What are the uses of mycophenolate (immunosuppressive agent)?

Mycophenolate Uses in Clinical Medicine

Mycophenolate mofetil (MMF) is primarily indicated for the prophylaxis of organ rejection in recipients of allogeneic kidney, heart, or liver transplants, in combination with other immunosuppressants. 1

Transplant Medicine Applications

Solid Organ Transplantation

• Kidney transplantation: Standard dose of 1g twice daily orally or intravenously (IV) over no less than 2 hours in adults; 600 mg/m² orally twice daily (up to maximum of 2g daily) in pediatric patients 1
• Heart transplantation: 1.5g twice daily orally or IV in adults; 600-900 mg/m² orally twice daily in pediatric patients 1
• Liver transplantation: 1.5g twice daily orally or 1g twice daily IV in adults; 600-900 mg/m² orally twice daily in pediatric patients 1

MMF has largely replaced azathioprine as the antimetabolite of choice in transplant immunosuppressive regimens due to its superior efficacy in preventing acute rejection 2. It is typically used in combination with calcineurin inhibitors (CNIs) like tacrolimus or cyclosporine and corticosteroids.

Mechanism of Action

Mycophenolate mofetil is a prodrug that is rapidly hydrolyzed to its active form, mycophenolic acid (MPA), which:

• Selectively inhibits inosine monophosphate dehydrogenase (IMPDH), a key enzyme in de novo purine synthesis 3
• Causes lymphocyte-selective arrest of cell division with minimal effect on other tissues 4
• Suppresses both T and B lymphocyte proliferation 2
• Decreases expression of adhesion molecules responsible for recruiting inflammatory cells 3

Non-Transplant Uses

Autoimmune Disorders

• Immune thrombocytopenia (ITP): Used at doses of 500-2000 mg per day in adults and 1300 mg/m² per day (maximum 2000 mg) in children 2

  • Produces responses in approximately 50% of patients by 1 month
  • Durable response rates of 56.7-61.9% 2

• Psoriasis: Though not FDA-approved for this indication, open-label studies have shown:

  • Mean PASI reduction of 47% at 12 weeks when dosed at 2-3g daily
  • 40-70% reduction in PASI in 7 of 11 patients in another small study 2

Monitoring Requirements

Regular monitoring is essential during MMF therapy:

• Complete blood count (CBC):
  • Weekly for the first month
  • Twice monthly for second and third months
  • Monthly for remainder of first year
  • Every 1-3 months thereafter 2
• Renal/hepatic function tests: Follow similar schedule as CBC 2
• Therapeutic drug monitoring: May be considered in high-risk patients, those on CNI-sparing regimens, or when unexpected rejection or infections occur 3

Major Adverse Effects

• Gastrointestinal effects: Most common side effects include diarrhea (up to 35%), nausea, vomiting, and abdominal pain 2
• Hematologic effects: Leukopenia, anemia, thrombocytopenia, and red blood cell aplasia 2
• Infectious complications: Increased susceptibility to opportunistic infections 2, 1
• Pregnancy risks: FDA black box warning due to teratogenic effects; contraindicated during pregnancy 2, 1
• Malignancy risk: Increased risk of lymphoma and skin cancers (FDA black box warning) 1
• Neurologic complications: Rare cases of progressive multifocal leukoencephalopathy 2

Important Drug Interactions

• Antacids containing aluminum or magnesium: Decrease absorption of MMF 2
• Cholestyramine, colestipol: Reduce absorption 2
• Azathioprine: Avoid co-administration due to increased inhibition of purine metabolism 2
• Acyclovir/ganciclovir: MMF can increase plasma concentrations, especially with renal impairment 2
• Live vaccines: Should be avoided during MMF therapy 2

Clinical Pearls and Pitfalls

1. Pregnancy prevention: Women of childbearing potential must use effective contraception before, during, and for 6 weeks after MMF therapy due to teratogenic risk 1

2. Dosing adjustments: Reduce or interrupt dosing in the event of neutropenia 1

3. Administration timing: IV formulation should be administered within 24 hours following transplantation until patients can tolerate oral medication, for up to 14 days 1

4. Potential benefits in cancer patients: Some evidence suggests mycophenolate may be associated with lower cancer rates due to its activity against inosine monophosphate dehydrogenase, which is expressed at high levels in some solid tumors 2

5. Avoid rapid IV administration: Must not be administered by rapid or bolus IV injection 1

6. Blood/semen donation: Patients should avoid blood donation during therapy and for 6 weeks thereafter; semen donation should be avoided during therapy and for 90 days thereafter 1