Mycophenolate mofetil

Mycophenolate mofetil

Introduction

Mycophenolate mofetil is a potent immunosuppressant that interferes with DNA synthesis and acts through suppression of B and T lymphocytes. Australian marketing approval is for prevention of rejection of solid organ allografts. It also has a well-recognised range of off-label uses including treatment of some autoimmune diseases; in these diseases, benefits may be apparent in several weeks, but it may take a number of months for maximum benefit. Because of its potency, mycophenolate should be used only under appropriate specialist supervision.

Pharmacokinetics

When given orally, mycophenolate mofetil is well absorbed with a bioavailability of about 94%, which is not affected by food. It is a prodrug that is hydrolysed to active mycophenolic acid in the liver. Mycophenolic acid is metabolised by hepatic glucuronidation and also undergoes enterohepatic recirculation which can result in secondary increases in the serum level 6 to 12 hours post dose. Mycophenolate is ultimately excreted in the urine, mainly (87%) as the glucuronide. Care is required in dosing in renal failure.

Adverse effects

The most common adverse effects are gastrointestinal, including nausea, vomiting and diarrhoea. These can be minimised by taking mycophenolate with food. Other adverse effects include bone marrow suppression (eg anaemia, thrombocytopenia, leucopenia) or stimulation, hypertension, chest pain, cough, dyspnoea, electrolyte and metabolic disturbances, renal damage, haematuria, acne, lymphoproliferative disease, headache, dizziness, insomnia and tremor. There is also a potential for increased infections and some cancers.

Monitoring

Blood level testing is poorly developed, and regular full blood counts are required to monitor for neutropenia. A full blood count should be performed weekly for 1 month, twice monthly for 2 months, then monthly for the rest of the first year. Dose reduction or cessation is required if the patient becomes neutropenic.