Safety and Efficacy First

From the meeting of the FDA Cardiovascular and Renal Drugs Advisory Committee, Adelphi, Md. 

Like cost-effectiveness, convenience is on the list of topics that cannot be taken into account when a Food and Drug Administration advisory panel decides whether or not to recommend approval of a drug. But for the oral anticoagulant rivaroxaban, under review for the prevention of deep vein thromboses and pulmonary emboli in patients who have had hip or knee replacement surgery, the topic was hard to avoid during extensive discussion of the drug’s risks and benefits. That’s because, if approved, rivaroxaban would be the first oral anticoagulant to become available since warfarin was approved over 40 years ago. And unlike warfarin, rivaroxaban is not titrated and patients on the drug do not need regular blood draws to check INR.

Panel members commented that if approved rivaroxaban could help improve compliance with the American College of Chest Physicians and American Academy of Orthopedic Surgeon guidelines for prophylaxis of DVT and PE after hip and knee surgery, and that having an oral option would be a significant advantage.

But Dr. Richard Pazdur, director of the FDA office of oncology drug products, reminded panelists that safety and efficacy of a drug should come first, then convenience can be discussed. “It’s not about convenience, it’s about safety and efficacy that has to be demonstrated first, then a discussion of convenience can be entertained,” he said. If convenience was considered over uncertainty over safety, the FDA would “simply approve more convenient toxic placebos.”

Most of the panel supported approval, despite reservations about more cases of excess bleeding and elevated liver enzymes in patients treated with the drug in trials than in patients on enoxaparin. But they agreed that the benefits exceeded those potential risks, and recommended that the potential for severe hepatotoxicity be followed closely.

Panel members also expressed concern that once the drug becomes available, clinicians would prescribe it off-label for periods longer than the short-term use studied in the trials (35 days after hip surgery and 14 days after a hip replacement).

The FDA’s deadline for an approval decision is May 28 and approval is likely, since the FDA usually follows the advice of its advisory panels.

Pharma giant Johnson & Johnson also is studying rivaroxaban for indications that will be treated for extended periods of time (including acute coronary syndromes and secondary prevention of DVT/PE) and those studies are expected to provide more useful data about the potential hepatoxicity issue.

—Elizabeth Mechcatie
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Filed under Cardiovascular Medicine, Hospital and Critical Care Medicine, Orthopedic Surgery, Surgery

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