II. Indications
- FDA Approved Indications
- Solid Organ Transplant (heart, liver, Kidney)
- Immunosuppression (maintenance prevention of rejection)
- Solid Organ Transplant (heart, liver, Kidney)
- Other, off-label Indications
- Lupus Nephritis
- Uveitis (refractory)
- Autoimmune Bullous Dermatoses (Pemphigus, Bullous Pemphigoid)
- Refractory Rheumatoid Arthritis
III. Contraindications
- Hypoxanthine-Guanine Phosphoribosyl-Transferase Deficiency
IV. Mechanism
- Inosine monophosphate dehydrogenase (IMPDH)
- IMPDH is key to conversion of inosine monophosphate (IMP) to guanosine monophosphate (GMP)
- Guanosine monophosphate (GMP) is in turn converted to the guanine purine Nucleotides (GDP, GTP, and dGTP)
- Guanine purine Nucleotide is key to DNA and RNA synthesis, as well as Energy Metabolism (GTP)
- Mycophenolate Mofetil is a prodrug of Mycophenolic acid (MPA)
- Mycophenolate is rapidly metabolized in vivo to the active Mycophenolic acid (MPA)
- Mycophenolic acid (MPA) is a Purine Synthesis Inhibitor
- MPA primarily effects T Cell and B Cell proliferation and Antibody production
- MPA is a potent, non-competitive and reversible inhibitor of IMPDH
- IMPDH inhibition decreases DNA and RNA synthesis
- IMPDH effects de novo Purine synthesis but not the salvage pathway Purine synthesis
- Lymphocytes are selectively affected, as they rely on de novo Purine synthesis of guanine
V. Medications
- Mycophenolate or Mycophenolic acid Intravenous Solution
- Mycophenolate or Mycophenolic acid Immediate Release (Cellcept)
- Capsules: 250 mg
- Tablets: 500 mg
- Suspension: 200 mg/ml
- Oral solution contains Aspartame (avoid in Phenylketonuria)
- Mycophenolate or Mycophenolic acid Extended Release (MyFortic)
- Extended Release Tablets: 180 mg, 360 mg
VI. Dosing
- See other references for specific dosing regimens per indication
- Prescribers are typically specialists knowledgeable about the risks and monitoring
- Decrease dose in renal dysfunction, and adjust doses based on serum levels
- Avoid rapid infusion or IV bolus administration (risk of reaction)
- Typical oral doses are 500 to 1000 mg twice daily in Rheumatoid Arthritis
VII. Adverse Effects
-
Bone Marrow suppression
- Neutropenia
- Red Blood Cell Aplasia
- Secondary malignancy (including Lymphoma, Skin Cancer)
- Serious opportunistic Infections
- Progressive Multifocal Leukoencephalopathy (PML)
- Acute Inflammatory Syndrome
- Local Reactions (esp. with IV bolus or rapid infusion)
- Impaired Driving
- Gastrointestinal
- Nausea or Vomiting
- Diarrhea
- Abdominal Pain
- Gastrointestinal Hemorrhage
- Bowel perforation
VIII. Safety
- Pregnancy Category D
- Risk of first trimester pregnancy loss and congenital malformations
- Use reliable Contraception (Oral Contraceptives may also be rendered less effective by Mycophenolate)
- Men should avoid unprotected intercourse or semen donation during and for 3 months after last dose
- Avoid in Lactation
- Avoid blood donation during and for 6 weeks after last Mycophenolate dose
- Monitoring
- Obtain Tuberculosis Testing (e.g. PPD) before starting Mycophenolate
- Mycophenolate serum concentrations (periodically and with dosing changes, interacting medications)
- Complete Blood Count (Rheumatoid Arthritis monitoring protocol)
- Obtain baseline
- Obtain weekly for first month, twice monthly for next 2 months and then monthly
IX. Drug Interactions
-
Antacids
- Avoid Antacids (Magnesium or aluminum hydroxide) for at least 2 hours after dose
- Proton Pump Inhibitors (PPIs) may reduce Mycophenolate absorption and efficacy (monitor levels)
- Drugs that modify enterohepatic circulation affect Mycophenolate serum levels (esp. lowering serum level)
- Cyclosporine
- Trimethoprim/sulfamethoxazole
- Bile Acid Sequestrants (Cholestyramine)
- Rifampin
- Antibiotics alter bowel flora (Aminoglycosides, Cephalosporins, Fluoroquinolones and Penicillins)
- Drugs that affect Glucuronidation
- Telmisartan (induces Glucuronidation, decreasing Mycophenolate levels)
- Isavuconazole (inhibits Glucuronidation, raising Mycophenolate levels)
- Calcium free Phosphate Binders lower Mycophenolate levels
- Drugs that compete for Renal Tubular Secretion (esp. in Renal Insufficiency) raise Mycophenolate levels
-
Oral Contraceptives
- See safety as above
- Decreased Levonorgestrel levels (risk of lower Oral Contraceptive efficacy)
- Use other reliable Contraception
-
Live Attenuated Vaccines
- Avoid with Mycophenolate
X. Resources
- Mycophenolate (DailyMed)
- Mycophenolate Extended Release (DailyMed)
Images: Related links to external sites (from Bing)
Related Studies
mycophenolate (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
MYCOPHENOLATE 200 MG/ML SUSP | Generic | $3.12 per ml |
MYCOPHENOLATE 250 MG CAPSULE | Generic | $0.19 each |
MYCOPHENOLATE 500 MG TABLET | Generic | $0.30 each |
cellcept (on 7/19/2023 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
CELLCEPT 200 MG/ML ORAL SUSP | Generic | $3.12 per ml |
mycophenolic acid (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
MYCOPHENOLIC ACID DR 180 MG TB | Generic | $0.24 each |
MYCOPHENOLIC ACID DR 360 MG TB | Generic | $0.39 each |
Ontology: Mycophenolic Acid (C0026933)
Definition (NCI) | An antineoplastic antibiotic derived from various Penicillium fungal species. Mycophenolic acid is an active metabolite of the prodrug mycophenolate mofetil. Mycophenolic acid inhibits inosine monophosphate dehydrogenase (IMPDH), preventing the formation of guanosine monophosphate and synthesis of lymphocyte DNA that results in inhibition of lymphocyte proliferation, antibody production, cellular adhesion, and migration of T and B lymphocytes. Mycophenolic acid also has antibacterial, antifungal, and antiviral activities. (NCI04) |
Definition (MSH) | An antibiotic substance derived from Penicillium stoloniferum, and related species. It blocks de novo biosynthesis of purine nucleotides by inhibition of the enzyme inosine monophosphate dehydrogenase. Mycophenolic acid is important because of its selective effects on the immune system. It prevents the proliferation of T-cells, lymphocytes, and the formation of antibodies from B-cells. It also may inhibit recruitment of leukocytes to inflammatory sites. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1301) |
Definition (CSP) | antibiotic substance derived from Penicillium stoloniferum and related species which blocks de novo biosynthesis of purine nucleotides by inhibition of the enzyme inosine monophosphate dehydrogenase; mycophenolic acid has selective effects on the immune system, preventing the proliferation of T cells, lymphocytes, and the formation of antibodies from B cells. |
Concepts | Lipid (T119) , Antibiotic (T195) |
MSH | D009173 |
SnomedCT | 409331009, 409330005 |
English | Acid, Mycophenolic, 4-Hexenoic acid, 6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-, (E)-, 4-Hexenoic acid, 6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-5-phthalanyl)-4-methyl-, (E)-, -Hexenoic acid, 6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-, (E)-, mycophenolic acid (medication), mycophenolic acid, MYCOPHENOLIC ACID, Mycophenolic Acid [Chemical/Ingredient], Mycophenolic acid (product), Mycophenolic acid (substance), Mycophenolic acid, MPA, Acide mycophenolique, Acido micofenolico, Acidum mycophenolicum, Mycophenolic Acid |
Swedish | Mykofenolsyra |
Czech | kyselina mykofenolová |
Finnish | Mykofenolihappo |
Russian | MIKOFENOLOVAIA KISLOTA, МИКОФЕНОЛОВАЯ КИСЛОТА |
Spanish | Ácido Micofenólico, ácido micofenólico (producto), ácido micofenólico (sustancia), ácido micofenólico |
Polish | Kwas mykofenolowy |
Japanese | セルセプト, ミコフェノール酸, ミコフェノール酸ジナトリウム, ミコフェノール酸ナトリウム, ミコフェノラートモフェチル, ミコフェノール酸モフェチル |
French | Acide mycophénolique |
German | Mycophenolsäure |
Italian | Acido micofenolico |
Portuguese | Ácido Micofenólico |
Ontology: mycophenolate mofetil (C0209368)
Definition (NCI) | The morpholinoethyl ester of mycophenolic acid (MPA) with potent immunosuppressive properties. Mycophenolate stops T-cell and B-cell proliferation through selective inhibition of the de novo pathway of purine biosynthesis. In vivo, the active metabolite, MPA, reversibly inhibits inosine 5'-monophosphate dehydrogenase, an enzyme involved in the de novo synthesis of guanine nucleotides. MPA displays high lymphocyte specificity and cytotoxicity due to the higher dependence of activated lymphocytes on both salvage and de novo synthesis of guanine nucleotides relative to other cell types. (NCI04) |
Definition (NCI_NCI-GLOSS) | A drug used to prevent graft-versus-host disease (GVHD) after organ transplants. It is also being studied in the prevention of GVHD after stem cell transplants for cancer, and in the treatment of some autoimmune disorders. Mycophenolate mofetil is a type of immunosuppressive agent. |
Definition (CSP) | immunosuppressant used in the prophylaxis of organ rejection. |
Definition (PDQ) | The morpholinoethyl ester of mycophenolic acid (MPA) with potent immunosuppressive properties. Mycophenolate stops T-cell and B-cell proliferation through selective inhibition of the de novo pathway of purine biosynthesis. In vivo, the active metabolite, MPA, reversibly inhibits inosine 5'-monophosphate dehydrogenase, an enzyme involved in the de novo synthesis of guanine nucleotides. MPA displays high lymphocyte specificity and cytotoxicity due to the higher dependence of activated lymphocytes on both salvage and de novo synthesis of guanine nucleotides relative to other cell types. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42797&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42797&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1468" NCI Thesaurus) |
Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
MSH | C063008 |
SnomedCT | 109131004, 386976000 |
English | mycophenolic acid morpholinoethyl ester, mycophenolate mofetil (medication), Mycophenolate Mofetil, MYCOPHENOLATE MOFETIL, mycophenolate mofetil [Chemical/Ingredient], mofetil mycophenolate, Mycophenolate mofetil, Mycophenolate mofetil (product), Mycophenolate mofetil (substance), mycophenolate mofetil, MMF |
Spanish | micofenolato mofetilo, micofenolato mofetilo (producto), micofenolato de mofetilo (producto), micofenolato de mofetilo (sustancia), micofenolato de mofetilo |
Ontology: Cellcept (C0592558)
Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
MSH | C063008 |
English | Cellcept, CellCept, cellcept |