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Drug-Induced Pulmonary Disease

By

Joyce Lee

, MD, MAS, University of Colorado Denver

Last full review/revision Jun 2021| Content last modified Jun 2021
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Drug-induced pulmonary disease is not a single disorder, but rather a common clinical problem in which a patient without previous pulmonary disease develops respiratory symptoms, chest x-ray changes, deterioration of pulmonary function, histologic changes, or several of these findings in association with drug therapy. Over 150 drugs or categories of drugs have been reported to cause pulmonary disease; the mechanism is rarely known, but many drugs are thought to provoke a hypersensitivity response. Some drugs (eg, nitrofurantoin) can cause different injury patterns in different patients.

Depending on the drug, drug-induced syndromes can cause interstitial fibrosis, organizing pneumonia, asthma, noncardiogenic pulmonary edema, pleural effusions, pulmonary eosinophilia, pulmonary hemorrhage, or veno-occlusive disease (see table Substances With Toxic Pulmonary Effects).

Table
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Substances With Toxic Pulmonary Effects

Condition

Drug or Agent

Aspirin, beta-blockers (eg, timolol), cocaine, dipyridamole, IV hydrocortisone (rarely in aspirin-sensitive patients with asthma), interleukin-2, methylphenidate, nitrofurantoin, protamine, sulfasalazine, vinca alkaloids (with mitomycin-C)

Organizing pneumonia

Amiodarone, bleomycin, checkpoint inhibitors, cocaine, cyclophosphamide, methotrexate, minocycline, mitomycin-C, penicillamine, sulfasalazine, tetracycline

Azathioprine plus 6-mercaptopurine, busulfan, fluoxetine, methotrexate, radiation

Amphotericin B, bleomycin, busulfan, carbamazepine, checkpoint inhibitors, chlorambucil, cocaine, cyclophosphamide, diphenylhydantoin, flecainide, heroin, melphalan, methadone, methotrexate, methylphenidate, methysergide, mineral oil (via chronic microaspiration), nitrofurantoin, nitrosoureas, procarbazine, silicone (sc injection), tocainide, vinca alkaloids (with mitomycin-C)

Noncardiac pulmonary edema

Beta-adrenergic agonists (eg, ritodrine, terbutaline), chlordiazepoxide, cocaine, cytarabine, ethiodized oil (IV, and via chronic microaspiration), gemcitabine, heroin, hydrochlorothiazide, methadone, mitomycin-C, phenothiazines, protamine, sulfasalazine, tocolytic agents, tricyclic antidepressants, tumor necrosis factor, vinca alkaloids (with mitomycin-C)

Parenchymal hemorrhage

Anticoagulants, azathioprine plus 6-mercaptopurine, cocaine, mineral oil (via chronic microaspiration), nitrofurantoin, radiation

Amiodarone, anticoagulants, bleomycin, bromocriptine, busulfan, check-point inhibitors, granulocyte-macrophage colony-stimulating factor, IL-2, methotrexate, methysergide, mitomycin-C, nitrofurantoin, para-aminosalicylic acid, procarbazine, radiation, tocolytic drugs (eg, terbutaline)

Amiodarone, amphotericin B, bleomycin, carbamazepine, checkpoint inhibitors, cocaine, diphenylhydantoin, ethambutol, etoposide, granulocyte-macrophage colony-stimulating factor, isoniazid, methotrexate, minocycline, mitomycin-C, nitrofurantoin, para-aminosalicylic acid, procarbazine, radiation, sulfasalazine, sulfonamides, tetracycline, trazodone

Pulmonary vascular disease

Appetite suppressants (eg, dexfenfluramine, fenfluramine, phentermine), busulfan, cocaine, heroin, methadone, methylphenidate, nitrosoureas, radiation

Diagnosis is based on observation of responses to withdrawal from and, if practical, reintroduction to the suspected drug.

Treatment of Drug-Induced Pulmonary Disease

  • Stopping the drug

Treatment is stopping the drug that is causing pulmonary disease.

Prevention of Drug-Induced Pulmonary Disease

A screening pulmonary function test is commonly done in patients about to begin or already taking drugs with pulmonary toxicities, but the benefits of screening for prediction or early detection of toxicity are unproved.

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