Gout: heart disease, CKD up risk for severe skin reactions with allopurinol

  • Yokose C & al.
  • CMAJ
  • 30 Sep 2019

  • International Clinical Digest
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Takeaway

  • Patients with gout and comorbid heart disease and/or chronic kidney disease (CKD) are at increased risk for severe cutaneous reactions with allopurinol (Zyloprim, Aloprim).

Why this matters

  • Initiating allopurinol at a lower dose (≤100 mg daily) may attenuate this risk.

Study design

  • Province-based population study of 130,325 allopurinol initiators in British Columbia, Canada during 1997-2015.
  • Primary endpoint: hospitalization for severe allopurinol-related adverse events within 3 months of initiation, followed by drug discontinuation.
  • Funding: Canadian Institutes of Health Research. 

Key results

  • 109 patients were admitted to hospital for allopurinol-associated cutaneous adverse events.
    • Events became apparent in the first 10 days, peaked at 1 month, and declined thereafter.
  • In multivariate analysis, heart disease was associated with a 55% higher relative risk (RR) for hospitalization (aRR=1.55; 95% CI, 1.01-2.37).
  • Risk was 88% higher with CKD (aRR=1.88; 95% CI, 1.17-3.02).
  • Risk was more than doubled with initial allopurinol dose >100 mg daily (aRR=2.78; 95% CI, 1.75-4.43).
  • Risk was 11-fold higher in patients with heart disease plus CKD initially receiving >100 mg allopurinol daily (aRR=11.13; 95% CI, 4.66-26.58) vs patients with neither condition started at lower doses.
    • Lower initial dosing reduced aRR from 11.13 to a nonsignificant 2.28 (95% CI, 0.68-7.58).
  • No association observed for diuretics (aRR=1.26; 95% CI, 0.83-1.92).

Limitations

  • Observational design, reliance on diagnostic codes.