From the Guidelines
Warfarin's effectiveness can be significantly altered by many common medications, and it is crucial to monitor INR levels closely when initiating or changing medications in patients taking warfarin. Medications that potentiate (increase) warfarin's effects include antibiotics like ciprofloxacin, erythromycin, and metronidazole, as well as sulfonamides, such as sulfaphenazole and sulfamethoxazole, which can inhibit the CYP2C9 isoenzyme and increase the risk of bleeding 1. Pre-emptive warfarin dose reductions of 25% and 33% for sulfamethoxazole and metronidazole, respectively, are recommended when co-administered with warfarin 1.
Some key points to consider when managing patients on warfarin include:
- Antibiotics can alter the gut microbiome, increasing the risk of bleeding, and some antibiotics, such as ciprofloxacin and metronidazole, can also inhibit warfarin metabolism, further increasing this risk 1
- Statins, such as atorvastatin, rosuvastatin, and simvastatin, may increase INR levels, although the effect is generally not considered clinically significant, and close monitoring is recommended 1
- Cholestyramine and other bile acid sequestrants can interfere with warfarin absorption, and spacing warfarin administration 2 hours before or 6 hours after bile acid sequestrant administration can help mitigate this interaction 1
- Certain anti-hyperlipidemic medications, such as gemfibrozil and fenofibrate, may also interact with warfarin, although the evidence is less clear, and case reports suggest that gemfibrozil may potentiate warfarin's effects 1
It is essential for patients on warfarin to consult their healthcare provider before starting any new medication, including over-the-counter products and herbal supplements, to minimize the risk of adverse interactions and maintain optimal anticoagulation. Additionally, patients should maintain consistent vitamin K intake through diet to avoid fluctuations in warfarin effectiveness. Regular monitoring of INR levels and close communication with healthcare providers can help prevent complications and ensure the safe use of warfarin in clinical practice.
From the FDA Drug Label
Numerous factors, alone or in combination, including changes in diet, medications, botanicals and genetic variations in the CYP2C9 and VKORC1 enzymes (see CLINICAL PHARMACOLOGY, Pharmacogenomics) may influence the response of the patient to warfarin Drugs may interact with warfarin sodium tablets through pharmacodynamic or pharmacokinetic mechanisms Pharmacodynamic mechanisms for drug interactions with warfarin sodium tablets are synergism (impaired hemostasis, reduced clotting factor synthesis), competitive antagonism (vitamin K), and altered physiologic control loop for vitamin K metabolism (hereditary resistance) Pharmacokinetic mechanisms for drug interactions with warfarin sodium tablets are mainly enzyme induction, enzyme inhibition, and reduced plasma protein binding. The following factors, alone or in combination, may be responsible for INCREASED PT/INR response:
- fluoroquinolones
- tolbutamide
- diclofenac
- naproxen
- trimethoprim/sulfamethoxazole
- dicumarol
- neomycin
- urokinase
- diflunisal
- norfloxacin
- valdecoxib
- disulfiram
- ofloxacin
- valproate
- doxycycline
- olsalazine
- vitamin E
- erythromycin
- omeprazole
- zafirlukast
- esomeprazole
- oxandrolone
- ezetimibe
- oxymetholone
- fenofibrate
- pantoprazole The following factors, alone or in combination, may be responsible for DECREASED PT/INR response:
- phenytoin
- aminoglutethimide
- cyclophosphamide
- pravastatin
- amobarbital
- dicloxacillin
- prednisone
- atorvastatin
- ethchlorvynol
- primidone
- azathioprine
- glutethimide
- propylthiouracil
- butabarbital
- griseofulvin
- raloxifene
- butalbital
- haloperidol
- ranitidine
- carbamazepine
- meprobamate
- rifampin
- chloral hydrate
- 6-mercaptopurine
- secobarbital
- chlordiazepoxide
- methimazole
- spironolactone
- chlorthalidone
- moricizine hydrochloride
- sucralfate
- cholestyramine
- nafcillin
- trazodone
- clozapine
- paraldehyde
- vitamin C (high dose)
- corticotropin
- pentobarbital
- vitamin K
- cortisone
- phenobarbital
Medications that can potentiate the effects of warfarin:
- Antibiotics: fluoroquinolones, trimethoprim/sulfamethoxazole, neomycin
- Anti-inflammatory medications: diclofenac, naproxen, valdecoxib, diflunisal, norfloxacin
- Anticonvulsants: none listed
- Other medications: tolbutamide, dicumarol, urokinase, disulfiram, valproate, doxycycline, olsalazine, vitamin E, erythromycin, omeprazole, zafirlukast, esomeprazole, oxandrolone, ezetimibe, oxymetholone, fenofibrate, pantoprazole
Medications that can inhibit the effects of warfarin:
- Anticonvulsants: phenytoin, primidone, carbamazepine, rifampin, phenobarbital
- Antibiotics: none listed
- Anti-inflammatory medications: none listed
- Other medications: aminoglutethimide, cyclophosphamide, pravastatin, amobarbital, dicloxacillin, prednisone, atorvastatin, ethchlorvynol, azathioprine, glutethimide, propylthiouracil, butabarbital, griseofulvin, raloxifene, butalbital, haloperidol, ranitidine, meprobamate, secobarbital, chlordiazepoxide, methimazole, spironolactone, chlorthalidone, moricizine hydrochloride, sucralfate, cholestyramine, nafcillin, trazodone, clozapine, paraldehyde, vitamin C (high dose), corticotropin, pentobarbital, vitamin K, cortisone 2
From the Research
Medications that Interact with Warfarin
- The following medications can potentiate or inhibit the effects of warfarin:
- Medications that can decrease the risk of warfarin-related bleeding:
- Proton pump inhibitors (PPIs) 3
- Medications that can interact with warfarin through pharmacokinetic and pharmacodynamic mechanisms:
- Various medications that can affect warfarin's mechanism of action or increase the risk of bleeding 4
Mechanisms of Interaction
- Pharmacokinetic interactions: can be monitored using International Normalized Ratio (INR) levels 4
- Pharmacodynamic interactions: require knowledge of potential interactions and INR monitoring to predict and manage interactions 4
Patient Populations at Risk
- Elderly patients: may be at increased risk for hemorrhage and may require careful attention to warfarin management due to alterations in pharmacokinetics, pharmacodynamics, and increased risk for hemorrhage 5