Ciprofloxacin with Warfarin Interaction Details

Brand Names Associated with Ciprofloxacin

Brand Names Associated with Warfarin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 19, 2023

Interaction Effect

An increased risk of bleeding

Interaction Summary

The concomitant use of ciprofloxacin with warfarin may result in increased INR and thereby increase the risk for bleeding. 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 ciprofloxacin with an antibiotic with a low-risk profile for bleeding, such as clindamycin and cephalexin . However, 2 studies demonstrated minimal effect on INR values or PT with addition of ciprofloxacin to warfarin . If concomitant use is deemed necessary, early and more frequent monitoring of INR is recommended , especially during initiation and discontinuation of the antibiotic .

Severity

Major

Onset

Delayed

Evidence

Established

How To Manage Interaction

Concomitant use of ciprofloxacin and warfarin should be approached with caution as this may result in increased INR and thereby increase the risk for bleeding. When possible, substitute ciprofloxacin for an antibiotic with a low-risk interaction profile for bleeding, such as clindamycin or cephalexin. If concomitant use of ciprofloxacin and warfarin is required, early and more frequent monitoring of the patient's INR is recommended , especially during initiation and discontinuation of ciprofloxacin .

Mechanism Of Interaction

Disruption of vitamin K synthesis

Literature Reports

A) In a retrospective study of veterans (N=22272), 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 .

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) .

C) No significant changes in INR values were reported for patients placed on warfarin anticoagulation therapy with addition of ciprofloxacin 500 mg twice daily for 10 days. In a randomized, double-blind, placebo-controlled trial, the study found no significant increase in INR occurred in either group and no significant differences existed between the groups. Furthermore, none of the patients experienced a bleeding event during the study .

D) No significant change in prothrombin times were observed in 9 patients taking warfarin when ciprofloxacin 500 mg twice daily was added for 7 days. The possibility that the drug interaction between these two agents is dose-related could not be excluded by this study. Larger studies using various doses of ciprofloxacin are needed to more clearly define this interaction .

Ciprofloxacin Overview

• Ciprofloxacin is used to treat or prevent certain infections caused by bacteria such as pneumonia; gonorrhea (a sexually transmitted disease); typhoid fever (a serious infection that is common in developing countries); infectious diarrhea (infections that cause severe diarrhea); and infections of the skin, bone, joint, abdomen (stomach area), and prostate (male reproductive gland), Ciprofloxacin is also used to treat or prevent plague (a serious infection that may be spread on purpose as part of a bioterror attack) and inhalation anthrax (a serious infection that may be spread by anthrax germs in the air on purpose as part of a bioterror attack). Ciprofloxacin may also be used to treat bronchitis, sinus infections, or urinary tract infections but should not be used for bronchitis and sinus infections, or certain types of urinary tract infections if there are other treatment options. Ciprofloxacin extended-release (long-acting) tablets are used to treat kidney and urinary tract infections; however, some types of urinary tract infections should only be treated with ciprofloxacin extended release tablets if no other treatment options are available. Ciprofloxacin is in a class of antibiotics called fluoroquinolones. It works by killing bacteria that cause infections.

• Antibiotics such as ciprofloxacin will not work for colds, flu, or other viral infections. Using antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.

Warfarin Overview

• Warfarin is used to prevent blood clots from forming or growing larger in your blood and blood vessels. It is prescribed for people with certain types of irregular heartbeat, people with prosthetic (replacement or mechanical) heart valves, and people who have suffered a heart attack. Warfarin is also used to treat or prevent venous thrombosis (swelling and blood clot in a vein) and pulmonary embolism (a blood clot in the lung). Warfarin is in a class of medications called anticoagulants ('blood thinners'). It works by decreasing the clotting ability of the blood.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.