Analysis of Drug-Drug Interactions in Swiss Claims Data Using Tizanidine and Ciprofloxacin as a Prototypical Contraindicated Combination

Background: Potential drug-drug interactions (pDDIs) are described in various case reports, but few studies have evaluated the impact of specific combinations on a population level. Objective: To analyze the type and frequency of multiple contraindicated (X-pDDIs) and major interactions (D-pDDIs) and to subsequently assess the impact of the particular combination of tizanidine and ciprofloxacin on outpatient physician visits and hospitalizations. Methods: Anonymized Swiss claims data from 524 797 patients in 2014-2015 were analyzed. First, frequencies of X- and D-pDDIs were calculated. Next, a retrospective cohort study was conducted among patients prescribed tizanidine and ciprofloxacin (exposed, n = 199) or tizanidine and other antibiotics (unexposed, n = 960). Hospitalizations and outpatient physician visits within 7, 14, and 30 days after initiation of antibiotic therapy were evaluated using multiple binary logistic regression and multiple linear regression. Results: The relative frequencies of X- and D-pDDIs were 0.4% and 6.65%, respectively. In the cohort study, significant associations between exposure to tizanidine and ciprofloxacin and outpatient physician visits were identified for 14 and 30 days (odds ratio [OR] = 1.61 [95% CI = 1.17-2.24], P = 0.004, and OR = 1.59 [95% CI = 1.1-2.34], P = 0.016). A trend for increased risk of hospitalization was found for all evaluated time periods (OR = 1.68 [95% CI = 0.84-3.17], OR = 1.52 [95% CI = 0.63-3.33], and OR = 2.19 [95% CI = 0.88-5.02]). Conclusion and Relevance: The interaction between tizanidine and ciprofloxacin is not only relevant for individual patients, but also at the population level. Further investigation of the impact of other clinically relevant DDIs is necessary to improve patient safety and reduce avoidable health care utilization.