Coumadin: 7 things you should know

Medically reviewed by Carmen Pope, BPharm. Last updated on July 5, 2023.

1. How it works

• Coumadin is a brand (trade) name for warfarin.
• Coumadin (warfarin) works by blocking the formation of vitamin K-dependent clotting factors and inhibiting a vitamin K-dependent enzyme complex, as well as two anticoagulant proteins. This increases the time it takes for blood to clot. This may be described as "thinning the blood".
• Coumadin belongs to the class of drugs known as coumarins. Coumadin may also be called an anticoagulant.

2. Upsides

• May be used to prevent and treat deep vein thrombosis (DVT) or pulmonary embolism (PE). Decreases the body's ability to form new blood clots
• Also used to prevent blood clots from developing as a result of atrial fibrillation or cardiac valve replacement or to treat a blood clot that has developed because of either of these conditions.
• Used to decrease the risk of death, another heart attack, or other thromboembolic events, such as a stroke, after a heart attack.
• Prevents further extension of the formed clot.
• Prevents secondary thromboembolic complications from developing that could have serious or fatal consequences.
• Has a long history of use.
• No dosage adjustment is needed for patients with kidney disease; however, more frequent monitoring of anticoagulation is advised in those with compromised kidney function.
• Available in 9 different strengths, each of which is a different color: 1mg, 2mg, 2.5mg, 3mg, 4mg, 5mg, 6mg, 7.5mg, and 10mg.
• Available as a generic under the name warfarin.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Major and fatal bleeding. Bleeding is more likely to occur within the first month.
• Other common side effects include gastrointestinal disturbances (such as nausea, vomiting, diarrhea, taste perversion, abdominal pain, flatulence, and bloating), skin reactions (such as a rash or dermatitis), hair loss (alopecia), and elevated liver enzymes.
• Has a narrow therapeutic range - meaning that there is a fine line between too much and too little. For this reason, regular blood monitoring of the international normalized ratio (INR) - a standardized number that determines the ability of your blood to clot - is required. The frequency of monitoring varies; daily monitoring is required initially. Ongoing monitoring frequency depends on patient response but may need to increase for numerous reasons such as during times of illness or with dietary or medication changes.
• The dosage of Coumadin needs to be individualized for each person, depending on how they respond to the drug, measured by their INR. The initial dose of Coumadin is influenced by age, race, body weight, sex, concomitant medications, and comorbidities. An INR greater than 4.0 appears to provide no additional therapeutic benefits. An INR of 2.5 (range 2.0 to 3.0) is recommended for most indications.
• If a patient's CYP2C9 and VKORC1 genotypes are not known then the initial dose of Coumadin is usually 2 to 5 mg once daily. Typical maintenance doses are from 2 to 10 mg/day.
• Rarely, tissue necrosis or gangrene of the skin and other tissues may occur. Potentially fatal calciphylaxis (the accumulation of calcium in the small blood vessels of the fat and skin tissues) may also occur rarely.
• Emboli may be released as a result of Coumadin therapy. These may lodge in the kidneys, pancreas, spleen, liver, or feet ("purple toes syndrome"). Some cases have progressed to necrosis or death.
• Cannot break apart established blood clots, nor can it reverse damage to tissue that has already been starved of oxygen. It can; however, prevent the extension of existing blood clots and reduce the risk of part of that blood clot breaking off and lodging in another artery or vein. Does not reverse existing tissue damage.
• Should not be used by women who are pregnant or planning to become pregnant, except under specialist advice (for example for women with mechanical heart valves who are pregnant and who have a high risk of thromboembolism) because warfarin can harm a developing baby.
• May not be suitable for some people, including those with a history of kidney disease. More frequent monitoring of anticoagulation may be necessary for those with kidney problems. The risks of Coumadin treatment may also be increased in certain populations such as those with moderate to severe liver disease, an indwelling catheter, an infectious disease or disturbances of the intestinal flora, use of an indwelling catheter, deficiency in protein-C-mediated anticoagulant response, severe to moderate high blood pressure, diabetes, polycythemia vera, vasculitis, or undergoing eye surgery. Some people are resistant to the effects of Coumadin (called hereditary resistance).
• Since it takes several days for the full effect of Coumadin to be achieved, heparin is preferred for initial rapid anticoagulation. Conversion to Coumadin may begin concurrently with heparin or be delayed for 3 to 6 days. Overlap Coumadin therapy with heparin for 4 to 5 days or until the desired INR has been reached.
• Should not be used as initial therapy in people with certain disorders, such as heparin-induced thrombocytopenia (HIT), although treatment may be considered after the platelet count has normalized.
• Interacts with numerous drugs including some antibiotics, heart medications, oral contraceptives, pain medications, and acid suppressants. Coumadin also interacts with several types of plants and fruits, including coenzyme Q10, St. John’s wort, ginseng, echinacea, ginkgo, golden seal, as well as grapefruit, and cranberry juice. See here for a full list of interactions.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

• Coumadin is effective at "thinning the blood" (reducing the ability of the blood to clot); however, several factors can affect blood levels including diet, ethnicity, other medications, and illness. Too much Coumadin can cause major and potentially fatal bleeding.

5. Tips

• Be aware that foods containing vitamin K can affect Coumadin therapy. Try to eat a normal, balanced diet so that you maintain a consistent intake of vitamin K. Avoid eating too much of the same thing (for example, a whole plate of broccoli or a big bowl of salad greens). Foods high in vitamin K include kale, collards, broccoli, spinach, and other green leafy vegetables. Cranberry juice and alcohol may also affect Coumadin levels so limit your intake of these.
• No one dosage fits all. The dosage schedule for Coumadin needs to be tailored for each person depending on their INR response to the drug and the condition being treated. Patient factors such as age, weight, race (Asian patients may need lower dosages), body weight, sex, concomitant medications, and comorbidities all affect dosage as do some genetic factors (for example, CYP2C9 and VKORC1 genotypes). Your doctor will advise you.
• An initial lower starting dose of Coumadin is recommended for seniors or people who are frail or of Asian descent.
• Loading doses (a bigger dose at the start of treatment) are no longer routinely recommended as these increase the risk of bleeding without offering any more rapid protection against clot formation.
• If you miss a dose, and it is the same day, you may take that dose of Coumadin. However, if you do not discover the missed dose until the next day, do not double up on the dose (just forgo the missed dose). The effect of Coumadin lasts for over 24 hours and missing one dose is unlikely to have a detrimental effect.
• You may need to temporarily stop or change your Coumadin dosing schedule if you have planned surgery (including eye surgery) or a dental procedure. Discuss this with your surgeon or dentist before the procedure.
• Some factors or conditions can also increase INR, such as diarrhea, liver disease, poor nutritional state, fat in the stool (steatorrhea), or vitamin K deficiency. Factors that decrease INR include increased vitamin K intake or an inherited resistance to warfarin.
• Monitor yourself for signs of bleeding such as blood in your stools or urine, nose bleeds, bleeding gums, excessive menstrual bleeding, or excessive bruising, and seek immediate medical advice. Also take care to minimize your risk of bleeding - avoid full-contact sports, be careful with knives, and try to minimize your risk of falling.
• Always adhere to your prescribed dosage schedule. Ask your doctor before you take or discontinue ANY other drug, including over-the-counter medicines and botanical (herbal) products. Ensure you get your blood levels monitored as instructed.
• Wear or carry identification that states you are taking Coumadin tablets, in case of an emergency.
• Contact your doctor if you develop severe diarrhea, an infection, or fever, as concurrent illness may affect your response to Coumadin.
• Should not be used if you are pregnant or planning to become pregnant, except under specialist advice (for example for women with mechanical heart valves who are pregnant and who have a high risk of thromboembolism) because warfarin can harm a developing baby. Breastfeeding is also not recommended unless the benefits outweigh the risks.
• Although Coumadin and Jantoven are both brands of warfarin, small changes in their formulation may mean your body reacts differently to each brand. Most experts recommend you stick with the same brand of warfarin to help keep your INR levels stable.

6. Response and effectiveness

• Some slowing of the blood's ability to clot may be noticed within 24 hours; however, it can take from 72 to 96 hours for the full effects to be seen. One dose of Coumadin lasts for 2 to 5 days; however, daily dosing is needed to keep blood levels consistent. Effects are likely to accumulate with repeated dosing because of the time it takes for the affected vitamin K-dependent clotting factors to replenish. Desired INR range varies depending on the condition being treated and specific guidelines; however, the majority of guidelines aim for a target INR of 2.5 (range 2-3).
• Treatment duration also varies, from three months to life-long depending on the condition and other patient factors; generally, until the danger of thrombosis or embolism has passed.
• INR readings greater than 4 are associated with a higher risk of bleeding with no additional therapeutic benefit in most people.

7. Interactions

Medicines that interact with Coumadin may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with Coumadin. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with Coumadin include:

• acetaminophen
• amiodarone
• antibiotics or antifungals (may affect INR)
• anticonvulsants such as carbamazepine, phenytoin or valproic acid
• antimicrobial agents, such as ciprofloxacin, clarithromycin, erythromycin, metronidazole
• apixaban
• aspirin
• cimetidine
• co-enzyme Q10
• corticosteroids, such as prednisone and methylprednisone
• dabigatran
• ginseng
• medications that inhibit or induce CYP1A2 enzymes, such as acyclovir, allopurinol, caffeine, oral contraceptives, montelukast, omeprazole
• medications that inhibit or induce CYP2C9 enzymes, such as amiodarone, capecitabine, fluconazole, aprepitant, bosentan, or rifampin
• medications that inhibit or induce CYP3A4 enzymes, such as fluconazole, ketoconazole, or ritonavir
• methotrexate
• mifepristone
• NSAIDs, such as ibuprofen, diclofenac, etodolac, and naproxen
• omeprazole
• rifampin
• smoking
• St John's Wort
• tinzaparin.

Coumadin is metabolized by several CYP450 enzymes, such as CYP2C9, 2C19, 2C8, 2C18, 1A2, and 3A4. Any inhibitor of CYP2C9, 1A2, or 3A4 has the potential to increase the effect of Coumadin (increase the INR). Any inducers of CYP2C9, 1A2, or 3A4 have the potential to decrease the effect of Coumadin (decrease the INR).

In general, any medicine that can increase the risk of bleeding (such as clopidogrel, SSRI antidepressants [eg, citalopram, duloxetine, fluoxetine, venlafaxine], fish oils) may interact with Coumadin.

Large amounts of vitamin K in the diet (such as that from spinach, green tea, chard, and kale) can also reduce the effectiveness of Coumadin.

Alcohol may increase the risk of stomach bleeding with Coumadin.

Note that this list is not all-inclusive and includes only common medications that may interact with Coumadin. You should refer to the prescribing information for Coumadin for a complete list of interactions.

References

• Coumadin (warfarin) [Package Insert]. Revised 07/2022. Bristol-Myers Squibb Pharma Company https://www.drugs.com/pro/coumadin.html

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Coumadin only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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