Can infection and thrombocytopenia be reasons to hold Cellcept (mycophenolate mofetil) in a kidney transplant patient?

Holding Cellcept in Kidney Transplant Patients with Infection and Thrombocytopenia

Yes, both infection and thrombocytopenia are valid reasons to hold or reduce Cellcept (mycophenolate mofetil) in kidney transplant patients, as this medication causes myelosuppression and increases infection risk through immunosuppression. 1, 2, 3

Thrombocytopenia as an Indication to Hold Cellcept

When neutropenia develops (ANC < 1.3 x 10³/µL), the FDA label explicitly states that dosing with mycophenolate mofetil should be interrupted or the dose reduced. 3 While this guidance specifically addresses neutropenia, the same principle applies to thrombocytopenia given that mycophenolate causes bone marrow suppression affecting all cell lines. 1, 2

Hematologic Monitoring Requirements

• The American Society of Hematology recommends CBC monitoring weekly for the first month, twice monthly for months 2-3, and monthly for the remainder of the first year. 2
• Mycophenolate mofetil is associated with hematologic adverse effects including leukopenia, anemia, and thrombocytopenia. 1
• Severe neutropenia (ANC < 0.5 x 10³/µL) developed in up to 2% of renal transplant patients receiving mycophenolate mofetil. 3

Clinical Context for Thrombocytopenia

The evidence shows that mycophenolate causes dose-dependent myelosuppression, and anemia caused by these drugs is often associated with leukopenia and/or thrombocytopenia. 4 In transplant settings, thrombotic microangiopathy can occur with calcineurin inhibitors, which may compound thrombocytopenia risk. 4

Infection as an Indication to Hold Cellcept

All transplant patients are at increased risk of opportunistic infections, and this risk increases with total immunosuppressive load. 3 The presence of active infection, particularly serious infection, warrants holding or reducing mycophenolate mofetil. 2, 3

Infection Risk Profile

• Fatal infection/sepsis occurred in approximately 2% of renal transplant patients receiving mycophenolate mofetil in controlled studies. 3
• Serious life-threatening infections such as meningitis and infectious endocarditis have been reported. 3
• There is evidence of higher frequency of certain serious infections such as tuberculosis and atypical mycobacterial infection. 3
• Opportunistic infections including CMV, herpes simplex, herpes zoster, and fungal infections occur commonly in patients on mycophenolate. 3

Specific Infection Considerations

The Infectious Diseases Society of America notes increased risk of opportunistic infections due to immunosuppression with mycophenolate. 2 Patients should be monitored for signs of infection and report fever immediately. 2

Practical Management Algorithm

When to Hold Mycophenolate:

1. Active serious infection (bacterial sepsis, pneumonia, meningitis, endocarditis): Hold until infection is controlled. 3
2. Severe thrombocytopenia: Hold or reduce dose, perform appropriate diagnostic tests. 3
3. Neutropenia (ANC < 1.3 x 10³/µL): Interrupt dosing or reduce dose per FDA guidance. 3
4. Combined cytopenias: Strong indication to hold given myelosuppressive mechanism. 1, 2

When to Resume:

• For infections: Resume once clinical evidence shows infection is controlled, typically after completing appropriate antimicrobial therapy and resolution of fever/systemic symptoms. 2
• For cytopenias: Resume at reduced dose once counts recover to acceptable levels (specific thresholds should be determined based on severity and clinical context). 3
• Wound healing should be complete (typically ~14 days) if held perioperatively, with no evidence of surgical site or non-surgical site infections. 4

Important Caveats

Balancing Rejection Risk

In patients with severe systemic lupus erythematosus (SLE) or organ transplant recipients, there is indirect evidence from transplant patients who continue anti-rejection therapy through surgical periods. 4 However, this applies to elective procedures, not active infections or severe cytopenias. 4

The American Association for the Study of Liver Diseases notes that mycophenolate is used to reduce calcineurin inhibitor doses and minimize nephrotoxicity. 1 Holding mycophenolate increases rejection risk, so decisions must weigh infection/bleeding risk against rejection risk. 4

Dose Adjustment vs. Complete Holding

In renal transplant patients with severe chronic renal impairment (GFR < 25 mL/min/1.73 m²), doses greater than 1 g twice daily should be avoided, and patients should be carefully observed. 3 This demonstrates that dose reduction rather than complete cessation may be appropriate in some scenarios. 3

Drug Interactions During Infection Treatment

• Mycophenolate increases plasma concentration of acyclovir or ganciclovir, especially with renal impairment. 2
• Coadministration with azathioprine may increase purine metabolism inhibition and should be avoided. 2
• Trimethoprim-sulfamethoxazole and ganciclovir, commonly used for infection prophylaxis/treatment, may cause additive myelosuppression. 4