofetil 2 g/day experienced a better outcome than mycophenolate mofetil 3 g/day in two of the three studies.
Patients in all treatment groups who terminated treatment early were found to have a poor outcome with respect to graft loss or patient death at 1 year.
Table 5 Renal Transplant Studies Cumulative Incidence of Combined Graft Loss or Patient Death at 12 Months Study Mycophenolate mofetil 2 g/day Mycophenolate mofetil 3 g/day Control (Azathioprine or Placebo) USA 8.5% 11.5% 12.2% Europe/Canada/Australia 11.7% 11% 13.6% Europe 8.5% 10% 11.5% Pediatrics One open-label, safety and pharmacokinetic study of mycophenolate mofetil oral suspension 600 mg/m 2 bid (up to 1 g bid) in combination with cyclosporine and corticosteroids was performed at centers in the US (9), Europe (5) and Australia (1) in 100 pediatric patients (3 months to 18 years of age) for the prevention of renal allograft rejection.
Mycophenolate mofetil was well tolerated in pediatric patients (see ADVERSE REACTIONS ), and the pharmacokinetics profile was similar to that seen in adult patients dosed with 1 g bid mycophenolate mofetil capsules (see CLINICAL PHARMACOLOGY: Pharmacokinetics ).
The rate of biopsy-proven rejection was similar across the age groups (3 months to < 6 years, 6 years to < 12 years, 12 years to 18 years).
The overall biopsy-proven rejection rate at 6 months was comparable to adults.
The combined incidence of graft loss (5%) and patient death (2%) at 12 months posttransplant was similar to that observed in adult renal transplant patients.
Cardiac Transplant A double-blind, randomized, comparative, parallel-group, multicenter study in primary cardiac transplant recipients was performed at 20 centers in the United States, 1 in Canada, 5 in Europe and 2 in Australia.
The total number of patients enrolled was 650; 72 never received study drug and 578 received study drug.
Patients received mycophenolate mofetil 1.5 g bid (n=289) or azathioprine 1.5 to 3 mg/kg/day (n=289), in combination with cyclosporine (Sandimmune ® or Neoral ®) and corticosteroids as maintenance immunosuppressive therapy.
The two primary efficacy endpoints were: (1) the proportion of patients who, after transplantation, had at least one endomyocardial biopsy-proven rejection with hemodynamic compromise, or were retransplanted or died, within the first 6 months, and (2) the proportion of patients who died or were retransplanted during the first 12 months following transplantation.
Patients who prematurely discontinued treatment were followed for the occurrence of allograft rejection for up to 6 months and for the occurrence of death for 1 year.
1 .
Rejection: No difference was established between mycophenolate mofetil and azathioprine (AZA) with respect to biopsy-proven rejection with hemodynamic compromise.
2.
Survival: Mycophenolate mofetil was shown to be at least as effective as AZA in preventing death or retransplantation at 1 year (see Table 6 ).
Table 6 Rejection at 6 Months/Death or Retransplantation at 1 Year All Patients Treated Patients AZA N = 323 Mycophenolate mofetil N = 327 AZA N = 289 Mycophenolate mofetil N = 289 Biopsy-proven rejection with hemodynamic compromise at 6 months Hemodynamic compromise occurred if any of the following criteria were met: pulmonary capillary wedge pressure ≥ 20 mm or a 25% increase; cardiac index < 2 L/min/m 2 or a 25% decrease; ejection fraction ≤ 30%; pulmonary artery oxygen saturation ≤ 60% or a 25% decrease; presence of new S 3 gallop; fractional shortening was ≤ 20% or a 25% decrease; inotropic support required to manage the clinical condition.
121 (38%) 120 (37%) 100 (35%) 92 (32%) Death or retransplantation at 1 year 49 (15.2%) 42 (12.8%) 33 (11.4%) 18 (6.2%) Hepatic Transplant A double-blind, randomized, comparative, parallel-group, multicenter study in primary hepatic transplant recipients was performed at 16 centers in the United States, 2 in Canada, 4 in Europe and 1 in Australia.
The total number of patients enrolled was 565.
Per protocol, patients received mycophenolate mofetil 1 g bid intravenously for up to 14 days followed by mycophenolate mofetil 1.5 g bid orally or azathioprine 1 to 2 mg/kg/day intravenously followed by azathioprine 1 to 2 mg/kg/day orally, in combination with cyclosporine (Neoral ®) and corticosteroids as maintenance immunosuppressive therapy.
The actual median oral dose of azathioprine on study was 1.5 mg/kg/day (range of 0.3 to 3.8 mg/kg/day) initially and 1.26 mg/kg/day (range of 0.3 to 3.8 mg/kg/day) at 12 months.
The two primary endpoints were: (1) the proportion of patients who experienced, in the first 6 months posttransplantation, one or more episodes of biopsy-proven and treated rejection or death or retransplantation, and (2) the proportion of patients who experienced graft loss (death or retransplantation) during the first 12 months posttransplantation.
Patients who prematurely discontinued treatment were followed for the occurrence of allograft rejection and for the occurrence of graft loss (death or retransplantation) for 1 year.
Results In combination with corticosteroids and cyclosporine, mycophenolate mofetil obtained a lower rate of acute rejection at 6 months and a similar rate of death or retransplantation at 1 year compared to azathioprine.
Table 7 Rejection at 6 Months/Death or Retransplantation at 1 Year AZA N = 287 Mycophenolate mofetil N = 278 Biopsy-proven, treated rejection at 6 months (includes death or retransplantation) 137 (47.7%) 107 (38.5%) Death or retransplantation at 1 year 42 (14.6%) 41 (14.7%)
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.
Unit dose packages of 100 (10 x 10) NDC 68084-801-01
GERIATRIC USE
Geriatric Use Clinical studies of mycophenolate mofetil did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
Other reported clinical experience has not identified differences in responses between the elderly and younger patients.
In general dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal or cardiac function and of concomitant or other drug therapy.
Elderly patients may be at an increased risk of adverse reactions compared with younger individuals (see ADVERSE REACTIONS ).
INDICATIONS AND USAGE
Renal, Cardiac, and Hepatic Transplant Mycophenolate mofetil tablet, USP is indicated for the prophylaxis of organ rejection in patients receiving allogeneic renal, cardiac or hepatic transplants.
Mycophenolate mofetil tablets, USP should be used concomitantly with cyclosporine and corticosteroids.
Mycophenolate mofetil intravenous is an alternative dosage form to mycophenolate mofetil capsules, tablets and oral suspension.
Mycophenolate mofetil intravenous should be administered within 24 hours following transplantation.
Mycophenolate mofetil intravenous can be administered for up to 14 days; patients should be switched to oral mycophenolate mofetil as soon as they can tolerate oral medication.
PEDIATRIC USE
Pediatric Use Based on pharmacokinetic and safety data in pediatric patients after renal transplantation, the recommended dose of mycophenolate mofetil oral suspension is 600 mg/m 2 bid (up to a maximum of 1 g bid).
Also see CLINICAL PHARMACOLOGY , CLINICAL STUDIES , ADVERSE REACTIONS , and DOSAGE AND ADMINISTRATION .
Safety and effectiveness in pediatric patients receiving allogeneic cardiac or hepatic transplants have not been established.
PREGNANCY
Pregnancy Pregnancy Category D See WARNINGS section.
Use of MMF during pregnancy is associated with an increased risk of first trimester pregnancy loss and an increased risk of congenital malformations, especially external ear and other facial abnormalities including cleft lip and palate, and anomalies of the distal limbs, heart, esophagus, kidney and nervous system.
In animal studies, congenital malformations and pregnancy loss occurred when pregnant rats and rabbits received mycophenolic acid at dose multiples similar to and less than clinical doses.
If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
Risks and benefits of mycophenolate mofetil should be discussed with the patient.
When appropriate, consider alternative immunosuppressants with less potential for embryofetal toxicity.
In certain situations, the patient and her healthcare practitioner may decide that the maternal benefits outweigh the risks to the fetus.
For those females using mycophenolate mofetil at any time during pregnancy and those becoming pregnant within 6 weeks of discontinuing therapy, the healthcare practitioner should report the pregnancy to the Mycophenolate Pregnancy Registry (1-800-617-8191).
The healthcare practitioner should strongly encourage the patient to enroll in the pregnancy registry.
The information provided to the registry will help the healthcare community better understand the effects of mycophenolate in pregnancy.
In the National Transplantation Pregnancy Registry (NTPR), there were data on 33 MMF-exposed pregnancies in 24 transplant patients; there were 15 spontaneous abortions (45%) and 18 live-born infants.
Four of these 18 infants had structural malformations (22%).
In postmarketing data (collected 1995-2007) on 77 females exposed to systemic MMF during pregnancy, 25 had spontaneous abortions and 14 had a malformed infant or fetus.
Six of 14 malformed offspring had ear abnormalities.
Because these postmarketing data are reported voluntarily, it is not always possible to reliably estimate the frequency of particular adverse outcomes.
These malformations are similar to findings in animal reproductive toxicology studies.
For comparison, the background rate for congenital anomalies in the United States is about 3%, and NTPR data show a rate of 4 to 5% among babies born to organ transplant patients using other immunosuppressive drugs.
In animal reproductive toxicology studies, there were increased rates of fetal resorptions and malformations in the absence of maternal toxicity.
Female rats and rabbits received mycophenolate mofetil (MMF) doses equivalent to 0.02 to 0.9 times the recommended human dose for renal and cardiac transplant patients, based on body surface area conversions.
In rat offspring, malformations included anophthalmia, agnathia, and hydrocephaly.
In rabbit offspring, malformations included ectopia cordis, ectopic kidneys, diaphragmatic hernia, and umbilical hernia.
NUSRING MOTHERS
Nursing Mothers Studies in rats treated with mycophenolate mofetil have shown mycophenolic acid to be excreted in milk.
It is not known whether this drug is excreted in human milk.
Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from mycophenolate mofetil, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
BOXED WARNING
WARNING: EMBRYOFETAL TOXICITY, MALIGNANCIES AND SERIOUS INFECTIONS Use during pregnancy is associated with increased risks of first trimester pregnancy loss and congenital malformations.
Females of reproductive potential (FRP) must be counseled regarding pregnancy prevention and planning (see WARNINGS and PRECAUTIONS).
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 prescribe mycophenolate mofetil.
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 (see WARNINGS and PRECAUTIONS).
INFORMATION FOR PATIENTS
Information for Patients See Medication Guide Inform females of reproductive potential that use of mycophenolate mofetil during pregnancy is associated with an increased risk of first trimester pregnancy loss and an increased risk of congenital malformations, and advise them as to the appropriate steps to manage these risks, including that they must use acceptable contraception (see WARNINGS: Embryofetal Toxicity, PRECAUTIONS: Pregnancy Exposure Prevention and Planning ).
Discuss pregnancy testing, pregnancy prevention and planning with females of reproductive potential.
In the event of a positive pregnancy test, females should be counseled with regard to whether the maternal benefits of mycophenolate treatment may outweigh the risks to the fetus in certain situations.
Females of reproductive potential must use acceptable birth control during entire mycophenolate mofetil therapy and for 6 weeks after stopping mycophenolate mofetil, unless the patient chooses to avoid heterosexual intercourse completely (abstinence) (see PRECAUTIONS: Pregnancy Exposure Prevention and Planning, Table 8 ).
For patients who are considering pregnancy, discuss appropriate alternative immunosuppressants with less potential for embryofetal toxicity.
Risks and benefits of mycophenolate mofetil should be discussed with the patient.
Give patients complete dosage instructions and inform them about the increased risk of lymphoproliferative disease and certain other malignancies.
Inform patients that they need repeated appropriate laboratory tests while they are taking mycophenolate mofetil.
Advise patients that they should not breastfeed during mycophenolate mofetil therapy.
DOSAGE AND ADMINISTRATION
Renal Transplantation 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 mycophenolate mofetil demonstrated an overall better safety profile than did patients receiving 3 g/day of mycophenolate mofetil.
Pediatrics (3 months to 18 years of age) The recommended dose of mycophenolate mofetil oral suspension is 600 mg/m 2 administered twice daily (up to a maximum daily dose of 2 g/10 mL oral suspension).
Patients with a body surface area of 1.25 m 2 to 1.5 m 2 may be dosed with mycophenolate mofetil capsules at a dose of 750 mg twice daily (1.5 g daily dose).
Patients with a body surface area >1.5 m 2 may be dosed with mycophenolate mofetil capsules or tablets at a dose of 1 g twice daily (2 g daily dose).
Cardiac Transplantation 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.
Hepatic Transplantation 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.
Mycophenolate Mofetil Capsules, Tablets and Oral Suspension The initial oral dose of mycophenolate mofetil 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 C max by 40%.
Therefore, it is recommended that mycophenolate mofetil be administered on an empty stomach.
However, in stable renal transplant patients, mycophenolate mofetil may be administered with food if necessary.
Patients should be instructed to take a missed dose as soon as they remember, except if it is near the next scheduled dose, and then continue to take mycophenolate mofetil at the usual times.
Note If required, mycophenolate mofetil oral suspension can be administered via a nasogastric tube with a minimum size of 8 French (minimum 1.7 mm interior diameter).
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 (see CLINICAL PHARMACOLOGY: Pharmacokinetics ).
No data are available for cardiac transplant patients with severe hepatic parenchymal disease.
Geriatrics The recommended oral dose of 1 g bid for renal transplant patients, 1.5 g bid for cardiac transplant patients, and 1g bid administered intravenously or 1.5 g bid administered orally in hepatic transplant patients is appropriate for elderly patients (see PRECAUTIONS: Geriatric Use ).
Mycophenolate Mofetil Intravenous Adults Mycophenolate mofetil intravenous is an alternative dosage form to mycophenolate mofetil capsules, tablets and oral suspension recommended for patients unable to take oral mycophenolate mofetil.
Mycophenolate mofetil intravenous should be administered within 24 hours following transplantation.
Mycophenolate mofetil intravenous can be administered for up to 14 days; patients should be switched to oral mycophenolate mofetil as soon as they can tolerate oral medication.
Mycophenolate mofetil intravenous must be reconstituted and diluted to a concentration of 6 mg/mL using 5% Dextrose Injection USP.
Mycophenolate mofetil intravenous is incompatible with other intravenous infusion solutions.
Following reconstitution, mycophenolate mofetil intravenous must be administered by slow intravenous infusion over a period of NO LESS THAN 2 HOURS by either peripheral or central vein.
CAUTION: MYCOPHENOLATE MOFETIL INTRAVENOUS SOLUTION MUST NOT BE ADMINISTERED BY RAPID OR BOLUS INTRAVENOUS INJECTION (see WARNINGS).
Dosage Adjustments In renal transplant patients with severe chronic renal impairment (GFR < 25 mL/min/1.73 m 2) outside the immediate posttransplant period, doses of mycophenolate mofetil 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 (see CLINICAL PHARMACOLOGY: Pharmacokinetics and PRECAUTIONS: Patients with Renal Impairment ).
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 < 1.3 x 10 3/µL), dosing with mycophenolate mofetil should be interrupted or the dose reduced, appropriate diagnostic tests performed, and the patient managed appropriately (see WARNINGS: Neutropenia, ADVERSE REACTIONS, and PRECAUTIONS: Laboratory Tests ).