Moxifloxacin with Warfarin Interaction Details

Brand Names Associated with Moxifloxacin

Brand Names Associated with Warfarin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Jan 04, 2024

Interaction Effect

Increased risk of bleeding

Interaction Summary

Coadministration of moxifloxacin and single-dose warfarin in healthy subjects had no significant effect on prothrombin time or the pharmacokinetics of warfarin. However, several case reports have described significant and prolonged increases in INR following inpatient oral moxifloxacin therapy in mostly elderly patients who were stabilized on warfarin . In a nested case-control study of continuous warfarin users aged 65 years or older, there was a 2-fold increase in risk of bleeding requiring hospitalization with exposure to any antibiotic therapy, including quinolones. The suggested mechanism of interaction is alteration in intestinal flora that synthesize vitamin K. When possible, substitute moxifloxacin with an antibiotic with a low-risk profile for bleeding. If concomitant use is deemed necessary, more frequent monitoring of INR , prothrombin time, and other applicable coagulation tests is recommended when these agents are coadministered , especially during initiation and discontinuation of the antibiotic . Monitor patients for signs of bleeding . Discontinuation of moxifloxacin may be considered if the INR becomes elevated .

Severity

Major

Onset

Delayed

Evidence

Established

How To Manage Interaction

Use caution when moxifloxacin and warfarin or its derivatives are coadministered as this has resulted in significant and prolonged increases in INR, particularly in elderly patients. When possible, substitute moxifloxacin for an antibiotic with a low-risk profile for bleeding. If concomitant use of moxifloxacin and warfarin is required, more frequent monitoring of the patient's INR . prothrombin time, and other applicable coagulation tests is recommended , especially during initiation and discontinuation of moxifloxacin . Monitor patients for signs of bleeding . Consider discontinuing moxifloxacin therapy and use an alternative therapy if the INR becomes elevated .

Mechanism Of Interaction

Disruption of vitamin K synthesis

Literature Reports

A) 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) .

B) In healthy subjects (n=24), coadministration of oral moxifloxacin 400 mg once daily for 8 days had no significant effect on prothrombin time or the pharmacokinetics of warfarin, which was administered as a single, oral, 25-mg dose on day 5. However, moxifloxacin and other quinolones have been reported to increase the anticoagulant effects of warfarin or its derivatives .

C) A case series described significant and prolonged increases in INR following in-patient moxifloxacin therapy in 5 elderly patients (age range, 63 to 92 years) who were receiving warfarin concurrently for atrial fibrillation. All patients were stabilized on warfarin doses of 2 to 5 mg/day, and INR and hemoglobin values at time of admission ranged from 2.2 to 3.3 and 13.3 to 15.4 g/dL, respectively. In all patients, within 3 to 7 days after oral administration of moxifloxacin 400 mg/day, the INR values increased ranging from 3.4 to 12.8. In 3 of the 5 patients, warfarin was discontinued and vitamin K was administered. In 1 of these 3 patients, a significant decrease in Hb level, with endoscopic evidence of bleeding, also necessitated 2 units each of packed RBCs and fresh frozen plasma. Two of these 3 patients died later from complications of COPD and CHF, respectively. Using the Naranjo probability scale, a moxifloxacin-warfarin interaction was probable cause in these 3 patients. In the remaining 2 patients, warfarin was discontinued in 1 patient while it was continued with a reduced dosage (2 mg/day) in the other patient. As no signs of significant bleeding were evident in these 2 patients, vitamin K was not administered. Using the Naranjo probability scale, a moxifloxacin-warfarin interaction was the possible cause in these 2 patients. The mechanism for this interaction is unknown .

D) Significant and prolonged increases in INR occurred following in-patient oral moxifloxacin therapy in 3 patients (age range, 50 to 78 years) who were receiving warfarin concurrently. Two of the patients had been stabilized on warfarin 5 mg/day and INR values were within desired range (2.5 to 3.5). Within 1 to 3 days of starting moxifloxacin 400 mg/day in both patients (patients 1 and 2), the INR increased to 3.4 and 6.3, respectively. Despite withholding warfarin in patient 1, the INR rose to 5.7 and 6.2 over the next 2 days, but subsequently dropped down to 1.4 over the next 6 days. Warfarin was re-initiated concurrently with moxifloxacin 400 mg/day and the INR gradually rose from 1.4 to 3.2. One day after discontinuing moxifloxacin after 13 days of treatment, the INR climbed to 4.1 prompting withholding of warfarin. In patient 2, warfarin was withheld and vitamin K 10 mg was given for an INR of 7.3. Moxifloxacin was subsequently discontinued and warfarin was re-initiated at 5 mg/day. At discharge, INR values were 3.9 and 1.5 for patients 1 and 2, respectively. The third patient, who was receiving intravenous levofloxacin and piperacillin-tazobactam for postoperative pneumonia, was initiated on warfarin (titrated to 4 to 5 mg/day) for atrial fibrillation and had stable INR values (1.2 to 1.8). One day after replacing levofloxacin with moxifloxacin 400 mg/day (day 15), the patient's INR rose to 3.3, prompting a decrease in warfarin dosage and subsequent withholding of warfarin. Moxifloxacin was discontinued after 3 doses and INR at discharge (day 19) was 3.8. The mechanism for this interaction is unknown .

E) A case series described significant and prolonged increases in INR following in-patient oral moxifloxacin therapy in 3 frail, elderly patients (age range, 76 to 85 years) who were also receiving warfarin. All patients had normal hepatic and renal function but low serum albumin levels (18 to 32 g/L). Two of the patients, who medical history was significant for atrial fibrillation and heart disease, had been stabilized on warfarin (INR range in 1 patient, 2.5 to 4). The third patient, who was admitted for surgical removal of a thrombotic embolus, was initiated on heparin and warfarin. However, after an initial overshoot of INR, heparin was discontinued and warfarin was withheld, which led to an initial downward trend in her INR. In all 3 patients, moxifloxacin 400 mg daily was initiated following development of lower respiratory tract infection while in the hospital, and this resulted in sudden increases in INR to peaks of 7.4 to 10. Despite discontinuation of warfarin in the first 2 patients and no warfarin in the third patient, the INR values remained elevated for 7 to 14 days. The mechanism for this interaction was unknown. While other concurrent medications (allopurinol, amiodarone) in 1 patient may have affected warfarin's metabolism, they were given concurrently with warfarin with no significant changes in INR. Careful monitoring of coagulation parameters is recommended in patients, especially the elderly, receiving concomitant warfarin and fluoroquinolones such as moxifloxacin. Alternative antibiotic therapy may also be considered .

Moxifloxacin Overview

• Moxifloxacin is used to treat certain infections caused by bacteria such as pneumonia, and skin, and abdominal (stomach area) infections. Moxifloxacin is also used to prevent and treat plague (a serious infection that may be spread on purpose as part of a bioterror attack. Moxifloxacin may also be used to treat bronchitis or sinus infections but should not be used for these conditions if there are other treatment options available. Moxifloxacin is in a class of antibiotics called fluoroquinolones. It works by killing the bacteria that cause infections.

• Antibiotics such as moxifloxacin 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.