Understanding Which Drugs Cause ILD: A Guide to Drug-Induced Interstitial Lung Disease

October 6, 2025 •

4 min read

While many life-saving medications exist, drug-induced interstitial lung disease (DIILD) is a recognized but potentially overlooked side effect, accounting for 3% to 5% of all ILD cases. Understanding which drugs cause ILD is a critical first step for patients and clinicians to ensure early detection and management of this serious condition.

Quick Summary

Drug-induced interstitial lung disease (DIILD) can result from exposure to certain medications like chemotherapy agents, amiodarone, methotrexate, and specific antibiotics. This condition causes lung inflammation and potential scarring. Management involves discontinuing the causative drug and sometimes using corticosteroids in severe cases.

Key Points

Diverse Drug Causes: Interstitial lung disease can be triggered by medications from multiple classes, including chemotherapy drugs (Bleomycin, Methotrexate), cardiovascular agents (Amiodarone), antibiotics (Nitrofurantoin), and immunosuppressants (Leflunomide, TNF-α inhibitors).
Non-Specific Symptoms: The symptoms of drug-induced ILD, such as shortness of breath, fever, and cough, are often non-specific and can be mistaken for other respiratory illnesses.
Varying Onset: The onset of DIILD can be unpredictable, ranging from an acute reaction shortly after starting a drug to a chronic, long-term development of fibrosis.
Key Risk Factors: Pre-existing lung disease, advanced age, higher cumulative drug dose, and smoking history can increase a person's risk of developing drug-induced ILD.
Crucial Role of Diagnosis: Diagnosis involves a careful review of medication history and imaging, as there are no specific physiological or pathological patterns unique to DIILD.
Importance of Discontinuation: The cornerstone of treatment is stopping the offending medication. In severe cases, corticosteroids may be used to reduce inflammation.
Prognosis is Variable: Prognosis is dependent on the specific drug, the severity of the lung damage, and how early the condition is identified and treated.

What is Drug-Induced Interstitial Lung Disease (DIILD)?

Drug-induced interstitial lung disease (DIILD) is a pulmonary disorder caused by an adverse reaction to certain medications, leading to inflammation and/or scarring in the lungs' interstitium. Unlike infectious pneumonia, DIILD is noninfectious. Its severity and onset vary widely, and symptoms can appear days to years after starting a drug. Diagnosing DIILD can be difficult due to non-specific clinical, radiological, and pathological findings, highlighting the importance of a thorough medication history.

Key Drug Categories Associated with ILD

Numerous medications, over 500 in total, have the potential to cause DIILD, though the risk varies. Major categories of implicated drugs include:

Chemotherapy Drugs: Antineoplastic agents are significant contributors to DIILD. Notable examples include Bleomycin, associated with a risk potentially exceeding 10%; Methotrexate, which can cause acute or chronic pneumonitis; and Immune Checkpoint Inhibitors, which have increased DIILD incidence. Other drugs like Cyclophosphamide, Mitomycin C, and Gemcitabine have also been linked to lung injury.
Cardiovascular Agents: Certain heart medications, particularly antiarrhythmics, are known causes of DIILD. Amiodarone is a frequently implicated cardiac drug with a risk often dependent on dose and duration. Statins have also been rarely associated with ILD in case reports.
Anti-inflammatory and Immunosuppressant Drugs: Used for autoimmune diseases and in transplant recipients, these can cause lung toxicity. Methotrexate and Leflunomide, used for rheumatoid arthritis, can trigger or worsen ILD. Biologic agents like TNF-alpha inhibitors (Infliximab, Etanercept, Adalimumab) also carry a risk. mTOR inhibitors such as Everolimus are linked to pneumonitis.
Antibiotics: Some antibiotics can lead to lung injury. Nitrofurantoin is associated with acute reactions and chronic fibrosis, especially with long-term use in elderly women. Sulfasalazine, a sulfonamide, is another implicated antibiotic.
Other Medications: Various other drugs, including antidepressants and illicit substances, have been connected to lung damage.

Risk Factors and Considerations for DIILD

Several factors can increase the likelihood of developing DIILD when taking these medications:

Pre-existing Lung Disease: Conditions like COPD or existing ILD elevate the risk.
Age: Older individuals may have an increased susceptibility.
Cumulative Dose: The total amount of certain drugs, like Bleomycin and Amiodarone, impacts toxicity risk.
Genetic Factors: Some genetic variations may predispose individuals to drug-induced lung injury.
Combination Therapies: Using multiple pneumotoxic drugs or radiotherapy concurrently can increase the risk.
High Oxygen Therapy: High supplemental oxygen can worsen lung damage with certain drugs like bleomycin.

Diagnosis and Management of DIILD

Diagnosis requires a high clinical suspicion and a detailed medication history. Investigations are necessary to confirm DIILD and exclude other causes like infections. Key diagnostic steps typically include:

Imaging: HRCT scans of the chest are vital for revealing characteristic patterns of lung injury.
Pulmonary Function Tests: These may show restrictive patterns but are not specific to DIILD.
Bronchoalveolar Lavage or Biopsy: May be used to rule out infection and characterize the lung injury.

Management focuses on two main approaches:

Drug Discontinuation: Immediately stopping the causative medication is crucial and often leads to improvement, although fibrosis may remain.
Corticosteroid Therapy: Systemic corticosteroids may be used in more severe cases to reduce inflammation, with varying effectiveness depending on the drug and type of injury.

A Comparison of Common DIILD Culprits


Drug Class	Example Drugs	Common ILD Pattern	Key Considerations
Chemotherapy	Bleomycin, Gemcitabine	DAD, Fibrosis, OP	Risk increases with cumulative dose and oxygen therapy.
	Methotrexate	Hypersensitivity pneumonitis	Typically occurs early in treatment, can be severe.
	ICIs (e.g., Nivolumab)	OP, HP, NSIP	Potentially fatal, more common with combination therapy.
Cardiovascular	Amiodarone	NSIP, OP, Fibrosis	Dose and duration are major risk factors; hyperdense lung parenchyma on CT.
Antibiotics	Nitrofurantoin	HP (acute), Fibrosis (chronic)	More common in elderly females on long-term prophylaxis.
Immunosuppressants	Leflunomide, TNF-α Inhibitors	Exacerbation of existing ILD, HP	Caution in patients with pre-existing ILD.

Note: This is not an exhaustive list. The pattern and severity of DIILD can vary and are not always predictable. (Pneumotox online platform serves as a helpful reference).

Conclusion

Drug-induced interstitial lung disease is a serious but often manageable complication of many necessary medical treatments. While the risk is present, the key to a better outcome lies in increased awareness, diligent monitoring for respiratory symptoms, and proactive communication between patients and healthcare providers. Early recognition and immediate cessation of the causative agent, sometimes followed by a course of corticosteroids, can reverse or halt the progression of lung damage. For patients on long-term medications known to cause DIILD, discussing potential side effects and establishing a monitoring plan with their doctor is the best course of action. Vigilance and swift intervention are the most effective tools for mitigating the risks associated with medication-related lung toxicity.

Frequently Asked Questions

Pneumonia is lung inflammation caused by an infection from bacteria, viruses, or fungi. Drug-induced pneumonitis is a type of ILD where inflammation is caused by a reaction to a medication or irritant, not an infection.

Acute episodes may resolve completely after the causative drug is stopped, sometimes hastened by corticosteroids. However, chronic forms, especially with extensive fibrosis, may cause irreversible lung damage.

Symptoms can appear anywhere from a few days to years after beginning a medication, depending on the drug and the individual's reaction. The onset is not always predictable.

Bleomycin is the most classic example of a chemotherapy drug causing ILD. Others include methotrexate, cyclophosphamide, and modern immune checkpoint inhibitors used in cancer therapy.

Yes, if amiodarone is withdrawn early, the inflammation can often resolve, especially in cases of pneumonitis. However, significant pulmonary fibrosis may be permanent.

If you suspect your medication is causing lung issues, contact your healthcare provider immediately. They can evaluate your symptoms, perform necessary tests, and determine if the drug needs to be stopped.

For patients on high-risk medications, especially chemotherapy, proactive monitoring with imaging (CT scans) and pulmonary function tests can be useful for early detection. Monitoring duration may vary by drug type.