Drug dosage modifications in 24 million in-patient prescriptions covering eight years: A Danish population-wide study of polypharmacy

Polypharmacy has generally been assessed by raw counts of different drugs administered concomitantly to the same patients; not with respect to the likelihood of dosage-adjustments. To address this aspect of polypharmacy, the objective of the present study was to identify co-medications associated with more frequent dosage adjustments. The data foundation was electronic health records from 3.2 million inpatient admissions at Danish hospitals (2008-2016). The likelihood of dosage-adjustments when two drugs were administered concomitantly were computed using Bayesian logistic regressions. We identified 3,993 co-medication pairs that associate significantly with dosage changes when administered together. Of these pairs, 2,412 (60%) did associate with readmission, mortality or longer stays, while 308 (8%) associated with reduced kidney function. In comparison to co-medications pairs that were previously classified as drug-drug interactions, pairs not classified as drug-drug interactions had higher odds ratios of dosage modifications than drug pairs with an established interaction. Drug pairs not corresponding to known drug-drug interactions while still being associated significantly with dosage changes were prescribed to fewer patients and mentioned more rarely together in the literature. We hypothesize that some of these pairs could be associated with yet to be discovered interactions as they may be harder to identify in smaller-scale studies.