What medications affect the INR?

October 12, 2025 •

4 min read

The list of medications, foods, and herbal substances with the potential to interact with warfarin—either enhancing or diminishing its anticoagulant effect—is exhaustive and continues to expand. Understanding what medications affect the INR is crucial for anyone taking the anticoagulant warfarin to manage their risk of bleeding and clotting effectively.

Quick Summary

The International Normalized Ratio (INR) is a measure of blood clotting time, most notably monitored in individuals on warfarin. Many prescription drugs, over-the-counter medications, and herbal supplements can significantly raise or lower INR levels, often by influencing how the liver metabolizes warfarin.

Key Points

INR is Influenced by Many Drugs: The anticoagulant effect of warfarin, measured by the INR, can be increased or decreased by a wide range of medications, including antibiotics, antifungals, heart medications, and pain relievers.
Liver Enzymes Play a Central Role: Many interactions occur because a drug either inhibits or induces the CYP liver enzymes responsible for metabolizing warfarin, altering its concentration in the body.
Herbal and OTC Supplements are Not Harmless: Patients must be aware that many herbal remedies and over-the-counter supplements, such as St. John's Wort and fish oil, can affect INR and increase bleeding risk, and should always be discussed with a doctor.
Increased Monitoring is Necessary for Safety: When starting or stopping any new interacting medication, more frequent INR monitoring is vital to ensure that warfarin dosing remains safe and effective.
Lifestyle Factors Matter: Consistent daily intake of vitamin K-rich foods and stable alcohol consumption are important for maintaining a steady INR level and should be discussed with a healthcare provider.

Understanding INR and Warfarin

The International Normalized Ratio (INR) is a standardized calculation derived from a prothrombin time (PT) test, which measures how long it takes for a person's blood to clot. For individuals on warfarin, a vitamin K antagonist, the INR is a critical tool for ensuring the medication is effective while not posing an excessive risk of bleeding. Warfarin works by blocking the liver's ability to use vitamin K to produce certain clotting factors. A therapeutic INR range (typically 2.0 to 3.0 for most conditions) indicates that clotting time is sufficiently slowed to prevent dangerous blood clots.

Because warfarin has a narrow therapeutic window, its effectiveness is highly sensitive to interactions with other substances. Medications can affect the INR through several mechanisms, including inhibiting or inducing the liver's cytochrome P450 (CYP) enzymes, displacing warfarin from protein-binding sites in the bloodstream, or altering the body's vitamin K levels.

Medications That Increase INR

An increased INR signifies that blood clotting is taking longer, which can raise the risk of dangerous bleeding. Numerous medications are known to potentiate the effect of warfarin. The most significant interactions often occur through the inhibition of CYP2C9, the primary enzyme responsible for warfarin metabolism.

Common medication classes that can increase INR:

Antibiotics: Certain antibiotics, such as sulfamethoxazole-trimethoprim (Bactrim) and metronidazole (Flagyl), can significantly raise INR levels by inhibiting CYP2C9. Others like macrolides and fluoroquinolones may also increase INR.
Antifungals: Azole antifungals, especially fluconazole, are strong CYP2C9 inhibitors that can lead to major increases in INR.
Cardiovascular Drugs: Amiodarone is known to raise INR by inhibiting CYP enzymes. Some statins may also cause a modest increase.
Pain Relievers: High doses of acetaminophen and NSAIDs can increase INR or bleeding risk.
Antidepressants: SSRIs like fluoxetine and sertraline can affect warfarin metabolism and increase bleeding risk.

Medications That Decrease INR

A decreased INR indicates faster blood clotting, increasing the risk of a clot. This can occur when medications induce liver enzymes that metabolize warfarin more quickly.

Common medication classes that can decrease INR:

Antibiotics: Rifampin, dicloxacillin, and nafcillin can induce CYP enzymes, reducing warfarin's effectiveness.
Antiepileptics: Certain anti-seizure medications, including carbamazepine and phenytoin, are potent enzyme inducers that can significantly decrease INR.
Herbal Supplements: St. John's Wort is a powerful enzyme inducer that can significantly reduce warfarin's efficacy. Others like ginseng and Coenzyme Q10 have also been linked to decreases.

Herbal and Over-the-Counter Interactions

Herbal products and OTC supplements can have significant interactions with warfarin.

Herbal supplements that may increase bleeding risk:

Danshen, Dong Quai, Ginkgo Biloba, and Garlic.
Vitamin E (doses over 400 IU/day).
Fish Oil/Omega-3 Fatty Acids.

Herbal supplements that may decrease INR:

St. John's Wort.
Ginseng.
Coenzyme Q10.

Managing INR Fluctuations

Managing INR when starting or stopping interacting medications requires close collaboration with a healthcare provider and increased monitoring.

Increase Monitoring: Check INR more frequently, especially within the first two weeks of a change.
Adjust Warfarin Dose: The warfarin dose may need adjustment based on INR readings and the interaction.
Consider Alternatives: For unstable INR, switching to a DOAC may be appropriate.
Address Lifestyle Factors: Consistency in vitamin K intake and avoiding binge drinking are important for stable INR.

Summary of INR-Affecting Medications


Medication/Class	Effect on INR	Mechanism	Clinical Consideration
Antibiotics (e.g., Metronidazole, Bactrim)	Increase	CYP2C9 enzyme inhibition	Requires close monitoring; potential for significant INR elevation.
Antibiotics (e.g., Rifampin, Dicloxacillin)	Decrease	CYP enzyme induction	May require temporary warfarin dose increase; monitor closely.
Amiodarone	Increase	Decreased warfarin metabolism via CYP inhibition	Requires significant warfarin dose reduction and long-term monitoring.
Fluconazole	Increase	CYP2C9 enzyme inhibition	Potential for significant INR elevation, even with short-term use.
St. John's Wort	Decrease	CYP enzyme induction	Avoid use in warfarin patients due to a significant decrease in efficacy.
Ginkgo Biloba	Increase	Anti-platelet effect	Increases risk of bleeding, monitor for bruising and other signs.
NSAIDs (e.g., Ibuprofen)	Increase	May inhibit warfarin metabolism	Increases bleeding risk; should be used with caution, if at all.
Carbamazepine	Decrease	CYP enzyme induction	May require substantial warfarin dose increase; monitor closely.

Conclusion

The list of substances that can influence INR is extensive. Open communication with healthcare providers is the most effective way to prevent serious complications. Always inform your doctor or pharmacist before starting, stopping, or changing any medication, including OTCs and herbals, to ensure proper monitoring and adjustments. Consistency in diet and medication timing helps maintain stable INR levels. Vigilance regarding potential interactions is paramount to patient safety.

Managing Fluctuating INR in Patients on Warfarin - Provides further details on managing INR fluctuations.

Key Takeaways

Broad Interactions: Many common medications, from antibiotics to antifungals and antidepressants, can significantly impact INR levels by affecting warfarin metabolism.
CYP Enzymes: The primary mechanism behind many drug-warfarin interactions is the inhibition or induction of cytochrome P450 (CYP) liver enzymes, particularly CYP2C9.
Herbals and OTCs: Herbal supplements like St. John's Wort and ginkgo biloba, and OTC pain relievers like high-dose acetaminophen or NSAIDs, can alter INR and increase bleeding risk.
Increased Monitoring: Whenever a new medication is started or stopped, or a dose is changed, increased INR monitoring is essential to detect any potential interactions and allow for timely warfarin dose adjustments.
Consistency is Key: A stable diet, especially regarding vitamin K intake, and consistent medication timing are crucial for maintaining a stable INR for patients on warfarin.

Frequently Asked Questions

Sulfamethoxazole-trimethoprim (Bactrim) and metronidazole (Flagyl) are particularly known for significantly increasing INR by inhibiting the liver enzyme CYP2C9. Other antibiotics like macrolides and fluoroquinolones can also have an effect.

Yes, high-dose acetaminophen (over 2000mg/day) can increase INR. Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen also increase bleeding risk and should be used with caution, if at all, when taking warfarin.

Yes, many herbal supplements can interact with warfarin. St. John's Wort can significantly decrease INR, while others like danshen, dong quai, ginkgo biloba, and garlic can increase bleeding risk by raising INR or inhibiting platelets.

Inform your doctor or pharmacist that you are taking warfarin so they can plan for increased INR monitoring. Depending on the interaction's severity, your warfarin dose may need to be temporarily adjusted.

No, avoiding all vitamin K-rich foods is not recommended. The key is consistency. Maintain a stable intake of foods like spinach and kale so your warfarin dose can be appropriately set. Sudden, major changes in your vitamin K intake are what can cause INR fluctuations.

INR should be monitored more frequently for a few weeks after starting or stopping a new prescription. The most significant effects of many drug interactions typically manifest within 3 to 5 days.

A high INR indicates that the blood is taking too long to clot, which increases the risk of excessive and potentially life-threatening bleeding. This is why careful management of drug interactions is critical.