Guidelines for the Institutional Use of Factor VIIa (Recombinant)
Recombinant activated factor seven (VIIa) is a vitamin K-dependent glycoprotein that is structurally similar to human plasma-derived factor VIIa. It has received approval from the Food and Drug Administration (FDA) for the treatment of bleeding episodes in patients with hemophilia A or B who have developed inhibitors to factor VIII or factor IX, respectively. It promotes hemostasis by activating the coagulation cascade. Complexing with tissue factor at the site of vascular injury, recombinant factor VIIa cleaves factor X to the enzyme-activated factor X. Factor X promotes the conversion of prothrombin to thrombin and of fibrinogen to fibrin, leading to the formation of a hemostatic plug.
Factor VIIa (recombinant) has been primarily used in the treatment of bleeding episodes in hemophiliac patients with inhibitors to factor VIII or IX and patients with acquired he-mophilia due to auto-antibodies. The current recommended dose of factor VIIa (recombinant) in the treatment of bleeding episodes in these patients is 90 µg/kg i.v. In this population, factor VIIa (recombinant) has been associated with adverse thromboembolic events, including myocardial infarction, cerebrovascular infarct, venous thrombosis, and disseminated intravascular coagulopathy (DIC).
However, the medical literature provides anecdotal reports of factor VIIa (recombinant) use for a growing list of unlabeled indications, including the reversal of warfarin toxicity, treatment of pediatric patients with coagulation dysfunction, and treatment of patients with coagulation disorders caused by hepatic disease. One randomized controlled trial found that factor VIIa (recombinant) reduced blood loss and blood-product requirements in patients undergoing high-risk surgical procedures, and another revealed that factor VIIa (recombinant) controlled the bleeding associated with intracerebral hemorrhage (ICH). Doses for the treatment of uncontrolled hemorrhage in other clinical settings have varied from 15 to 180 µg/kg i.v.
Our institution, the University of Virginia Health System (UVHS), added factor VIIa (recombinant) to its formulary on August 27, 1999. Informal institutional guidelines restricted the use of factor VIIa (recombinant) to patients with hemophilia A or B with inhibitors, patients with autoimmune antibodies to factor VIII, and patients with bleeding associated with liver disease. These guidelines were developed by the hematology–oncology service to identify the clinical conditions for which patients could receive factor VIIa (recombinant). The pharmacy and therapeutics (P&T) committee did not approve these informal guidelines. The informal guidelines also allowed the use of factor VIIa (recombinant) for the treatment of intractable bleeding, central nervous system bleeding, and warfarin reversal. However, a formal hematology consultation and documentation of the specific risks and benefits in the patient’s medical record were required for the unlabeled indications. The initial gatekeeper was a hematologist who had significant experience with factor VIIa (recombinant). The hematologist or her designated hematology fellows (not assigned through a formal P&T committee process) approved or disapproved the release of the drug for all consultations. However, the approval process became overwhelming for the hematologist because of the increased demand for factor VIIa (recombinant) for unlabeled indications.
The unlabeled uses of factor VIIa (recombinant) are constrained by high costs and limited clinical efficacy data. Currently, there are no national guidelines for the unlabeled indications of factor VIIa (recombinant); before April 2005, our institution did not have formal prescribing guidelines for the agent. Inappropriate use of the anticoagulation factor may negatively affect drug expenditures. Hoffman and colleagues10 identified factor VIIa (recombinant) as a major contributor to escalating pharmacy drug budgets in many of todayÂ’s major academic medical centers. During the 2004 fiscal year, UVHS spent approximately $970,000 on this agent alone.
We conducted a project at UVHS to determine our usage pattern of factor VIIa (recombinant) and establish formal prescribing guidelines for the use of the drug within the institution.
Recombinant activated factor seven (VIIa) is a vitamin K-dependent glycoprotein that is structurally similar to human plasma-derived factor VIIa. It has received approval from the Food and Drug Administration (FDA) for the treatment of bleeding episodes in patients with hemophilia A or B who have developed inhibitors to factor VIII or factor IX, respectively. It promotes hemostasis by activating the coagulation cascade. Complexing with tissue factor at the site of vascular injury, recombinant factor VIIa cleaves factor X to the enzyme-activated factor X. Factor X promotes the conversion of prothrombin to thrombin and of fibrinogen to fibrin, leading to the formation of a hemostatic plug.
Factor VIIa (recombinant) has been primarily used in the treatment of bleeding episodes in hemophiliac patients with inhibitors to factor VIII or IX and patients with acquired he-mophilia due to auto-antibodies. The current recommended dose of factor VIIa (recombinant) in the treatment of bleeding episodes in these patients is 90 µg/kg i.v. In this population, factor VIIa (recombinant) has been associated with adverse thromboembolic events, including myocardial infarction, cerebrovascular infarct, venous thrombosis, and disseminated intravascular coagulopathy (DIC).
However, the medical literature provides anecdotal reports of factor VIIa (recombinant) use for a growing list of unlabeled indications, including the reversal of warfarin toxicity, treatment of pediatric patients with coagulation dysfunction, and treatment of patients with coagulation disorders caused by hepatic disease. One randomized controlled trial found that factor VIIa (recombinant) reduced blood loss and blood-product requirements in patients undergoing high-risk surgical procedures, and another revealed that factor VIIa (recombinant) controlled the bleeding associated with intracerebral hemorrhage (ICH). Doses for the treatment of uncontrolled hemorrhage in other clinical settings have varied from 15 to 180 µg/kg i.v.
Our institution, the University of Virginia Health System (UVHS), added factor VIIa (recombinant) to its formulary on August 27, 1999. Informal institutional guidelines restricted the use of factor VIIa (recombinant) to patients with hemophilia A or B with inhibitors, patients with autoimmune antibodies to factor VIII, and patients with bleeding associated with liver disease. These guidelines were developed by the hematology–oncology service to identify the clinical conditions for which patients could receive factor VIIa (recombinant). The pharmacy and therapeutics (P&T) committee did not approve these informal guidelines. The informal guidelines also allowed the use of factor VIIa (recombinant) for the treatment of intractable bleeding, central nervous system bleeding, and warfarin reversal. However, a formal hematology consultation and documentation of the specific risks and benefits in the patient’s medical record were required for the unlabeled indications. The initial gatekeeper was a hematologist who had significant experience with factor VIIa (recombinant). The hematologist or her designated hematology fellows (not assigned through a formal P&T committee process) approved or disapproved the release of the drug for all consultations. However, the approval process became overwhelming for the hematologist because of the increased demand for factor VIIa (recombinant) for unlabeled indications.
The unlabeled uses of factor VIIa (recombinant) are constrained by high costs and limited clinical efficacy data. Currently, there are no national guidelines for the unlabeled indications of factor VIIa (recombinant); before April 2005, our institution did not have formal prescribing guidelines for the agent. Inappropriate use of the anticoagulation factor may negatively affect drug expenditures. Hoffman and colleagues10 identified factor VIIa (recombinant) as a major contributor to escalating pharmacy drug budgets in many of todayÂ’s major academic medical centers. During the 2004 fiscal year, UVHS spent approximately $970,000 on this agent alone.
We conducted a project at UVHS to determine our usage pattern of factor VIIa (recombinant) and establish formal prescribing guidelines for the use of the drug within the institution.
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