What medications can cause pleural effusion?

October 13, 2025 •

4 min read

While most people associate pleural effusion with conditions like pneumonia or heart failure, a surprising number of medications can also lead to this condition, a phenomenon often overlooked by both patients and clinicians. Drug-induced pleural effusion is relatively uncommon but presents a significant diagnostic challenge and can lead to unnecessary invasive procedures if not identified correctly.

Quick Summary

Drug-induced pleural effusion is a rare adverse effect, manifesting as fluid accumulation in the lung cavity due to medication. This condition can be caused by various drugs through hypersensitivity, toxicity, or other mechanisms. Identifying the causative medication is crucial, as discontinuation often resolves the effusion, preventing further complications.

Key Points

Diverse Causes: Numerous medications from different classes, including cardiovascular drugs, antibiotics, and chemotherapy agents, can cause pleural effusion.
Complex Mechanisms: DIPE can result from various mechanisms, including hypersensitivity reactions, direct toxicity to the pleura, or systemic conditions like drug-induced lupus.
Diagnosis of Exclusion: Diagnosing DIPE is challenging and requires ruling out more common causes like infection, heart failure, and malignancy.
Clinical Clues: A detailed drug history and observing a temporal link between medication use and symptom onset are critical for identifying DIPE.
Key Treatment: The most effective treatment involves discontinuing the causative medication, which often leads to the resolution of the effusion.
Fluid Analysis: Pleural fluid characteristics can provide diagnostic clues, such as eosinophilia in some hypersensitivity reactions or specific autoantibodies in drug-induced lupus.
Steroid Use: In cases involving significant inflammation, corticosteroids may be used alongside drug withdrawal to manage the effusion.

Understanding Drug-Induced Pleural Effusion

Drug-induced pleural effusion (DIPE) occurs when fluid abnormally accumulates in the pleural space, the area between the lungs and the chest wall, as a direct result of medication use. The mechanism behind DIPE can be complex and is not always fully understood, varying widely among different drug classes. Possible causes range from acute hypersensitivity reactions and direct toxicity to the pleura, to systemic effects such as fluid retention or drug-induced lupus. In some cases, as with nonsteroidal anti-inflammatory drugs (NSAIDs) used for pneumonia, a medication may prolong or complicate an existing lung infection, leading to a more challenging effusion.

Medications and their mechanisms

The list of medications linked to pleural effusion is extensive and includes everything from common antibiotics to specialized chemotherapy agents. Awareness of these potential side effects is critical for patients and healthcare providers. Promptly identifying a drug-related cause can help avoid unnecessary diagnostic tests and allow for targeted management, often involving discontinuation of the offending agent.

Common classes of drugs that cause pleural effusion

Cardiovascular agents: Drugs used to treat heart conditions or hypertension are known culprits. For instance, the antiarrhythmic medication amiodarone can cause pulmonary toxicity and effusions. Some antihypertensive agents, like minoxidil and certain ACE inhibitors (e.g., cilazapril, imidapril), have also been reported to cause fluid buildup.
Chemotherapy drugs: Several anti-cancer drugs have pulmonary toxicity as a known side effect, including pleural involvement. Medications like methotrexate, cyclophosphamide, and bleomycin can cause pleural effusions, especially at higher doses. The tyrosine kinase inhibitor dasatinib is also well-documented for its association with pleural effusions.
Antibiotics: Some antibiotics, most notably nitrofurantoin, are known to cause pleural effusions, often as part of a hypersensitivity reaction. Sulfa drugs can also trigger this response. In these cases, eosinophilia may be present in the blood and pleural fluid.
Ergot derivatives: These drugs, including methysergide and bromocriptine, have been linked to pleural and retroperitoneal fibrosis, which can present as pleural effusion.
NSAIDs: While generally a low risk, NSAIDs like ibuprofen have been associated with pleural effusions, sometimes with eosinophilia, often after prolonged use or in the context of underlying infection.
Immunomodulators: Agents such as TNF-alpha inhibitors (e.g., infliximab) and certain anticonvulsants (e.g., phenytoin, valproic acid) can cause drug-induced lupus or hypersensitivity reactions, manifesting as pleural effusions.

Recognizing and diagnosing DIPE

The diagnosis of DIPE is often one of exclusion, requiring a detailed patient history and careful elimination of other, more common causes of pleural effusion, such as heart failure, infection, or malignancy. Key indicators that a medication may be the cause include a temporal relationship between drug initiation and symptom onset, and the improvement or resolution of symptoms upon drug discontinuation.

Typical clinical presentation includes:

Dyspnea (shortness of breath)
Pleuritic chest pain (sharp pain worsened by deep breathing or coughing)
Nonproductive cough
Fever and general malaise, particularly in hypersensitivity cases

Diagnostic tools involve a chest X-ray or CT scan to visualize the fluid, followed by a thoracentesis to analyze the pleural fluid. The fluid characteristics can offer clues, though no specific finding is definitive for DIPE. For example, some drug-induced effusions are characteristically eosinophilic (high level of eosinophils), while those associated with drug-induced lupus often show antinuclear antibodies (ANA).

Comparison of selected drugs causing pleural effusion


Drug Class	Specific Examples	Mechanism	Fluid Characteristics	Time to Onset
Antiarrhythmics	Amiodarone, Procainamide	Direct toxicity, drug-induced lupus	Exudative, lymphocytic	Weeks to years
Chemotherapy Agents	Methotrexate, Bleomycin, Dasatinib	Direct toxicity, hypersensitivity, capillary leak	Exudative, variable cell count	Days to months
Antibiotics	Nitrofurantoin, Sulfa drugs	Hypersensitivity reaction	Exudative, often eosinophilic	Acute onset, but can be delayed
NSAIDs	Ibuprofen, Etoricoxib	Hypersensitivity, possible blunted immune response	Exudative, variable (sometimes eosinophilic)	Weeks
Ergot Alkaloids	Methysergide, Bromocriptine	Pleural fibrosis (serotonergic effect)	Exudative, fibrotic changes	Chronic use, months to years

Treatment and prognosis

The primary and most effective treatment for DIPE is to identify and withdraw the causative medication, if clinically appropriate. In many cases, this action alone leads to a resolution of the pleural effusion. Steroids may also be used, particularly in cases with significant inflammation or hypersensitivity reactions, to suppress the immune response. The prognosis is generally good once the offending drug is removed. However, patients on critical, non-replaceable medications (like amiodarone) may require ongoing management with lower doses or additional therapy. In severe cases with marked respiratory distress, therapeutic thoracentesis (draining the fluid) may be necessary to provide symptomatic relief. For more persistent cases, particularly those involving fibrosis, other interventions may be needed. A key step is to consult resources like the PNEUMOTOX database, which specializes in drug-induced lung diseases, for further information and confirmation.

Conclusion

Drug-induced pleural effusion is a significant, albeit uncommon, medical complication. Its diagnosis requires a high degree of clinical suspicion, a meticulous medication history, and careful exclusion of other potential causes. Medications across various classes, from cardiovascular to oncology treatments, have been implicated, each with specific mechanisms of action. The cornerstone of treatment is withdrawing the offending medication, which often leads to resolution of the effusion. Awareness of this condition is vital for preventing misdiagnosis, avoiding unnecessary procedures, and ensuring optimal patient outcomes.

Frequently Asked Questions

Drug-induced pleural effusion is a relatively rare adverse drug reaction. However, due to potential underdiagnosis and misidentification, the precise prevalence is difficult to determine.

Symptoms can include shortness of breath (dyspnea), pleuritic chest pain that worsens with deep breaths or coughing, a dry nonproductive cough, and sometimes fever, depending on the underlying mechanism.

Diagnosis typically involves taking a detailed drug history and performing a chest X-ray or CT scan. If fluid is present, a thoracentesis (fluid drainage) is done to analyze the pleural fluid and rule out other causes like infection, heart failure, or cancer.

The primary treatment is to discontinue the medication suspected of causing the effusion. In some cases, steroids may be prescribed to help resolve inflammation. If the effusion is large and causing breathing difficulty, draining the fluid may be necessary.

Yes, some blood pressure medications can cause pleural effusion. Examples include certain ACE inhibitors, minoxidil, and the antiarrhythmic medication amiodarone.

Yes, several chemotherapy drugs, including methotrexate, bleomycin, and cyclophosphamide, are known to have pleural effusion as a potential side effect.

Drug-induced lupus is a syndrome mimicking systemic lupus erythematosus, caused by certain drugs. Medications like procainamide and hydralazine can cause this syndrome, and pleural effusion is a common manifestation.