Fatal adverse drug reactions: A worldwide perspective in the World Health Organization pharmacovigilance database

Abstract

Funding informationAgence Nationale de Sécurité du Médicament et des produits de santé Aims: Adverse drug reactions (ADRs) are important causes of death. However, the main involved drugs are relatively unknown. The present study was performed to characterise death-related drugs recorded in a large pharmacovigilance database during the last 10 years.Methods: A retrospective analysis of VigiBase, the World Health Organization pharmacovigilance database, was performed investigating fatal ADRs registered between 1 January 2010 and 31 December 2019 in male and female patients aged ≥18 years and reported by physicians. Analyses were descriptive investigating age, sex and suspected drugs. Differences in reporting according to sex, age and continents were investigated using disproportionality analysis with calculation of reporting odds ratio and its 95% confidence interval.Results: Among the 23 millions ADRs recorded in VigiBase, 3 250 967 were included with 43 685 fatal. They were reported mainly in patients older than 75 years. The 3 most frequently involved drug classes were antineoplastic/immunomodulating drugs followed by nervous system and cardiac drugs. The top 3 individual drugs were denosumab, lenalidomide and thalidomide with marked differences according to age, sex, continents and countries. The risk of reporting fatal ADRs was higher in males, in the Americas and in patients ≥65 years. Conclusion:Fatal ADRs registered in a large pharmacovigilance database during the last 10 years correspond to just over 1% of the total number of ADRs. They occurred more in males, after 65 years and with antineoplastic/immunomodulating drugs in general. Our study also highlighted, for the first time, important differences in fatal ADRs between continents and countries.

Drug-Related Deaths in a Tertiary Hospital: Characteristics of Spontaneously Reported Cases and Comparison to Cases Detected from a Retrospective Study

“…The results of both studies indicate that DRDs are more commonly observed in male patients over 65 years old, which supports the findings of the retrospective analysis of Vigibase [31].…”

“…It is interesting to point out that from both pharmacovigilance studies, the most common DRDs were hemorrhages and infections, which supports the findings in a recent retrospective analysis of VigiBase, the largest pharmacovigilance database in the world, from the World health Organization, [31] and a meta-analysis of observational studies in European hospitals [12]. Therefore, the most common involved drugs were anticoagulants and/or anti-thrombotics, and antineoplastic agents [12,31]. Preventive measures should be implemented to promote and improve closer follow-up of anticoagulant use.…”

The Person’s Care Requires a Sex and Gender Approach

“…Interestingly, an analysis of the Swedish national pharmacovigilance database (2008–2011) shows that women and men have higher rates of nonserious and severe reactions, respectively [ 89 ]. Data from VigiBase show that fatal ADR occur more in men, in the elderly over 65 years, and in Americans [ 90 ], indicating the importance of sex–gender, age, and geographical localization. Interestingly, paradoxical ADR (which are opposite reactions to the drug’s pharmacological effects) seem to be more frequent in men than in women [ 91 ].…”

“…Sex and gender differences partly depend on differences in pharmacokinetics and pharmacodynamics; however, the role of the above-mentioned factors in the drug’s safety profiles is not known. However, patient adherence to a therapy or drug prescription depends on the sex and gender of patients and sex and gender of physicians, geographical localization, and microbiota [ 38 , 88 , 90 ].…”

Just a Reflection: Does Drug Repurposing Perpetuate Sex-Gender Bias in the Safety Profile?

“…Notably, most drugs have been excluded from the market because of their toxic effects, which have been described mainly in women ( [20] and cited literature). Women seem to be admitted to hospitals for ADR more than men ( [130], however, about this last point there are no univocal data [131,132]). Besides, women have a bigger immune response to vaccines than men [82,83], but they also have more common severe side effects [133][134][135].…”