Is there a difference between generic Warfarin and Coumadin?

Jill,

Coumadin is the trade name for warfarin, an oral anticoagulant. For years it has been available as both generic and trade and millions of patients use this drug in one form or the other.

The FDA mandates that the bioavailability of a generic be close to, but not exactly the same as, the trade drug (80 to 125% of the target chemical). This is probably close enough for many medications where the dose of the drug is not as personalized as it is for warfarin.

Some of my colleagues feel strongly that the trade product Coumadin is superior to the generic warfarin, but there is actually very little data in the scientific literature to support this. The only significant study on the topic (Ann Pharmacother 39 (7-8): 1188–93) showed equivalence between the two preparations. I personally don't feel that most patients obtain significant additional benefit by being on the more expensive non-generic.

You'll have to decide for yourself. You may wish to consult the knowlegeable mid-level providers in my group for their opinions since they manage the day-to-day operations of our anticoagulation clinic.

Will you continue warfarin therapy for patients with chronic atrial fib or those patients that fail cardioversions? Thanks for the blogs - they are informative and helpful.

Historically, the yearly risk of significant bleeding for patients on warfarin is ~3%. It is the comparison of an atrial fibrillation patient's stroke risk to their bleeding risk which allows us to identify those who may benefit from the use of warfarin.
A stroke risk score of 0 equates to a yearly stroke risk of 1.9% and a stroke risk score of 1 equates to a yearly stroke risk of 2.8%. In these cases, the risk of a bleeding event on warfarin is higher than the risk of a stroke off of warfarin. We advise these patients not to use warfarin.
Not until an atrial fibrillation patient has a stroke risk score of 2 does their risk of stroke exceed the magical 3% threshold. These patients have a stroke risk of 4% per year when they are not on warfarin. Therefore, all patients with atrial fibrillation and a stroke risk score of 2 or greater may benefit from warfarin in the absence of an absolute or relative contraindication to the drug.

Thanks to Dr. Thibodeau for helping me answer Danielle's question. I might add that we in the medical community have historically done a poor job of getting those patient onto warfarin who need it most. I think a lot of it has to do with the fact that we simply forget to think about stroke risk in these patients.

Thanks for the educational posts above.

At 45 yrs old, I've was diagnosed with A-Fib about 1 month ago. I have not had any significantly noticable symtoms, have received normal Echo & Thallium Stress test results and continue to be active and excercise regularly.

I did take 5mg of warfarin daily for about 5 days, but had a bleeding / brusing scare with a minor finger injury (impact trama with a softball). A Day later, my 68 year old mother passed away from a massive brain hemmorage (she had been on Coumadin for 3 yrs for A-fib).

I want to make sure I protect myself, but am concerned about the bleeding risks.

The Stroke risk assessment mentioned above seems relative. Can you tell me a bit about how my stoke risk could be determined?

Thx

Tim,

You've correctly pointed out the potential risks of being on the anticoagulant warfarin (Coumadin). Thankfully the tragic brain bleeds are quite rare among the millions of patients who are on the drug. I'm sorry your mother had to be the exception.

I found a great website that will calculate your risk of stroke using a simple calculator:

http://www.mdcalc.com/chads2-score-for-atrial-fibrillation-stroke-risk

It's based on a simple algorithm called the CHADS2 score that has been validated in several large studies. You get a point for every risk parameter you have (congestive heart failure, diabetes, high blood pressure, age greater than 75) and two points if you've had a previous stroke.

If your score is zero you are at low risk (less than a half percent per year) for stroke. Given the risk of bleeding on warfarin you are better off on aspirin alone (watch my blog in the next couple weeks for my recommendation for the best dose of aspirin).

If you score 2 or higher you are at high risk and should be on warfarin. A score of 1 puts you in the intermediate risk category, and the choice of warfarin versus aspirin would be up for debate.

You are 45 years old and if your health is good enough for softball you likely have a low CHADS2 score. Unless you have diabetes, high blood pressure, or congestive heart failure I'd recommend aspirin alone.

Thanks for your question.

My husband has been taking coumadin for nearly a year after suffering severe blood clots in his leg which spread to his lungs. The last several months he has experienced a loss of appetite, weight loss, numbness in his legs and overall weakness. Tests do not show any physical problems. He is blaming the coumadin and after stopping the medication, has his appetite back is actually eating again. The doctors will not agree that the coumadin is to blame. I don't know who to listen to anymore.

Sue Z,

Thanks for the comments. I'm glad your husband is feeling better. I won't be able to answer your question but I can at least give you my opinion.

Your doctors are essentially right about coumadin. My experience with the drug is that it is remarkably free of side effects (aside from the obvious side effect of easy bruising and bleeding).

Having said that I also hold to the axiom: Any drug can cause any side effect in at least a rare number of patients. When it comes to the question of unusual side effects from meds I maintain that you can never say never.

In the case of your husband, you may wish to find out from your doctor if he really needs to continue on coumadin anyway. The general guideline for blood thinners is that they can be stopped after 6-12 months in patients who have suffered their first pulmonary embolus (clot to lung).

You can also look to the future. My suspicion is that we will soon see the approval of a new medication (dabigatran) for the prevention of pulmonary embolus. This is a drug that is unrelated to coumadin and is generally quite well tolerated.

Good luck with everything!

Dr. VDG

Dr. Van De Graaff:

Being in the alternative medical care field for over 15 years has shown me more than the 3% risk of significant bleeding which you wrote about above this post. Why is it that conventional doctors like yourself fail to recommend a natural protocol to control blood clotting for atrial fibrillation? It's sad that warafin is considered the "standard treatment" in these types of cases. In my opinion you can treat the atrial fibrillation and the risk of clotting naturally, without having to use rat poison, no matter how "safe" the main stream medical field says it may be.

In my experience, and this is real life experience with people who actually follow the recommendations and are getting better, the patients should be tested for heavy metals and should avoid fried foods and trans fatty acids, they must also increase their vegetable intake. In addition to this I recommend supplementing with garlic, vitamin E, vitamin C, and ginkgo biloba. It's especially important to take omega-3s such as plant based fatty acid. Your body converts omega-3s into prostaglandins, which can be beneficial hormones that lubricate the blood vessels and get incorporated into the platelets (the clotting cells of the blood). This makes them less likely to spontaneously aggregate and incite a clot.

This is a great alternative for those fearful of taking anticoagulant blood thinners, such as coumadin. To date I have never seen one patient experience a toxic effect from the combination, unlike coumadin. Nor have I seen anyone develop a blood clot. You don't have to take rat poison (coumadin) for the rest of your life.

Rick,

I have to admit you've delved into a subject about which I confess great ignorance: alternative medicine. I can't say that I know enough about the supplements you mention to render a meaningful opinion, but I can make a couple comments.

We've found that medications that block platelet function (such as aspirin and Plavix) don't do a very good job of preventing stroke with AF. This is because the clots that form in the atrium of the heart are composed more of fibrin protein than platelet cells and the protein clotting pathway is what is specifically targeted by warfarin.

In modern medicine we have the advantage of being able to base our recommendations on the results of numerous well run research studies involving thousands of patients. In the area of stroke prevention in AF, the use of warfarin has been particularly well studied with what I consider conclusive results. Such peer-reviewed, large scale trials do not exist for alternative treatments of AF.

Finally, I long ago learned not to base my treatment recommendations too heavily on assumptions of how things work without going back to published research. As noted in a previous blog report of mine (http://blogalegent.com/Cardiology-Assumptions), medical history is full of therapies that seem to make perfect sense until they come under the microscope of scientific testing. This may explain why I and other "conventional" doctors fail to offer alternative therapies like the one you describe.

Thanks for your comments and your interest in this subject.

Dr. VDG

I am 29 and was diagnosed with DVT and PE slightly over a week ago. The doctors have run tons of blood tests and so far everything has come back normal. They are now attributing the clots in my legs and lungs to the birth control pills I was taking for 12 years. Its been a week and a new ct scan of my chest done just 2 days ago shows the smaller clots in the lower lobe of my lungs have already dissolved and no problems with my chest or lungs. I have to admit that although warfarin saved my life by preventing a catastrophic PE, I am incredibly nervous about the potential side effects. I am constantly anxious and nervous and find it difficult to sleep at night for fear of internal bleeding. I have had slight vaginal bleeding on and off when my INR was around 2.8. My last INR was 3.6 and my doctor took me of warfarin for 2 days and switched me from 5 ml a day dose to alternating between 2.5 and 5 each day until my next blood test this Friday. I have had a crackling mucous cough and post nasal drip since I was in the hospital and today I coughed up a small amount of blood and there is always a small amount of blood on the tissue when I blow my nose. I am concerned about this but have had several bleeding side effects from this medication so far and can't run to the emergency room every time I experience a side effect. I have no other symptoms or side effects and feel fine otherwise except for this cold and mucous cough with blood. I will notify my DR about the blood but I just need to know the risks of having a severe bleed at a relatively low INR being as young as I am and absent any injury. I find myself worrying more about the bleeding than this disease itself!! I want to ask my DR to take me off this medicine but I know that is so dangerous. Please help calm my nerves!!! I m petrified.

Lauren,

Let me take a crack at trying to figure out a way to alleviate some of your anxiety about the bleeding risk associated with warfarin.

Let's start with some background on your condition. Without knowing the details of your health history I'd have to guess that your risk of suffering another pulmonary embolism (PE) is moderately elevated (less so if you go off your contraceptive pill). Getting a PE is a really big deal--this is one disease that can easily kill a young healthy person. Thanfully, being on warfarin will cut the risk of PE by at least 82% (based on a metaanalysis of several large studies--and that's in old people who are at much higher risk of recurrent PE). The good news for you is that you will likely be able to quit warfarin after a prescribed period of time (3-6 months, or more depending on your health) and transition to aspirin alone.

So, you've got a health issue that's a problem (bad) but that can be treated (good) and prevented (better) with a medication that you'll ultimately be able to stop (much better).

Let's now take a look at the "worst case scenarios." What if you do develop bleeding? Coughing up a little blood with a sinus infection doesn't really fall into that category, but what if you develop a full-blown nose bleed (forgive the pun)? Well, according to my brother, an ENT surgeon who routinely comes into the ER to pack the noses of 90 year old patients with out of control INRs, no one dies from this problem. True, it can be a hassle to have your nose packed, but you'll live. Besides, we can quickly reverse the effects of warfarin with fresh frozen plasma and vitamin K. What about other bleeding sites? Uterine and gastrointestinal bleeding can also be easily stopped and the warfarin reversed.

The scariest of all is the intracranial hemorrhage, or bleed in the brain. Thankfully, the risk of that is so nearly close to zero in a 29-year-old patient that you stand a better chance of getting struck by lightning while out celebrating your lottery victory on a warm sunny day in Omaha in February. It just won't happen.

True, Lauren, your risk of easy bruising and bleeding from nicks and cuts is about 100% when you're on warfarin. But what's the risk of those things progressing to something more significant? About zilch as long as you remain compliant with the dosing your doctor recommends.

So, humor your doctor for a while and stay on the warfarin. Try not to worry about it and just be grateful that you are able to take a medication that is so effective at keeping you from having another PE and that you won't have to be on it forever.

Good luck, Lauren. I know you'll do fine.

Dr. VDG

Dr.Van De Graaff. Without any previous strokes,falls,etc,etc,what is the risk of a 'brain stroke' for a 86yr old woman taking coumadin. I have briefly read a few recent articles saying,there has been a significant increase of brain strokes in the elderly on coumadin. But they did not say whether this was due to previous strokes,falls,etc,etc. Or just from taking the drug. Also i do not believe in taking coumadin as a preventative for a-fib. Especially for a 86yr old. What is your take on this. Thanks for your time. Take care. Bill.

Bill,

Thanks for your question. Without knowing more details about the woman in question it would be tough to pin down an expected risk of stroke. Hypertension, heart failure, diabetes, and other problems will influence the risk of stroke with AF.

Let's just assume that your 86-year-old is perfectly healthy (except for the AF, that is). The risk of stroke for her would be 5% per year. In other words, follow 20 people just like her for one year and one of them will have a stroke. Doesn't seem that high in and of itself, but that's just one year. Over ten years nearly half will suffer a stroke. Remember, even in the absence of AF, stroke remains the number one cause of disability and the number two cause of death worldwide.

Now let's look at risk of cerebral hemorrhage (ICH). In those in this age range without warfarin, the risk of ICH is about 0.15% per year. Warfarin increases this risk to 0.3% to 0.5% per year. Therefore, in your patient with AF, the risk of stroke off warfarin is about 10 times higher than the risk of ICH on warfarin. The math really comes out in favor of treating these patients with warfarin.

I can understand that you would feel uncomfortable with the idea of a powerful blood thinner in an elderly lady (the idea gives me pause as well), but the numbers really argue in favor of treatment. We have decades of experience with millions of patients on which to base these recommendations and until something else better comes along warfarin remains our best protection against stroke.

Dr. VDG

i have had three leg DVTS since 1997. (two in one leg and one in the other). Was also diagonsed with bipolar disorder in 1995,at the age of 41. (I never believed I had bipolar disorder, but undiagnosed Graves Disease. I had thyroid removed 1n 2000. Since I am in my late 50's now, I am concerned about the extreme discoloration of my left leg, the tissue paper thinness of the skin, particularly close to my left ankle bone. I have been seeing a specialist since early spring, and he has told me that there are no surgical options available to me. He wrote a prescription for the surgical compressione hose, and when I see him again, he will exam and icrease the prescripion. I'm losing weight, but isn't there something called a green filter that might replace the coumadin. I am desparte. i don't want to be followed up in a wound care center, or worse facing partial amputations. Any suggestions

Janice,

Sounds like you've had a tough go of things. The discoloration you describe in your leg probably comes from the condition "chronic venous stasis" associated with your prior DVTs. The clots in the legs damaged the large veins and now the blood from your feet have to return through the smaller, higher-pressure veins in the legs. This results in chronic swelling and discoloration of the lower legs, but generally doesn’t lead to the need for amputation (that’s more of an arterial problem).

There are no really good options to treat this. The best options are these 4:

1. Compression stockings. The goal here is to keep the fluid in the blood from leaking out into the tissue of the legs. You're also helping the function of the veins by applying external pressure to promote flow back up the legs.
2. Gravity. Unlike the arterial system, the veins don't have a powerful pump (i.e. the heart) pushing blood through the system. The veins rely on the squeezing function of the calf muscles to "milk" the blood back up the legs. One way to help this along is to put gravity to work. The best way would be to dangle yourself "bat-like" upside down all day, an obviously impractical solution. Next best would be to keep your legs raised above the level of your heart whenever you're not up and around. Instead of sitting on the couch try lying on the floor with your legs up on the couch.
3. Exercise. As noted above, it’s the squeezing of the calf and leg muscles that send the blood from the feet up to the heart. The more squeezing, the better the flow. Exercise also stimulates the formation of better collateral veins in the legs and over time can permanently improve flow.
4. Weight loss. Janice, you didn’t tell me if you’re overweight or not, but we know that obesity puts additional pressure on the venous return from the legs. Another accompanying problem can be sleep apnea—if you suspect at all that you have this you should talk to your doctor—that can make leg swelling very difficult to treat.

You asked about a Greenfield filter. This is an umbrella-shaped device that is easily inserted into the inferior vena cava (the main vein in the abdomen that delivers blood from the lower half of the body to the heart) via a small puncture in the vein of the groin. It’s easy to have done and very low risk. The purpose is to catch and filter any clots that arise in the legs and travel toward the heart and lungs. It’s a reasonably good alternative for warfarin in patients who cannot tolerate or who do not want to take warfarin. Most of us prefer warfarin to the filter, but I’ll bet your doctor could be persuaded to at least consider it. The bad news is that the filter won’t make your legs any better—-it’s just meant to serve as another safety mechanism to prevent clots in the legs from become life-threatening clots in the lungs.

Finally, your comment title mentioned the interaction between Depakote and warfarin. This interaction doesn’t produce any untoward effect except for decreasing the amount of warfarin you need (by raising the relative effectiveness of warfarin) and whoever helps monitor your INR levels can easily accommodate for this interaction.

Good luck with all this.

Dr. VDG

My healthy 81 year old mother had knee replacement surgery. She got a blood clot three days later, then an infection in the surgical area, which lead to heavy antibiotics. She then got C-Diff. She is now home, taking 3 mg warfarin for the clot, and vancocin for the C-Diff, along with oxycodon for pain. She also still takes her levpthyroxine, lexapro and avalide that she's taken for years. She has very swollen legs and feet so the doctor put her on 40 mg furosemide along with Klor-Con M10 er tablets for her potassium levels. Her swelling has not gone down even slightly in the two days she's been on the furosemide. Should she be on something other than warfarin, which is the only med that I think could be causing this very significant swelling. Your advice would be greatly appreciated.

Chris,

It sounds like your mother has been through a lot lately. I doubt the warfarin is the culprit with her swollen legs and with recent surgery, a blood clot, and a debilitated state the warfarin is a potentially life-saving treatment for her. At this point there is no good alternative for this medication. Lasix decreases swelling only by making the kidneys produce more urine. In the case of your mother the swelling is probably due to more of anatomical obstruction (recent clot, recent surgery) than an overall excess of blood volume. In this instance I wouldn't expect to Lasix to have too much effect. The therapy of choice for her is time--time for veins to heal from the clot and for the swelling in the knee to resolve. As she heals and becomes more active the swelling will slowly diminish. In my experience many patients with knee replacements (and for that matter, patients with clots in their legs) often have some degree of edema that persists for years.

Please wish her good luck and we hope she's back on her feet soon. Thanks for the note.

Dr. VDG

I underwent 2 valve replacements 22 years ago,I was 32 years old at the time. I quickly went back into a-fib and have been on Coumadin for the full 22 years. I am also a nurse and have a patient with a similar situation. We both check our INRs regularly. My question is this, I am aware that both of us will need to be anticoagulated for the rest of our lives (our valves are mechanical), but are there any current studies for a drug that won't need to be monitored as frequently?
Thank You

Good question, Cindy. I have a good answer, but not one that will help you very much. There is a new class of medications that blocks thrombin directly and is therefore easier to dose and much more predictable in its effect. This class includes a drug called dabigatran that has been successfully studied in people with atrial fibrillation and deep venous thrombosis. Despite the fact that I was one of the primary investigators for dabigatran among patients with atrial fibrillation I have no inside knowledge about if or when the FDA will approve this medication for use in the United States.

Even if it does get approved, however, dabigatran (and others like it) will likely not replace warfarin in patients like you who have mechanical valves--the risk of stroke in these patients is simply too high. At some point, once the direct thrombin inhibitors have become commonplace, someone will launch a research study that involves patients with metal valves, but that will probably not come for many years.

So, Cindy, don't hold your breath--you'll need to be on warfarin for a while still.

Dr. VDG