Pradaxa, generic name dibigatron, has the potential to change the way we manage atrial fibrillation to prevent stroke. Stroke is one of the most feared medical problems for many patients, and atrial fibrillation is one of the biggest risk factors for stroke. Stroke is the third leading cause of death in the U.S. and the leading cause of long term disability. Having atrial fibrillation increases a person’s risk of having a stroke about five fold and is the cause of 15-20% of strokes in America, over 100,000 strokes a year. Most patients with atrial fibrillation are candidates for long-term anticoagulation, and until Pradaxa was approved by the FDA in October, 2010 patients were either treated with oral warfarin, injectable low molecular weight heparin, or with less effective anti-platelet medications like aspirin.
Warfarin has been the choice of most physicians and patients for prevention of stroke in patients with atrial fibrillation because it works well. The annual risk of stroke in patients with atrial fibrillation is 4.5% without warfarin anticoagulation, and 1.4% with warfarin treatment. This risk varies a great deal from individual to individual depending on associated risk factors like coexisting hypertension, diabetes, congestive heart failure, prior TIA or stroke and age over 75. A scoring algorithm called the CHADS2 score is often used to better assess an individual’s risk. For most patients the absolute reduction in risk of stroke is high enough that most physicians have encouraged most of their atrial fibrillation patients to take warfarin. Warfarin therapy is no small undertaking though and has very significant bleeding risks. Several major problems are involved with use of warfarin as an anticoagulant:
- A patient has to wait several days for the anticoagulation effects of warfarin to take effect. During this time the patient needs to be tested frequently, sometimes daily, to assess whether the prescribed dose of warfarin is just right.
- It often takes one to several weeks to get the dose just right. Then after the INR is just right they will still need monthly blood tests to assure they remain adequately but not overly anticoagulated. If this sounds like a big hassle and expense you are very perceptive. It is.
- Many drugs interfere with warfarin metabolism and so drug interactions are notoriously difficult to manage in patients on warfarin.
- Because Warfarin is a vitamin K antagonist dietary variation in vitamin K content can have a significant effect on the anticoagulation effect of warfarin.
- The therapeutic window for warfarin dosage is quite narrow, meaning the difference in dose between not enough and too much can be quite small. It is very difficult to predict what dose an individual patient will need.
Pradaxa is approved by the FDA for treatment of atrial fibrillation at a single fixed dose for most patients. It is dosed at 150 mg twice daily, and is effective within hours of taking the first dose. It works at least as well as warfarin to prevent stroke in patients with non-valvular atrial fibrillation, and overall the Pradaxa side effects profile is generally lower than with warfarin. In addition Pradaxa has far fewer drug interactions than warfarin which is notoriously affected by both diet changes and innumerable other medications. Bleeding risks with Pradaxa seem to be about the same overall as with warfarin. There may be a minimally lower risk of major cerebral hemorrhage and a higher risk of gastrointestinal bleeding with Pradaxa vs. warfarin.
The big issue holding back the widespread use of Pradaxa seems to be its cost. In a recent cost effectiveness analysis in the Annals of Internal Medicine for use in patients age >65 with non-valvular heart disease, assuming a daily cost of Pradaxa at $13.60 the conclusion was that Pradaxa has incrememtally higher costs and incrementally higher added years of life. Currently Pradaxa costs $230./ 60 doses , ie. 30 days supply or $7.66/day at Costco.com. With this lower cost than assumed in the study it seems like Pradaxa may win in the cost effective analysis.
I believe this study takes into consideration the lower risk of cerebral hemorrhage complications that can often lead to very expensive hospitalizations and long term nursing home care with Pradaxa. When I talk with other physicians they generally tell me that they would rather deal with GI bleeding, which is slightly more common with Pradaxa, than with intracranial bleeding which is slightly more common with warfarin. I’ll be interested to see more post marketing cost analysis comparisons as they become available, and to see how many patients are switched from warfarin to Pradaxa, and how many new patients are started on each of these medications.
I will not be surprised if as more physicians gain experience with Pradaxa, and more cost analysis is done, that Pradaxa will become the standard of care for treatment of atrial fibrillation for stroke prevention in patients at high enough risk of stroke to warrant the risks of therapy.
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A potential side effect of Pradaxa is dizziness & weakness. What causes this? Is it a drop in blood pressure?
Karen: In the U.S. Pradaxa has been approved for stroke prevention in atrial fibrillation, not for lower extremity deep vein thrombosis and pulmonary embolus, so I cannot say much about the lung blood clots. After pulmonary emboli from DVT the clots persist for some time, just the anticoagulant line warfarin is designed to prevent new clots, not dissolve the existing ones. Not sure if this helps. .DrP.
My mother is being switched from warfarin to pradaxa. My concern is whether or not pradaxa is useful for keeping bloodclots at bay. She started on warfarin 2 1/2 years ago due to clots in her lungs. A recent trip to the ER revealed that she still has the clots, just reduced in size. This came as a surprise since we had been under the impression that the clots had been eradicated.
Nancy: There is not felt to be a benefit to checking the INR while on Pradaxa. The studies all used it at fixed doses and showed efficacy. DrP.
Is there any value to doing a PT/INR to see if Pradax is working?
Dr. Pullen,
My dad is 63 years old, recently diagnosed with AFIB and placed on Pradaxa. He is c/o weakness while on this drug. He has been on it now for a month. I am concerned because I work in a hospital where a patient came with GI Bleeding and HGB of 3.1! She had started on Pradaxa a little over a month ago. This is very disturbing especially since there are no “Real” labs to do or “Antidote” for this medication.
Christine: The studies that I have seen show a somewhat higher incidence of gastrointestinal bleeding with Pradaxa vs. Warfarin. Discuss this option with your physician, but it does not look like Pradaxa is a better choice from what you have stated here. DrP.
I have been taking warfarin for many years due to recurring blood clots (deep vein thrombosis.) I have also developed a severe form of gastritis, which is dangerous due to bleeding issues. Would Pradaxa be safer on my stomach than Warfarin? I am convinced that my stomach problems began with the introduction of warfarin. Until then, I had never had stomach problems: pain, nausea, lack of digestion and absorption.
Thank you very much.
Mensik: You need to discuss this with your physician. DrP.
I have had atrial fibrillation for last 9 years,3 days ago I got a stroke,I am on Pradaxa now.Is it possible that taking 3 tabs of Atasol30 could have caused stroke? Six days ago I had a small accident not serious but very painfull.
Dr. Pullen
I nad a kidney removed in June 2006,Would only having one kidney stop me from taking Pradaxa
Regards
Brian
Rita T: If by “good” results you mean what is the theraputic range for INR then it varies depending on the situation, either 2.- 3.0 for most patitents, to 2.5 – 3.5 in patients at higher risk of clot formation like those with some types of artificial valves. You need to consult the physician caring for the patient to see what the is goal for an individual patient.
Hi Dr P, Greetings from Cape Town South Africa …. my dad has just been put on Warfarin and has been doing regular INR tests to check the dosage. What is a “good” result for INR test? Am going to check with his cardiologist whether Pradaxa or something similar is available in SA. Thank you & kind regards !
Lee: An issue like this is for you to discuss with your doctor.
I have afib having had two heart ablations. How concerned should I be over blood in my stool while taking 150 mg of Pradaxa, twice daily? I’ve had five instances of bleeding in the last three weeks. Have been on Pradaxa for six weeks. Never experienced this problem with Warfarin. Had a colonoscopy two weeks ago with everything clear.
Charles: A novel thought. I know of no data to base an opinion on. I think it depends upon your feelings about the idea and your physicians knowledge and experience.
I have paroxysmal atrial fibrillation. It occurs about every 60 days lasting around 24 hrs. My CHADS score is 0 and I’m taking a 325 aspirin daily. My doctor suggested using Pradaxa but only during an episode. It will act within a few hours and provide better stroke protection then aspirin after that. Take a pill when the episode starts and continue for 3 days. Because it will take several hours to take effect this plan is not as good as continuous use but avoids the downsides of continuous use. What do you think of this plan and do you see any downsides?
True but the half life is short and the wait is almost as the time to reverse warfarin.
The major concern with pradaxa is that its effects cannot be reversed. So that means if the dose is too much for your body to handle, you will just have to accept the bleeding.
Otherwise, this drug is superior to warfarin in my opinion.
Pam: You can discuss this with your doctor but at this time the only FDA indication for pradaxa is stroke prevention in non-valvular atrial fibrillation.
My daughter is 21 and has been on Coumadin for 7-8 years. She had a blood clot (kidney) due to APS (Antiphospholipid Antibody Syndrome). Would Pradaxa be suitable for her to try?
Thank you,
Pam
John Bott: Pradaxa is not FDA approved for valvular heart disease at this time.
My wife has a St. Jude Aorta valve and is on warfarin for the rest of her life. Can Pradaxa be used for mechanical valve patients? Is there any testing being done for all the ‘other’ patients using warfarin? Warfarin is dirt cheap at The-Mart but pro-time tests are not.
Daniel: Warfarin is a drug that requires very careful monitoring, i.e. getting the regular INR checks etc, and unless you are able and willing to get these checks some physicians would not prescribe warfarin to you as the risk of bleeding is just too high. I have not seen seizures from warfarin and seizures are not listed in the prescriber’s guidelines that I can see, but nearly any side effect is possible with any medication. You need to see your physician and anti-coagulation clinic regularly.
A question???…I am 65yrs & have never been suspect to having epilepsy but due to heart surgery 16years ago i am on ‘warfarin’ 4ever and a month ago i had a few ‘seizures’apparently due to incorrect warfarin dosages where i self-medicated which i shouldnt have & never had my monthly INR checks???…they seem to think i had ‘epileptic fits’and prescribed ‘EPILIM’to prevent a seizure occurring???…I firmly believe i had these seizures because of incorrect warfarin dosages and not epilepsy???..yr comments pls****
jjim bear – The dose of Pradaxa is generally fixed, not dependent on the coumadin dose. For most people it is the 150 mg twice daily, though there exceptions and I cannot tell you specifically for yourself, you need to consult your physician to see if it is an option for you.
currently taking 22 mgs a week of coumadin, INR check every 2 months with results at 2.2 ! what would dosage be with pradaxa ?!
The cost difference has everything to do with our system of patents and contract differences and nothing to do with the dosing difference. I cannot comment on the dose difference except to say that the best overall results in the studies I read were with the higher dose. The reason Canadians can buy the drug for less may be that the Canadian government single payer system can negotiate aggressively for better prices from all of pharma due to there being no other buyer in the country. It is safe to say that the manufacturer is not selling their drug to the Canadian health care system at a loss, so they are making a profit. I’d love a reply from you to let me know if your are buying the drug through the Canadian Health care system or outside the system. If it is outside the system and the $4.89/day is the full cost then we Americans are truly being ripped off again by pharma. It is common practice for companies to charge less for branded drugs in other countries than they charge in the U.S.
I live in Canada (where it’s called ‘Pradax’), and just started taking it today at a dose of 110 mg twice daily. In addition to the dosage difference, the difference in cost is staggering – I am paying $CDN 4.89 per day, close to half the quoted Costco cost. Am I at greater risk with the lower dosage. The almost 50% reduction cannot be due to the strength alone??
Comments, and many thanks.
Jamie
Vitamin K obviously will not reverse the anticoagulation, but one advantage of pradaxa in this regards is that the pradaxa effect only lasts about 24 hours. — DrP
If you go to the ER with a bleed while on Pradaxa, what can be given to reverse the effects. With coumadin you can be given vitamin K, correct?
I’m not aware of a specific restriction, but drinking enough to put you at risk for gastritis and bleeding, or of falls and injury would of course be concerns. — DrP
Are alcohol beverages restricted with Pradaxa? If so, to what extent?
No regular testing needed. That’s one of the big advantages of Pradaxa.– DrP
I have a-fib and I am just starting on Pradaxa to avoid the interactions I was having with Warfarin. Is there a need for regular blood checks like I had when taking warfarin?
Just wondering if Pradaxa will be approved by the VA someday (over- looking the cost factor) as a replacement for warfarin which I’m not at all pleased to take everyday.
There is nothing you might think of as natural that has the anticoagulant effects like warfarin or Pradaxa.
Just had the procedure cardioversion for an a-fib episode. Put on Pradaxa for thirty days and not happy about having to take this medication with so many possible side effects. Are the any natural supplements that would do the same thing that Pradaxa does. Please advise. Thank you.
Will do, thank you for your comment
I cannot answer this because there are so many other variables. The potassium and the Pradaxa are essentially unrelated to there must be other meds or issues. You need to ask your doctor.
Interested to know whether it is safe to be taking Potassium Chloride once daily, two tablets, strength 600mg per tablet with Pradaxa, dose 110mg tablet twice daily?
As is my usual response to individual medical advice on this blog, you need to discuss this issue with your physician. That said if a patient has normal renal function, and normal liver function the dose of Pradaxa is the same for everyone as approved by the FDA, 150 mg twice daily. Pradaxa is for atrial fibillation only, not DVT or other indications for anticoagulation, and is not approved for those with valvular heart disease. It is up to you and your doctor to decide if pradaxa is indicated and appropriate for you. Some 81 year old patients are at too high risk for bleeding from falls, GI issues, or other reasons to use either Pradaxa or warfarin.
What would the dosage be for pradaxa fro a 81 year old who is on coumarin with a fib ?
Not that I’m aware of as it acts directly rather than by blocking the vitamin K dependent liver process of making clotting factors which are much more sensitive to what you eat.
With coumadin there are foods that are contraindicated. Are there any such contraindications for Pradaxa?
I anticipate yes.
Will pradaxa be covered by medicare prescription insuranse in the near future
Pat, Note I looked into cost issues more and found a recent cost analysis in the Annals of Int. Medicine that suggests that Pradaxa is a cost effective option, and it assumes costs higher than costs may really be at this time.
The costs were very rough. Pradaxa is not indicated for treatment or prevention of blood clots in the legs or for pulmonary embolus therapy. (yet) Also not for stroke prevention with valvular heart disease. Still a-fib is very common. As I mentioned I look forward to a formal cost analysis by those more skilled at that than me.
This drug sounds quite promising for the indicated illness. Are the cost comparisons actually accurate? I take Warfarin for a prior blood clot in my leg, DVT if you will, and I know the INR test is quick but more like $130.00 per visit before insurance deductions etc. So this would make the case to use Pradaxa even stronger.
Is Pradaxa a substitute drug for other uses of Warfarin? For instance in cases where Warfarin is used as a therapeutic to prevent blood clots etc in other parts of the body??
Regards,
Pat