From the Guidelines
When patients are treated with warfarin, medications such as antibiotics (e.g., ciprofloxacin, metronidazole, and trimethoprim-sulfamethoxazole), NSAIDs (e.g., ibuprofen, naproxen, and aspirin), and certain antifungals (e.g., fluconazole and itraconazole) should be avoided due to potentially dangerous interactions that can increase the risk of bleeding or enhance warfarin's effect. These interactions can occur through various mechanisms, including the inhibition of cytochrome P450 enzymes that metabolize warfarin, displacement of warfarin from plasma proteins, or direct impact on clotting mechanisms 1. Key medications to avoid or use with caution include:
- Antibiotics: ciprofloxacin, metronidazole, trimethoprim-sulfamethoxazole, and certain macrolides like clarithromycin and erythromycin
- NSAIDs: ibuprofen, naproxen, and aspirin (except in certain circumstances)
- Antifungals: fluconazole and itraconazole
- Antidepressants: SSRIs like fluoxetine and paroxetine
- Anticonvulsants: phenytoin and carbamazepine
- Herbal supplements: St. John's wort, ginkgo biloba, and garlic
- Other anticoagulants and antiplatelets: clopidogrel, dabigatran, and rivaroxaban It is essential for patients on warfarin to inform their healthcare providers about all medications they take and maintain regular INR monitoring when starting or stopping any medication to minimize the risk of adverse interactions 1.
From the FDA Drug Label
Medications of unknown interaction with coumarins are best regarded with caution. When these medications are started or stopped, more frequent PT/INR monitoring is advisable. It has been reported that concomitant administration of warfarin and ticlopidine may be associated with cholestatic hepatitis
- Increased and decreased PT/INR responses have been reported (oral) (17-Alkyl Penicillins, intravenous, Gout Treatment Agents Testosterone Derivatives) (fluoroquinolones) The following factors, alone or in combination, may be responsible for INCREASED PT/INR response:
- dicumarol
- diflunisal
- disulfiram
- doxycycline
- fenofibrate
- fluoroquinolones
- omeprazole
- oxandrolone
- oxyphenbutazone
- phenylbutazone
- quinidine
- sulfinpyrazone
- sulfonamides
- thyroid drugs
- trimethoprim/sulfamethoxazole The following factors, alone or in combination, may be responsible for DECREASED PT/INR response:
- aminoglutethimide
- atorvastatin
- azathioprine
- carbamazepine
- chlordiazepoxide
- cyclophosphamide
- dicloxacillin
- ethchlorvynol
- glutethimide
- griseofulvin
- haloperidol
- meprobamate
- methimazole
- nafcillin
- phenobarbital
- phenytoin
- primidone
- rifampin
- secobarbital
- spironolactone
- sulfonamides
- trazodone
- vitamin K
Medications to avoid with warfarin include:
- Ticlopidine due to the risk of cholestatic hepatitis
- Dicumarol due to increased PT/INR response
- Other medications that may increase or decrease PT/INR response, as listed above 2 2
From the Research
Medications to Avoid with Warfarin
When patients are treated with warfarin, several medications should be avoided due to the increased risk of bleeding. These include:
- Nonsteroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors, as they can increase the risk of gastrointestinal bleeding and general bleeding 3, 4
- Antiplatelet regimens, such as aspirin and clopidogrel, which can increase the risk of clinically relevant bleeding 4, 5
- Antimicrobials, such as antibiotics, which can increase the risk of bleeding 4, 5
- Selective serotonin reuptake inhibitors (SSRIs) and mirtazapine, which can increase the risk of bleeding 4
- Loop diuretics, which can increase the risk of bleeding 4
- Cytochrome P-450 (CYP)-inducing anticonvulsants, such as carbamazepine, which can decrease the anticoagulant effect of warfarin and require frequent warfarin dose adjustments 6
Important Considerations
It is essential to note that the risk of bleeding can be increased when warfarin is combined with certain medications. Therefore, patients should be cautious when taking these medications together, and healthcare providers should closely monitor their patients' international normalized ratio (INR) levels and adjust warfarin doses as needed. Additionally, some medications, such as proton pump inhibitors (PPIs), may have a protective effect against warfarin-related gastrointestinal bleeding 4.