From the Guidelines
Numerous medications can raise International Normalized Ratio (INR) levels, potentially increasing bleeding risk in patients taking warfarin or other anticoagulants, and it is crucial to monitor INR levels closely when initiating or stopping these medications. Common medications that elevate INR include:
- Antibiotics such as ciprofloxacin, erythromycin, metronidazole, and trimethoprim-sulfamethoxazole, which can disrupt gut flora that produce vitamin K or inhibit warfarin metabolism 1
- Antifungals like fluconazole and itraconazole, which strongly inhibit the cytochrome P450 enzymes that metabolize warfarin 1
- Many pain medications, including NSAIDs (ibuprofen, naproxen), acetaminophen (at doses exceeding 2g daily for extended periods), and some opioids
- Cardiovascular drugs that raise INR, including amiodarone, propafenone, and statins, such as fluvastatin, lovastatin, rosuvastatin, and simvastatin, which may interact with warfarin by displacing it from plasma protein binding and inhibiting CYP3A4 1
- Psychiatric medications, such as SSRIs (fluoxetine, sertraline), which can affect warfarin dosing and increase the risk of bleeding 1
- Certain herbal supplements, including St. John's wort, which can enhance clearance of warfarin via induction of CYP2C9, 2C19, and 3A4, and garlic, ginkgo biloba, which may also interact with warfarin 1 Patients on warfarin should inform healthcare providers about all medications they take, including over-the-counter drugs and supplements. More frequent INR monitoring is necessary when starting or stopping these medications, and dosage adjustments of warfarin may be required to maintain therapeutic INR levels and prevent bleeding complications.
From the FDA Drug Label
The following factors, alone or in combination, may be responsible for INCREASED PT/INR response: EXOGENOUS FACTORS: Potential drug interactions with warfarin sodium tablets are listed below by drug class and by specific drugs. Classes of Drug also: other medications affecting blood elements which may modify hemostasis dietary deficiencies prolonged hot weather unreliable PT/INR determinations
- Increased and decreased PT/INR responses have been reported (oral) (17-Alkyl Penicillins, intravenous, Gout Treatment Agents Testosterone Derivatives) (fluoroquinolones) (topical) ogen dextran (intravaginal, oral, systemic) activator (t-PA) dextrothyroxine moricizine hydrochloride* tolbutamide diazoxide nalidixic acid tramadol diclofenac naproxen trimethoprim/sulfamethoxazole dicumarol neomycin urokinase diflunisal norfloxacin valdecoxib disulfiram ofloxacin valproate doxycycline olsalazine vitamin E erythromycin omeprazole zafirlukast esomeprazole oxandrolone zileuton ethacrynic acid oxaprozin ezetimibe oxymetholone fenofibrate pantoprazole
Medications that can affect or raise International Normalized Ratio (INR) levels include:
- 17-Alkyl Penicillins
- Gout Treatment Agents
- Testosterone Derivatives
- Fluoroquinolones
- Dextran
- Activator (t-PA)
- Dextrothyroxine
- Moricizine hydrochloride
- Tolbutamide
- Diazoxide
- Nalidixic acid
- Tramadol
- Diclofenac
- Naproxen
- Trimethoprim/sulfamethoxazole
- Dicumarol
- Neomycin
- Urokinase
- Diflunisal
- Norfloxacin
- Valdecoxib
- Disulfiram
- Ofloxacin
- Valproate
- Doxycycline
- Olsalazine
- Vitamin E
- Erythromycin
- Omeprazole
- Zafirlukast
- Esomeprazole
- Oxandrolone
- Zileuton
- Ethacrynic acid
- Oxaprozin
- Ezetimibe
- Oxymetholone
- Fenofibrate
- Pantoprazole 2
From the Research
Medications that Affect or Raise INR Levels
Several medications can interact with warfarin, affecting International Normalized Ratio (INR) levels. These include:
- Antibiotics such as trimethoprim/sulfamethoxazole, ciprofloxacin, levofloxacin, metronidazole, fluconazole, azithromycin, and clarithromycin, which can increase the risk of bleeding events 3
- Statins like simvastatin, which can moderately increase INR values and require closer monitoring 4
- Macrolide antibiotics such as telithromycin, which can elevate INR and increase the risk of bleeding complications 5
Herbal Interactions
Certain herbal supplements can also interact with warfarin, affecting INR levels:
- St. John's wort (Hypericum perforatum), which can decrease warfarin concentrations and increase the risk of bleeding or reduce the efficacy of warfarin 6, 7
- Ginkgo biloba, which can cause bleeding when combined with warfarin 6
- Garlic (Allium sativum), which can increase clotting time and INR when taken with warfarin 6
- Danshen (Salvia miltiorrhiza), which can enhance anticoagulation and increase the risk of bleeding when taken with warfarin 6
Key Considerations
When prescribing or taking medications that interact with warfarin, it is essential to: