((A-234)) (A-234) Regional Differences in Tramadol Safety Reports: A Global Pharmacovigilance Analysis

Background: Despite significant health risks, including dependence, poisoning, cardiotoxicity, and serotonergic effects, tramadol is one of the most widely used opioids globally. Unlike most opioid analgesics, tramadol is not internationally controlled by the United Nations, therefore, regulations are made at the National level, which may lead to regional differences in usage patterns and adverse event (AE) risks.

Objectives: To characterize individual case safety reports (ICSRs) associated with tramadol between 1983 and 2024, stratified by geographical region.

Methods: We extracted all ICSRs with tramadol from the WHO VigiBase using VigiLyze up to April 2024 and summarized ICSR characteristics by geographical region (Africa, Asia, Europe, Oceania, the Americas). We identified the top three reporting countries, co-reported drugs, and AEs within each region.

Results: A total of 150,594 ICSRs were identified from Asia (n=97,237, 65%), Africa (n=1,125, 0.7%), Europe (n=29,447, 20%), the Americas (n=20,760, 14%), and Oceania (n=2,025, 1.3%). The three top reporting countries by region were: Asia (South Korea [76%], Thailand [6%], India [n=5%]), Africa (Tanzania [21%], South Africa [19%], Nigeria [16%]), Europe (France [34%], Spain [19%], Italy [11%], Oceania (Australia [86%] and New Zealand [14%]), and the Americas (US [56%], Brazil [n=11%], Mexico [10%]). Apart from sex (~66% female), regional differences were observed.
In Oceania, the Americas, and Europe, >65% of ICSRs had co-reported drugs, with opioids and benzodiazepines among the top 10, while in Asia and Africa, most ICSRs had no co-reported drugs (57% and 43%). Asia had the lowest proportion of serious (5%) cases. When all regions were combined, the proportion of serious cases was lower (16%) than in the Americas (41%), Europe (36%), and Africa (17%). In Oceania, 92% of ICSRs had missing values for seriousness. Fatal events were most common in the Americas (19%) and lowest in Asia (0.1%), with other regions reporting ~3%.

Conclusions: Tramadol safety reports in the WHO VigiBase show notable regional differences. ICSRs in the Americas, Oceania, and Europe were more often serious and with co-reported central nervous system-depressive drugs. In contrast, reports from Asia (mainly from South Korea) had fewer co-reported drugs, fewer AEs, and were less often serious. With 65% of all ICSRs originating from Asia, the global profile of tramadol was skewed by one country. These differences, particularly in AEs and severity, may reflect variations in prescribing patterns, pharmacovigilance systems, or tramadol’s safety profile across regions. Therefore, future pharmacovigilance studies should consider reporting region and country level differences.