Can Allopurinol Cause Interstitial Lung Disease?
Yes, allopurinol can rarely cause severe allergic reactions including interstitial lung disease, and if a rash develops, allopurinol should be stopped immediately. 1
Severe Allergic Reactions to Allopurinol
Allopurinol hypersensitivity syndrome (AHS) is a rare but serious adverse effect that can manifest with multiple organ involvement, including pulmonary complications such as interstitial lung disease. 1
The risk of AHS is significantly elevated in certain populations, particularly patients of Southeast Asian descent and African Americans who carry the HLA-B*5801 allele, warranting genetic testing before initiating therapy in these high-risk groups. 2
If any rash develops during allopurinol therapy, the drug must be discontinued immediately to prevent progression to more severe manifestations of hypersensitivity, which can include pulmonary involvement. 1
Risk Mitigation Strategies
Starting allopurinol at low doses (≤100 mg/day, and lower in patients with chronic kidney disease stage ≥3) with subsequent dose titration significantly reduces the risk of hypersensitivity reactions including those affecting the lungs. 1
Higher starting doses and the presence of chronic kidney disease are both associated with increased risk of AHS, making the low-dose initiation strategy particularly important in vulnerable populations. 1
Dose reduction of 50% or more is recommended in patients with renal failure to minimize accumulation of allopurinol and its metabolites, which may contribute to adverse reactions. 2
Clinical Monitoring
Patients should be educated about the warning signs of hypersensitivity reactions and instructed to stop the medication and seek immediate medical attention if they develop a rash or other concerning symptoms. 1
The incidence of severe allergic reactions is rare when appropriate prescribing practices are followed, including low-dose initiation and dose adjustment for renal function. 1
Important Caveats
While interstitial lung disease is a recognized complication of allopurinol hypersensitivity syndrome, it represents a rare adverse event rather than a common side effect. 1
The benefits of allopurinol in treating gout and preventing complications typically outweigh the risks when the medication is prescribed appropriately with low-dose initiation and proper monitoring. 1
Allopurinol remains the strongly recommended first-line urate-lowering therapy for all patients with gout, including those with moderate-to-severe chronic kidney disease, due to its efficacy, tolerability, safety profile when dosed correctly, and lower cost compared to alternatives. 1