Analysis of heat stroke and heat exhaustion cases in EudraVigilance pharmacovigilance database

Background The frequency and intensity of heat waves have increased and will keep increasing. This meteorological phenomenon, which is considered one of the most dangerous, can affect the entire population, but certain populations are at greater risk. Concretely, elderly people are more prompt to suffer from chronic diseases and therefore to be on medication that can interact with the different temperature-regulating systems of the body. So far, there are no published studies that have analyzed pharmacovigilance databases to characterize the association between specific pharmaceuticals and heat-related adverse reactions. Objective Therefore, in this study, we aimed to investigate the reported cases of heat exhaustion or heat stroke, associated with any drug notified to the European pharmacovigilance database (EudraVigilance). Method The Basque Country Pharmacovigilance Unit selected spontaneous reports recorded in EudraVigilance from January 1, 1995, to January 10, 2022. "Heat Stroke" and "Heat Exhaustion" preferred terms were selected. Non-cases, used as controls, were all the other adverse drug reaction reports recorded in EudraVigilance for the same time period. Results In total, 469 cases were obtained. Mean age: 49.74 +/- 8 years, 62.5% were male, and the majority (94.7%) were considered serious by EU criteria. Fifty-one active substances fulfilled the criteria to generate a signal of disproportionate reporting. Conclusions The majority of implicated drugs belong to therapeutic groups that are already mentioned in different heatillness prevention plans. But we also show that drugs aimed to treat multiple sclerosis and several cytokines were also associated with heat-related adverse effects.