Sing Chet Lee1, Wee Kee Wo1, Hee Sheong Yeoh1, Norleen Mohamed Ali1, Vidhya Hariraj2. 1. National Pharmaceutical Regulatory Agency, Ministry of Health, Malaysia, Lot 36, Jalan Universiti, 46200, Petaling Jaya, Selangor, Malaysia. 2. National Pharmaceutical Regulatory Agency, Ministry of Health, Malaysia, Lot 36, Jalan Universiti, 46200, Petaling Jaya, Selangor, Malaysia. vidhya@npra.gov.my.
Abstract
INTRODUCTION: 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. OBJECTIVES: We aimed to identify risk factors for allopurinol-induced SCARs and to assess their impact on fatality. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
INTRODUCTION: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. OBJECTIVES: We aimed to identify risk factors for allopurinol-induced SCARs and to assess their impact on fatality. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Entities:
Keywords:
Allopurinol; Fatality; Pharmacovigilance; Severe cutaneous adverse drug reaction; Stevens–Johnson syndrome
Authors: Sarah F Keller; Na Lu; Kimberly G Blumenthal; Sharan K Rai; Chio Yokose; Jee Woong J Choi; Seoyoung C Kim; Yuqing Zhang; Hyon K Choi Journal: Ann Rheum Dis Date: 2018-04-13 Impact factor: 19.103