Drug-induced pneumonitis (DIP) refers to inflammation of the lung parenchyma with alveolar and/or interstitial infiltration that occurs due to a drug reaction. Etiology is unproven; however, DIP may be due to a hypersensitivity reaction to the causative drug. The incidence rates of DIP vary by agent; notable agents with incidence rates are listed below. The reaction is most strongly associated with antineoplastic agents and the antiarrhythmic agent amiodarone. Factors that may increase the risk of developing DIP include advanced age, smoking and tobacco use, history of chest radiation, and history of lung cancer. There have been reported rechallenges with a previously causative drug where DIP does not recur.

In its mildest form, the reaction is asymptomatic. Severe forms can cause life-threatening dyspnea and lead to acute respiratory distress syndrome (ARDS) or pulmonary fibrosis. Symptomatic patients may report dry, nonproductive cough, dyspnea, exercise intolerance, chest pain, fatigue, and, less commonly, fever. The physical examination can show tachypnea, tachycardia, bibasilar crackles, hypoxemia, and cyanosis. Chest imaging may reveal bilateral basilar reticular interstitial patterns, alveolar infiltrates, nodular diffuse opacities, or ground glass opacities.

The reaction can occur shortly after the initiation of causative drug therapy, generally within a few days or 1-6 months. However, it has been reported as late as years after drug discontinuation. Suspect DIP in patients with cough and dyspnea who do not improve with broad-spectrum antibiotics but do improve with corticosteroids and discontinuation of causative drug.

DIP is a diagnosis of exclusion.

Notable drug classes and drugs with incidence as listed on the drug label:
Tyrosine kinase inhibitors:

• Osimertinib: interstitial lung disease / pneumonitis ≤ 56%
• Tepotinib: < 10%
• Dasatinib: 1% to < 10%
• Capmatinib: 2.7%
• Brigatinib: interstitial lung disease / pneumonitis 5.1%

Monoclonal antibodies (immune checkpoint inhibitors):

• Durvalumab: ≤ 34%
• Pembrolizumab: 11% 
• Trastuzumab deruxtecan: interstitial lung disease including pneumonitis: 16%
• See also immune checkpoint inhibitor-related adverse effects

mTOR inhibitors:

• Everolimus: 19%
• Sirolimus: Postmarketing experience

Antiarrhythmic agent:

• Amiodarone: hypersensitivity or interstitial / alveolar pneumonitis: 17%

Antineoplastic antibiotics:

• Bleomycin: 10% pulmonary adverse reactions, with pneumonitis being most frequent 
• Mitomycin: infrequent

PARP inhibitor:

• Olaparib: 2%

Antimetabolite antineoplastic agent:

• Methotrexate: 1%

Alkylating agent:

• Cyclophosphamide: Postmarketing experience

Taxanes:

• Paclitaxel: Postmarketing experience
• Docetaxel: Postmarketing experience

See Drug Reaction Data for a comprehensive list with supporting evidence.