{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T02:25:18Z","timestamp":1782181518832,"version":"3.54.5"},"reference-count":42,"publisher":"Georg Thieme Verlag KG","issue":"05","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2014]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>There is major concern about coumarins interacting with various drug classes and increasing the risk of overanticoagulation. The aim of the study was to assess bleeding risk in patients with concurrent use of antibiotics and phenprocoumon, the most widely prescribed coumarin in many European countries. We conducted a nested-case-control study within a cohort of 513,338 incident and continuous phenpro-coumon users \u226518 years of age using claims data of the statutory health insurance company AOK, covering 30% of the German population. Bleeding risk associated with current use of antibiotics for systemic use (antibacterials\/antimycotics) was calculated using conditional logistic regression in 13,785 cases with a bleeding event and 55,140 risk-set sampling-matched controls. Bleeding risk associated with any antibacterial use in phenprocoumon users was significantly increased [odds ratio (OR) 2.37, 95% confidence interval (CI) 2.20\u20132.56]. The association was stronger for gastrointestinal than for cerebral bleeding (OR 2.09, 95% CI 1.84\u20132.38 and OR 1.34, 95% CI 1.03\u20131.74, respectively) and highest for other\/unspecified bleeding (OR 2.92, 95% CI 2.62\u20133.26). Specific antibiotic classes were strongly associated with bleeding risk, e.g. cotrimoxazole (OR 3.86, 95% CI 3.08\u20134.84) and fluorquinolones (OR 3.13, 95% CI 2.74\u20133.59), among those highest for ofloxacin (OR 5.00, 95% CI 3.01\u20138.32). Combined use of phenprocoumon and antimycotics was not significantly associated with bleeding risk. Risk was not significantly modified by age (pint=0.25) or sex (pint=0.96). The association was stronger the closer the antibiotic exposure was to the bleeding event. Among continuous phenprocoumon users, antibiotics \u2013 particularly quinolones and co-trimoxazole \u2013 should be prescribed after careful consideration due to an increased bleeding risk. Close monitoring of international normalised ratio levels after prescription is recommended.<\/jats:p>","DOI":"10.1160\/th13-09-0723","type":"journal-article","created":{"date-parts":[[2014,1,16]],"date-time":"2014-01-16T12:47:05Z","timestamp":1389876425000},"page":"912-922","source":"Crossref","is-referenced-by-count":12,"title":["Risk of bleeding and antibiotic use in patients receiving continuous phenprocoumon therapy"],"prefix":"10.1160","volume":"112","author":[{"given":"Peter","family":"Ihle","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Harder","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Schubert","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sascha","family":"Abbas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2017,11,30]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1160\/TH08-04-0116","article-title":"Pharmacogenetic differences between warfarin, acenocoumarol and phenprocoumon","volume":"100","author":"M Beinema","year":"2008","journal-title":"Thromb Haemost"},{"key":"ref2","first-page":"421","volume-title":"Antithrombotika und Antih\u00e4morrhagika","author":"L Hein","year":"2011"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.2165\/00003088-200544120-00003","article-title":"Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol","volume":"44","author":"M Ufer","year":"2005","journal-title":"Clin Pharmacokinet"},{"key":"ref4","first-page":"754919.","article-title":"Pharmacogenetics of anticoagulants","volume":"2010","author":"A Rane","year":"2010","journal-title":"Hum Genomics Proteomics"},{"key":"ref5","first-page":"421","article-title":"Anticoagulation by oral treatment with vitamin K antagonists","volume":"28","author":"B Kemkes-Matthes","year":"2008","journal-title":"Hamostaseologie"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1002\/jps.2600741003","article-title":"Metabolic fate of phenprocoumon in humans","volume":"74","author":"S Toon","year":"1985","journal-title":"J Pharm Sci"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s00228-004-0740-5","article-title":"Identification of cytochromes P450 2C9 and 3A4 as the major catalysts of phenprocoumon hydroxylation in vitro","volume":"60","author":"M Ufer","year":"2004","journal-title":"Eur J Clin Pharmacol"},{"key":"ref8","first-page":"244","article-title":"Bleeding complications and liver injuries during phenprocoumon treatment: a multicentre prospective observational study in internal medicine departments","volume":"110","author":"S Schmiedl","year":"2013","journal-title":"Dtsch Arztebl Int"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1001\/archinte.165.10.1095","article-title":"Systematic overview of warfarin and its drug and food interactions","volume":"165","author":"AM Holbrook","year":"2005","journal-title":"Arch Intern Med"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1503\/cmaj.070946","article-title":"Drug interactions with warfarin: what clinicians need to know","volume":"177","author":"DN Juurlink","year":"2007","journal-title":"CMAJ"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/clpt.2008.150","article-title":"Warfarin with fluoroquinolones, sulfonamides, or azole antifungals: interactions and the risk of hospitalization for gastrointestinal bleeding","volume":"84","author":"H Schelleman","year":"2008","journal-title":"Clin Pharmacol Ther"},{"key":"ref12","first-page":"640","article-title":"Administrative claims analysis of the relationship between warfarin use and risk of hemorrhage including drug-drug and drug-disease interactions","volume":"12","author":"K Zhang","year":"2006","journal-title":"J Manag Care Pharm"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1007\/s11606-005-0113-5","article-title":"The risk of overanticoagulation with antibiotic use in outpatients on stable warfarin regimens","volume":"20","author":"JJ Glasheen","year":"2005","journal-title":"J Gen Intern Med"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1160\/TH05-03-0166","article-title":"Drug interactions and risk of acute bleeding leading to hospitalisation or death in patients with chronic atrial fibrillation treated with warfarin","volume":"94","author":"C Gasse","year":"2005","journal-title":"Thromb Haemost"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.amjmed.2011.08.014","article-title":"Concurrent use of warfarin and antibiotics and the risk of bleeding in older adults","volume":"125","author":"J Baillargeon","year":"2012","journal-title":"Am J Med"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.amjopharm.2012.09.006","article-title":"Warfarin-antibiotic interactions in older adults of an outpatient anticoagulation clinic","volume":"10","author":"PK Ghaswalla","year":"2012","journal-title":"Am J Geriatr Pharmacother"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1002\/pds.2219","article-title":"Major bleeding risk associated with warfarin and co-medications in the elderly population","volume":"20","author":"AI Vitry","year":"2011","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1001\/archinternmed.2010.37","article-title":"Hemorrhage during warfarin therapy associated with cotrimoxazole and other urinary tract anti-infective agents: a population-based study","volume":"170","author":"HD Fischer","year":"2010","journal-title":"Arch Intern Med"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1055\/s-0037-1613289","article-title":"Overanticoagulation associated with combined use of antibacterial drugs and acenocoumarol or phenprocoumon anticoagulants","volume":"88","author":"LE Visser","year":"2002","journal-title":"Thromb Haemost"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1111\/j.1538-7836.2008.02844.x","article-title":"Risk of major bleeding during concomitant use of antibiotic drugs and coumarin anticoagulants","volume":"06","author":"FJ Penning-van Beest","year":"2008","journal-title":"J Thromb Haemost"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1007\/s00228-011-1031-6","article-title":"Drug interactions with phenprocoumon and the risk of serious haemorrhage: a nested case-control study in a large population-based German database","volume":"67","author":"K Jobski","year":"2011","journal-title":"Eur J Clin Pharmacol"},{"key":"ref23","first-page":"279","article-title":"Mortality following myocardial infarction in women and men: an analysis of insurance claims data from inpatient hospitalizations","volume":"105","author":"G Heller","year":"2008","journal-title":"Dtsch Arztebl Int"},{"key":"ref24","first-page":"375","article-title":"Rehabilitation in Geriatric Patients after Ischemic Stroke - A Comparison of 2 Organisational Systems in Germany Using Claims Data of a Statutory Health Insurance Fund]","volume":"52","author":"S Abbas","year":"2013","journal-title":"Rehabilitation"},{"key":"ref25","first-page":"288","article-title":"The relationship of in-hospital and post-discharge complications and implications for quality measurement in hip replacement surgery - an analysis of AOK administrative data","volume":"75","author":"E Jeschke","year":"2013","journal-title":"Gesundheitswesen"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/sj.clpt.6100036","article-title":"VKORC1 and CYP2C9 genotypes and phenprocoumon anticoagulation status: interaction between both genotypes affects dose requirement","volume":"81","author":"T Schalekamp","year":"2007","journal-title":"Clin Pharmacol Ther"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"e312.","DOI":"10.1371\/journal.pmed.0020312","article-title":"A C1173T dimorphism in the VKORC1 gene determines coumarin sensitivity and bleeding risk","volume":"02","author":"PH Reitsma","year":"2005","journal-title":"PLoS Med"},{"key":"ref28","first-page":"111","volume-title":"Case-control studies","author":"KJ Rothman","year":"2008","edition":"3rd"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1097\/01.mlr.0000182534.19832.83","article-title":"Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data","volume":"43","author":"H Quan","year":"2005","journal-title":"Med Care"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/0021-9681(87)90171-8","article-title":"A new method of classifying prognostic comorbidity in longitudinal studies: development and validation","volume":"40","author":"ME Charlson","year":"1987","journal-title":"J Chronic Dis"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1067\/mcp.2002.124470","article-title":"Overanticoagulation associated with combined use of antifungal agents and coumarin anticoagulants","volume":"71","author":"LE Visser","year":"2002","journal-title":"Clin Pharmacol Ther"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"21","DOI":"10.3821\/1913-701X-144.1.21","article-title":"Drug interactions involving warfarin: practice tool and practical management tips","volume":"144","author":"TJ Bungard","year":"2011","journal-title":"Can Pharm J"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1111\/j.1742-1241.2011.02694.x","article-title":"Are the risk factors listed in warfarin prescribing information associated with anticoagulation-related bleeding?","volume":"65","author":"WT Chen","year":"2011","journal-title":"A systematic literature review. Int J Clin Pract"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1093\/qjmed\/hcm076","article-title":"Risk factors for anticoagulation-related bleeding complications in patients with atrial fibrillation: a systematic review","volume":"100","author":"M Hughes","year":"2007","journal-title":"QJM"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1002\/pds.3193","article-title":"Does additional confounder information alter the estimated risk of bleeding associated with phenprocoumon use--results of a two-phase study","volume":"21","author":"S Behr","year":"2012","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1097\/EDE.0b013e3181632ca0","article-title":"Confounding in database pharmacoe-pidemiology studies","volume":"19","author":"JA Delaney","year":"2008","journal-title":"Epidemiology"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1055\/s-0037-1616088","article-title":"Characteristics of anticoagulant therapy and comorbidity related to overanticoagulation","volume":"86","author":"FJ Penning-van Beest","year":"2001","journal-title":"Thromb Hae-most"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.thromres.2005.06.015","article-title":"Accuracy of coding for possible warfarin complications in hospital discharge abstracts","volume":"118","author":"T Arnason","year":"2006","journal-title":"Thromb Res"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1007\/s00228-013-1510-z","article-title":"Novel oral anticoagulants: clinical pharmacology, indications and practical considerations","volume":"69","author":"S Harder","year":"2013","journal-title":"Eur J Clin Pharmacol"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1160\/TH13-02-0150","article-title":"Gastrointestinal bleeding with the new oral anticoagulants - defining the issues and the management strategies","volume":"110","author":"J Desai","year":"2013","journal-title":"Thromb Hae-most"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1093\/jac\/21.3.281","article-title":"Antibiotic-associated hypoprothrombinaemia","volume":"21","author":"JJ Lipsky","year":"1988","journal-title":"J Antimicrob Che-mother"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1002\/(SICI)1099-1557(199903\/04)8:2<81::AID-PDS411>3.0.CO;2-G","article-title":"Risk of bleeding and hypoprothrombi-naemia associated with NMTT side chain antibiotics: using cefoperazone as a test case","volume":"08","author":"BL Strom","year":"1999","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1160\/TH08-11-0730","article-title":"Bleeding with anticoagulation therapy - who is at risk, and how best to identify such patients","volume":"102","author":"G Palareti","year":"2009","journal-title":"Thromb Haemost"}],"container-title":["Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1160\/TH13-09-0723.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T12:07:43Z","timestamp":1685534863000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1160\/TH13-09-0723"}},"subtitle":["A case-control study nested in a large insurance- and population-based German cohort"],"short-title":[],"issued":{"date-parts":[[2014]]},"references-count":42,"journal-issue":{"issue":"05","published-online":{"date-parts":[[2017,11,21]]},"published-print":{"date-parts":[[2014,11]]}},"URL":"https:\/\/doi.org\/10.1160\/th13-09-0723","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0340-6245","2567-689X"],"issn-type":[{"value":"0340-6245","type":"print"},{"value":"2567-689X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014]]}}}