Indications

• Psoriatic Arthritis (see Psoriatic Arthritis, [[Psoriatic Arthritis]])
• Rheumatoid Arthritis (RA) (see Rheumatoid Arthritis, [[Rheumatoid Arthritis]])

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Pharmacology

• Dihydroorotate Dehydrogenase Inhibitor: inhibition of pyrimidine synthesis

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Administration

• PO

Dose-Adjustment

• Hepatic
• Renal

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Adverse Effects

Gastrointestinal Adverse Effects

• Hepatotoxicity (see xxxx, [[xxxx]]): toxicity is synergistic with methotrexate

Pulmonary Adverse Effects

Acute Interstitial Pneumonia/Acute Lung Injury-ARDS (see Interstitial Lung Disease-Etiology, [[Interstitial Lung Disease-Etiology]] and Acute Lung Injury-ARDS, [[Acute Lung Injury-ARDS]])

• Epidemiology
  • Prevalence: occurred in 61/5053 patients in post-marketing studies
    • However, some studies note no increased risk of pulmonary toxicity in leflunomide-treated patients unless they were also treated with methotrexate or had pre-existing lung disease
  • Risk Factors for Pulmonary Toxicity
    • Loading Dose
    • Low Body Weight
    • Pre-Existing Lung Disease
    • Smoking History
• Diagnosis
  • Bronchoscopy with Bronchoalveolar Lavage (BAL): increased CD4/CD8 ratio
  • Thoracoscopic/Open Lung Biopsy: diffuse alveolar damage with secondary organizing pneumonia
• Prognosis: 24 reported deaths were reported in post-marketing studies

Diffuse Alveolar Hemorrhage (DAH) (see Diffuse Alveolar Hemorrhage, [[Diffuse Alveolar Hemorrhage]])

• Epidemiology: rare case reports

Hypersensitivity Pneumonitis (HP) (see Hypersensitivity Pneumonitis, [[Hypersensitivity Pneumonitis]])

• Epidemiology
• Diagnosis
  • CXR/Chest CT: interstitial infiltrates
  • Thoracoscopic/Open Lung Biopsy: granulomas

Induction of Rheumatoid Nodules (see Lung Nodule or Mass, [[Lung Nodule or Mass]])

• Epidemiology

Pulmonary Alveolar Proteinosis (PAP) (see Pulmonary Alveolar Proteinosis, [[Pulmonary Alveolar Proteinosis]])

• Epidemiology: rare case reports

Pulmonary Hypertension (see Pulmonary Hypertension, [[Pulmonary Hypertension]])

• Epidemiology: case reports

Pulmonary Infiltrates with Eosinophilia (see Drug-Induced Pulmonary Eosinophilia, [[Drug-Induced Pulmonary Eosinophilia]])

• Epidemiology: case reports

Other Adverse Effects

• xxxx
• xxxx
• xxxx
• xxxx

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References

• Leflunomide (Arava): hematologic, hepatic and respiratory reaction. Canadian Adverse Reaction Newsletter 2002; 12: 2-3
• Interstitial pneumonia in a patient undergoing treatment with leflunomide: drug-induced toxicity. J Pneumol 2003; 29: 395-400
• Leflunomide induced acute interstitial pneumonia. Journal of Rheumatology 2005; 32: 1160-1163
• Leflunomide-related lung injury in patients with rheumatoid arthritis: imaging features. Mod Rheumatol 2005: Volume 15, Number 3, 173-179
• Pulmonary alveolar proteinosis associated with a disease-modifying antirheumatoid arthritis drug. Respirology 2006; 11: 663-665
• Leflunomide use and the risk of interstitial lung disease in rheumatoid arthritis. Arthritis & Rheumatism. Volume 54, Issue 5, pages 1435–1439, May 2006
• Leflunomide-induced nodulosis in a case of Rheumatoid arthritis. APLAR Journal of Rheumatology. Volume 10, Issue 3, pages 246–247, September 2007
• Hypersensitivity pneumonitis associated with leflunomide therapy. J Rheumatol. 2007 Sep;34(9):1934-7
• Intrapulmonary rheumatoid nodules in a patient with long-standing rheumatoid arthritis treated with leflunomide. Pathol Oncol Res. 2008 Mar;14(1):101-4
• Factors associated with fatal outcome of leflunomide-induced lung injury in Japanese patients with rheumatoid arthritis. Rheumatology (2009) 48 (10): 1265-1268
• An Elderly Man With Rheumatoid Arthritis and Dyspnea. CHEST April 2009 vol. 135 no. 4 1090-109
• Leflunomide-induced pulmonary hypertension in a young woman with rheumatoid arthritis: a case report. Cardiovasc Toxicol. 2012 Jun;12(2):180-3. doi: 10.1007/s12012-012-9153-3 [MEDLINE]