Consensus recommendations for the off-label use of recombinant human factor VIIa (NovoSeven®) therapy

Objective: To rationalize decision-making concerning the growing and costly off-label use of recombinant human factor VII (rFVIIa, NovoSeven®) therapy. Options: Using rFVIIa therapy for patients with bleeding or providing usual care (e.g., continued clotting factor replacement). Outcome: Morbidity and mortality related to continued bleeding or thrombosis. Evidence: A literature review was performed to assess the efficacy and safety of off-label rFVIIa therapy. An expert consensus panel reviewed the data. Most studies were case series or reports. Only four randomized trials were available in the peer-reviewed literature at the time of the panel's deliberations. The Rand Corporation/University of California at Los Angeles Appropriateness Method was used to rate 41 clinical scenarios as "appropriate," "uncertain," or "inappropriate" in a comparison of risks and benefits in an environment with constrained health care costs. Values: The panel comprised nine geographically diverse clinicians to represent the interests of clinical specialties, including anesthesiology/critical care, surgery, transfusion medicine/hematology, pharmacy, neurology/critical care, and practice environments. Benefits, Harms, and Costs: The panel's recommendations are expected to limit the use of rFVIIa to the most appropriate circumstances, thus minimizing associated risks and costs. These suggestions should be considered consistent with the quality and quantity of the available evidence and should be adjusted as new evidence emerges. Recommendations: The panel rated the use of rFVIIa as "appropriate" in limited circumstances: (1) cardiac, thoracic aortic, or spinal surgery; hepatic resection; hysterectomy; or postpartum bleeding (when significant clotting factor replacement has failed); (2) for severe multiple trauma (only if surgery and substantial blood replacement are unsuccessful); and (3) for nontraumatic intracranial bleeding (only if less than four hours has elapsed since symptom onset or if traumatic bleeding is associated with anticoagulant use and hematoma expansion). Doses of 20 to 40 mcg/kg were recommended for non-emergent anticoagulant reversal. Doses of 41 to 90 mcg/kg were recommended for all other scenarios.