Should Cellcept (mycophenolate mofetil) be held in immunocompromised patients with influenza?

Should CellCept Be Held During Influenza Infection?

CellCept (mycophenolate mofetil) should generally be continued during influenza infection, but dose reduction or temporary interruption should be strongly considered if the patient develops severe disease, persistent viral replication, or significant neutropenia, while balancing the risk of graft rejection.

Treatment Approach for Immunocompromised Patients with Influenza

Immediate Antiviral Therapy is Critical

• Initiate oseltamivir immediately for all immunocompromised patients with suspected or confirmed influenza, regardless of symptom duration 1, 2.
• Immunocompromised patients benefit from antiviral therapy even when started beyond 48 hours after symptom onset, with significant mortality reduction (OR 0.21) 1, 2.
• Treatment should be started empirically without waiting for laboratory confirmation during influenza season 1, 2.

CellCept Management During Influenza

The FDA label and clinical guidelines provide the following framework:

• The FDA label warns that patients on mycophenolate are at increased risk of serious infections, including viral infections, which may lead to hospitalization and death 3.
• Consider dose reduction or discontinuation when patients develop new infections or reactivate viral infections, weighing the risk that reduced immunosuppression represents to the functioning allograft 3.

Specific clinical scenarios requiring CellCept adjustment:

• Persistent viral replication: If the patient has evidence of persistent influenza viral replication after 7-10 days (demonstrated by persistently positive RT-PCR or viral culture) and remains ill during or after antiviral treatment, dose reduction should be strongly considered 1.
• Severe neutropenia: If neutropenia develops (ANC < 1.3 x 10³/μL), CellCept dosing should be interrupted or reduced 3.
• Progression to lower respiratory tract disease: Patients developing pneumonia or respiratory failure may benefit from temporary dose reduction to allow better immune response while maintaining antiviral therapy 1.

Monitoring Requirements

• Monitor complete blood counts, as neutropenia may be related to mycophenolate itself, concomitant medications, or viral infections 3.
• The development of neutropenia is most common 31-180 days post-transplant but can occur with acute viral infections 3.
• Patients should report immediately any evidence of infection, unexpected bruising, bleeding, or bone marrow depression 3.

Antiviral Treatment Considerations

Dosing and Duration

• Standard oseltamivir dosing is 75 mg twice daily for 5 days in adults 1, 2.
• Longer courses (e.g., 10 days) and treatment until resolution of symptoms should be considered in immunocompromised patients, though this remains controversial 1.
• Some centers use higher doses (150 mg twice daily) in immunocompromised patients with mixed results 1.

Expected Benefits

• 50% reduction in pneumonia risk 1, 2.
• Significant mortality benefit in high-risk patients 2.
• Reduced viral shedding and transmission risk 2.

Critical Pitfalls to Avoid

• Do not withhold antiviral therapy while waiting for laboratory confirmation in immunocompromised patients 1, 2.
• Do not automatically discontinue CellCept without considering graft rejection risk—this decision requires careful individualized assessment 3.
• Do not use corticosteroids as adjunctive therapy for influenza treatment unless clinically indicated for other reasons, as they are not beneficial and may prolong viral shedding 1, 4.
• Do not delay antiviral therapy beyond 48 hours when possible, though benefit persists even with later initiation 1, 2.

Vaccination Considerations for Future Prevention

• Immunocompromised patients on mycophenolate should receive inactivated influenza vaccine annually, though response may be blunted 1, 5, 6.
• High-dose or adjuvanted influenza vaccines may provide better immunogenicity in transplant recipients 1, 6.
• Live attenuated influenza vaccine (LAIV) is contraindicated in immunocompromised patients 1, 3.
• Vaccination of household contacts and healthcare workers is critical given suboptimal vaccine response in immunocompromised patients 5, 7.