Abstract
Objectives
The objective was to assess whether the concurrent use of tramadol and vitamin K antagonists (VKAs) leads to an increased risk of excessive anticoagulation.
Design
The study was designed as a case–control study, nested within users of VKA and with tramadol use as our main exposure. We used conditional logistic regression to control for potential confounders.
Setting
Prescription data from primary care were obtained from Odense Pharmacoepidemiological Database (OPED). Information about hospital admissions was obtained from the patient administrative system of Funen County (FPAS).
Subjects
Both cases and controls were selected from users of VKA. Cases were defined by being hospitalised with a main diagnosis indicating excessive anticoagulation. For each case, we selected 15 controls among VKA users, matched by age and sex.
Main outcome measure
Odds ratio for experiencing excessive anticoagulation attributable to the use of tramadol.
Results
A total of 178 patients were included, 30 of which were exposed to tramadol, along with 2643 controls, 114 of which were exposed to tramadol. The adjusted odds-ratio for experiencing excessive anticoagulation during use of tramadol was 3.1 (1.9–5.2). This corresponds to, on average, one excess case per 250 treatment years (CI 125–584). The result is potentially confounded by concomitant paracetamol use and the presence of acute illness.
Conclusion
Caution is advised when using tramadol in patients using VKA, and if possible, an alternative pain-medication should be used.
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Acknowledgments
The authors would like to thank Rasmus Steen Pedersen, Michael Due Larsen and Søren Ilsøe Moreno for valuable comments on the manuscript.
Conflicts of interest
Jesper Hallas has received fees for teaching from the Danish Association of the Pharmaceutical Industry and research grants from Nycomed, MSD and Pfizer. The remaining authors declare that they have no potential conflicts of interest.
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Pottegård, A., Meegaard, P.M., Holck, L.H. et al. Concurrent use of tramadol and oral vitamin K antagonists and the risk of excessive anticoagulation: a register-based nested case–control study. Eur J Clin Pharmacol 69, 641–646 (2013). https://doi.org/10.1007/s00228-012-1363-x
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DOI: https://doi.org/10.1007/s00228-012-1363-x