Is nitrofurantoin or ciprofloxacin (Cipro) safer to use with warfarin (Coumadin)?

From the Guidelines

Ciprofloxacin is generally considered less safe than nitrofurantoin when taken with warfarin. This is because ciprofloxacin is a strong CYP1A2 inhibitor, which can increase serum R-warfarin concentrations and elevate the INR, increasing the risk of adverse bleeding 1. In contrast, nitrofurantoin does not have a significant interaction with warfarin that would increase the risk of bleeding to the same extent as ciprofloxacin.

When considering the use of either antibiotic with warfarin, it is essential to monitor INR levels closely, especially in the first week of antibiotic therapy 1. The choice between these antibiotics should also consider the specific infection being treated, local resistance patterns, and individual patient factors. For example, nitrofurantoin should be avoided in patients with poor kidney function (creatinine clearance <30 mL/min) and is not appropriate for treating systemic infections 1.

Key considerations when prescribing antibiotics to patients on warfarin include:

• Monitoring INR levels closely, especially in the first week of antibiotic therapy
• Considering the specific infection being treated and local resistance patterns
• Avoiding nitrofurantoin in patients with poor kidney function
• Being aware of the potential for ciprofloxacin to increase the risk of bleeding due to its inhibition of warfarin metabolism. It is crucial to weigh these factors and consider the potential risks and benefits when selecting an antibiotic for patients on warfarin therapy 1.

From the FDA Drug Label

Quinolones, including ciprofloxacin, have been reported to enhance the effects of the oral anticoagulant warfarin or its derivatives When these products are administered concomitantly, prothrombin time or other suitable coagulation tests should be closely monitored.

There is no information about nitrofurantoin in the provided drug labels. The labels only discuss ciprofloxacin and its potential interaction with warfarin. Ciprofloxacin may enhance the effects of warfarin, and close monitoring of prothrombin time is recommended when these products are administered concomitantly. No conclusion can be drawn about the safety of nitrofurantoin with warfarin based on the provided information 2 2.

From the Research

Comparison of Nitrofurantoin and Ciprofloxacin with Warfarin

• The safety of nitrofurantoin and ciprofloxacin when used with warfarin is a concern due to potential interactions that may increase the risk of bleeding 3.
• Ciprofloxacin is considered a high-risk antibiotic for interaction with warfarin, and its use has been associated with an increased risk of bleeding events (hazard ratio [HR] 1.87; 95% confidence interval [CI], 1.42-2.50) 3.
• There is no direct evidence in the provided studies comparing the safety of nitrofurantoin and ciprofloxacin with warfarin.
• However, it is known that antibiotics can interact with warfarin, increasing the risk of significant bleeding events, and careful monitoring of the international normalized ratio (INR) is essential, especially in geriatric or cancer populations who are at an increased risk of major hemorrhage 4, 3, 5.

Risk of Bleeding with Warfarin and Antibiotics

• The risk of bleeding with warfarin is closely related to the maintenance of the INR within the therapeutic range, and a supra-therapeutic INR puts patients at risk of bleeding 4.
• The use of high-risk antibiotics, such as ciprofloxacin, with warfarin increases the risk of serious bleeding events, and early INR evaluation may mitigate this risk 3.
• Patients who bleed when their INR is in the target range may have defective thrombin generation related to a lower level of factor IX than expected 6.

Monitoring and Management of Warfarin Therapy

• Careful monitoring of the INR is essential to minimize the risk of bleeding and thromboembolic complications in patients taking warfarin 4, 3, 5.
• The effectiveness and safety of warfarin are closely related to the maintenance of the INR within the therapeutic range, and optimization of the risk-benefit ratio is crucial to maximize efficacy and safety 4.
• Patients taking warfarin concomitantly with other drugs are at a higher risk of elevated INR, and multiple possible drug-drug interactions have been identified, including acetaminophen, ramipril, and furosemide 7.