From the Guidelines
Drugs that can cause interstitial lung disease (ILD) include leflunomide, methotrexate, TNFi, and abatacept, as well as chemotherapeutic agents like bleomycin, cyclophosphamide, gemcitabine, and busulfan, according to the most recent evidence 1. The list of medications associated with ILD is extensive and varied, encompassing several classes of drugs.
- Chemotherapy medications such as bleomycin, methotrexate, cyclophosphamide, gemcitabine, and busulfan are well-documented causes of ILD, as they can induce lung injury through direct cytotoxic effects or by triggering an immune response 1.
- Cardiovascular drugs, including amiodarone, statins, and ACE inhibitors, have also been linked to ILD, although the mechanisms may differ and include immune-mediated reactions or direct toxicity to lung tissue.
- Certain antibiotics like nitrofurantoin, sulfasalazine, and specific antibacterials can cause ILD, often through idiosyncratic reactions or hypersensitivity.
- Biologics and targeted therapies, such as rituximab, infliximab, etanercept, and checkpoint inhibitors (e.g., pembrolizumab, nivolumab), are associated with ILD, potentially due to their effects on the immune system and the balance between inflammatory and anti-inflammatory pathways.
- Other medications, including anti-inflammatory drugs (NSAIDs), and recreational substances like cocaine and heroin, can also lead to ILD, highlighting the importance of a thorough drug history in patients presenting with lung disease. The development of drug-induced ILD depends on several factors, including the dose and duration of treatment, individual patient characteristics (such as age, pre-existing lung disease, and genetic predisposition), and the specific drug involved 1. Management of drug-induced ILD typically involves discontinuation of the offending drug and, in severe cases, administration of corticosteroids to reduce inflammation, underscoring the need for early recognition and intervention to improve outcomes 1.
From the FDA Drug Label
Methotrexate-induced lung disease, including acute or chronic interstitial pneumonitis, is a potentially dangerous lesion, which may occur acutely at any time during therapy and has been reported at low doses. The drug that can cause interstitial lung disease (ILD) is methotrexate 2.
- Methotrexate has been reported to cause interstitial pneumonitis, which is a type of ILD.
- This condition can occur at any time during therapy and has been reported even at low doses.
From the Research
Drugs Associated with Interstitial Lung Disease
The following drugs have been associated with interstitial lung disease (ILD):
- Chemotherapeutics 3
- Molecular targeting agents 3
- Immune checkpoint inhibitors 3
- Antibiotics, such as nitrofurantoin 3, 4
- Antiarrhythmics 3
- Conventional or biological disease-modifying antirheumatic drugs 3
- Methotrexate, which can cause methotrexate-associated pneumonitis and is used to treat rheumatoid arthritis 5, 6
Specific Drug-Induced ILD
Some specific examples of drug-induced ILD include:
- Nitrofurantoin, which has been linked to the development of ILD in patients taking the drug long-term 4
- Methotrexate, which has been associated with pneumonitis and ILD in patients with rheumatoid arthritis 5, 6
- Checkpoint inhibitors, which have a high frequency of lung toxicity and may require mitigation strategies to prevent ILD 3
Diagnosis and Treatment
Diagnosis of drug-induced ILD is typically made by identifying exposure to a drug known to cause lung toxicity and excluding alternative causes of ILD 3. Treatment involves discontinuing the culprit drug and, in some cases, using systemic glucocorticoids or other therapies to manage symptoms and slow disease progression 3, 5, 6