Systematic analysis of drug-associated myocarditis reported in the World Health Organization pharmacovigilance database

While multiple pharmacological drugs have been associated with myocarditis, temporal trends and overall mortality have not been reported. Here we report the spectrum and main features of 5108 reports of drug-induced myocarditis, in a worldwide pharmacovigilance analysis, comprising more than 21 million individual-case-safety reports from 1967 to 2020. Significant association between myocarditis and a suspected drug is assessed using disproportionality analyses, which use Bayesian information component estimates. Overall, we identify 62 drugs associated with myocarditis, 41 of which are categorized into 5 main pharmacological classes: antipsychotics (n = 3108 reports), salicylates (n = 340), antineoplastic-cytotoxics (n = 190), antineoplastic-immunotherapies (n = 538), and vaccines (n = 790). Thirty-eight (61.3%) drugs were not previously reported associated with myocarditis. Antipsychotic was the first (1979) and most reported class (n = 3018). In 2019, the two most reported classes were antipsychotics (54.7%) and immunotherapies (29.5%). Time-to-onset between treatment start and myocarditis is 15 [interquartile range: 10; 23] days. Subsequent mortality is 10.3% and differs between drug classes with immunotherapies the highest, 32.5% and salicylates the lowest, 2.6%. These elements highlight the diversity of presentations of myocarditis depending on drug class, and show the emerging role of antineoplastic drugs in the field of drug-induced myocarditis.