Mycophenolic Acid Education

Mechanism of Action
MPA is an antiporliferative drug that interferes with the de novo pathway of purine synthesis by inhibiting a vital enzyme, inosine monophosphate dehydrogenase, and blocking the production of guanosine nucleotides. This results in the suppression of lymphocyte proliferation and the synthesis of antibodies by B lymphocytes, thereby suppressing the immune system.^{1, 2}

Clinical Indications
MPA is mainly indicated for the following:

• Prevention of transplant rejection in renal and cardiac transplant patients

     • Usually used in combination with cyclosporine and corticosteroids ³

• Treatment of dermatological disorders such as atopic dermatitis, psoriasis, and pemphigus
• Treatment of immunological disorders such as inflammatory bowel disease, myasthenia gravis, rheumatoid arthritis, lupus nephritis, and Wegener’s granulomatosis ⁴

Adverse Effects

• Myelosuppression ¹
• Gastrointestinal side effects, including nausea, vomiting, and diarrhea ¹
• Increased risk of leukopenia, anemia, drug-induced fever, and infection ²
• Opportunistic infections such as herpes simplex and zoster, and cytomegalovirus infections
• Lymphoproliferative disorders ³
• Progressive multifocal leukoencephalopathy occurs in some patients ⁵

Drug Interactions
The metabolism of MPA results in the formation of a pharmacologically inactive compound, mycophenolic acid glucuronide (MPAG), which may be reconverted to MPA during enterohepatic recirculation. Co-administration of MPA with other drugs metabolized by similar pathways can lead to various drug interactions. ^{2, 3}

• MPA absorption is lowered if concomitantly administered with antacids
• Tacrolimus increases 6 and cholestyramine significantly reduces the plasma concentration of MPA
• Fluoroquinolones and metronidazole administered along with MPA reduces MPA’s bioavailability
• Probenecid reduces the renal clearance of MPA

Dosage and Administration ¹

MPA is available in two forms:

• Prodrug: Mycophenolate mofetil (MMF)

     • Safe and effective dose of the prodrug form (MMF) of MPA is 1-2 g per day

• Enteric coated form: Mycophenolate sodium (EC-MPS)

     • Usually administered at a starting dose of 720 mg, twice daily, either 1 hour before or 2 hours after the food intake

Monitoring of MPA ^{6, 7}
The suggested therapeutic target ranges for MPA plasma concentration is 1-3.5 mg/L and 1.9-4 mg/L, when concomitantly administered with cyclosporine and tacrolimus, respectively. The precise estimation of MPA levels can be obtained by drawing serial blood samples up to 12 hours after the administration of the drug (AUC_0-12h). However, multiple sampling over a long period of time (12 hours) is inconvenient. Hence, it is important to establish a single time point concentration that correlates well with AUC.

• Several studies have shown that sampling around 2-3 hours post administration of the drug correlates well with MPA AUC_0-12h