title: Bleeding complications and liver injuries during phenprocoumon treatment: a multicentre prospective observational study in internal medicine departments.
abstract: BACKGROUND
  Even after the recent approval of newer oral anticoagulants for clinical use, the vitamin K antagonist phenprocoumon remains an important treatment option for many patients. In order to quantify the hitherto "accepted" risks of phenprocoumon treatment, we analyzed adverse drug reactions (ADRs) that led to hospitalization on the internal medicine wards of four German pharmacovigilance centers.
  
  
  METHODS
  We prospectively analyzed ADRs leading to hospitalization on the internal medicine wards of the hospitals belonging to the German Network of Regional Pharmacovigilance Centers (Rostock, Greifswald, Jena, and the Sophien- und Hufeland-Klinikum in Weimar) in the years 2000 to 2008.
  
  
  RESULTS
  The 851 patients hospitalized for a phenprocoumon-associated ADR accounted for 12.4% of the 6887 ADR-related hospitalizations in the period of the study. 723 (85%) were admitted for a hemorrhage, usually in the gastrointestinal tract (482 patients); 8 patients died as a consequence of hemorrhage associated with phenprocoumon exposure. Using drug utilization data for the catchment areas of the participating hospitals, we calculate a rate of 5 to 7 hemorrhages leading to hospitalization in an internal medicine ward per 1000 patient-years under phenprocoumon treatment. One-third of the patients who had a hemorrhage were taking other interacting drugs, mainly inhibitors of platelet aggregation and non-steroidal anti-inflammatory drugs. Among the patients who were taking phenprocoumon because of a history of thromboembolic events or for atrial fibrillation, 60% to 70% of those who had hemorrhages had an international normalized ratio (INR) that was above the upper limit of the therapeutic range. Phenprocoumon-associated impairment of liver function arose in 23 patients (2.7%).
  
  
  CONCLUSIONS
  In this study, about one-eighth of all ADR-related admissions to hospital internal medicine wards were associated with phenprocoumon. There is a need for a comparative risk-benefit assessment of phenprocoumon and the newer oral anticoagulants under real-life conditions.
authors.affiliation: Philipp Klee-Institute for Clinical Pharmacology, HELIOS Clinic Wuppertal, Department of Clinical Pharmacology, School of Medicine, Faculty of Health, Witten/Herdecke University.
authors.forename: Sven
authors.initials: S
authors.lastname: Schmiedl
authors.forename: Marietta
authors.initials: M
authors.lastname: Rottenkolber
authors.forename: Jacek
authors.initials: J
authors.lastname: Szymanski
authors.forename: Werner
authors.initials: W
authors.lastname: Siegmund
authors.forename: Marion
authors.initials: M
authors.lastname: Hippius
authors.forename: Katrin
authors.initials: K
authors.lastname: Farker
authors.forename: Bernd
authors.initials: B
authors.lastname: Drewelow
authors.forename: Joerg
authors.initials: J
authors.lastname: Hasford
authors.forename: Petra
authors.initials: P
authors.lastname: Thürmann
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology*; D015897:Comorbidity; D005260:Female; D005858:Germany / Q000453:epidemiology; D006470:Hemorrhage / Q000453:epidemiology*; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D007388:Internal Medicine / Q000706:statistics & numerical data*; D008297:Male; D060735:Pharmacovigilance; D010644:Phenprocoumon / Q000627:therapeutic use*; D015995:Prevalence; D011446:Prospective Studies; D018570:Risk Assessment; D013923:Thromboembolism / Q000453:epidemiology* / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D010644:Phenprocoumon