FDA approves Pradaxa to treat DVT, PE

Stephan Moll, MD

On April 7, the FDA approved dabigatran for the treatment of venous thromboembolism based on the results of the phase 3 RECOVER and RECOVER II trials. The approved dose is 150 mg twice daily for patients with a creatinine clearance >30 mL/min.

A main caveat is that, for patients with acute VTE, the drug is approved only to be used after 5 to 10 days of initial parenteral anticoagulation based on the phase 3 clinical trial designs. The same caveat will, by the way, apply to edoxaban (Savaysa, Daiichi Sankyo) if/when it becomes FDA approved for the treatment of VTE (see Table). This need for an initial parenteral anticoagulant for the first 5 to 10 days before the oral anticoagulant drug is started is, obviously, a major disadvantage, as it complicates the anticoagulant management: The patient needs to learn how to inject low–molecular-weight heparin (LMWH) and has the expense of the costly LMWHs before being switched to the new oral anticoagulant.

Rivaroxaban (Xarelto, Janssen) and apixaban [Eliquis; Bristol-Myers Squibb, Pfizer (FDA approval status pending, see Table)] do not have this limitation. They were used immediately upon the diagnosis of VTE in the phase 3 acute VTE treatment trials, without the need for initial LMWH therapy, giving them a clear advantage in the management of acute VTE over dabigatran and edoxaban. As for the long-term secondary prevention of VTE, dabigatran is also not an attractive treatment option in this situation because of its twice-daily dosing schedule (many patients prefer a once-daily dosing regimen); high renal drug clearance and, thus, its dependence on renal function; and very wide range of inter-individual drug half-life, even in patients with normal renal function, making it impossible to know when prior to surgeries or procedures to stop the drug for effective hemostasis.

Thus, although this FDA approval is noteworthy, dabigatran is not an attractive option for VTE treatment for the patient and clinician when other, more convenient options are available, such as rivaroxaban at the moment and apixaban once/if it becomes FDA approved for VTE treatment. The only time I would see dabigatran as an option is if there is a financial advantage of the drug to the patient — ie, if it is treated preferentially by an insurance plan and a patient has less of a copay for dabigatran than for another one of the new oral anticoagulants — specifically rivaroxaban and, if/once FDA approved, apixaban. Finally, it is always good to have choices, even if it is only to keep drug prices down when competition exists. Thus, the approval of dabigatran is a welcome addition to our VTE treatment options.