Is medicinal ketamine associated with urinary dysfunction issues? Assessment of both the European Medicines Agency (EMA) and the UK Yellow Card Scheme pharmacovigilance database-related reports

Objective: A range of ketamine-induced uropathy (KIU) issues have been typically described in ketamine misusers. Conversely, more knowledge is needed in terms of medicinal ketamine-related urological disturbances, since ketamine prescribing is being increasingly considered for a range of medical and psychopathological conditions. Methods: To assess medicinal KIU issues, we aimed at analyzing both the 2005–2017 European Medicines Agency (EMA) and the 2006–2018 UK Yellow Card Scheme (YCS) pharmacovigilance databases. Results: A total number (eg, all categories) of 11 632 EMA ketamine-related adverse drug reaction (ADR) reports were here identified. Out of these, some 9971 ADRs (eg, 85.7% of the total) were judged as “suspect” and were here analyzed. Some 1758 ADRs (17.7% of 9971, corresponding to 194 individual patients) referred to urological issues, relating to either kidney/ureter (922 ADRs) or bladder/urethra (837 ADRs). Ketamine was the sole drug administered in 156/194 (80.4%) cases/patients. Although most cases occurred in the 1 month-1 year time frame following the start of ketamine prescribing, in 30 cases the ADR occurred within 48 hours. Most ADR-related cases resolved, although both sequelae (18 cases) and fatalities (79/1758; 4.5%) were recorded. Overall, YCS data were consistent with EMA findings, with some 50/217 (23%) ADRs referring to renal/urinary disorders. Conclusions: Current data may only represent a gross underestimate of the KIU real prevalence issues. It is here suggested that chronic treatment involving higher doses/repeated exposure to ketamine be restricted to the context of controlled trials or clinical audits.