Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2022 Dec;78(12):1889-1898.
doi: 10.1007/s00228-022-03411-1. Epub 2022 Nov 3.

Use of tramadol and the risk of bleeding complications in patients on oral anticoagulants: a systematic review and meta-analysis

Clara Lévy  1   2 , Laëtitia Gosselin  1   3 , Ana-Maria Vilcu  1 , Olivier Steichen  4   5
Affiliations
Free article
Meta-Analysis

Use of tramadol and the risk of bleeding complications in patients on oral anticoagulants: a systematic review and meta-analysis

Clara Lévy et al. Eur J Clin Pharmacol. 2022 Dec.
Free article

Abstract

Purpose: This systematic review and meta-analysis aimed to determine whether tramadol intake increases the risk of bleeding in patients receiving oral anticoagulants.

Methods: This systematic review was registered on PROSPERO, CRD42022327230. We searched PubMed and Embase up to 14 April 2022, and references and citations of included studies were screened. Comparative and non-comparative studies exploring bleeding complications among adult patients on oral anticoagulants and tramadol were included. Risk of bias was assessed using an adaptation of the Drug Interaction Probability Scale for case reports and case series and the Newcastle-Ottawa Scale for comparative studies. A meta-analysis was performed for the risk of serious bleeding (leading to hospitalisation or death) associated with tramadol in patients on vitamin K antagonists.

Results: A total of 17 studies were included: 1 case series, 12 case reports, 2 case-control studies and 2 cohort studies. Most of the studies described tramadol-vitamin K antagonists' concomitant use; one case-control study also assessed dabigatran and rivaroxaban; one case report involved dabigatran. Among case reports/series, a total of 33 patients had a bleeding complication while using tramadol and an oral anticoagulant. The 4 comparative studies reported an increased bleeding risk during tramadol and vitamin K antagonist intake which was statistically significant in one study; the pooled risk ratio of serious bleeding was 2.68 [95% CI: 1.45 to 4.96; p < 0.001].

Conclusion: This systematic review confirms an association between tramadol use and risk of bleeding in patients on vitamin K antagonists. Evidence is too limited to assess whether this risk extends to patients on direct oral anticoagulants, and further studies are needed.

Keywords: Bleeding; Direct oral anticoagulants; Oral anticoagulants; Tramadol; Vitamin K antagonists.

PubMed Disclaimer

Comment in

References

    1. Raskob G (1996) Oral anticoagulant therapy. Curr Opin Hematol. https://doi.org/10.1097/00062752-199603050-00005 - DOI - PubMed
    1. Hirsh J, Dalen J, Anderson DR et al (2001) Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest 119:8S-21S. https://doi.org/10.1378/chest.119.1_suppl.8s - DOI - PubMed
    1. Chen A, Stecker E, A. Warden B (2020) Direct oral anticoagulant use: a practical guide to common clinical challenges. JAHA 9:e017559. https://doi.org/10.1161/JAHA.120.017559 - DOI - PubMed - PMC
    1. Levine MN, Raskob G, Beyth RJ et al (2004) Hemorrhagic complications of anticoagulant treatment: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 126:287S-310S. https://doi.org/10.1378/chest.126.3_suppl.287S
    1. Risser A, Donovan D, Heintzman J, Page T (2009) NSAID prescribing precautions. Am Fam Physician 80:1371–1378 - PubMed