{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:18:23Z","timestamp":1792513103927,"version":"4.5.0"},"reference-count":43,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,7,30]],"date-time":"2023-07-30T00:00:00Z","timestamp":1690675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Warfarin administration poses a notable challenge in clinical practice due to the increased susceptibility of patients to major bleeding, particularly when co-administered with other medications capable of modulating its metabolic pathways. Among these medications, antibiotics have been recognized as potential agents that can either induce or inhibit cytochrome P450-2C9, thereby impacting the effects of warfarin. A wealth of evidence from numerous studies consistently supports an elevated risk of serious bleeding in patients concurrently receiving antibiotics and warfarin therapy. This narrative review elucidates the intricate interactions between warfarin and various antibiotic classes. Notably, significant increases in the International Normalized Ratio (INR) were observed among warfarin-treated patients receiving penicillin derivatives, fluoroquinolones, TMP-SMX, and macrolides. Conversely, investigations have also demonstrated a reduction in INR levels in patients on warfarin when exposed to rifampin, a potent inducer of cytochrome P-450. Intriguingly, cephalosporin antibiotics and amoxicillin\/clavulanate, despite not interfering with the cytochrome P450 system, exhibited a positive association with increased INR values. The findings of this narrative review underscore the importance of diligent monitoring in patients on warfarin requiring concomitant antibiotic therapy, as this surveillance strategy proves pivotal in mitigating the risk of major bleeding complications. Additionally, for patients necessitating cytochrome P450 inhibitors such as penicillin derivatives, fluoroquinolones, TMP-SMX, and macrolides, the consideration of dose reduction in warfarin therapy may confer substantial benefits in reducing the occurrence of major bleeding events. Similarly, patients who are co-administered rifampin alongside warfarin necessitate vigilant monitoring, with a potential need for escalating warfarin doses to counteract the risk of a hypercoagulable state.<\/jats:p>","DOI":"10.3390\/life13081661","type":"journal-article","created":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T01:28:46Z","timestamp":1690766926000},"page":"1661","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Warfarin and Antibiotics: Drug Interactions and Clinical Considerations"],"prefix":"10.3390","volume":"13","author":[{"given":"Alexis J.","family":"Vega","sequence":"first","affiliation":[{"name":"School of Medicine, Louisiana State University Health Sciences Center at Shreveport, 1501 Kings Highway, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin","family":"Smith","sequence":"additional","affiliation":[{"name":"School of Medicine, Louisiana State University Health Sciences Center at Shreveport, 1501 Kings Highway, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah Grace","family":"Matejowsky","sequence":"additional","affiliation":[{"name":"School of Medicine, Louisiana State University Health Sciences Center at Shreveport, 1501 Kings Highway, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine J.","family":"Thornhill","sequence":"additional","affiliation":[{"name":"School of Medicine, Louisiana State University Health Sciences Center at Shreveport, 1501 Kings Highway, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant E.","family":"Borne","sequence":"additional","affiliation":[{"name":"School of Medicine, Louisiana State University Health Sciences Center at Shreveport, 1501 Kings Highway, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chizoba N.","family":"Mosieri","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Louisiana State University Health Sciences Center at Shreveport, 1501 Kings Highway, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4545-4523","authenticated-orcid":false,"given":"Sahar","family":"Shekoohi","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Louisiana State University Health Sciences Center at Shreveport, 1501 Kings Highway, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7961-3931","authenticated-orcid":false,"given":"Elyse M.","family":"Cornett","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Louisiana State University Health Sciences Center at Shreveport, 1501 Kings Highway, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2464-0187","authenticated-orcid":false,"given":"Alan D.","family":"Kaye","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Louisiana State University Health Sciences Center at Shreveport, 1501 Kings Highway, Shreveport, LA 71103, USA"},{"name":"Department of Pharmacology, Louisiana State University Health Sciences Center at Shreveport, 1501 Kings Highway, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,30]]},"reference":[{"key":"ref_1","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":"Holbrook","year":"2005","journal-title":"Arch. Intern. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1111\/j.1365-2125.2006.02806.x","article-title":"Warfarin: Almost 60 years old and still causing problems","volume":"62","author":"Pirmohamed","year":"2006","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_3","unstructured":"(2023, July 23). Antithrombotic Therapy in Atrial Fibrillation\u2014ScienceDirect. Available online: https:\/\/www.sciencedirect.com\/science\/article\/abs\/pii\/S0012369215607875?via%3Dihub."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1038\/s41569-021-00570-z","article-title":"Global epidemiology of valvular heart disease","volume":"18","author":"Coffey","year":"2021","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1161\/CIRCOUTCOMES.113.000661","article-title":"Cost-Effectiveness of Oral Anticoagulants for Treatment of Atrial Fibrillation","volume":"6","author":"Canestaro","year":"2013","journal-title":"Circ. Cardiovasc. Qual. Outcomes"},{"key":"ref_6","unstructured":"(2023, July 23). Heart Disease and Stroke Statistics\u20142023 Update: A Report from the American Heart Association | Circulation. Available online: https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIR.0000000000001123."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e026723","DOI":"10.1161\/JAHA.122.026723","article-title":"Trends in Oral Anticoagulant Use Among 436\u2009864 Patients with Atrial Fibrillation in Community Practice, 2011 to 2020","volume":"11","author":"Navar","year":"2022","journal-title":"J. Am. Heart Assoc."},{"key":"ref_8","first-page":"9","article-title":"Cost of warfarin versus direct oral anticoagulants","volume":"66","author":"Mannarino","year":"2020","journal-title":"Can. Fam. Physician"},{"key":"ref_9","unstructured":"Patel, S., Singh, R., Preuss, C.V., and Patel, N. (2023, March 27). Warfarin, StatPearls, Available online: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470313\/."},{"key":"ref_10","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":"Baillargeon","year":"2012","journal-title":"Am. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.amjmed.2014.01.044","article-title":"Serious Bleeding Events due to Warfarin and Antibiotic Co-prescription in a Cohort of Veterans","volume":"127","author":"Lane","year":"2014","journal-title":"Am. J. Med."},{"key":"ref_12","unstructured":"Yip, D.W., and Gerriets, V. (2023, March 27). Penicillin, StatPearls, Available online: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK554560\/."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1592\/phco.27.10.1467","article-title":"Interaction between warfarin and nafcillin: Case report and review of the literature","volume":"27","author":"Kim","year":"2007","journal-title":"Pharmacotherapy"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1345\/aph.1C243","article-title":"Warfarin and Amoxicillin\/Clavulanate Drug Interaction","volume":"37","author":"Davydov","year":"2003","journal-title":"Ann. Pharmacother."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/S1079-2104(96)80433-1","article-title":"Amoxicillin-related postextraction bleeding in an anticoagulated patient with tranexamic acid rinses","volume":"82","author":"Bandrowsky","year":"1996","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod."},{"key":"ref_16","first-page":"352","article-title":"Warfarin: Dangers with antibiotics","volume":"350","author":"Wood","year":"1993","journal-title":"Dent. Update"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1002\/jcph.583","article-title":"Warfarin-drug interactions: An emphasis on influence of polypharmacy and high doses of amoxicillin\/clavulanate","volume":"56","author":"Ali","year":"2016","journal-title":"J. Clin. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"161","DOI":"10.18773\/austprescr.2021.035","article-title":"Fluoroquinolone antibiotics and adverse events","volume":"44","author":"Baggio","year":"2021","journal-title":"Aust. Prescr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1345\/aph.1C074","article-title":"Levofloxacin and Warfarin Interaction","volume":"36","author":"Jones","year":"2002","journal-title":"Ann. Pharmacother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1007\/s11096-008-9265-9","article-title":"Retrospective assessment of potential interaction between levofloxacin and warfarin","volume":"31","year":"2009","journal-title":"Pharm. World Sci."},{"key":"ref_21","unstructured":"Bui, T., and Preuss, C.V. (2023, March 27). Cephalosporins, StatPearls, Available online: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK551517\/."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e19","DOI":"10.1345\/aph.1Q771","article-title":"Hemarthrosis in a Patient on Warfarin Receiving Ceftaroline: A Case Report and Brief Review of Cephalosporin Interactions with Warfarin","volume":"46","author":"Bohm","year":"2012","journal-title":"Ann. Pharmacother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1177\/0897190014544798","article-title":"Ceftriaxone Potentiates Warfarin Activity Greater Than Other Antibiotics in the Treatment of Urinary Tract Infections","volume":"29","author":"Saum","year":"2016","journal-title":"J. Pharm. Pract."},{"key":"ref_24","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":"Schelleman","year":"2008","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_25","unstructured":"(2023, April 12). Hemorrhage during Warfarin Therapy Associated with Cotrimoxazole and Other Urinary Tract Anti-Infective Agents: A Population-Based Study. Available online: https:\/\/reference.medscape.com\/medline\/abstract\/20386005."},{"key":"ref_26","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":"Vitry","year":"2011","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s00228-020-03057-x","article-title":"A case series of the rifampin-warfarin drug interaction: Focus on practical warfarin management","volume":"77","author":"Yang","year":"2021","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_28","unstructured":"Patel, P.H., and Hashmi, M.F. (2023, March 28). Macrolides, StatPearls, Available online: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK551495\/."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.tibs.2018.06.011","article-title":"How macrolide antibiotics work","volume":"43","author":"Mankin","year":"2018","journal-title":"Trends Biochem. Sci."},{"key":"ref_30","unstructured":"(2023, March 28). BPJ 44: The Appropriate Use of Macrolides. Available online: https:\/\/bpac.org.nz\/BPJ\/2012\/May\/macrolides.aspx."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1007\/s00246-005-0819-5","article-title":"Interaction of Antibiotics and Warfarin in Pediatric Cardiology Patients","volume":"26","author":"Johnson","year":"2005","journal-title":"Pediatr. Cardiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e24427","DOI":"10.1002\/jcla.24427","article-title":"Mechanism of action, resistance, synergism, and clinical implications of azithromycin","volume":"36","author":"Heidary","year":"2022","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_33","unstructured":"Dhand, A., and Snydman, D. (2009). Antimicrobial Drug Resistance, Humana Press."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"D1074","DOI":"10.1093\/nar\/gkx1037","article-title":"DrugBank 5.0: A major update to the DrugBank database for 2018","volume":"46","author":"Wishart","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"676","DOI":"10.7326\/0003-4819-121-9-199411010-00009","article-title":"Interactions of Warfarin with Drugs and Food","volume":"121","author":"Wells","year":"1994","journal-title":"Ann. Intern. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1055\/s-0038-1627100","article-title":"Population Impact of Drug Interactions with Warfarin: A Real-World Data Approach","volume":"118","author":"Gaist","year":"2018","journal-title":"Thromb. Haemost."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"901","DOI":"10.7326\/0003-4819-116-11-901","article-title":"Aging and the Anticoagulant Response to Warfarin Therapy","volume":"116","author":"Gurwitz","year":"1992","journal-title":"Ann. Intern. Med."},{"key":"ref_38","first-page":"56","article-title":"Oral anticoagulation treatment\u2014control, risks, benefits, and informed consent","volume":"142","author":"Froom","year":"2003","journal-title":"Harefuah"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1046\/j.1365-2141.2003.04652.x","article-title":"Oral anticoagulation in surgical procedures: Risks and recommendations","volume":"123","author":"Torn","year":"2003","journal-title":"Br. J. Haematol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.jsps.2015.02.004","article-title":"Factors influencing warfarin response in hospitalized patients","volume":"23","author":"Ali","year":"2015","journal-title":"Saudi. Pharm. J. SPJ"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1111\/imj.13944","article-title":"Flucloxacillin-warfarin interaction: An under-appreciated phenomenon","volume":"48","author":"Chaudhuri","year":"2018","journal-title":"Intern. Med. J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1055\/s-0039-1693462","article-title":"The Effect of Flucloxacillin on Warfarin Anticoagulation: A Swedish Register-Based Nationwide Cohort Study","volume":"119","author":"Mannheimer","year":"2019","journal-title":"Thromb. Haemost."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1002\/cpt.1662","article-title":"Ischemic Stroke and Systemic Embolism in Warfarin Users With Atrial Fibrillation or Heart Valve Replacement Exposed to Dicloxacillin or Flucloxacillin","volume":"107","author":"Hellfritzsch","year":"2020","journal-title":"Clin. Pharmacol. Ther."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/8\/1661\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:22:37Z","timestamp":1760127757000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/8\/1661"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,30]]},"references-count":43,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["life13081661"],"URL":"https:\/\/doi.org\/10.3390\/life13081661","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,30]]}}}