Allopurinol-Induced Severe Cutaneous Adverse Drug Reactions: An Analysis of Spontaneous Reports in Malaysia (2000–2018)



Allopurinol-induced severe cutaneous adverse drug reactions (SCARs) are potentially debilitating and life-threatening reactions, which can cause a financial burden to the healthcare system.


We aimed to identify risk factors for allopurinol-induced SCARs and to assess their impact on fatality.


Adverse drug reaction (ADR) reports with allopurinol as suspected drug were extracted from the Malaysian pharmacovigilance database from year 2000 to 2018. Multiple logistic regression analysis was used to identify significant predictors of allopurinol-induced SCARs. We further analysed the association between covariates and SCARs-related fatality in a separate model. Level of significance was set at p value < 0.05.


Out of 1747 allopurinol ADR reports, 612 involved SCARs (35%). The strongest predictors significantly associated with SCARs were underlying renal disease (odds ratio [OR] 2.02; 95% confidence interval [CI] 1.36, 3.00; p = 0.001), allopurinol-prescribed dose of 300 mg/day or higher (OR 1.72; 95% CI 1.38, 2.15; p < 0.001), females (OR 1.54; 95% CI 1.24, 1.93; p < 0.001), age 65 years and above (OR 1.31; 95% CI 1.04, 1.64; p = 0.020), and allopurinol-prescribed indication. SCARs cases were higher in patients who received allopurinol for unspecified hyperuricaemia (OR 1.87; 95% CI 1.29, 2.70; p = 0.001) and off-label indications (OR 3.45; 95% CI 2.20, 5.42; p < 0.001) compared to registered indications. Fatality was associated with older age and a diagnosis of Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) overlap or TEN.


Malaysian pharmacovigilance data show that predictors of allopurinol-induced SCARs were elderly females, patients with underlying renal disease and high allopurinol doses. These patients need close monitoring and must be educated to stop allopurinol at the first signs of rash.

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We would like to thank the Director General of Health Malaysia for his permission to publish this study. We would also like to thank Dr. Azuana Ramli for her valuable input and our pharmacovigilance colleagues for their beneficial discussions, some of which contributed in the writing of this paper.


The authors received no financial support for the research, authorship, and/or publication of this article.

Author information




NMA, LSC, and VH conceived and designed the study. WWK, NMA, and LSC extracted and reviewed the data. LSC, YHS, and VH were involved in data analysis and interpretation. LSC and YHS drafted the manuscript. VH revised the manuscript. All authors read and approved the final manuscript for submission.

Corresponding author

Correspondence to Vidhya Hariraj BPharm (Hons), MPharm (Clin.Pharm), PhD (Pharm).

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The authors declared no potential conflicting interests in respect to the research, authorship, and/or publication of this article.

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Lee, S.C., Wo, W.K., Yeoh, H.S. et al. Allopurinol-Induced Severe Cutaneous Adverse Drug Reactions: An Analysis of Spontaneous Reports in Malaysia (2000–2018). Ther Innov Regul Sci (2021).

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  • Allopurinol
  • Severe cutaneous adverse drug reaction
  • Pharmacovigilance
  • Stevens–Johnson syndrome
  • Fatality