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Drug-Induced Pulmonary Disease

By

Joyce Lee

, MD, MAS, University of Colorado Denver

Last full review/revision Sep 2019| Content last modified Sep 2019

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).

(See also Overview of Interstitial Lung Disease.)

Substances With Toxic Pulmonary Effects

Condition

Drug or Agent

Asthma

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, cocaine, cyclophosphamide, methotrexate, minocycline, mitomycin-C, penicillamine, sulfasalazine, tetracycline

Hypersensitivity pneumonitis

Azathioprine plus 6-mercaptopurine, busulfan, fluoxetine, radiation

Interstitial pneumonia or fibrosis

Amphotericin B, bleomycin, busulfan, carbamazepine, 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

Pleural effusion

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

Pulmonary infiltrate with eosinophilia

Amiodarone, amphotericin B, bleomycin, carbamazepine, 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.

Drugs Mentioned In This Article

Drug Name Select Trade
hydrochlorothiazide MICROZIDE
chlordiazepoxide LIBRIUM
cyclophosphamide CYTOXAN (LYOPHILIZED)
methylphenidate CONCERTA, RITALIN
hydrocortisone CORTEF, SOLU-CORTEF
mercaptopurine PURINETHOL
nitrofurantoin FURADANTIN, MACROBID, MACRODANTIN
bromocriptine PARLODEL
penicillamine CUPRIMINE
carbamazepine TEGRETOL
sulfasalazine AZULFIDINE
methotrexate OTREXUP
Azathioprine IMURAN
chlorambucil LEUKERAN
tetracycline ACHROMYCIN V
dipyridamole PERSANTINE
procarbazine MATULANE
phentermine ADIPEX-P
gemcitabine GEMZAR
minocycline MINOCIN
terbutaline No US brand name
Amiodarone CORDARONE
fluoxetine PROZAC, SARAFEM
ethambutol MYAMBUTOL
mitomycin MITOSOL
trazodone OLEPTRO
etoposide ETOPOPHOS
isoniazid LANIAZID
methadone DOLOPHINE
melphalan ALKERAN
busulfan MYLERAN
timolol TIMOPTIC

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