From the Guidelines
When adjusting warfarin while on nitrofurantoin, more frequent INR monitoring is necessary, ideally within 3-5 days of starting nitrofurantoin and then weekly until stable. Nitrofurantoin can potentially increase warfarin's anticoagulant effect, raising the risk of bleeding, as all antibiotics can alter the gut microbiome, which is a rich source of vitamin K, and thereby potentiate anticoagulant effects of warfarin 1. The warfarin dose may need to be reduced by approximately 15-25% based on INR results, though this varies by individual, similar to the recommended pre-emptive warfarin dose reductions of 25% and 33% for sulfamethoxazole and metronidazole respectively, when co-administered with warfarin 1. Target INR should remain the same as before (typically 2-3 for most indications). If the INR rises above the therapeutic range, temporarily hold or reduce the warfarin dose according to the degree of elevation. The interaction occurs because nitrofurantoin can inhibit vitamin K-producing gut bacteria and may affect warfarin metabolism through cytochrome P450 pathways. Some key points to consider when managing this interaction include:
- Monitoring INR closely whenever antibiotics are initiated in the setting of chronic warfarin use 1
- Being aware of the potential for increased risk of bleeding with certain antibiotics, such as sulfamethoxazole and metronidazole 1
- Considering the antibiotic dose and its contribution to the severity of the interaction 1
- Educating patients to watch for signs of bleeding such as unusual bruising, nosebleeds, blood in urine or stool, and to seek immediate medical attention if these occur. Once nitrofurantoin is discontinued, INR should be checked again within 5-7 days as warfarin requirements may return to baseline.
From the Research
Adjusting Warfarin While on Nitrofurantoin
- There are no direct studies on adjusting warfarin while on nitrofurantoin, but general guidelines for managing warfarin therapy can be applied 2, 3, 4.
- When initiating warfarin therapy, a 5-mg dose is recommended, and the International Normalized Ratio (INR) should be monitored frequently, especially in the first 24 hours 2.
- Adjusting a steady-state warfarin dose depends on the measured INR values and clinical factors, with most changes altering the total weekly dose by 5% to 20% 2.
- Patients who have an elevated INR will need more frequent testing and may also require vitamin K1, while those with excessive INR and clinically important bleeding require clotting factors and vitamin K1 2.
Interactions with Antibiotics
- Antibiotics can interact with warfarin, increasing the risk of excessive anticoagulation and bleeding events 5, 6.
- Certain antibiotics, such as trimethoprim/sulfamethoxazole, ciprofloxacin, and levofloxacin, are considered high-risk for interaction with warfarin and may require closer monitoring of INR values 6.
- Early INR evaluation after co-prescription of warfarin and antibiotics may help mitigate the risk of serious bleeding events 6.
Monitoring and Management
- Patients on warfarin therapy should be monitored closely, and both the clinician and the patient should be alert to potentially interacting variables 4.
- The INR should be used to monitor all patients receiving warfarin, and the goal therapeutic INR range is most commonly 2 to 3 3.
- Validated decision-support tools should be used to guide dosing, and self-testing and self-management can be safe options for patients receiving warfarin who are motivated and show competence 3.