Warfarin and Levofloxacin Injection: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Warfarin
Levofloxacin Injection
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
An increased risk of bleeding
Interaction Deep Dive
The concurrent use of levofloxacin and warfarin has been associated with increases in INR or prothrombin time and clinical episodes of bleeding1. In a nested case-control study and a retrospective cohort study, there was a 48% to 2-fold increase in risk of bleeding requiring hospitalization with exposure to any antibiotic therapy. The suggested mechanism of interaction is alteration in intestinal flora that synthesize vitamin K. When possible, substitute levofloxacin with an antibiotic with a low-risk profile for bleeding, such as clindamycin and cephalexin 34. If concomitant use is deemed necessary, early and more frequent monitoring of INR is recommended 3, especially during initiation and discontinuation of the antibiotic 5.
Why it happens (mechanism)
Disruption of vitamin K synthesis
Literature reports
3 reports — tap to read
a) In a retrospective study of veterans (N=22,272), coadministration of warfarin and high-risk antibiotics (those with known interaction with warfarin resulting in increased bleeding risk) significantly increased the risk of hospital admission due to serious bleeding by 48% compared with low-risk antibiotics. In the high-risk antibiotics group, azithromycin significantly increased the risk of bleeding by 93% where as other antibiotics had nonsignificant increases individually (fluconazole had an increased risk of 111%, sulfamethoxazole/trimethoprim 79%, clarithromycin 71%, metronidazole 63%, ciprofloxacin 42%, and levofloxacin 30%) compared with low-risk antibiotics clindamycin and cephalexin. INR monitoring within 3 to 14 days of antibiotic therapy reduced the risk of serious bleeding 3.
b) Initiation of antibiotics in patients on continuous warfarin therapy resulted in a significantly increased risk of serious bleeding requiring hospitalization according to a nested case-control study of United States Medicare part D beneficiaries aged 65 years and older (n=38,762). Patients on warfarin who received any antibiotic were twice as likely to be hospitalized for bleeding compared with matched controls on warfarin who were not exposed to antibiotics (adjusted odds ratio (aOR), 2.01; 95% CI, 1.62 to 2.5). Additionally, continuous-warfarin users were twice as likely to have a bleeding event that required hospitalization within 60 days of antibiotic exposure compared with non-exposure. Antibiotic exposure greater than 60 days from the index bleed was not significantly associated with increased risk of bleeding. Specific antibiotics with the highest bleeding risk were azole antifungals (aOR, 4.57; 95% CI, 1.9 to 11.03), followed by cotrimoxazole (aOR, 2.7; 95% CI, 1.46 to 5.05), cephalosporins (aOR, 2.45; 95% CI, 1.52 to 3.95), penicillins (aOR, 1.92; 95% CI, 1.21 to 2.07), macrolides (aOR, 1.86; 95% CI, 1.08 to 3.21), and quinolones (aOR, 1.69; 95% CI, 1.09 to 2.62) 4.
c) Concomitant use of levofloxacin and warfarin has been associated with increases in INR or prothrombin time and clinical episodes of bleeding. Although there was no significant effect on Cmax, AUC, and other disposition parameters for warfarin when coadministered with levofloxacin and no effect of warfarin on levofloxacin absorption or disposition during a clinical study of healthy volunteers, there have been postmarketing reports of levofloxacin enhancing the effects of warfarin when the 2 drugs were coadministered 1.
Common questions
Can I take Warfarin and Levofloxacin Injection together?
An increased risk of bleeding Always confirm with your pharmacist or prescriber before making any change.
How serious is the Warfarin and Levofloxacin Injection interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Warfarin or Levofloxacin Injection need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (6)
- Product Information: LEVAQUIN(R) multiple routes, forms, levofloxacin multiple routes, forms. Janssen Pharmaceuticals, Inc. (Per FDA), Titusville, NJ, 2012.
- Product Information: LEVAQUIN(R) oral tablets, solution, IV injection, 5% dextrose IV injection, levofloxacin oral tablets, solution, IV injection, 5% dextrose IV injection. Ortho-McNeil-Janssen Pharmaceuticals, Inc, Raritan, NJ, 2008. DailyMed
- Lane MA, Zeringue A, & McDonald JR: Serious bleeding events due to warfarin and antibiotic co-prescription in a cohort of veterans. Am J Med 2014; 127(7):657-663.e2. PubMed
- Baillargeon J, Holmes HM, Lin YL, et al: Concurrent use of warfarin and antibiotics and the risk of bleeding in older adults. Am J Med 2012; 125(2):183-189. DOI
- Product Information: COUMADIN(R) oral tablets, intravenous injection powder lyophilized for solution, warfarin sodium oral tablets, intravenous injection powder lyophilized for solution. Bristol-Myers Squibb Company (per FDA), Princeton, NJ, 2011. DailyMed
- Ahmed A, Stephens JC, Kaus CA, et al: Impact of preemptive warfarin dose reduction on anticoagulation after initiation of trimethoprim-sulfamethoxazole or levofloxacin. J Thromb Thrombolysis 2008; 26(1):44-48. PubMed
Keep reading about Warfarin
Keep reading about Levofloxacin Injection
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