Retrospective assessment of potential interaction between levofloxacin and warfarin

Orfila, G. Mercadal; García, Berta Gracia; Leiva‐Badosa, Elisabet; Badía, Maria Perayre; Martínez, Concepción Reynaldo; Masanés, R. Jódar

doi:10.1007/s11096-008-9265-9

Cited by 19 publications

(5 citation statements)

References 13 publications

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“…Smaller retrospective studies have demonstrated increased INR and bleeding risk with levofloxacin use 21, 26 but a systematic review of the effect of ciprofloxacin, levofloxacin, or moxifloxacin among warfarin users reported that findings were inconsistent across studies. 27 In view of this, this association should be further investigated in future studies.…”

Section: Discussionmentioning

confidence: 99%

Concurrent Use of Warfarin and Antibiotics and the Risk of Bleeding in Older Adults

Baillargeon¹,

Holmes²,

Lin³

et al. 2012

The American Journal of Medicine

116

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Background Antibiotic medications are associated with an increased risk of bleeding among patients receiving warfarin. The recent availability of data from the Medicare Part D prescription drug program provides an opportunity to assess the association of antibiotic medications and the risk of bleeding in a national population of older adults receiving warfarin. Methods We conducted a case-control study nested within a cohort of 38,762 patients aged 65 years and older who were continuous warfarin users, using enrollment and claims data for a 5% national sample of Medicare beneficiaries with Part D benefits. Cases were defined as persons hospitalized for a primary diagnosis of bleeding and were matched with three control subjects on age, race, gender, and indication for warfarin. Logistic regression analysis was used to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the risk of bleeding associated with prior exposure to antibiotic medications. Results Exposure to any antibiotic agent within the 15 days of the event/index date was associated with an increased risk of bleeding (aOR 2.01; 95% CI, 1.62-2.50). All six specific antibiotic drug classes examined [azole antifungals (aOR, 4.57; 95% CI, 1.90-11.03), macrolides (aOR, 1.86; 95% CI, 1.08-3.21), quinolones (aOR, 1.69; 95% CI, 1.09-2.62), cotrimoxazole (aOR, 2.70; 95% CI, 1.46-5.05), penicillins (aOR, 1.92; 95% CI, 1.21-2.07) and cephalosporins (aOR, 2.45; 95% CI, 1.52-3.95) were associated with an increased risk of bleeding. Conclusion Among older continuous warfarin users, exposure to antibiotic agents—particularly azole antifungals—was associated with an increased risk of bleeding.

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Section: Discussionmentioning

confidence: 99%

Concurrent Use of Warfarin and Antibiotics and the Risk of Bleeding in Older Adults

Baillargeon¹,

Holmes²,

Lin³

et al. 2012

The American Journal of Medicine

116

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“…In a statistical review of 30 patients who were hospitalized and concurrently taking warfarin and levofloxacin, statistical analysis revealed a significant increase in the INR with a supporting p -value of 0.0001 [ 20 ].…”

Section: Resultsmentioning

confidence: 99%

Warfarin and Antibiotics: Drug Interactions and Clinical Considerations

Vega,

Smith,

Matejowsky

et al. 2023

Life

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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.

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“…However, the exact mechanism of action of the interaction remains unknown. Various mechanisms have been proposed to explain the interaction but it has not been clearly elucidated …”

Section: Case Descriptionmentioning

confidence: 99%

“…According to the literature review conducted by Carrol and Carrol on the interaction between warfarin and fluoroquinolones, there is insufficient evidence to recommend complete avoidance of the two drugs in combination. However, all the case reports that associate concomitant use of warfarin and levofloxacin with an increase in INR, and the reported episodes of bleeding during post‐marketing use, cannot be ignored . No data could be identified in the medical literature indicating an interaction between acenocoumarol and levofloxacin.…”

Section: Case Descriptionmentioning

confidence: 99%

Probable interaction between acenocoumarol and levofloxacin: a case series

et al. 2015

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Retrospective assessment of potential interaction between levofloxacin and warfarin

Abstract: The results of this study reaffirm the hypothesis that concomitant administration of levofloxacin and warfarin leads to INR increase; hence close monitoring of INR is advisable when patients are prescribed this combination of drugs.

Cited by 19 publications

References 13 publications

Concurrent Use of Warfarin and Antibiotics and the Risk of Bleeding in Older Adults

Concurrent Use of Warfarin and Antibiotics and the Risk of Bleeding in Older Adults

Warfarin and Antibiotics: Drug Interactions and Clinical Considerations

Probable interaction between acenocoumarol and levofloxacin: a case series

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