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 |