Prevalence of adverse drug combinations in a large post-mortem toxicology database

The prevalence of important adverse drug combinations was studied among the 37,367 cases included in the Finnish post-mortem toxicology database during 2000-2006. The new SFINX interaction database (Swedish, Finnish, INteraction X-referencing) was utilised to identify adverse drug combinations. Consequently, the 24 drugs chosen for the study generated 96 two-compound combinations possessing potentially severe interactions. The total number of hits for the combinations found in the post-mortem database was 267, which accounts for approximately 0.71% of all cases. The potential role of adverse drug interaction (ADI) in these cases was evaluated from the background information and death certificate. The possible ADI cases comprised 23% of all hits and 0.17% of all cases analysed. In cases with a pharmacodynamic mechanism, the most prominent combinations were medicines causing serotonin syndrome or a beta(1)-blocker with verapamil or diltiazem. In cases with a pharmacokinetic mechanism, half of the cases involved digoxin in combination with verapamil. In one third of the possible ADI cases, a forensic pathologist had noted the studied compounds as an underlying or contributing cause of death, although the agents' specific role in ADIs was rarely recognised.