Key result
Concordance between self-reported and pharmacy database records for CYP2D6-mediated potential drug-drug interactions peaked at a 3-month window with a kappa of 0.545 (95% CI 0.544-0.545).
Why the study?
Drug-drug interactions are major contributors to adverse drug reactions, making it important to investigate their frequency and concordance in the population.
Cross-Sectional (n=80,837)
Effect estimate: Kappa 0.545 (95% CI 0.544-0.545)
CYP2D6/2C19/2C9-mediated potential DDIs occur in 1-2% of the general population, and concordance between self-reported and pharmacy data varies by time window, medication type, sex, and age.
Moderate agreement at 3 months cautions against single-source DDI assessment; leaves open optimal data integration for pharmacoepidemiologic studies.
BACKGROUND: Drug-drug interaction (DDI) is one of the main contributors to adverse drug reactions and therefore, it is important to study its frequency in the population. We aimed to investigate frequency and concordance on CYP2D6, CYP2C19, and CYP2C9 (CYP2D6/2C19/2C9)-mediated potential DDIs at the Lifelines cohort and linked data from the pharmacy database IADB.nl. METHODS: As part of the University of Groningen PharmLines Initiative, data were collected on CYP2D6/2C19/2C9-related substrate/inhibitors from entry questionnaires of Lifelines participants and linked information from the pharmacy database IADB.nl. CYP2D6/2C19/2C9 related co-prescriptions were divided based on the type of drugs i.e. chronically used medication (CM) or occasionally used medication (OM). This resulted in the combination of two chronically used drugs (CM-CM), chronically and occasionally used medication (CM-OM), and two occasionally used drugs (OM-OM). To measure the agreement level, cohen's kappa statistics and test characteristics were used. Results were stratified by time window, gender, and age. RESULTS: Among 80,837 medicine users in the Lifelines, about 1-2 per hundred participants were exposed to a CYP2D6/2C19/2C9-mediated potential DDI. Overall, the overlapping time window of three months produced the highest mean kappa values between the databases i.e. 0.545 (95% CI:0.544-0.545), 0.512 (95% CI:0.511-0.512), and 0.374 (95% CI:0.373-0.375), respectively. CM-CM had a better level of agreement (good) than CM-OM (fair to moderate) and OM-OM combination (poor to moderate). The influence of gender on concordance values was different for different CYPs. Among older persons, agreement levels were higher than for the younger population. CONCLUSIONS: CYP2D6/2C19/2C9-mediated potential DDIs were frequent and concordance of data varied by time window, type of combination, sex and age. Subsequent studies should rather use a combination of self-reported and pharmacy database information.
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Bahar et al. (2020) conducted a cross-sectional in Potential drug-drug interactions (CYP2D6, CYP2C19, CYP2C9) (n=80,837). Self-reported medication data (Lifelines cohort) vs. Pharmacy database data (IADB.nl) was evaluated on Concordance (Cohen's kappa) of CYP2D6-mediated potential DDIs at a 3-month overlapping time window (Kappa 0.545, 95% CI 0.544-0.545). Concordance between self-reported and pharmacy database records for CYP2D6-mediated potential drug-drug interactions peaked at a 3-month window with a kappa of 0.545 (95% CI 0.544-0.545).
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