Investigating in VigiBase over 6000 cases of pneumonia in clozapine-treated patients in the context of the literature: focus on high lethality and the association with aspiration pneumonia

Abstract

The literature associates clozapine with pneumonia/aspiration pneumonia. Areas covered: Clozapine reports to the international pharmacovigilance database (VigiBase™) were analyzed for pneumonia/aspiration pneumonia from introduction to May 10, 2023. VigiBase uses the information component (IC) as a statistical signal. Expert Opinion: There were 5572 cases of pneumonia, 775 of aspiration pneumonia, and 45 combined leading to 6392 cases of all types of pneumonia. The IC was 3.52 for aspiration pneumonia, introduced as a VigiBase label in 2003, and 1.91 for pneumonia. Patients were reclassified as 3628 with no signs of aspiration and 1533 with signs. Signs of aspiration were strongly associated with some co-medications: olanzapine, odds ratio (OR)= 23.8, 95% confidence interval (CI), 14.9-380; risperidone OR= 18.6, CI, 11.4-30.4; valproic acid, OR= 5.5, CI, 4.5-6.6; and benzodiazepines OR= 5.5, CI, 4.5-6.6. In 2415 cases with completed data, fatal outcomes made up 45% (signs of aspiration made no difference), but there was wide variability from 0% (females <45 years of age; duration ≤30 days) to 76% (males >64 years of age; duration >1 year). During the first week, pneumonia was associated with: 1) very high titration doses, 2) very small doses in Parkinson’s disease and 3) overrepresentation in Japan.