Drug-Drug Interactions and the Risk of Emergency Hospitalizations: A Nationwide Population-Based Study

Several studies suggest a significant risk of hospitalization because of drug-drug interactions in the general population. However, to our knowledge, this risk has never been measured precisely in a large population.

We aimed to estimate the risk of emergency hospitalization associated with exposure to the contraindicated concomitant use of interacting drugs in the general population.

A self-controlled case-series analysis was carried out on a cohort of 150,000 subjects randomly selected from the French national health insurance database, between 01/01/2016 and 31/12/2016. Exposure to the contraindicated concomitant use of interacting drugs was defined as the overlapping period of dispensings of drugs contraindicated because of clinically meaningful drug-drug interactions. The main outcome, incidence rate ratios, comparing the incidence rate of emergency hospitalizations during each category of exposure time periods with that during the reference period, was estimated using the conditional Poisson regression model.

Over the study period, 967 subjects were exposed to at least one contraindicated concomitant use of interacting drug and 177 had been exposed and presented at least one emergency hospitalization. Compared to the unexposed follow-up time, the risk of emergency hospitalization increased during exposure to contraindicated concomitant use of interacting drug periods (incidence rate ratio: 2.41; 95% confidence interval 1.55-3.76). This could translate into 7200 (4500-8900) potentially preventable emergency hospitalizations yearly in France.

We evidenced an almost 2.5-fold increase in the risk of emergency hospitalizations during periods of exposure to contraindicated concomitant use of interacting drugs, with a potential public health impact exceeding 7000 preventable hospitalizations yearly in France. These results confirm the need to reinforce training in prescription practices and tools for prevention concerning contraindicated concomitant use of interacting drugs. These would especially concern drugs involved in an increase in long QT syndrome when associated such as citalopram, and highly prescribed drugs with a risk of overdose if co-prescribed with cytochrome P450 inhibitors, such as antigout and lipid-lowering drugs.