In a patient with myasthenia gravis (MG) on mycophenolate (Cellcept), can mycophenolate be continued in the presence of an active infection?

Management of Mycophenolate in Myasthenia Gravis Patients with Active Infection

In a myasthenia gravis patient on mycophenolate with active infection, mycophenolate should be temporarily discontinued or dose-reduced while the infection is being treated, then resumed once the infection has resolved.

Rationale for Discontinuation During Active Infection

The FDA label for mycophenolate explicitly warns that patients receiving immunosuppressants, including mycophenolate mofetil, are at increased risk of developing bacterial, fungal, protozoal and new or reactivated viral infections, including opportunistic infections, with risk increasing with total immunosuppressive load 1. The label further states to "consider dose reduction or discontinuation of mycophenolate mofetil in patients who develop new infections or reactivate viral infections, weighing the risk that reduced immunosuppression represents to the functioning allograft" 1.

While this guidance originates from transplant medicine, the principle applies directly to myasthenia gravis management, where the risk-benefit calculation differs from transplantation—there is no risk of graft rejection, making temporary discontinuation safer 1.

Infection Risk Profile with Mycophenolate

• Serious infections requiring hospitalization and potentially leading to death are well-documented complications of mycophenolate therapy 1
• Specific high-risk infections include polyomavirus-associated nephropathy (especially BK virus), JC virus-associated progressive multifocal leukoencephalopathy (PML), cytomegalovirus infections, and viral reactivation of hepatitis B and hepatitis C 1
• The risk of lymphoproliferative disorders, including T-cell lymphoproliferative lesions, has been reported in myasthenia gravis patients on long-term mycophenolate therapy 2

Clinical Decision-Making Algorithm

Step 1: Assess infection severity

• For mild infections (upper respiratory tract infections, uncomplicated urinary tract infections): Consider continuing mycophenolate at reduced dose (50% reduction) while treating infection 1
• For moderate-to-severe infections (pneumonia, sepsis, opportunistic infections): Discontinue mycophenolate immediately 1
• For life-threatening infections: Discontinue mycophenolate and consider alternative acute management strategies for myasthenia gravis 1

Step 2: Monitor myasthenia gravis disease activity

• Patients should be monitored for worsening myasthenic symptoms including changes in speech, swallowing, respiratory difficulties, and diplopia 3
• Perform pulmonary function assessment with negative inspiratory force (NIF) and vital capacity (VC) if respiratory symptoms develop 4, 5
• Continue pyridostigmine at current dose (maximum 120 mg four times daily) to maintain symptomatic control 3, 5

Step 3: Bridge therapy during mycophenolate interruption

• Maintain or increase corticosteroids (prednisone 0.5-1.5 mg/kg daily) to prevent myasthenic exacerbation 5
• For severe myasthenic worsening during infection treatment, consider IVIG (2 g/kg over 5 days) or plasmapheresis as rescue therapy 4, 5

Step 4: Resume mycophenolate after infection resolution

• Restart at previous maintenance dose once infection has clinically resolved and inflammatory markers have normalized 6
• Monitor complete blood counts weekly for first month after resumption, then monthly 1

Monitoring Requirements During Active Infection

• Complete blood counts should be monitored weekly during active infection, as neutropenia (ANC <1.3 x 10³/μL) may develop and requires dose interruption 1
• Patients should be instructed to report immediately any evidence of infection, unexpected bruising, bleeding, or manifestations of bone marrow depression 1
• Monitor for specific opportunistic infections including BK virus nephropathy, PML (presenting with hemiparesis, apathy, confusion, cognitive deficiencies, ataxia), and CMV reactivation 1

Critical Medication Interactions During Infection Treatment

• Avoid fluoroquinolone antibiotics, aminoglycoside antibiotics, and macrolide antibiotics, as these can worsen myasthenic symptoms and potentially trigger myasthenic crisis 4, 3, 5
• If acyclovir or ganciclovir are used for viral infections, monitor closely as mycophenolate can increase plasma concentrations of these antivirals, especially with renal impairment 7
• Avoid live vaccines while on mycophenolate therapy 7

Long-Term Safety Considerations

• Mycophenolate has been used successfully in myasthenia gravis with 82% of patients receiving immunosuppressants for at least 1 year, achieving remission or minimal manifestations in 47-85% depending on disease subtype 8
• The drug is generally well-tolerated with dose-dependent side effects, and serious complications appear related to treatment duration and patient characteristics 8
• Tapering mycophenolate appears safe after years of disease stability, with relapses being mild, transient, and responsive to dose increases, though tapering should occur slowly (500 mg/day every 12 months) 6

Common Pitfalls to Avoid

• Do not continue full-dose mycophenolate during serious active infections—the immunosuppression outweighs benefits in this acute setting 1
• Do not use contraindicated antibiotics (fluoroquinolones, aminoglycosides, macrolides) that could precipitate myasthenic crisis while the patient is already vulnerable from infection 4, 3, 5
• Do not abruptly stop all immunosuppression without bridging with corticosteroids or having rescue therapy (IVIG/plasmapheresis) available, as myasthenic crisis could develop 4, 5
• Do not restart mycophenolate before infection has fully resolved, as this increases risk of infection persistence or progression 1