Login
Subscribe
Warfarin (COUMADIN, JANTOVEN) is one of the oldest and most widely prescribed anticoagulants (blood thinners), having been used in medical practice for more than 60 years. Patients taking warfarin should be aware that it has clinically important interactions with numerous other prescription and over-the-counter medications, as well as some dietary supplements.
Millions of patients in the U.S. take anticoagulants like warfarin on a long-term basis to prevent the formation of dangerous clots...
Warfarin (COUMADIN, JANTOVEN) is one of the oldest and most widely prescribed anticoagulants (blood thinners), having been used in medical practice for more than 60 years. Patients taking warfarin should be aware that it has clinically important interactions with numerous other prescription and over-the-counter medications, as well as some dietary supplements.
Millions of patients in the U.S. take anticoagulants like warfarin on a long-term basis to prevent the formation of dangerous clots in the heart, veins or arteries. These drugs offer great benefit by preventing devastating consequences of undesired clot formation, such as strokes, lung damage, limb loss and, in some cases, death.
However, the benefits of anticoagulants come at the price of an increased risk of potentially life-threatening bleeding. Thus, treatment with these drugs always involves a delicate balance between preventing harmful clots and avoiding serious bleeding. Many factors, including use of many drugs that interact with anticoagulants, can tilt this balance in one direction or the other.
INR tests
Warfarin works by blocking the production of certain proteins called vitamin K-dependent clotting factors by the liver.
The dosage of warfarin is adjusted based on monitoring with periodic blood tests that measure the international normalized ratio (INR). For healthy people, a normal INR value is 1.1 or less.[1] For most patients treated with warfarin, the desired INR range is between 2 and 3.
An INR higher than 3 markedly increases the risk of dangerous bleeding, whereas a value of less than 2, in people needing to use warfarin, may not provide sufficient protection from harmful clots.
Increased risk of bleeding[2],[3]
Table 1, below, lists examples of the many oral drugs that when taken concomitantly (at the same time) with warfarin can increase the risk of bleeding. The list of such drugs includes antibiotics, antifungal drugs, drugs for abnormal heart rhythms, nonsteroidal anti-inflammatory drugs (NSAIDs), selective serotonin reuptake inhibitor (SSRI) antidepressants and cholesterol-lowering statin drugs, among others.
Many of the drugs that interact with warfarin do so by inhibiting liver enzymes involved in the breakdown of the anticoagulant, thereby increasing warfarin exposure and potentially raising the INR above 3.
Some of the drugs — particularly the NSAIDs, SSRI antidepressants and antiplatelet drugs — increase the risk of bleeding by inhibiting platelets, which are cell-like structures in the blood that together with vitamin K-dependent clotting factors form blood clots to stop bleeding.
Certain dietary supplements, including garlic and ginkgo biloba, also may increase the risk of bleeding in patients taking warfarin.
Table 1: Examples of Oral Drugs That Increase the Risk of Bleeding When Taken Concomitantly With Warfarin
| Generic Name | Brand Name(s)† | Drug Class |
|---|---|---|
| allopurinol* | LOPURIN, ZYLOPRIM | Gout drug |
| amiodarone* | PACERONE | Abnormal heart rhythm drug |
| amoxicillin | AMOXIL, LAROTID | Penicillin-type antibiotic |
| aspirin | BAYER ASPIRIN, DURLAZA, ECOTRIN, VAZALORE | NSAID |
| azithromycin* | ZITHROMAX | Macrolide antibiotic |
| celecoxib** | CELEBREX | NSAID |
| ciprofloxacin* | CIPRO | Fluoroquinolone antibiotic |
| citalopram* | CELEXA | SSRI antidepressant |
| clarithromycin* | BIAXIN XL | Macrolide antibiotic |
| clopidogrel* | PLAVIX | Antiplatelet drug |
| diclofenac** | CAMBIA, ZIPSOR, ZORVOLEX | NSAID |
| dronedarone** | MULTAQ | Abnormal heart rhythm drug |
| erythromycin | E.E.S., ERY-TAB, ERYC, ERYPED | Macrolide antibiotic |
| escitalopram* | LEXAPRO | SSRI antidepressant |
| fluconazole | DIFLUCAN | Antifungal drug |
| fluoxetine* | PROZAC, SARAFEM, SELFEMRA | SSRI antidepressant |
| fluvastatin** | LESCOL XL | Cholesterol-lowering statin drug |
| ibuprofen | ADVIL, IBU-TAB, MIDOL LIQUID GELS, MOTRIN IB, TAB-PROFEN | NSAID |
| indomethacin** | INDOCIN, TIVORBEX | NSAID |
| itraconazole*** | ONMEL, SPORANOX, TOLSURA | Antifungal drug |
| ketoconazole** | generic only | Antifungal drug |
| levofloxacin* | generic only | Fluoroquinolone antibiotic |
| methotrexate* | OTREXUP, RASUVO, TREXALL, XATMEP | Cancer and immunosuppression drug |
| moxifloxacin** | AVELOX | Fluoroquinolone antibiotic |
| naproxen | ALEVE, ANAPROX DS, NAPRELAN, NAPROSYN | NSAID |
| ofloxacin* | generic only | Fluoroquinolone antibiotic |
| paroxetine* | PAXIL, PEXEVA | SSRI antidepressant |
| piroxicam** | FELDENE | NSAID |
| sertraline* | ZOLOFT | SSRI antidepressant |
| simvastatin**** | FLOLIPID, ZOCOR | Cholesterol-lowering statin drug |
| sulindac* | generic only | NSAID |
| tamoxifen* | SOLTAMOX | Breast cancer drug |
†Brand-name combination products were excluded.
*Designated as Limited Use
**Designated as Do Not Use
***Designated as Do Not Use except for serious fungal infections
****High-dose simvastatin (80 milligrams) is designated as Do Not Use. Lower-dose forms are acceptable.
Increased risk of blood clots[4],[5]
Many other oral drugs, when taken concomitantly with warfarin, can decrease the blood levels of warfarin, thereby potentially decreasing the INR below 2 and increasing the risk of dangerous blood clots (see Table 2, below, for a list of examples). Each of these drugs increases the activity of liver enzymes involved in the breakdown of warfarin, thus accelerating the removal of the anticoagulant from the blood.
This list includes the asthma and allergy medication montelukast (SINGULAIR); the diabetes drug pioglitazone (ACTOS); drugs for excessive daytime sleepiness due to narcolepsy, obstructive sleep apnea or shift-work sleep disorder; the stomach-acid-reducing proton pump inhibitor omeprazole (PRILOSEC); and certain seizure drugs, among others.
Certain dietary supplements, including co-enzyme Q10, St. John’s wort and ginseng, also may decrease the anticoagulation effects of warfarin and increase the risk of blood clots.
Table 2: Examples of Oral Drugs That Can Increase the Risk of Dangerous Blood Clots When Taken Concomitantly With Warfarin
| Generic Name | Brand Name(s)† | Drug Class |
|---|---|---|
| armodafinil* | NUVIGIL | Drug for excessive daytime sleepiness |
| carbamazepine | CARBATROL, EPITOL, EQUETRO, TEGRETOL, TERIL | Seizure drug |
| modafinil* | PROVIGIL | Drug for excessive daytime sleepiness |
| montelukast** | SINGULAIR | Asthma/allergy drug |
| omeprazole* | PRILOSEC | Proton pump inhibitor |
| phenytoin | DILANTIN, PHENYTEK | Seizure drug |
| pioglitazone** | ACTOS | Diabetes drug |
| prednisone | RAYOS | Glucocorticoid |
| rifampin | RIFADIN, RIFAMATE, RIMACTANE | Antibiotic |
| rufinamide | BANZEL | Seizure drug |
†Brand-name combination products were excluded.
*Designated as Limited Use
**Designated as Do Not Use
Other important drug interactions
Warfarin can interfere with the breakdown of the cholesterol-lowering drug simvastatin (FLOLIPID, ZOCOR).[6] This interaction increases the risk of simvastatin-induced myopathy (muscle damage). In severe cases, this condition can progress to rhabdomyolysis, a life-threatening, muscle-destroying condition that can lead to sudden kidney failure and death.
What You Can Do
If you need treatment with warfarin, review a list of all your prescription and over-the-counter medications with your doctor to assess for potentially significant drug interactions. Be aware that many other drugs not listed in this article also may have dangerous interactions with warfarin. In addition, alert any health care professional prescribing you a new medication that you are taking warfarin and consult with your doctor or pharmacist before taking a new over-the-counter medication or dietary supplement.
If you are taking warfarin, you should avoid concomitant use of interacting drugs whenever possible. For example, if you develop an infection that requires antibiotic treatment, ask your doctor to prescribe an antibiotic that does not interact with warfarin if possible.
If use of an interacting drug is medically necessary while taking warfarin, you should undergo more frequent monitoring of INR levels if the interacting drug can affect the INR, especially during initiation, dosage changes and discontinuation of the interacting drug. You also should be alert for signs of bleeding — such as unusual bruising, nosebleeds, bleeding gums, pink or brown urine, red or black stools, coughing up blood or vomiting blood or material that looks like coffee grounds — and signs of dangerous blood clots — such as swelling and pain in one leg, chest pain, shortness of breath and stroke-like symptoms such as weakness on one side of the body.
References
[1] Mayo Clinic. Prothrombin time. November 6, 2018. https://www.mayoclinic.org/tests-procedures/prothrombin-time/about/pac-20384661. Accessed May 7, 2020.
[2] Bristol-Myers Squibb Company. Label: warfarin (). December 2020. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=d91934a0-902e-c26c-23ca-d5accc4151b6&type=display. Accessed May 7, 2020.
[3] IBM Micromedex. Drug interactions. http://www.micromedexsolutions.com/home/dispatch. Search term: “warfarin.” Accessed May 7, 2020.
[4] Bristol-Myers Squibb Company. Label: warfarin (COUMADIN). December 2020. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=d91934a0-902e-c26c-23ca-d5accc4151b6&type=display. Accessed May 7, 2020. [See “Warfarin Label_December 2019”]
[5] IBM Micromedex. Drug interactions. http://www.micromedexsolutions.com/home/dispatch. Search term: “warfarin.” Accessed May 7, 2020.
[6] Ibid.
