Mycophenolic Acid (mycophenolate sodium)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Mycophenolate mofetil and mycophenolate sodium are immunosuppressive agents. Mycophenolate mofetil is hydrolyzed in vivo to mycophenolic acid, the pharmacologically active metabolite. Mycophenolate sodium delayed-release tablets release the active moiety, mycophenolic acid, in the intestine.
Mycophenolate mofetil, the 2-morpholinoethyl ester of mycophenolic acid, is an antimetabolite immunosuppressive agent. Following oral administration, mycophenolate mofetil is absorbed and hydrolyzed in vivo to the pharmacologically active metabolite, mycophenolic acid. Mycophenolic acid exhibits a cytostatic and reversible effect on T- and B-cells.
Mycophenolic acid is a selective, noncompetitive, reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), an essential enzyme in de novo guanosine synthesis. Because T- and B-cells are very dependent on de novo synthesis of purines (e.g., guanosine) for their proliferation, mycophenolic acid inhibits de novo guanosine nucleotide synthesis and blocks DNA synthesis.
The mechanism of action of mycophenolic acid is multifaceted. Mycophenolic acid alters cellular checkpoints responsible for metabolic programming of lymphocytes; it shifts transcriptional activities in lymphocytes from a proliferative state to catabolic processes. In vitro, mycophenolic acid modulates transcriptional activities in human CD4+ T-lymphocytes by suppressing the Akt/mTOR and STAT5 pathways, which causes the T-cells to become less responsive to antigenic stimulation.
Mycophenolic acid also enhances the expression of negative co-stimulators such as CD70, programmed death-1 (PD-1), cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), and transcription factor FoxP3, in addition to decreasing the expression of positive co-stimulators CD27 and CD28. The drug inhibits proliferative responses of T- and B-cells to both mitogenic and allospecific stimulation, antibody responses, as well as the production of cytokines from lymphocytes and monocytes (e.g., granulocyte-macrophage colony-stimulating factor, interferon-gamma, interleukin-17, and tumor necrosis factor-alpha). By preventing glycosylation of lymphocyte and monocyte glycoproteins involved in intercellular adhesion to endothelial cells, mycophenolic acid may inhibit recruitment of leukocytes to sites of inflammation and graft rejection.
Mycophenolate sodium also is an immunosuppressive agent. Following oral administration of mycophenolate sodium delayed-release tablets, mycophenolic acid (the active moiety) is released. Mycophenolate sodium has been shown to prevent acute rejection in rat models of kidney and heart allotransplantation; the drug also decreases antibody production in mice.
Mycophenolate mofetil is well absorbed following oral administration, having an absolute bioavailability of 94% relative to IV mycophenolate mofetil. Following oral and IV administration, mycophenolate mofetil undergoes rapid and complete metabolism to mycophenolic acid, the active metabolite. Mycophenolate mofetil (CellCept(R)) tablets, capsules, and oral suspension are bioequivalent.
The mycophenolic acid AUC appears to increase in a dosage-proportional manner in kidney transplant patients receiving multiple oral doses of mycophenolate mofetil up to a daily dosage of 3 g. In the early posttransplant period (i.e., <40 days posttransplant), kidney, heart, and liver transplant patients had mean mycophenolic acid AUCs and peak plasma concentrations approximately 20--41% and 32%--44% lower, respectively, compared to the late transplant period (i.e., 3--6 months posttransplant). Following administration of mycophenolate mofetil IV 1 g twice daily over 2 hours to kidney transplant patients for 5 days, mean mycophenolic acid AUCs were approximately 24% higher than those observed after oral administration of a similar dose in the immediate posttransplant phase.
In liver transplant patients, administration of mycophenolate mofetil IV 1 g twice daily followed by 1.5 g orally twice daily resulted in mean mycophenolic acid AUC estimates similar to those found in kidney transplant patients administered 1 g twice daily.
Mycophenolate sodium exhibits linear and dose-proportional pharmacokinetics over the dosage range of 360--2160 mg. Following oral administration of mycophenolate sodium delayed-release, enteric-coated tablets, mycophenolic acid is released in the intestine. The absolute bioavailability of mycophenolic acid following oral administration of mycophenolate sodium delayed-release tablets in stable renal transplant patients has been reported to be 72%.
Following oral administration of mycophenolate sodium delayed-release tablets, the median time to peak plasma concentrations of the drug is 1.5-2.75 hours compared with 0.5-1 hour reported with conventional preparations of mycophenolate mofetil. Administration of mycophenolate sodium (as delayed-release tablets) or mycophenolate mofetil with food does not affect the AUC of mycophenolic acid; however, decreases by about 33 or 40%, respectively, of the peak plasma concentrations of mycophenolic acid have been observed. Mycophenolate sodium delayed-release tablets cannot be used interchangeably with mycophenolate mofetil tablets or capsules without clinician supervision because the rate of absorption following the administration of these two agents is not equivalent.
Mycophenolic acid is >=97-98% bound to plasma protein (mainly albumin). Mycophenolate mofetil undergoes complete metabolism to mycophenolic acid; metabolism occurs presystemically following oral administration. Mycophenolic acid is metabolized by glucuronyl transferase to form the phenolic glucuronide of mycophenolic acid (MPAG), the predominant metabolite, which is not pharmacologically active.
In vivo, MPAG is converted back to mycophenolic acid via enterohepatic recirculation; concurrent administration of drugs that interfere with such recirculation (e.g., cholestyramine) may decrease plasma concentrations of mycophenolic acid.
Ninety-three percent of an orally administered dose of mycophenolate mofetil is excreted in urine (mainly (about 87%) as MPAG) and 6% is excreted in feces. Following administration of mycophenolate sodium, most of the dose (greater than 60%) of mycophenolic acid is excreted in urine as MPAG, and 3% is excreted in urine as unchanged mycophenolic acid. Following administration of mycophenolate mofetil, the mean apparent half-life of mycophenolic acid is 17.9 hours following oral administration and 16.6 hours following IV administration.
Following administration of mycophenolate sodium, the mean elimination half-lives of mycophenolic acid and MPAG ranged between 8--16 hours and 13--17 hours, respectively. Mycophenolic acid and MPAG usually are not removed by dialysis.
Mycophenolate mofetil (CellCept(R), Myhibbin(R)) is used in conjunction with other immunosuppressants for the prevention of rejection of kidney, heart, or liver allografts in adult and pediatric patients >=3 months of age.
Generic name: mycophenolate sodium
Pronunciation: (MYE-koe-FEN-oh-late SOE-dee-um)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Mycophenolic Acid
Indications
The following indications are listed for Mycophenolic Acid:
- Prevention Of Kidney Transplant Rejection
Also known as: Kidney Transplant Rejection Prophylaxis, Renal Transplant Rejection Prophylaxis.
Dosing
Dosage of mycophenolate mofetil and mycophenolate mofetil hydrochloride are both expressed in terms of mycophenolate mofetil. Dosage of mycophenolate sodium is expressed in terms of mycophenolic acid.
Mycophenolate mofetil tablets, capsules, and oral suspension (CellCept(R)) reportedly are bioequivalent. Mycophenolate sodium delayed-release tablets should not be used interchangeably with mycophenolate mofetil tablets, capsules, or oral suspension without supervision of a clinician, because absorption of the drug from these preparations is not equivalent.
If neutropenia (absolute neutrophil count (ANC) of less than 1300/mm3) develops, mycophenolate therapy should be temporarily discontinued or the dosage reduced; suitable diagnostic tests should be performed, and appropriate patient management should be instituted.
Mycophenolate mofetil is available as oral capsules, film-coated tablets, or powder for oral suspension, and as mycophenolate mofetil hydrochloride lyophilized powder for injection for IV infusion (CellCept(R)). Mycophenolate mofetil is also available as a ready-to-use oral suspension (Myhibbin(R)). Mycophenolate sodium is available as oral delayed-release (enteric-coated) tablets (Myfortic(R)).
Do not use mycophenolate mofetil or mycophenolate sodium without the supervision of a clinician with experience in immunosuppressive therapy.
Do not use mycophenolate mofetil oral dosage forms (capsules, tablets, or oral suspension) interchangeably with mycophenolic sodium delayed-release tablets without supervision of a clinician with experience in immunosuppressive therapy.
Because of the teratogenic potential of the drug, mycophenolate oral and parenteral preparations should be handled and prepared with care.
If a dose of mycophenolate mofetil is missed, the dose should be taken as soon as it is remembered unless it is closer than 2 hours to the next scheduled dose; in this case, continue to take mycophenolate mofetil at the usual times.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
There is no enhanced messaging for this drug.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Known hypersensitivity to mycophenolate mofetil, mycophenolate sodium, mycophenolic acid, or any ingredient in the formulation.
*Mycophenolate mofetil hydrochloride for IV injection; mycophenolate mofetil oral suspension (Myhibbin(R)): known hypersensitivity to polysorbate (Tween(R)) 80.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
The most common adverse effects (>=20%) with mycophenolate mofetil therapy are diarrhea, leukopenia, infection, and vomiting; there is evidence of a higher frequency of certain types of infections (e.g., opportunistic infection).
The most common adverse effects (>=20%) with mycophenolate sodium therapy are anemia, leukopenia, constipation, nausea, diarrhea, vomiting, dyspepsia, urinary tract infection, cytomegalovirus infection, insomnia, and postoperative pain.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and effectiveness of mycophenolate mofetil have been established in pediatric patients >=3 months of age for the prophylaxis of organ rejection of allogenic renal, cardiac, or hepatic transplants. Use of mycophenolate mofetil in the kidney transplant population is supported by evidence from adequate and well-controlled studies in adults with additional data from one open-label, pharmacokinetic and safety study in pediatric patients. Use of mycophenolate mofetil in the pediatric cardiac or hepatic transplant population is supported by adequate and well-controlled studies and pharmacokinetic data in adult cardiac or hepatic transplant patients. Additional supportive data include pharmacokinetic data in pediatric kidney and liver transplant patients and published findings of the drug's clinical efficacy and safety in pediatric cardiac or hepatic transplant patients.
The combination of inactive ingredients (e.g., simethicone, sodium phosphate monobasic dihydrate, sodium phosphate dibasic dihydrate, glycerin) in mycophenolate mofetil oral suspension (Myhibbin(R)) may impact GI tolerability; monitor pediatric patients receiving the drug for signs and symptoms of GI intolerance.
Safety and efficacy of mycophenolate sodium (e.g., Myfortic(R) ) in stable renal transplant pediatric patients 5-16 years of age who were initiated on the drug >=6 months posttransplant is based on evidence from adequate and well-controlled studies in a similar population of adult renal transplant patients with additional pharmacokinetic data in stable renal transplant pediatric patients. Safety and efficacy of mycophenolate sodium have not been established in pediatric de novo renal transplant patients or in pediatric renal transplant patients <5 years of age. A mycophenolate sodium dosage form suitable for providing an appropriate dosage for pediatric patients with a body surface area less than 1.19 m2 is not commercially available in the US.
Limited data are available concerning use of mycophenolate sodium in pediatric patients. Following administration of a single dose of mycophenolate sodium (mycophenolic acid 450 mg/m2) delayed-release tablets in stable pediatric renal transplant patients 5-16 years of age, peak plasma concentrations and AUC of mycophenolic acid were 33 and 18% higher, respectively, than those reported in adults receiving the same dose based on body surface area (720 mg). The clinical importance of these findings remains to be determined. Pharmacokinetic data are not available in pediatric patients younger than 5 years of age.
Pharmacokinetic parameters, including AUC, in children 1-18 years of age receiving mycophenolate mofetil 600 mg/m2 (oral suspension) twice daily following renal transplantation, are similar to values in adult renal transplant recipients receiving 1 g twice daily.
A pregnancy exposure registry is available that monitors pregnancy outcomes in women exposed to mycophenolate during pregnancy and those becoming pregnant within 6 weeks of discontinuing the drug. To report a pregnancy or obtain information about the registry, visit https://mycophenolaterems.com or call 1-800-617-8191.
Mycophenolate may cause fetal toxicity when administered to pregnant women. Use of mycophenolate has been associated with increased risk of first-trimester pregnancy loss and serious congenital malformations in multiple organ systems, based on published data from pregnancy registries. Documented malformations include external ear and other facial abnormalities (e.g., cleft lip and palate) and anomalies of the distal limbs, heart, esophagus, kidney, and nervous system.
Congenital malformations and pregnancy loss have been observed in rats and rabbits receiving mycophenolate at doses less than the recommended human dose; maternal toxicity was not observed.
Apprise females of reproductive potential and pregnant women of the potential hazard. Consider alternative immunosuppressants with less potential for embryofetal toxicity.
Perform a blood or urine pregnancy test (i.e., having a sensitivity of at least 25 mIU/mL for HCG) immediately prior to beginning mycophenolate therapy, and repeat the pregnancy test with the same sensitivity 8--10 days later. Perform repeat pregnancy tests during routine follow-up visits.
There are no data on the presence of mycophenolate in human milk or the effects of the drug on milk production. Limited data are available from the National Transplantation Pregnancy Registry on the effects of mycophenolate on breast-fed children. Mycophenolic acid is distributed into milk in rats.
It is not possible to exclude potential risks to nursing infants. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for mycophenolate and any potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.
The manufacturers make no specific dosage recommendations for mycophenolate mofetil or mycophenolic acid (administered as mycophenolate sodium delayed-release tablets) in geriatric patients.
In general, dosage selection for geriatric patients should be cautious, taking into consideration the presence of decreased hepatic, renal, or cardiac function and of concomitant drug therapies.
Clinical studies of mycophenolate did not include sufficient numbers of patients 65 years of age or older to determine whether they respond differently than younger adults. While other clinical experience has not revealed differences in response, drug dosages should be selected cautiously in geriatric patients. The greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant diseases and drug therapy observed in the elderly also should be considered. Geriatric patients may be at increased risk of developing GI hemorrhage, pulmonary edema, or certain infections (e.g., invasive CMV infection) than younger patients.
The pharmacokinetics of mycophenolate mofetil and its metabolites have not been found to be altered in geriatric transplant patients compared to younger transplant patients. Pharmacokinetics of mycophenolate sodium in geriatric patients have not been formally studied.
ICD codes
No ICD codes are available for this drug.
Formulary status
Search health-plan coverage for this drug by ZIP code.
Choose the first character of a health plan name.
Last reviewed · Source: First Databank (FDB) drug data
On this page
Actions
Sign in to save favorites
Saving this drug requires a free Physicians Office Resource account.