A Clearinghouse for Information about Blood Clots (DVT/)PE) and Clotting Disorders (thrombophilia) provided as a public service by the University of North Carolina Blood Research Center

Pradaxa Approval – Great News!

The new oral anticoagulant Pradaxa® (Dabigatran) was approved by the FDA on October 20th, 2010 [ref 1,2]. As of Feb 3rd, 2012, Pradaxa® is only FDA approved for use in patients with atrial fibrillation. It is not approved yet for patients with DVT and PE.

The Drug’s Advantages

Pradaxa® is one of a group of new oral anticoagulants that have several advantages over warfarin:

  1. They do not need blood anticoagulant monitoring, because they have a predictable anticoagulant effect (i.e. one dose fits all; no more INR checks needed!);
  2. They do not interact with vitamin K in the food (so patients can eat what they want!);
  3. They have less drug interactions than warfarin (so taking other drugs, such as antibiotics, does not throw off the blood levels of these new anticoagulants 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 bridge with parenteral anticoagulants in the first few days when starting these new drugs);
  5. They have a short half-life, so they are quickly (within 24-36 hours) out of the system (so it is easy to stop them shortly before surgeries or other procedures – such as colonoscopy – without the need to bridge with injectable anticoagulants).

The other promising drugs in this new group of anticoagulants are Rivaroxaban (Xarelto®), Apixaban, Edoxaban, and others), none of which is FDA approved yet.

The Key Clinical Trials

The key atrial fibrillation trial [ref 3]  showed that Dabigatran in the dose approved (150 mg twice daily) was more effective than warfarin in preventing stroke, and was equally safe. The key DVT and PE trial [ref 4] 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.  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 (ref 5), but has not been published 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. I do not know whether the company making Dabigatran, Boehringer-Ingelheim,  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.

Cost of the Drug

As of November 1st, 2010, Pradaxa® is on the market and available at pharmacies. The monthly retail pharmacy price is between approximately $ 170 and $ 270.  However, what the cost to the individual customer/patient is depends, of course, 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® (or Xarelto®)  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:http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails

2.     FDA Dabigatran medication guide:http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022512s000MedGuide.pdf

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

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

5.     A second large phase 3 key DVT and PE trial: Schulman S et al. Blood 2011;118:95(abstract #205).

For Patients

This same information, written for patients and other non-health care professionals, is available at https://clotconnect.wordpress.com/2010/10/27/dabigatran-approval-–-great-news/

Disclosure: I have no relevant conflicts of interest regarding this post.

Last Updated: Feb 3rd, 2012

Clot Connect

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11 responses to “Pradaxa Approval – Great News!”

  1. My patient Has a metallic mitral valve sinus rhythm and recurrent strokes while on Coumadin and Plavix with left atrial sessile clot, can I use Pradaxa?

    • This is a complex patient with a strong clotting history. For a full assessment I would want to know a lot more details, including at what INR levels the recurrent strokes and the atrial clot occured.

      We do not know whether Pradaxa would be more effective than warfarin in this situation, particularly if a higher target INR was aimed for with warfarin. My own preference at this point: in such a complex/fragile/difficult patient I would rather work with an anticoagulant that I am well familiar with, that I can monitor, and which I can dose adjust to achieve a higher level of anticoagulation, i.e. a higher target INR (e.g. 3.0-4.0), rather than using a fixed-dose drug that I can not monitor.

  2. I am an oral surgeon and although I have not yet encountered a patient on Pradaxa, I would like to be prepared in advance to know what to do with these patients should they need a tooth extraction or other minor oral surgery procedure. I know that INR testing is of no benefit here. The question is while we currently do minor procedures on patients still on coumadin with INR under 3.0, is it safe to do minor procedures on these patients? It seems easy to stop the Pradaxa one day before, do the surgery and then start them back up once bleeding has stopped but I assume during that time period they have increased stroke risk. Any thoughts?

  4. Extended LMWH therapy is another option for patients with VTE in whom warfarin is problematic. As far as I know, it has been tested vs. warfarin only in cancer patients and for only six months, but the LMWH was found to be superior. It isn’t a huge stretch to use it for non cancer patients, though Pradaxa likely is preferable in most situations now that it is available.

    • The cost of Pradaxa to an individual patient depends on the patient’s insurance plan and reimbursement / copay policy. The monthly cost of Pradaxa may be less to a patient, if the copay arrangements are low, than the cost to a patient of Anticoagulation Clinic visits, if the copay for such visits is high – particularly if the patient’s INR is unstable and 2 or more Anticoagulation Clinic visits per months are needed. Thus, the individual considering Pradaxa, should inquire with his/her insurance carrier as to what the actual cost to him/her would be.

  6. “They are fully active within 2-3 hours of taking the first dose (so one does not need to bridge with parenteral anticoagulants in the first few days when starting these new drugs)”. Is there data available to confirm this? Has Boehringer Ingelheim made a statement that bridging isn’t necessary? If so, could you forward that information?

    • The pharmacokinetic data are available (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). As the parenteral anticoagulants, such as LMWH and Fondaparinux reach their peak activity 3-4 hours after injection, it would not make sense to think that they are needed as bridging therapy when starting a drug, like Pradaxa, that reaches its peak activity 2-3 hours after intake.

  8. […] Switch to Pradaxa®: One could consider switching the patient from warfarin to one of the injectable anticoagulants or to the new oral anticoagulant Pradaxa® (Dabigatran). While Pradaxa® is not approved for DVT and PE treatment at this point (Jan 28th, 2011), it is approved and available for the treatment of atrial fibrillation.  It has been studied in the treatment of DVT and PE and was found to be equally effective and safe as warfarin [ref 3].  I expect that the FDA may approve it within the next 12 months for the DVT and PE indication.  A detailed discussion on this topic is found in the Clot Connect bloghttp://clotconnectmd.wordpress.com/2010/11/23/pradaxa-approval-great-news/ […]