Mycophenolate

FDA Approved Indications
1. Solid Organ Transplant (heart, liver, Kidney)
  1. Immunosuppression (maintenance prevention of rejection)
Other, off-label Indications
1. Lupus Nephritis
2. Uveitis (refractory)
3. Autoimmune Bullous Dermatoses (Pemphigus, Bullous Pemphigoid)
4. Refractory Rheumatoid Arthritis

Inosine monophosphate dehydrogenase (IMPDH)
1. IMPDH is key to conversion of inosine monophosphate (IMP) to guanosine monophosphate (GMP)
2. Guanosine monophosphate (GMP) is in turn converted to the guanine purine Nucleotides (GDP, GTP, and dGTP)
3. 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)
1. Mycophenolate is rapidly metabolized in vivo to the active Mycophenolic acid (MPA)
Mycophenolic acid (MPA) is a Purine Synthesis Inhibitor
1. MPA primarily effects T Cell and B Cell proliferation and Antibody production
2. MPA is a potent, non-competitive and reversible inhibitor of IMPDH
3. IMPDH inhibition decreases DNA and RNA synthesis
  1. IMPDH effects de novo Purine synthesis but not the salvage pathway Purine synthesis
  2. Lymphocytes are selectively affected, as they rely on de novo Purine synthesis of guanine

Mycophenolate or Mycophenolic acid Intravenous Solution
Mycophenolate or Mycophenolic acid Immediate Release (Cellcept)
1. Capsules: 250 mg
2. Tablets: 500 mg
3. Suspension: 200 mg/ml
  1. Oral solution contains Aspartame (avoid in Phenylketonuria)
Mycophenolate or Mycophenolic acid Extended Release (MyFortic)
1. Extended Release Tablets: 180 mg, 360 mg

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

Pregnancy Category D
1. Risk of first trimester pregnancy loss and congenital malformations
2. Use reliable Contraception (Oral Contraceptives may also be rendered less effective by Mycophenolate)
3. 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
1. Obtain Tuberculosis Testing (e.g. PPD) before starting Mycophenolate
2. Mycophenolate serum concentrations (periodically and with dosing changes, interacting medications)
3. Complete Blood Count (Rheumatoid Arthritis monitoring protocol)
  1. Obtain baseline
  2. Obtain weekly for first month, twice monthly for next 2 months and then monthly

Antacids
1. Avoid Antacids (Magnesium or aluminum hydroxide) for at least 2 hours after dose
2. 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)
1. Cyclosporine
2. Trimethoprim/sulfamethoxazole
3. Bile Acid Sequestrants (Cholestyramine)
4. Rifampin
5. Antibiotics alter bowel flora (Aminoglycosides, Cephalosporins, Fluoroquinolones and Penicillins)
Drugs that affect Glucuronidation
1. Telmisartan (induces Glucuronidation, decreasing Mycophenolate levels)
2. Isavuconazole (inhibits Glucuronidation, raising Mycophenolate levels)
Calcium free Phosphate Binders lower Mycophenolate levels
1. Sevelamer
Drugs that compete for Renal Tubular Secretion (esp. in Renal Insufficiency) raise Mycophenolate levels
Oral Contraceptives
1. See safety as above
2. Decreased Levonorgestrel levels (risk of lower Oral Contraceptive efficacy)
3. Use other reliable Contraception
Live Attenuated Vaccines
1. Avoid with Mycophenolate