Class: Immunosuppressive Agents
Chemical Name: 6-(1,3-Dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-2-(4-morpholinyl)ethyl ester hexenoic acid
Molecular Formula: C23H31NO7C23H31NO7•HClC17H19NaO6C17H20O6
CAS Number: 116680-01-4
Brands: CellCept, Myfortic
- Immunosuppression
Immunosuppression may result in increased susceptibility to infection and possible development of lymphoma.1 27 43 44
Only clinicians experienced in immunosuppressive therapy and management of renal, cardiac, or hepatic transplant patients should prescribe mycophenolate.1 27
Patients should be managed in facilities equipped and staffed with appropriate laboratory and supportive resources; the clinician responsible for maintenance therapy should have complete information for patient follow-up.1 27
- Fetotoxicity
May cause fetal harm; potential risk of congenital malformations and loss of pregnancy.1 27 43 44 Women of childbearing potential must use contraception.1 27 43 44 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
Introduction
Immunosuppressive agent.1 2 3 4 5 6 7 Mycophenolate mofetil is a prodrug that is hydrolyzed in vivo to mycophenolic acid, the pharmacologically active metabolite.1 2 7 12 Mycophenolate sodium delayed-release tablets release the active moiety, mycophenolic acid, in the small intestine.27 28
Uses for Mycophenolate
Renal Allotransplantation
Prevention of rejection of renal allografts.1 3 4 5 6 12 27
Cardiac Allotransplantation
Prevention of rejection of cardiac allografts.1 7
Hepatic Allotransplantation
Prevention of rejection of liver allografts.1 9
Crohn’s Disease
Has been used in the management of Crohn’s Disease†.13 14 15 16 18 20 21 22 23 24 25 Not a first-line agent; reserved for patients who are refractory to or intolerant of other agents (e.g., azathioprine, mercaptopurine, methotrexate, infliximab).14 23
Mycophenolate Dosage and Administration
General
Distribute medication guide each time mycophenolate is dispensed.41 42 43 44
Administration
Administer mycophenolate mofetil and mycophenolate sodium orally;1 27 administer mycophenolate mofetil hydrochloride by IV infusion.1
In patients undergoing allotransplantation, the drug is used with cyclosporine and corticosteroids; other immunosuppressive agents (e.g., antithymocyte globulin, antilymphocyte globulin, muromonab-CD3, basiliximab, daclizumab) also have been used.1 3 4 5 6 27 28 29 30 31 Safety and efficacy of concomitant use with immunosuppressive drugs other than these agents not determined.1 32 (See Specific Drugs under Interactions.)
Handle with care.1
Mycophenolate mofetil: Do not crush tablets; do not open or crush capsules.1 43
Mycophenolate sodium: Do not crush, chew, or cut tablets.27 44 Tablets should be swallowed whole to maintain integrity of enteric coating.27
Avoid inhalation of powder in capsules or oral suspension (before and after reconstitution) and contact with skin or mucous membranes.1
Avoid contact with IV solution.1 In case of skin or mucous membrane contact, wash affected area with soap and water.1
If contact with eyes occurs, wash with water.1
Wipe up any spilled drug with a wet paper towel.1
Oral Administration
Mycophenolate mofetil: Administer orally as soon as possible following renal, cardiac, or hepatic transplantation.1
Mycophenolate mofetil: Administer preferably on an empty stomach, 1 hour before or 2 hours after food.1 43 May be given with food, if necessary, in stable renal transplant recipients.1 43 (See Food under Pharmacokinetics.) If a dose is missed, take the missed dose as soon as it is remembered unless it is almost time for the next dose.43 Do not take a double dose.43
Mycophenolate sodium: Administer as soon as possible following renal transplantation in adults.27 If a dose is missed, take the missed dose as soon as it is remembered unless it is almost time for the next dose.44 Do not take a double dose.44
Mycophenolate sodium: Administer in stable pediatric renal transplant recipients; safety and efficacy in de novo pediatric renal transplant recipients not established.27
Mycophenolate sodium: Administer on an empty stomach, 1 hour before or 2 hours after food.27 44 (See Food under Pharmacokinetics.)
Reconstitution
Mycophenolate mofetil for oral suspension: Reconstitute at time of dispensing by adding 94 mL of water (about 47 mL initially followed by another 47 mL after vigorous shaking for 1 minute) to provide a suspension containing 200 mg/mL.1 12 Shake bottle well again for 1 minute.1
Mycophenolate mofetil for oral suspension: Do not admix with other drugs.1
NG Tube
Mycophenolate mofetil for oral suspension: Can administer by nasogastric tube (minimum 1.7 mm in interior diameter; minimum French size number 8).1
IV Administration
Mycophenolate mofetil hydrochloride injection: Initiate within 24 hours following transplantation.1
Reserve IV administration for patients who cannot tolerate or are unable to take an oral dosage form.1
Administer IV for up to 14 days.1
Switch from parenteral to oral therapy as soon as possible.1
Do not mix or administer concurrently via the same infusion catheter with any other IV drugs or infusion admixtures.1
Reconstitution
Mycophenolate mofetil hydrochloride injection: Add 14 mL of 5% dextrose injection to a vial containing 500 mg of mycophenolate mofetil; shake vial gently.1
Use strict aseptic technique; drug contains no preservative.1
Dilution
For a 1-g infusion dose, add contents of 2 reconstituted vials to 140 mL of 5% dextrose injection to provide a solution containing 6 mg/mL.1
For a 1.5-g infusion dose, add the contents of 3 reconstituted vials to 210 mL of 5% dextrose injection to provide a solution containing 6 mg/mL.1
Start IV administration within 4 hours of reconstitution and dilution.1
Rate of Administration
Infuse over ≥ 2 hours by either a peripheral or central vein; do not administer by rapid IV (“bolus”) injection or rapid IV infusion.1
Dosage
Available as mycophenolate mofetil (oral capsules, tablets, for oral suspension) and mycophenolate mofetil hydrochloride (injection); dosage expressed in terms of mycophenolate mofetil.1
Available as mycophenolate sodium (delayed-release tablets); dosage expressed in terms of mycophenolic acid.27
Mycophenolate sodium delayed-release tablets should not be used interchangeably with mycophenolate mofetil tablets, capsules, or oral suspension without clinician supervision.27
If neutropenia (ANC <1300/mm3) develops, temporarily discontinue or reduce dosage.1 27 (See Hematologic Effects under Cautions.)
Pediatric Patients
Renal Allotransplantation
Mycophenolate mofetil capsules, tablets, and oral suspension
Oral
Children 3 months to 18 years of age: 600 mg/m2 as the oral suspension twice daily (maximum 1 g twice daily).1
Children with a body surface area of 1.25–1.5 m2: 750 mg as capsules twice daily.1
Children with a body surface area >1.5 m2: 1 g as capsules or tablets twice daily.1
Mycophenolate sodium delayed-release tablets
Oral
Children 5–16 years of age: 400 mg/m2 twice daily (maximum 720 mg twice daily).27
Children 5–16 years of age with a body surface area <1.19 m2: accurate dosage cannot be administered using commercially available tablets.27
Children 5–16 years of age with a body surface area of 1.19–1.58 m2: 1080 mg daily (given as three 180-mg tablets twice daily or as one 180-mg tablet and one 360-mg tablet twice daily).27
Children 5–16 years of age with a body surface >1.58 m2: 1440 mg daily (given as four 180-mg tablets twice daily or two 360-mg tablets twice daily).27
Adults
Renal Allotransplantation
Mycophenolate mofetil capsules, tablets, and oral suspension
Oral
1 g twice daily.1 No efficacy advantage with dosage of 1.5 g twice daily;1 2-g daily dosage associated with a superior safety profile compared with the 3-g daily dosage.1
Mycophenolate sodium delayed-release tablets
Oral
720 mg twice daily.27
Mycophenolate mofetil hydrochloride for injection
IV
1 g twice daily.1 No efficacy advantage with dosage of 1.5 g twice daily;1 2-g daily dosage associated with a superior safety profile compared with the 3-g daily dosage.1
Cardiac Allotransplantation
Mycophenolate mofetil capsules, tablets, and oral suspension
Oral
1.5 g twice daily.1
Mycophenolate mofetil hydrochloride for injection
IV
1.5 g twice daily.1
Hepatic Allotransplantation
Mycophenolate mofetil capsules, tablets, and oral suspension
Oral
1.5 g twice daily.1
Mycophenolate mofetil hydrochloride for injection
IV
1 g twice daily.1
Crohn’s Disease†
Mycophenolate mofetil capsules, tablets, and oral suspension
Oral
Dosages of 1–2 g daily have been used.14 15 19 21 23 24
Prescribing Limits
Pediatric Patients
Renal Allotransplantation
Mycophenolate mofetil capsules, tablets, and oral suspension
Oral
Children 3 months to 18 years of age: Maximum 1 g twice daily.1
Mycophenolate sodium delayed-release tablets
Oral
Children 5–16 years of age: Maximum 720 mg twice daily.27
Special Populations
Hepatic Impairment
Renal Allotransplantation
No dosage adjustment necessary in renal transplant recipients with severe hepatic parenchymal disease; not known whether dosage adjustment is needed for other hepatic diseases.1 27
Cardiac Allotransplantation
No data available for cardiac transplant recipients with severe hepatic parenchymal disease.1
Renal Impairment
Renal Allotransplantation
Dosage adjustment not necessary in renal transplant recipients experiencing postoperative delayed graft function.1 27
Mycophenolate mofetil capsules, tablets, or oral suspension or mycophenolate mofetil hydrochloride for injection: Avoid dosages >1 g twice daily in renal transplant recipients with severe chronic renal impairment (GFR <25 mL/minute per 1.73 m2) beyond the immediate posttransplant period.1
Cardiac Allotransplantation
No data available for cardiac transplant recipients with severe chronic renal impairment.1
Hepatic Allotransplantation
No data available for hepatic transplant recipients with severe chronic renal impairment.1
Geriatric Patients
Mycophenolate mofetil capsules, tablets, or oral suspension or mycophenolate mofetil hydrochloride for injection: Select dosage carefully.1 Dosage adjustment based solely on age is not necessary in geriatric patients ≥65 years of age.1
Mycophenolate sodium delayed-release tablets: Maximum 720 mg twice daily.27
Cautions for Mycophenolate
Contraindications
Known hypersensitivity to mycophenolate mofetil, mycophenolate sodium, mycophenolic acid, or any ingredient in the formulation.1 27
IV formulation contraindicated in patients with known severe hypersensitivity to IV polysorbate (Tween) 80.1
Warnings/Precautions
Warnings
Carcinogenicity
Increased risk of lymphoma and other malignancies, particularly of the skin in patients receiving immunosuppressive regimens.1 27 Risk appears to be related to the intensity and duration of immunosuppression rather than to any specific immunosuppressive agent.1 27
Fetal/Neonatal Morbidity and Mortality
May cause fetal harm when administered to pregnant women.1 27 33 35 36 40 Congenital malformations and increased incidence of spontaneous abortions reported during postmarketing surveillance and from the National Transplantation Pregnancy Registry (NTPR); teratogenicity and embryolethality demonstrated in animals.1 27 33 35 40
Use not recommended during pregnancy unless potential benefits justify risks to the fetus.1 27 33 Women of childbearing potential should have a negative blood or urine pregnancy test (i.e., sensitivity of at least 25 mIU/mL for human chorionic gonadotropin [HCG]) within 1 week prior to beginning therapy.1 27 40 Do not initiate therapy until a report of the pregnancy test is available indicating that results are negative.1 27 40
Women of childbearing potential should use 2 reliable forms of contraception 4 weeks prior to, during, and for 6 weeks following discontinuance of mycophenolate mofetil.1 27 40 If used during pregnancy or patient becomes pregnant while receiving the drug, apprise of potential fetal hazard and risk for loss of pregnancy; encourage patient to enroll in the NTPR.1 27
Infectious Complications
Increased susceptibility to infection (i.e., opportunistic infections, sepsis, life-threatening/fatal infections).1 27
Incidence of opportunistic infections in cardiac allograft recipients receiving mycophenolate was about 10% higher than in those receiving azathioprine; the difference was not associated with excess mortality due to infection or sepsis in patients receiving mycophenolate.1 Viral infections (e.g., cytomegalovirus [CMV] infections, herpes simplex, herpes zoster) reported more frequently in cardiac transplant recipients receiving mycophenolate than in those receiving azathioprine.1
Latent Viral Infections
Increased risk of reactivation of latent viral infections, including BK virus-associated nephropathy (BKVN).1 27 484 485 486 487 488 489 490 492 Principally observed in renal transplant patients (usually within the first year posttransplantation); may result in severe allograft dysfunction and/or graft loss.1 27 484 485 486 487 488 489 490 491 492 Reported in patients receiving immunosuppressive regimens containing mycophenolate mofetil.1 486 488 489 490 491 492 Risk appears to correlate with degree of overall immunosuppression rather than use of specific immunosuppressant.485 486 487 488 489 490 491 492 Monitor closely for signs of BKVN (e.g., deterioration in renal function);1 27 484 485 486 488 if BKVN develops, institute early treatment, and consider reducing immunosuppressive therapy.1 27 484 485 486 487 488 490 491 492
Progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain caused by the JC virus, reported in at least 17 patients receiving mycophenolate mofetil (CellCept); death occurred in at least 7 patients.37 38 39 These patients had concomitant exposure to other immunosuppressive agents (i.e., azathioprine, corticosteroids, cyclophosphamide, cyclosporine, tacrolimus) or had compromised immune function.1 27 37 38 Not reported to date with mycophenolate sodium (Myfortic).37 However, risk of PML with mycophenolate sodium expected to be the same as with mycophenolate mofetil; both drugs are metabolized to the same active metabolite (mycophenolic acid).37
Consider possible diagnosis of PML in any immunocompromised patient who develops neurologic manifestations.1 27 37 38 Refer patient to a neurologist as clinically indicated.1 27 37 38 If PML develops, consider decreasing total immunosuppression; weigh benefits of reduced immunosuppression against risk of potential graft rejection in organ transplant recipients.1 27 37 38
Hematologic Effects
Severe neutropenia (ANC <500/mm3) reported; observed most frequently between 31–180 days posttransplant.1 27 Neutropenia may be related to mycophenolate, concomitant therapies, viral infection, or a combination of these causes.1 27
Perform CBC weekly during the first month of therapy, twice monthly during the second and third months, and then monthly thereafter during the first year.1 27
Discontinue or adjust dosage if neutropenia develops, perform suitable diagnostic tests, and initiate appropriate patient management.1 27
Pure red cell aplasia (PRCA), a condition in which RBC precursors in the bone marrow are absent or nearly absent, reported in at least 41 patients receiving mycophenolate mofetil.1 27 495 496 497 498 Some of these patients also were receiving other immunosuppressive agents (e.g., alemtuzumab, azathioprine, tacrolimus); relative contribution of mycophenolate mofetil to development of PRCA not known.1 27 495 498 Consider risk of PRCA also in patients receiving mycophenolate sodium; both drugs converted to the same active metabolite (mycophenolic acid).27 495
PRCA may be reversible in some cases with dosage reduction or discontinuance.1 27 495 496 497 498 Consider possibility of graft rejection if immunosuppression reduced in transplant patients; implement any changes to immunosuppressive therapy under appropriate medical supervision.1 27 495 496
Major Toxicities
GI Effects
Severe GI bleeding (requiring hospitalization) has occurred; increased incidence of adverse GI effects (e.g., ulceration, hemorrhage, perforation) reported.1 3 4 27 Caution in patients with serious active GI disease.1 3 4 27
General Precautions
Hypoxanthine Phosphoribosyltransferase Deficiency
Avoid (on theoretical grounds) in patients with rare hereditary deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT), including Kelley-Seegmiller or Lesch-Nyhan syndrome.1 27 Mycophenolic acid inhibits inosine monophosphate dehydrogenase.1
Phenylketonuria
Oral suspension contains aspartame (Nutrasweet), which is metabolized in the GI tract to provide about 0.56 mg of phenylalanine per 5 mL of the suspension.1
Specific Populations
Pregnancy
Category D.1 27 33 34 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
Lactation
Distributed into milk in rats; not known whether distributed into human milk.1 27 Discontinue nursing or the drug.1 27 Avoid breast-feeding for at least 6 weeks after discontinuing mycophenolate sodium.27
Pediatric Use
Mycophenolate mofetil: Safety for the prevention of rejection of renal allografts in children 3 months to 18 years of age based on data from a pediatric pharmacokinetic and safety study.1
Mycophenolate mofetil: Safety and efficacy not established in pediatric patients <3 months of age receiving renal allografts.1
Mycophenolate mofetil: Safety and efficacy not established in pediatric patients <18 years of age receiving allogenic cardiac or hepatic transplants.1 12
Mycophenolate sodium: Safety and efficacy in stable renal transplant recipients 5–16 years of age based on data from a pediatric pharmacokinetic study and clinical studies in adults.27 Safety and efficacy not established in children <5 years of age; a mycophenolate sodium dosage form appropriate for pediatric patients with body surface area <1.19 m2 currently not available.27
Mycophenolate sodium: Safety and efficacy not established in de novo renal transplant patients.27
Mycophenolate mofetil: Safety profile in children generally is similar to that in adults; 10 11 however, the incidence of abdominal pain,1 fever,1 infection,1 pain,1 sepsis,1 diarrhea,1 vomiting,1 pharyngitis,1 respiratory tract infection,1 hypertension,1 and anemia1 higher in pediatric patients than in adults.1 10 Lymphoproliferative malignancies reported rarely; other types of malignancies not reported.1 Severe GI bleeding (requiring hospitalization) reported.1
Geriatric Use
Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.1 27 Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant diseases and drug therapy.1 27
Possible increased risk of developing GI hemorrhage, pulmonary edema, or certain infections (e.g., invasive CMV infection).1 27
Renal Impairment
Mycophenolate mofetil: No data available in cardiac or hepatic transplant recipients with severe chronic renal impairment; may use if potential benefits outweigh potential risks.1
Mycophenolate sodium: Follow patients with severe chronic renal impairment (GFR <25 mL/minute per 1.73m2) for adverse effects due to increased concentrations of free (unbound) mycophenolic acid and total mycophenolic acid glucuronide concentrations.27
Common Adverse Effects
Mycophenolate mofetil: Diarrhea,1 3 4 leukopenia,1 3 sepsis,1 vomiting,1 3 higher frequency of infections, including opportunistic infections1 3 4 (e.g., CMV infections,1 3 4 herpes zoster,3 herpes simplex,1 3 candidal infections,1 3 aspergillosis,3 4 Pneumocystis carinii pneumonia).1 3
Mycophenolate sodium: Constipation, diarrhea, nausea, urinary tract infection, nasopharyngitis.27
Interactions for Mycophenolate
Drugs That Alter Intestinal Flora
Possible disruption of enterohepatic recirculation; less mycophenolic acid available for absorption.1 27
Drugs That Interfere with Enterohepatic Recirculation
Possible decreased plasma concentrations of mycophenolic acid.1 27 Concomitant use not recommended.1 27
Drugs That Undergo Renal Tubular Secretion
Possible increased plasma concentrations of phenolic glucuronide of mycophenolic acid or other drugs that undergo renal tubular secretion.1
Vaccines
Vaccines may be less effective; avoid use of live virus vaccines.1 27 43 Influenza virus vaccine inactivated may be of value.1 27
Specific Drugs
Drug | Interaction | Comments |
|---|---|---|
Acyclovir | Mycophenolate mofetil: Increased plasma concentrations of acyclovir and the phenolic glucuronide of mycophenolic acid1 | Can be used concomitantly1 27 If used with mycophenolate sodium, monitor CBC27 Monitor patients with renal impairment1 |
Amoxicillin and clavulanic acid | Mycophenolate mofetil: Decreased trough concentrations of mycophenolic acid.1 493 May reduce glucuronidase-possessing enteric bacteria resulting in decreased enterohepatic recirculation of mycophenolic acid1 493 | Clinical importance not clear1 493 |
Antacids (aluminum- and magnesium- containing) | Decreased mycophenolic acid plasma concentrations and AUC when administered with Maalox TC 1 27 | May be used with antacids; do not administer simultaneously1 27 43 44 |
Azathioprine | Increased risk of bone marrow suppression1 | Concomitant use not recommended1 27 |
Cholestyramine | Decreased mycophenolic acid AUC1 27 | Concomitant use not recommended 1 27 |
Ciprofloxacin | Mycophenolate mofetil: Decreased trough concentrations of mycophenolic acid.1 493 May reduce glucuronidase-possessing enteric bacteria resulting in decreased enterohepatic recirculation of mycophenolic acid1 493 | Clinical importance not clear1 493 |
Co-trimoxazole | Pharmacokinetic interaction unlikely1 | |
Cyclosporine | Use of mycophenolate mofetil without cyclosporine results in increased systemic exposure to mycophenolic acid compared with use of mycophenolate mofetil in conjunction with cyclosporine;1 plasma cyclosporine concentrations not affected1 27 | Mycophenolate mofetil: Consider possibility of increased mycophenolic acid concentrations if drug is used without cyclosporine1 |
Ganciclovir | Possible increased plasma concentrations of the metabolites of both drugs in patients with renal impairment1 27 | Can be used concomitantly1 27 Monitor patients with renal impairment1 If used with mycophenolate sodium, monitor CBC27 |
Hormonal contraceptives (ethinyl estradiol, levonorgestrel, desogestrel, gestodene) | Mycophenolate mofetil: Decreased plasma levonorgestrel concentrations; no changes in ethinyl estradiol and 3-keto desogestrel concentrations1 Mycophenolate sodium: Pharmacokinetic interaction unlikely27 | Caution; use additional contraceptive methods1 27 |
Metronidazole | Mycophenolate mofetil: Possible decreased exposure to mycophenolic acid when administered concomitantly with metronidazole and norfloxacin; no substantial effect when administered with metronidazole1 | Concomitant use with norfloxacin and metronidazole not recommended1 |
Norfloxacin | Mycophenolate mofetil: Possible decreased exposure to mycophenolic acid when administered concomitantly with norfloxacin and metronidazole; no substantial effect when administered with norfloxacin1 | Concomitant use with norfloxacin and metronidazole not recommended1 |
Probenecid | Possible increased concentrations of mycophenolic acid and the phenolic glucuronide of mycophenolic acid 1 | |
Rifampin | Mycophenolate mofetil: Possible decreased systemic exposure to mycophenolic acid1 | Concomitant use not recommended unless benefit outweighs risk1 |
Salicylates | Possible increased free fraction of mycophenolic acid 1 | |
Sevelamer | Mycophenolate mofetil: Possible decreased plasma concentrations of mycophenolic acid1 | Concurrent administration not recommended; give sevelamer or other non-calcium-containing phosphate binders 2 hours after mycophenolate mofetil1 |
Sirolimus | Following use of an immunosuppressive regimen (i.e., mycophenolate mofetil, cyclosporine or tacrolimus, and a corticosteroid) for 12 weeks, switching from cyclosporine or tacrolimus to sirolimus associated with higher than expected incidence of acute rejection in cardiac transplant patients32 | Safety and efficacy of mycophenolate mofetil in combination with sirolimus after withdrawal of initial cyclosporine or tacrolimus therapy not established32 |
Valganciclovir | Possible increased plasma concentrations of the metabolites of both drugs in patients with renal impairment8 | Monitor patients with renal impairment1 |
Mycophenolate Pharmacokinetics
Absorption
Bioavailability
Mycophenolate mofetil: Rapidly absorbed following oral administration; bioavailability is 94%.1
Following oral and IV administration, mycophenolate mofetil undergoes rapid and complete metabolism to mycophenolic acid, the active metabolite.1
Mycophenolate sodium: Following oral administration of the delayed-release tablets, mycophenolic acid is released in the small intestine; bioavailability is 72%.27
Mycophenolate mofetil tablets, capsules, and oral suspension are bioequivalent.1 12
Mycophenolate sodium delayed-release tablets cannot be used interchangeably with mycophenolate mofetil tablets, capsules, or oral suspension without clinician supervision.27 Single oral doses of mycophenolate sodium delayed-release tablets (mycophenolic acid 720 mg) and mycophenolate mofetil 1 g result in bioequivalent mycophenolic acid exposure.28
Food
Food decreases peak plasma concentrations of mycophenolic acid (by 33–40%); no effect on the mycophenolic acid AUC.1 27
Special Populations
Plasma concentrations of free (unbound) mycophenolic acid and total mycophenolic acid glucuronide have increased in nontransplant individuals with severe chronic renal impairment (GFR <25 mL/minute per 1.73 m2).1 Plasma mycophenolic acid concentrations in patients with delayed graft function similar to values in patients not experiencing delayed graft function.1
Pharmacokinetic parameters, including AUC, in children 1–18 years of age receiving mycophenolate mofetil 600 mg/m2 (oral suspension) twice daily following renal transplantation similar to values in adult renal transplant recipients receiving 1 g twice daily.1
Peak plasma concentrations and AUC of mycophenolic acid in stable pediatric renal transplant patients 5–16 years of age receiving a single dose of mycophenolate sodium (mycophenolic acid 450 mg/m2) increased (33 and 18%, respectively) relative to adults receiving the same dose based on body surface area.27 Clinical importance not determined.27
Distribution
Plasma Protein Binding
Mycophenolic acid: ≥97–98% (mainly albumin).1 27
Elimination
Metabolism
Mycophenolate mofetil undergoes complete metabolism to mycophenolic acid; metabolism occurs presystemically following oral administration.1 Mycophenolic acid is metabolized by glucuronyl transferase to the phenolic glucuronide of mycophenolic acid.1 27 The phenolic glucuronide is converted to mycophenolic acid via enterohepatic recirculation.1 27
Elimination Route
Mycophenolate mofetil: Excreted in urine (93%) as the phenolic glucuronide of mycophenolic acid (87%) and in feces (6%).1
Mycophenolate sodium: Excreted principally in urine as phenolic glucuronide of mycophenolic acid (>60%) and as unchanged mycophenolic acid (3%).27
Half-life
Mycophenolic acid: 8–17.9 hours.1 27
Special Populations
Plasma concentrations of mycophenolic acid glucuronide higher in nontransplant subjects with severe renal impairment than in those with mild impairment or normal renal function.1 27
Plasma concentrations of mycophenolic acid glucuronide higher in transplant patients with delayed renal graft function than in patients not experiencing delayed graft function.1
Dialysis does not remove mycophenolic acid.1 27
Pharmacokinetic studies in patients with alcoholic cirrhosis indicate that hepatic mycophenolic acid glucuronidation is not affected by hepatic parenchymal disease; hepatic disease with other etiologies (e.g., biliary cirrhosis) may show a different effect.1
Stability
Storage
Oral
Capsules and Tablets
25°C (may be exposed to 15–30°C).1 27
Mycophenolate mofetil: Dispense in light-resistant containers (e.g., original container).1
Mycophenolate sodium: Dispense in tight containers.27
Suspension
25°C (may be exposed to 15–30°C).1 Store reconstituted suspension at 25°C (may be exposed to 15–30°C) for up to 60 days.1 Reconstituted suspension may be refrigerated; do not freeze.1
Parenteral
Powder for Injection
25°C (may be exposed to 15–30°C).1 Store reconstituted solution and solution for infusion at 25°C (may be exposed to 15–30°C).1
Compatibility
For information on systemic interactions resulting from concomitant use, see Interactions.
Parenteral
Solution CompatibilityHID
Compatible |
|---|
Dextrose 5% in water |
ActionsActions
Differs structurally and pharmacologically from othe
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