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Methotrexate Toxicity



My best freind was put on Methotrexate, after about three mos. he began coughing, trouble breathing, and tiredness. He was told the medicine had scarred his lungs, can this be corrected? If so how long will it take? He is on predisone. Are there any other treatments that would help?


Methotrexate is used as a chemotherapeutic agent as well as for the treatment of inflammatory diseases including severe rheumatoid arthritis (RA) and psoriasis. Methotrexate is most frequently prescribed for the treatment of RA and if methotrexate is prescribed for RA, patients typically take the medications orally on a weekly basis.

Methotrexate induced pulmonary toxicity/scarring occurs in 1-5% patients with RA and is most commonly seen in the first year of treatment (especially first 6 months). The signs and symptoms include fever, cough, shortness of breath, difficulty breathing, and crackles heard when breathing in air. Tiredness is also a possible side effect of methotrexate. Pulmonary toxicity is more likely to occur if a patient is receiving high daily and cumulative doses of methotrexate, high dose aspirin or non-steroidal anti-inflammatory drugs (NSAIDs, includes ibuprofen, naproxen, meloxicam, diclofenac, nabumetone, celecoxib etc.) or if the patient already has pre-existing lung disease including asthma or COPD.

If scarring of the lungs (called pulmonary fibrosis) has already occurred from methotrexate use, it is unfortunately irreversible. Methotrexate therapy should be discontinued and the physician should prescribe alternative therapy to treat RA. There are no current treatments available to reverse this scarring.

Prednisone, a corticosteroid, is frequently prescribed to improve the symptoms of pulmonary fibrosis. Prednisone is associated with adverse events if taking a high dose for a long period of time. Adverse events include insomnia, emotional instability, weight gain, glucose intolerance, glaucoma, Cushing’s syndrome and liver damage. To prevent these adverse events from occurring, prednisone initially may be prescribed for only 3-6 months. If benefit is seen without noticing adverse events, the physician may continue prednisone at lower doses for a longer period of time. Prednisone is typically discontinued if no improvement is seen after 6 months of therapy.

Pursuing a healthy lifestyle can help manage pulmonary fibrosis. If the patient is a smoker, it is important to stop smoking. Regular exercise, eating a healthy and balanced diet and getting plenty of rest will help his lungs and it will also help control the RA. Pulmonary rehabilitation clinics are also available to assist in improving lung function.

This response was prepared by Joori Noh, A PharmD. candidate at the College of Pharmacy.

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