title: Concurrent use of tramadol and oral vitamin K antagonists and the risk of excessive anticoagulation: a register-based nested case-control study.
abstract: OBJECTIVE
  The objective was to assess whether the concurrent use of tramadol and vitamin K antagonists (VKAs) leads to an increased risk of excessive anticoagulation.
  
  
  METHODS
  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.
  
  
  METHODS
  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).
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  Caution is advised when using tramadol in patients using VKA, and if possible, an alternative pain-medication should be used.
authors: Institute of Public Health, Clinical Pharmacology, University of Southern Denmark, Odense, Denmark. apottegaard@health.sdu.dk
authors: Anton
authors: A
authors: Pottegård
authors: Peter M
authors: PM
authors: Meegaard
authors: Line H V
authors: LH
authors: Holck
authors: Rene dePont
authors: Rd
authors: Christensen
authors: Hanne
authors: H
authors: Madsen
authors: Jesper
authors: J
authors: Hallas
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000009:adverse effects*; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D001777:Blood Coagulation / Q000187:drug effects*; D016022:Case-Control Studies; D015986:Confounding Factors, Epidemiologic; D003718:Denmark; D004347:Drug Interactions; D011307:Drug Prescriptions; D005260:Female; D006470:Hemorrhage / Q000097:blood / Q000139:chemically induced*; D006801:Humans; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D018579:Patient Selection; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D014147:Tramadol / Q000009:adverse effects*; D014812:Vitamin K / Q000037:antagonists & inhibitors*
chemical_list: D000701:Analgesics, Opioid; D000925:Anticoagulants; D014812:Vitamin K; D014147:Tramadol