When does mycophenolate (Cellcept) cause pulmonary injury?

From the Guidelines

Mycophenolate mofetil (MMF) can cause lung injury at any time during therapy, with the most common pulmonary complication being interstitial pneumonitis, which usually develops gradually over weeks to months. The risk factors for this complication include higher doses, concurrent use of other immunosuppressants, and pre-existing lung disease 1. Patients may present with progressive dyspnea, dry cough, fever, and hypoxemia, and radiographic findings often show bilateral interstitial infiltrates or ground-glass opacities.

Mechanism and Diagnosis

The mechanism involves direct toxicity to lung tissue and immune-mediated injury, with some cases showing features of hypersensitivity pneumonitis. Diagnosis requires exclusion of infection and other causes of lung injury, often necessitating bronchoscopy with bronchoalveolar lavage.

Management

Management typically involves discontinuation of mycophenolate and, in severe cases, corticosteroid therapy. Most patients improve within weeks after drug discontinuation, though complete resolution may take months and some patients may have residual fibrosis. It is essential to monitor patients on mycophenolate therapy for signs of lung injury, including progressive dyspnea, dry cough, and fever, and to discontinue the drug promptly if these symptoms occur.

Monitoring and Prevention

Regular monitoring of blood work, including CBC counts, and monitoring for drug-drug interactions are crucial for patients on mycophenolate therapy 1. Additionally, live vaccines should be avoided while patients are being treated with mycophenolate, and concomitant use of azathioprine should be avoided.

Recent Guidelines

Recent guidelines suggest that mycophenolate mofetil has surpassed cyclophosphamide as the initial treatment for SSc-interstitial lung disease, and nintedanib and possibly perfinidone can be considered in SSc pulmonary fibrosis 1. However, the primary concern remains the potential for lung injury, and clinicians should be vigilant in monitoring patients for this complication.

From the FDA Drug Label

Respiratory: Bronchiectasis, interstitial lung disease, fatal pulmonary fibrosis, have been reported rarely and should be considered in the differential diagnosis of pulmonary symptoms ranging from dyspnea to respiratory failure in post-transplant patients receiving mycophenolate mofetil. Mycophenolate (Cellcept) can cause pulmonary injury, including bronchiectasis, interstitial lung disease, and fatal pulmonary fibrosis, although these are rare. These conditions should be considered in the differential diagnosis of pulmonary symptoms in post-transplant patients receiving mycophenolate mofetil, ranging from dyspnea to respiratory failure 2.

From the Research

Mycophenolate-Induced Pulmonary Injury

• Mycophenolate (Cellcept) can cause pulmonary injury, as reported in a case study published in 1997 3.
• The study described a 51-year-old woman who experienced systemic reactions, recurrent respiratory failure, and progressive pulmonary fibrosis after receiving mycophenolate mofetil following cadaveric renal transplantation.
• The patient's condition improved only after mycophenolate was discontinued, suggesting a link between the drug and pulmonary toxicity.

Timing of Pulmonary Injury

• The exact timing of mycophenolate-induced pulmonary injury is not well-established, but the case study reported that symptoms began 10 days after transplantation 3.
• Another study published in 2013 found that mycophenolate did not cause significant changes in pulmonary function tests (PFTs) over a 2-year period in patients with interstitial lung disease associated with systemic sclerosis 4.
• However, the same study noted that mycophenolate was associated with a deterioration of lung high-resolution computed tomography (HRCT) findings at 2 years, suggesting potential long-term pulmonary effects.

Comparison with Other Immunosuppressants

• A study published in 2016 compared the incidence of adverse outcomes, including respiratory hospitalization, in patients with fibrotic connective tissue disease-associated interstitial lung disease treated with azathioprine or mycophenolate mofetil 5.
• The results showed that both treatments were associated with similar incidence rates of adverse outcomes, and both groups demonstrated pulmonary function stability over time.
• Another study published in 2013 found that mycophenolate mofetil improved lung function in patients with connective tissue disease-associated interstitial lung disease, with significant improvements in estimated percentage of predicted forced vital capacity (FVC%) and diffusing capacity (DLCO%) 6.