Pottegård, Anton6; Meegaard, P. M.5; Holck, L. H.5; Christensen, René dePont7; Madsen, Hanne8; Hallas, J.6
1 Clinical Pharmacology and Pharmacy, Department of Public Health, Det Sundhedsvidenskabelige Fakultet, SDU2 Research Unit of General Practice, Department of Public Health, Det Sundhedsvidenskabelige Fakultet, SDU3 Department of Biostatistics, Department of Public Health, Det Sundhedsvidenskabelige Fakultet, SDU4 Lung Medicine, Department of Clinical Research, Det Sundhedsvidenskabelige Fakultet, SDU5 unknown6 Clinical Pharmacology and Pharmacy, Department of Public Health, Det Sundhedsvidenskabelige Fakultet, SDU7 Research Unit of General Practice, Department of Public Health, Det Sundhedsvidenskabelige Fakultet, SDU8 Lung Medicine, Department of Clinical Research, Det Sundhedsvidenskabelige Fakultet, SDU
a register-based nested case-control study
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.
European Journal of Clinical Pharmacology, 2013, Vol 69, Issue 3, p. 641-646
Administration, Oral Aged Aged, 80 and over Analgesics, Opioid/*adverse effects Anticoagulants/administration & dosage/*adverse effects Blood Coagulation/*drug effects Case-Control Studies Confounding Factors (Epidemiology) Denmark Drug Interactions Drug Prescriptions Female Hemorrhage/blood/*chemically induced Humans Logistic Models Male Odds Ratio Patient Selection Registries Risk Assessment Risk Factors Tramadol/*adverse effects Vitamin K/*antagonists & inhibitors; Administration, Oral; Aged; Aged, 80 and over; Analgesics, Opioid; Anticoagulants; Blood Coagulation; Case-Control Studies; Confounding Factors (Epidemiology); Denmark; Drug Interactions; Drug Prescriptions; Female; Hemorrhage; Humans; Logistic Models; Male; Odds Ratio; Patient Selection; Registries; Risk Assessment; Risk Factors; Tramadol; Vitamin K