Patient Education Blog

Pradaxa approval – Great news!

Summary

The new oral “blood thinner” Pradaxa® (=Dabigatran) was approved by the FDA on October 20th, 2010 (ref 1 and 2). This is huge news! This is the first oral blood thinner alternative to warfarin (=Coumadin®, Jantoven®). At this point, Pradaxa® is only FDA approved for use in patients with irregular heart beat (= atrial fibrillation = a. fib). It is not approved yet for patients with DVT and PE.

The Drug’s Advantages

Pradaxa® is one of a group of new blood thinners that have several advantages over warfarin:

  1. They do not need blood monitoring, because they have a predictable blood thinning effect (i.e. one dose fits all; no more INR checks needed!);
  2. They do not interact with vitamin K in the food (so people can eat what they want!);
  3. They have less drug interactions than warfarin (so taking other drugs, for example antibiotics, does not throw off the blood levels of these new blood thinners and, thus, does not influence their effectiveness and safety);
  4. They are fully active within 2-3 hours of taking the first dose (so one does not need to give heparin or other blood thinners by injection in the first few days when starting these new oral drugs);
  5. They are quickly (within 24-36 hours) out of the blood system (so it is easy to stop them shortly before surgeries or other procedures – such as colonoscopy – without the need to bridge with injectable blood thinners).

The other promising drugs in this new group of blood thinners are Rivaroxaban (Xarelto®), Apixaban, Edoxaban, and others). Xarelto is also approved for atrial fibrillation, but neither for DVT and PE treatment. Apixaban and Edoxaban are not FDA approved at this point.

The Key Clinical Trials

The key a. fib trial(ref 3)  showed that Dabigatran in the dose approved (150 mg twice daily) was more effective than warfarin in preventing stroke, and equally safe. The key DVT and PE trial (ref 4; RECOVER I trial) showed that Dabigatran (150 mg twice daily) taken for at least 6 months after a diagnosis of DVT or PE was as effective and equally safe as warfarin. In Dec 2011 another big Pradaxa study in patients with DVT and PE (RECOVER II trial) was presented in abstract form at a medical meeting (Am Society of Hematology), but the study has not  been published yet in a peer review journal. I do not know whether the company making Dabigatran has yet applied for FDA approval for the use in DVT and PE. But I expect that we will hear more about this in the next few months, now that the 2nd big DVT/PE trial has been completed.

Cost of the Drug

As of November 1st, 2010, Pradaxa® is on the market and available at pharmacies. The monthly retail pharmacy price is approximately between $ 170 and $ 270.  However, what the cost to the individual customer/patient is depends on his/her insurance plan and copay. Each patient considering Pradaxa® should inquire with his/her insurance what his/her cost will be.

Personal Comment

Would I prescribe Pradaxa® off label for patients with DVT and PE, even though it is not yet FDA approved for that indication? I would not rush into it, but would prefer to wait to see what FDA decides on the DVT and PE indication, after review of all the DVT and PE data. However, if a patient poorly tolerates warfarin, has very fluctuating INRs, has a strong preference to switch away from warfarin, I would discuss  a switch to Pradaxa® even now. And,  if the patient is fully educated, understands that we would be using the drug in a non-FDA approved indication, and still wants to change, I would consider prescribing it for DVT and/or PE. However, my general preference would be to see clinical experience with the drug gained in the approved indication, before I would use it off label. Based on the very promising and convincing DVT and PE phase 3 study data, I expect that the drug will also soon be approved for DVT and PE treatment. Thus, it may be available for DVT and PE treatment within a year or so.

References:

1.     FDA Dabigatran approval information here

2.     FDA Dabigatran medication guide here

3.     The key a. fib trial: Wallentin L et al. Lancet. 2010 Sep 18;376(9745):975-83.

4.     The key DVT and PE trial (RECOVER I): Schulman S et al. N Engl J Med. 2009 Dec 10;361(24):2342-52.

5.     Most recent 2nd large DVT and PE trial (RECOVER II): Schulman S et al. Blood 2011;118:95 (abstract # 205).

Support Forum:  Questions or comments about Pradaxa and its use? Go to the online Clot Connect Support Forum, category “Anticoagulant Use (Blood Thinners)”.

For health care professionals:  This same information, written for health care professionals,  is available here.

Disclosure:  I have no financial conflict of interest relevant to this blog entry.

Last updated: Feb 3rd, 2012

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6 Responses to “Pradaxa approval – Great news!”

  1. Betty Carpenter says:

    To what extent are you concerned that it seems there is no antidote for this new medication?

    • Stephan Moll says:

      I am somewhat concerned that (a) no reversal agent is available for the new oral anticoagulants and that (b) no reversal strategies (backed up by clinical study data) for these drugs, particularly the FDA-approved Pradaxa® (Dabigatran), have yet been published in peer reviewed journals. It is key that the companies making these drugs and clinical investigators produce and publish data in peer-reviewed journals indicating how reversal of bleeding on these drugs can be handled effectively.

      In the event of bleeding complications in patients receiving Pradaxa®, management should, of course, be individualized according to the severity and location of the bleed. In the absence of data in humans we don’t know how to best manage a patient with major and life-threatening bleeding on Pradaxa®. Treatment options are: (a) charcoal to prevent residual drug in the stomach to be absorbed, (b) recombinant factor VIIa (NovoSeven®) intravenously, (c) prothrombin complex concentrates (PCCs; in the U.S.: Bebulin®, Profilnine®) intravenously with or without additional fresh frozen plasma (FFP), (d) activated prothrombin complex concentrates (aPCCs; FEIBA®) intravenously. (e) One could also consider the patient for one session of hemodialysis trying to get Pradaxa® out of the blood system. A lot of additional data are still needed to know how to best handle major bleeding on Pradaxa®.

      Personal Approach
      At this point, not knowing what the most effective and safest treatment is, I would likely give the patient who has a life-threatening bleed on Pradaxa®: (a) charcoal to prevent residual drug in the stomach to be absorbed, and (b) recombinant factor VIIa or a prothrombin complex concentrate (PCC) to try to reverse the drug effect.

      References
      1. van Ryn J. Dabigatran etexilate – a novel, reversible, oral direct thrombin inhibitor: Interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost 2010; 103: 1116–1127.
      2. Crowther MA. Managing bleeding in anticoagulated patients with a focus on novel therapeutic agents. J Thromb Haemost 2009; 7 (Suppl 1):107–110.

    • Stephan Moll says:

      It is legal to prescribe non FDA-approved drugs. It is very commonly done in a variety of diseases and with a number of different medications. Of course, there should be a detailed discussion with the patient; particularly when it comes to a drug that is new, and there is relatively little “real world” experience with the drug outside of clinical trials.

  2. Lorrie says:

    I am wondering if any new information regarding Pradaxa being used in patients with PE/DVTs has been released. In the past I have had both PE and DVTs on Coumandin. I am presently on Lovenox. But my doctor is considering switching me to Pradaxa. Thank you in advance for any information on this matter.

    Sincerely,
    Lorrie

    • Stephan Moll says:

      A large second DVT and PE trial (RECOVER II) was presented as an abstract in Dec 2011 at the annual meeting of the Am Soc Hematology (Schulman S et al. Blood 2011;118:95;abstract #205), but has not been published yet in a peer review journal. RECOVER II also showed that Dabigatran (150 mg twice daily) taken for at least 6 months after a diagnosis of DVT or PE was as effective and equally safe as warfarin. That is good news for people considering off label use of Pradaxa in DVT and PE. The blog post on Pradaxa has been updated. I expect that we will hear in the next few months from the FDA regarding approval of Pradaxa for DVT and PE – yes/no.