Kathrin Jobski1, Sigrid Behr, Edeltraut Garbe. 1. Bremen Institute for Prevention Research and Social Medicine (BIPS), University of Bremen, Achterstrasse 30, 28359, Bremen, Germany.
Abstract
PURPOSE: Phenprocoumon is the most frequently used vitamin K antagonist in Germany. The aim of this study was to estimate the risk of serious bleeding as a result of the use of drugs with potential interaction with phenprocoumon. METHODS: We conducted a nested case-control study in a cohort of 246,220 phenprocoumon users in the German Pharmacoepidemiological Research Database. Cases were patients hospitalised for haemorrhage of different kinds. Ten controls were matched to each case by health insurance, birth year and sex using incidence density sampling. Odds ratios (OR) with 95% confidence intervals (CI) of the risk of serious bleeding associated with combined use of phenprocoumon and potentially interacting drugs versus phenprocoumon alone were estimated using conditional logistic regression analysis. Our analyses considered multiple risk factors, such as bleeding history, other comorbidities or co-medication. RESULTS: Our study included 2,553 cases and 25,348 matched controls. An increased risk of bleeding was observed for the combined use of phenprocoumon and clopidogrel vs phenprocoumon use alone (OR: 1.83, 95% CI: 1.41-2.36). Antibiotic drugs associated with an increased risk of haemorrhage in the population of phenprocoumon users included the group of quinolones with ORs ranging from 2.74 (95% CI: 1.80-4.18) for ciprofloxacin to 4.40 (95% CI: 2.45-7.89) for levofloxacin, amoxicillin plus clavulanic acid (OR: 2.99, 95% CI: 1.39-6.42) and cotrimoxazole (OR 3.57, 95% CI: 2.36-5.40). Among non-steroidal anti-inflammatory drugs (NSAIDs), ketoprofen and naproxen were associated with the highest risks. CONCLUSION: Significantly elevated risks of major bleeding were mainly observed for drugs with known pharmacodynamic interaction with phenprocoumon, and less for drugs with possible pharmacokinetic interaction.
PURPOSE:Phenprocoumon is the most frequently used vitamin K antagonist in Germany. The aim of this study was to estimate the risk of serious bleeding as a result of the use of drugs with potential interaction with phenprocoumon. METHODS: We conducted a nested case-control study in a cohort of 246,220 phenprocoumon users in the German Pharmacoepidemiological Research Database. Cases were patients hospitalised for haemorrhage of different kinds. Ten controls were matched to each case by health insurance, birth year and sex using incidence density sampling. Odds ratios (OR) with 95% confidence intervals (CI) of the risk of serious bleeding associated with combined use of phenprocoumon and potentially interacting drugs versus phenprocoumon alone were estimated using conditional logistic regression analysis. Our analyses considered multiple risk factors, such as bleeding history, other comorbidities or co-medication. RESULTS: Our study included 2,553 cases and 25,348 matched controls. An increased risk of bleeding was observed for the combined use of phenprocoumon and clopidogrel vs phenprocoumon use alone (OR: 1.83, 95% CI: 1.41-2.36). Antibiotic drugs associated with an increased risk of haemorrhage in the population of phenprocoumon users included the group of quinolones with ORs ranging from 2.74 (95% CI: 1.80-4.18) for ciprofloxacin to 4.40 (95% CI: 2.45-7.89) for levofloxacin, amoxicillin plus clavulanic acid (OR: 2.99, 95% CI: 1.39-6.42) and cotrimoxazole (OR 3.57, 95% CI: 2.36-5.40). Among non-steroidal anti-inflammatory drugs (NSAIDs), ketoprofen and naproxen were associated with the highest risks. CONCLUSION: Significantly elevated risks of major bleeding were mainly observed for drugs with known pharmacodynamic interaction with phenprocoumon, and less for drugs with possible pharmacokinetic interaction.
Authors: Loes E Visser; Fernie J A Penning-van Beest; A A Harrie Kasbergen; Peter A G M De Smet; Arnold G Vulto; Albert Hofman; Bruno H Ch Stricker Journal: Clin Pharmacol Ther Date: 2002-06 Impact factor: 6.875
Authors: Daniel S Budnitz; Daniel A Pollock; Kelly N Weidenbach; Aaron B Mendelsohn; Thomas J Schroeder; Joseph L Annest Journal: JAMA Date: 2006-10-18 Impact factor: 56.272
Authors: G Palareti; N Leali; S Coccheri; M Poggi; C Manotti; A D'Angelo; V Pengo; N Erba; M Moia; N Ciavarella; G Devoto; M Berrettini; S Musolesi Journal: Lancet Date: 1996-08-17 Impact factor: 79.321
Authors: Rikke Sørensen; Morten L Hansen; Steen Z Abildstrom; Anders Hvelplund; Charlotte Andersson; Casper Jørgensen; Jan K Madsen; Peter R Hansen; Lars Køber; Christian Torp-Pedersen; Gunnar H Gislason Journal: Lancet Date: 2009-12-12 Impact factor: 79.321
Authors: Charles E Leonard; Meijia Zhou; Colleen M Brensinger; Warren B Bilker; Samantha E Soprano; Thanh Phuong Pham Nguyen; Young Hee Nam; Jordana B Cohen; Sean Hennessy Journal: Clin Pharmacol Ther Date: 2019-07-04 Impact factor: 6.875
Authors: Cornelia Czembirek; Wolfgang Paul Poeschl; Christina Eder-Czembirek; Michael Bernhard Fischer; Christos Perisanidis; Philip Jesch; Kurt Schicho; Angel Dong; Rudolf Seemann Journal: Clin Oral Investig Date: 2013-11-28 Impact factor: 3.573
Authors: Anton Pottegård; Peter M Meegaard; Line H V Holck; Rene dePont Christensen; Hanne Madsen; Jesper Hallas Journal: Eur J Clin Pharmacol Date: 2012-07-31 Impact factor: 2.953
Authors: Sven Schmiedl; Marietta Rottenkolber; Jacek Szymanski; Werner Siegmund; Marion Hippius; Katrin Farker; Bernd Drewelow; Joerg Hasford; Petra Thürmann Journal: Dtsch Arztebl Int Date: 2013-04-05 Impact factor: 5.594
Authors: Johannes Schweinfurth; Alexander Bauer; Frederic Bauer; Felix Sebastian Seibert; Benjamin Rohn; Maximilian Seidel; Sebastian Bertram; Ulrik Stervbo; Nina Babel; Timm Henning Westhoff Journal: Sci Rep Date: 2021-06-03 Impact factor: 4.379