Which Medications Cause Pleural Effusion? A Comprehensive Guide to Adverse Drug Reactions

October 13, 2025 •

4 min read

Although a relatively rare complication, certain medications are a known cause of pleural effusion, an abnormal buildup of fluid in the space surrounding the lungs. This drug-induced pulmonary toxicity can range from mild, self-resolving symptoms to severe, life-threatening conditions. Early identification of the causative medication is crucial for proper management and patient safety.

Quick Summary

An overview of medications and drug classes that can cause pleural effusion, detailing potential mechanisms like hypersensitivity reactions, direct toxicity, and indirect effects like drug-induced lupus. Also discussed are diagnostic procedures and the importance of drug cessation.

Key Points

A Wide Range of Medications Can Cause Pleural Effusion: While some drugs like amiodarone and chemotherapy agents are more frequently implicated, many others, including common antibiotics and blood pressure medications, can also be the cause.
Mechanisms Vary, from Allergy to Toxicity: The fluid accumulation can result from different pathways, such as hypersensitivity reactions (e.g., nitrofurantoin), direct toxicity (e.g., amiodarone), or by triggering an autoimmune response like drug-induced lupus (e.g., hydralazine).
Dasatinib is a Notable Cause in CML Treatment: This tyrosine kinase inhibitor has a relatively high and dose-dependent incidence of pleural effusions in patients with chronic myeloid leukemia (CML), potentially due to a lymphatic network disorder.
Diagnosis is Often by Exclusion: When evaluating a patient with a pleural effusion, particularly an exudative one without a clear cause, a thorough medication history is essential. Imaging and fluid analysis via thoracentesis are key diagnostic tools.
Cessation of the Drug is the Primary Treatment: In most cases, stopping the causative drug leads to improvement and resolution of the effusion, though this can take time. Corticosteroids may be used for more severe or refractory cases.
The Time of Onset Can Vary Widely: A drug-induced effusion can occur acutely within days or develop chronically after years of treatment, making the temporal association an important part of the diagnostic puzzle.

What Is Drug-Induced Pleural Effusion?

Drug-induced pleural effusion is the accumulation of excess fluid in the pleural space, the area between the lungs and the chest wall, as a side effect of medication. This condition can manifest in various ways, from mild and asymptomatic to severe and life-threatening. Unlike pleural effusions from other causes, such as infection or malignancy, the diagnosis is often one of exclusion, requiring a detailed drug history and temporal relationship between medication use and symptom onset.

Pathophysiological Mechanisms

The exact way a medication causes a pleural effusion is not always clear, but several mechanisms have been proposed based on different drug classes.

Hypersensitivity Reactions: Some drugs trigger an allergic response in the body, leading to inflammation of the pleura (pleuritis) and subsequent fluid buildup. This is often the mechanism for effusions caused by antibiotics like nitrofurantoin and sulfa drugs.
Direct Toxic Effect: Certain medications can be directly toxic to the pleural lining, causing damage that results in fluid accumulation. Amiodarone, a heart medication, is a prime example of a drug that can cause this type of toxicity, sometimes involving multiple organs.
Drug-Induced Lupus: Some medications can induce a lupus-like syndrome, an autoimmune condition where the body attacks its own tissues. Pleural effusions are a common feature of this syndrome, particularly with drugs like procainamide and hydralazine.
Capillary Leak Syndrome: This is a condition where fluid leaks from small blood vessels (capillaries) into surrounding tissues, including the pleural space. Some chemotherapeutic agents, such as interleukin-2, can cause this phenomenon.
Fibrotic Changes: Prolonged use of some drugs can lead to fibrotic changes (scarring) of the pleura, which can also result in an effusion. Ergot alkaloids and bromocriptine are known to cause such fibrotic pleuropulmonary disease.

Common Medications Implicated in Pleural Effusion

Several classes of drugs have been linked to pleural effusions, each with its own characteristics and risk profile. It is important to note that many of these are rare side effects.

Cardiovascular Agents
- Amiodarone: An antiarrhythmic drug known for its serious pulmonary toxicity, including pleural effusions. These effusions are typically exudative and can be loculated, though they are a rare manifestation. Discontinuation of the drug is often required for resolution.
- Procainamide & Hydralazine: Associated with drug-induced lupus, which can cause exudative pleural effusions. Positive anti-nuclear (ANA) and anti-histone antibody tests can aid in diagnosis.
- Beta-Blockers: While less common with modern formulations, older beta-blockers like practolol were linked to pleural effusions and fibrosis. Newer beta-blockers are generally safer.
Antimicrobial Drugs
- Nitrofurantoin: This antibiotic can cause both acute and chronic pulmonary reactions, including pleural effusions. The acute reaction is often a hypersensitivity response, while the chronic form involves oxidative stress.
- Sulfonamides: These antibiotics have been reported to cause hypersensitivity reactions leading to pleurisy and effusions.
Chemotherapeutic and Immunosuppressive Agents
- Methotrexate: Used for cancer and autoimmune diseases, methotrexate can cause pleuropulmonary toxicity. Effusions can be due to hypersensitivity or poor clearance of the drug, especially in high-dose therapy.
- Dasatinib: A tyrosine kinase inhibitor used for chronic myeloid leukemia. Pleural effusions are a common side effect, with mechanisms potentially involving a lymphatic network disorder. The incidence is dose-dependent.
- Bleomycin: Can cause a range of pulmonary toxicities, including pleural effusions and fibrosis.
Other Notable Drugs
- Bromocriptine: A dopamine agonist used for Parkinson's disease, associated with pleuropulmonary fibrosis and effusions, often chronic.
- Dantrolene: This muscle relaxant has been linked to pleural effusions and fibrosis.
- Phenytoin: An anticonvulsant that can, in rare cases, lead to pleural effusions, sometimes associated with drug-induced lupus.

Diagnosis and Management

The diagnosis of drug-induced pleural effusion is a process of elimination. It begins with a thorough medical history, including all medications (prescription and over-the-counter), the duration of use, and a timeline of symptoms. Diagnostic steps often include:

Imaging: A chest X-ray can confirm the presence of fluid, while a CT scan can provide more detail, especially for loculated effusions.
Thoracentesis: This procedure involves removing fluid from the pleural space with a needle. Analysis of the pleural fluid is critical to differentiate between an exudate (inflammatory) and a transudate (non-inflammatory), as well as to rule out other causes like cancer or infection. Eosinophilia in the pleural fluid may suggest a drug reaction.
Exclusion of Other Causes: Other conditions like congestive heart failure, pneumonia, and pulmonary embolism must be ruled out.
Drug Cessation: The cornerstone of management is discontinuing the suspected medication. In many cases, this leads to a resolution of the effusion, though it may take weeks or months.

Comparison of Key Drugs and Their Pleural Effects


Drug/Class	Proposed Mechanism	Typical Onset	Fluid Analysis	Management
Amiodarone	Direct toxicity, Hypersensitivity	Variable, months to years	Exudative, lymphocytic; can be loculated	Discontinue drug; Steroids if severe
Methotrexate	Hypersensitivity, Delayed excretion	Subacute to chronic	Exudative, may be eosinophilic	Discontinue drug; Steroids may help
Dasatinib	Lymphatic network disorder	Months into treatment	Exudative; often responds to dose reduction/interruption	Dose adjustment or discontinuation
Nitrofurantoin	Hypersensitivity (acute), Oxidant injury (chronic)	Acute (days-weeks), Chronic (months+)	Acute: Exudative with eosinophilia	Discontinue drug; Symptoms resolve rapidly in acute cases
Bromocriptine	Fibrotic changes	Months to years	Exudative, lymphocytic; chronic inflammation	Discontinue drug; improvement possible
Hydralazine/Procainamide	Drug-induced Lupus	Months to years	Exudative, often lymphocytic	Discontinue drug; Symptoms resolve

Conclusion

While drug-induced pleural effusion is a serious and potentially dangerous side effect, awareness and early recognition are key to a positive outcome. The condition often resolves upon withdrawal of the offending medication, though some cases may require additional measures such as corticosteroids or therapeutic drainage. For clinicians, considering a medication as the potential cause for an unexplained effusion, particularly in the absence of more common etiologies, is a vital diagnostic step that can prevent unnecessary invasive procedures. For patients, informing your healthcare provider of all medications and new or worsening respiratory symptoms is crucial for prompt diagnosis and effective treatment.

For more detailed information on a wide range of drug-induced respiratory diseases, resources like the PNEUMOTOX database can be a valuable tool.

Frequently Asked Questions

Amiodarone is the cardiovascular drug most commonly associated with pulmonary toxicity, including pleural effusions. The risk increases with higher doses and longer duration of therapy.

Yes, nitrofurantoin can cause pulmonary toxicity, including pleural effusions. The reaction can be acute, occurring within weeks of use, or chronic, developing after several months.

For methotrexate-induced lung toxicity, discontinuation of the drug is the primary treatment. While many patients improve, some chronic reactions may lead to irreversible fibrosis.

Diagnosis involves a complete drug history, imaging (chest X-ray, CT scan), and often a thoracentesis to analyze the fluid. It is a diagnosis of exclusion, meaning other more common causes like infection or malignancy must be ruled out first.

The first and most important step is to stop the offending medication. For significant fluid accumulation, thoracentesis may be performed. In some cases, such as with severe inflammation, corticosteroids may also be used.

Although less common, some nonsteroidal anti-inflammatory drugs (NSAIDs) have been linked to drug-induced pleural effusion, often as part of a hypersensitivity reaction.

Dasatinib-induced effusions often respond well to dose adjustment or discontinuation. While some cases may require additional management, many patients can be successfully managed without permanent damage.