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Thromb Haemost 2002; 88(05): 705-710
DOI: 10.1055/s-0037-1613289
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Schattauer GmbH

Overanticoagulation Associated with Combined Use of Antibacterial Drugs and Acenocoumarol or Phenprocoumon Anticoagulants

Loes E. Visser
1   Pharmacoepidemiology Unit, Departments of Internal Medicine and Epidemiology & Biostatistics
2   Hospital Pharmacy, Erasmus University Medical Centre Rotterdam, Rotterdam, The Netherlands
,
Fernie J. A. Penning-van Beest
1   Pharmacoepidemiology Unit, Departments of Internal Medicine and Epidemiology & Biostatistics
,
A. A. Harrie Kasbergen
3   Stichting Trombosedienst and Artsenlaboratorium Rijnmond, Rotterdam, The Netherlands
,
Peter A. G. M. De Smet
4   Scientific Institute Dutch Pharmacists, The Hague, The Netherlands
5   Department of Clinical Pharmacy, University Medical Centre St Radboud, Nijmegen, The Netherlands
,
Arnold G. Vulto
2   Hospital Pharmacy, Erasmus University Medical Centre Rotterdam, Rotterdam, The Netherlands
,
Albert Hofman
1   Pharmacoepidemiology Unit, Departments of Internal Medicine and Epidemiology & Biostatistics
,
Bruno H. Ch. Stricker
1   Pharmacoepidemiology Unit, Departments of Internal Medicine and Epidemiology & Biostatistics
6   Drug Safety Unit, Inspectorate for Health Care, The Hague, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 28 January 2002

Accepted after revision 28 May 2002

Publication Date:
08 December 2017 (online)

Also available at
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Summary

Background

Several case reports associated combined use of coumarins and antibacterial drugs with overanticoagulation. Despite the fact that these drugs are frequently prescribed concurrently, there is little quantitative information on the risks of such complications.

Objective

To study which antibacterial drugs are associated with overanticoagulation during therapy with coumarins.

Design

Population-based cohort study in a sample of the Rotterdam Study.

Subjects

All patients who were treated with acenocoumarol or phenprocoumon in the study period from April 1, 1991 through December 31, 1998 and for whom INR data were available.

Methods

Patients were followed until an INR 2: 6.0, the end of their treatment, death or end of the study period. Proportional hazards regression analysis was used to estimate the risk of an INR 2: 6.0 in relation to concomitant use of an oral anticoagulant and antibacterial drugs after adjustment for several potentially confounding factors such as age, gender, hepatic dysfunction, malignancies, and heart failure.

Results

Of the 1124 patients in the cohort, 351 developed an INR 2: 6.0. The incidence rate was 6.9 per 10,000 treatment days. Sulfamethoxazole combined with trimethoprim most strongly increased the risk of overanticoagulation with an adjusted relative risk of 20.1 (95% CI: 10.7-37.9). Stratification showed that the induction period of overanticoagulation varied between different antibacterial drugs.

Conclusion

In this study among outpatients of an anticoagulation clinic using acenocoumarol or phenprocoumon, several antibacterial drugs strongly increased the risk of overanticoagulation. Awareness of these drug interactions and more frequent monitoring of INR values during the initial stages of antibacterial drug therapy are warranted to minimize the risk of bleeding complications.

Keywords

Acenocoumarol - phenprocoumon - anticoagulants
 

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