Mycophenolate Mofetil (CellCept) Uses
Mycophenolate mofetil (CellCept) is primarily indicated for the prophylaxis of organ rejection in patients receiving allogeneic renal, cardiac, or hepatic transplants and must be used concomitantly with cyclosporine and corticosteroids. 1
Primary Indications
- Solid Organ Transplantation
- Approved for prevention of rejection in kidney, heart, and liver transplants 1
- Must be used in combination with calcineurin inhibitors (typically tacrolimus or cyclosporine) and corticosteroids 2
- Has replaced azathioprine as the preferred antimetabolite agent in transplant regimens due to better efficacy in reducing acute rejection episodes 2
Mechanism of Action
Mycophenolate mofetil is a prodrug that is converted to its active metabolite, mycophenolic acid, which:
- Selectively inhibits inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the de novo synthesis of guanosine nucleotides 3
- Preferentially affects T and B lymphocytes, which are more dependent on this pathway than other cell types 3
- Is a more potent inhibitor of the type II isoform of IMPDH (expressed in activated lymphocytes) than the type I isoform (expressed in most other cells) 3
- Prevents lymphocyte proliferation and antibody production, thereby suppressing immune responses to transplanted organs 2
Off-Label Uses
While not FDA-approved for these indications, mycophenolate mofetil is also used for:
- Management of steroid-refractory immune-related adverse events from cancer immunotherapy 2
- Treatment of autoimmune conditions such as:
- Autoimmune hepatitis
- Myositis
- Bullous diseases
- Interstitial lung disease
- Lupus nephritis 4
Clinical Benefits in Transplantation
- Reduces incidence of acute rejection compared to azathioprine in kidney and heart transplant recipients 5
- Allows for reduction of calcineurin inhibitor doses to minimize nephrotoxicity 2
- Can reverse ongoing acute rejection episodes in heart, kidney, and liver transplant patients 5
- Improves graft function when used to treat chronic lung or heart graft vasculopathy 5
Important Safety Considerations
- Pregnancy risks: FDA black box warning due to increased risk of miscarriage (49%) and birth defects (23%) 2
- Increased infection risk: Particularly cytomegalovirus and BK virus infections 6
- Malignancy risk: Higher risk of lymphoma and skin cancers 1
- Gastrointestinal effects: Common adverse effects include diarrhea, nausea, vomiting (up to 35% of patients) 2
- Hematologic effects: Bone marrow suppression leading to leukopenia, anemia, and thrombocytopenia 2
Formulations
- Available as mycophenolate mofetil (CellCept) and enteric-coated mycophenolate sodium (Myfortic) 7
- The enteric-coated formulation was developed to reduce gastrointestinal side effects by delaying release until the small intestine 7
In conclusion, mycophenolate mofetil is a cornerstone immunosuppressive medication primarily used to prevent organ rejection in transplant recipients, with additional utility in treating certain autoimmune conditions and immune-related adverse events.