Cellcept - Drug Monograph

Introduction

Cellcept (mycophenolate mofetil) is an immunosuppressive agent belonging to the antimetabolite class. It is a prodrug of mycophenolic acid (MPA) that is widely used in transplantation medicine to prevent organ rejection. Originally approved by the FDA in 1995, Cellcept has become a cornerstone therapy in solid organ transplantation and has also found applications in autoimmune conditions.

Mechanism of Action

Cellcept exerts its immunosuppressive effects through selective and reversible inhibition of inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the de novo pathway of guanosine nucleotide synthesis. This inhibition preferentially affects lymphocytes, which rely heavily on this pathway, thereby suppressing T- and B-cell proliferation, antibody formation, and cellular adhesion molecule expression. The result is a potent suppression of cell-mediated immune responses and antibody production.

Indications

• FDA-approved indications:

- Prevention of renal, cardiac, and hepatic transplant rejection (in combination with cyclosporine and corticosteroids)

• Off-label uses:

- Lupus nephritis - Myasthenia gravis - Inflammatory eye diseases - Pemphigus vulgaris - Other autoimmune conditions requiring immunosuppression

Dosage and Administration

• Oral: 1 g twice daily (maximum 1.5 g twice daily)
• IV: 1 g twice daily (switch to oral as soon as possible)

• Renal impairment: No dosage adjustment needed for GFR >25 mL/min
• Hepatic impairment: Monitor for increased MPA exposure
• Geriatric patients: Use with caution due to increased infection risk
• Pediatrics: 600 mg/m² twice daily (maximum 2 g/day)

Pharmacokinetics

• Absorption: Rapidly absorbed and hydrolyzed to active MPA; bioavailability ~94%
• Distribution: Extensive tissue binding; MPA protein binding ~97%
• Metabolism: Hepatic via glucuronidation to inactive metabolite MPAG
• Elimination: Primarily renal (87%) as MPAG; half-life 11-18 hours
• Food effects: Decreases MPA Cmax by 40%; recommend consistent administration relative to meals

Contraindications

• Hypersensitivity to mycophenolate mofetil, mycophenolic acid, or any component
• Combination with azathioprine due to excessive immunosuppression
• Pregnancy (Category D) unless benefits outweigh risks

Warnings and Precautions

• Increased infection risk: Serious and opportunistic infections may occur
• Progressive multifocal leukoencephalopathy (PML): Rare but fatal JC virus-associated condition
• Malignancies: Higher risk of lymphoma and skin cancer
• Myelosuppression: Monitor for neutropenia, anemia, thrombocytopenia
• GI toxicity: Hemorrhage, perforation, and ulceration may occur
• Immunizations: Avoid live vaccines during therapy
• Pregnancy warnings: Teratogenic effects; requires effective contraception

Drug Interactions

• Antacids containing magnesium/aluminum: Decrease MPA absorption
• Cholestyramine: Reduces MPA exposure via enterohepatic recirculation interruption
• Acyclovir/ganciclovir: Competes with MPAG for renal tubular secretion
• Probenecid: Increases MPA levels
• Oral contraceptives: Reduced efficacy possible
• Other immunosuppressants: Additive immunosuppressive effects

Adverse Effects

• Diarrhea, nausea, vomiting
• Leukopenia, anemia
• Hypertension
• Insomnia, tremor
• Peripheral edema
• Hypercholesterolemia

• Severe neutropenia (<1.5 x 10³/μL)
• Sepsis and opportunistic infections
• GI hemorrhage/perforation
• PML
• Lymphoproliferative disorders
• Pure red cell aplasia

Monitoring Parameters

• CBC with differential: Weekly first month, then twice monthly for 2-3 months, then monthly
• Renal function: Serum creatinine, BUN regularly
• Liver function tests: Periodically
• Therapeutic drug monitoring: MPA AUC in certain populations
• Pregnancy testing: Before initiation and during therapy in women of childbearing potential
• Signs of infection: Continuous monitoring
• Skin examinations: Regularly for malignancy screening

Patient Education

• Take consistently with regard to meals (same way each time)
• Do not crush, break, or chew tablets; capsules may be opened and mixed with food
• Maintain strict adherence to prescribed dosage
• Use effective contraception (two methods recommended) during and after treatment
• Report immediately: fever, sore throat, unusual bruising/bleeding, significant GI symptoms
• Avoid exposure to infections and practice good hygiene
• Use sun protection due to increased skin cancer risk
• Inform all healthcare providers about Cellcept use before any procedures or new medications
• Do not receive live vaccines without consulting healthcare provider
• Keep all follow-up appointments for laboratory monitoring

References

1. Allison AC, Eugui EM. Immunosuppressive and other effects of mycophenolic acid and an ester prodrug, mycophenolate mofetil. Immunol Rev. 1993;136:5-28. 2. Bullingham RE, Nicholls AJ, Kamm BR. Clinical pharmacokinetics of mycophenolate mofetil. Clin Pharmacokinet. 1998;34(6):429-455. 3. Cellcept® [package insert]. South San Francisco, CA: Genentech USA, Inc.; 2021. 4. Appel GB, Contreras G, Dooley MA, et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol. 2009;20(5):1103-1112. 5. KDIGO Clinical Practice Guideline for the Care of Kidney Transplant Recipients. Am J Transplant. 2009;9 Suppl 3:S1-S155. 6. US Food and Drug Administration. Cellcept prescribing information. Accessed January 2023. 7. Staatz CE, Tett SE. Clinical pharmacokinetics and pharmacodynamics of mycophenolate in solid organ transplant recipients. Clin Pharmacokinet. 2007;46(1):13-58.