Allopurinol‐induced Stevens‐Johnson syndrome and toxic epidermal necrolysis: Signal detection and preventability from Vietnam National pharmacovigilance database

Abstract

What Is Known and Objective Allopurinol, the first‐line medication for hyperuricemia is well‐known for its association with severe cutaneous adverse reactions, especially Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). In the current study, we analysed the Vietnamese spontaneous reporting database to identify signals and preventability of allopurinol‐induced SJS/TEN in Vietnam from 2010 to 2019. Methods Signal generation was assessed using the case/non‐case method. Reporting odds ratios (RORs) and 95% confidence intervals (95% CI) were calculated. Results Among 72,822 spontaneous ADR reports submitted to the Vietnam National Drug Information and Adverse Drug Reaction Monitoring Centre, 392 reports were on SJS/TEN, of which, 65 cases (16.6%) were related to allopurinol. The signals of allopurinol‐induced SJS/TEN in Vietnam started in 2014 (ROR of 3.531, 95% CI: 1.830–6.810) and annually increased until 2019 (ROR of 11.923, 95% CI: 8.508–16.710). The preventability assessment showed that no allopurinol‐induced SJS/TEN case was definitely unpreventable. 61.6% of the SJS/TEN cases were avoidable because they were associated with inappropriate prescribing such as unapproved indications, too high initial dose and even rechallenging in patients with a history of allopurinol allergy. What Is New and Conclusion The signals of allopurinol‐induced SJS/TEN in Vietnam started in 2014 and annually increased until 2019. Our first report specifically focusing on the ADR preventability of allopurinol showed that correction of medical errors relating to prescription could prevent more than 60% of SJS/TEN cases in Vietnamese allopurinol users. This is a feasible and practical solution, provided that there would be a systematic change in both healthcare systems and public awareness.

Agents for the Treatment of Gout: Current Advances and Future Perspectives

“…They also modified the chiral carbon of the sulfhydryl side chain, thereby potentially improving the safety and potency of the compound. Accordingly, compounds (38) were synthesized; the most active of these was compound 38a (DR = 96.1%) (Figure 14). 77 In the field of medicinal chemistry, even minimal chemical modifications can result in considerable changes in the inhibitor activity.…”

“…Consequently, allopurinol prevents UA formation by simultaneously inhibiting purine formation and purine oxidative metabolism. However, as a purine analogue, allopurinol can also interfere with normal purine metabolism, which may lead to serious side effects, including hypersensitivity, skin rash, gastrointestinal discomfort, eosinophilia, renal toxicity, toxic epidermal necrolysis, and Stevens–Johnson syndrome. − Therefore, it is necessary to optimize allopurinol to limit the occurrence of side effects.…”

Preparation of chitosan-coated hollow tin dioxide nanoparticles and their application in improving the oral bioavailability of febuxostat

“…A commonly used drug is allopurinol. However, it has serious side effects, such as Stevens-Johnson syndrome (SJS) ( Gupta et al, 2019 ; Huong et al, 2022 ; Liao et al, 2021 ). Febuxostat (FEB), unlike allopurinol, is a novel nonpurine selective inhibitor of xanthine oxidase that can inhibit uric acid synthesis and shows good therapeutic effects for hyperuricemia and gout ( Huong et al, 2022 ).…”

“…However, it has serious side effects, such as Stevens-Johnson syndrome (SJS) ( Gupta et al, 2019 ; Huong et al, 2022 ; Liao et al, 2021 ). Febuxostat (FEB), unlike allopurinol, is a novel nonpurine selective inhibitor of xanthine oxidase that can inhibit uric acid synthesis and shows good therapeutic effects for hyperuricemia and gout ( Huong et al, 2022 ). Although FEB has received much attention among antihyperuricemia drugs ( Becker et al, 2005 ), its low water solubility (below 0.0129 mg/mL) leads to poor gastrointestinal bioavailability, limiting its widespread use ( Londhe and Bakshi, 2023 ; Habib et al, 2021 ).…”