Severe Cutaneous Adverse Drug Reactions Associated with Allopurinol: An Analysis of Spontaneous Reporting System in Southern Italy

BACKGROUND: Allopurinol can induce severe cutaneous adverse reactions (SCARs), including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome, Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). AIMS AND METHODS: We analyzed the Individual Case Safety Reports (ICSRs) sent from January 2001 until April 2019 to the Campania regional Center of Pharmacovigilance (Southern Italy) that reported allopurinol as suspected, with a focus on those reporting at least one serious cutaneous adverse drug reaction (ADR). This study was aimed to describe the main characteristics of all ADRs associated with allopurinol, analyze the proportion of serious cutaneous ADRs of total ICSRs related to allopurinol and to compare the main features (age, sex, seriousness and outcome) of ICSRs that reported serious cutaneous ADRs with those that did not. RESULTS: The Campania regional Center of Pharmacovigilance received 108 ICSRs that reported allopurinol as suspected. ADRs occurred more frequently in the elderly (median age: 71 years) and female patients (53.7%). Fifty-seven percent of all ADRs were classified as serious and 58% had a favorable outcome. Fifty-six ICSRs reported at least one serious cutaneous ADR; among these ICSRs, 37 cases of SCARs were found [DRESS syndrome (n = 3; 5.4%), SJS (n = 8; 14.3%) and TEN (n = 26; 46.4%)]. Serious cutaneous ADRs commonly occurred in the elderly (median age: 73 years) and female patients (62.5%). They frequently required hospitalization (75%) and had an unfavorable outcome (46%). No statistically significant differences were found between ICSRs that reported serious cutaneous ADRs and ICSRs that did not report serious cutaneous ADRs except for the seriousness degree “Hospitalization or its prolongation” and the outcome degrees “Unfavorable” and “Favorable”. CONCLUSION: This study found that 52% (56/108) of all ICSRs having allopurinol as a suspected drug were serious cutaneous ADRs. Serious cutaneous ADRs associated with allopurinol frequently required hospitalization or prolonged hospitalization, and almost half had an unfavorable outcome.