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TABLE 3 . Reductions in Anti-Factor Xa Activity After Andexanet Infusion
Rivaroxaban-treated patients ( n = 26 )
Apixaban-treated patients ( n = 20 )
Enoxaparin-treated patients ( n = 1 )
Baseline anti-FXa activity
End of bolus
297.0 ± 171.0 ng / mL 16.8 ng / mL
174.5 ± 97.0 ng / mL 10.3 ng / mL
Percent change ( 95 % CI )
−89 % ( −58 to −94 )
−93 % ( −87 to −94 )
End of infusion
Percent change ( 95 % CI )
30.6 ng / mL −86 % ( −55 to −93 )
12.5 ng / mL −92 % ( −85 to −94 )
0.6 IU / mL 0.15 IU / mL NA 0.19 IU / mL NA output that could not otherwise be explained )
• acute overt bleeding associated with a decrease in hemoglobin level of ≤8 g / dL if no baseline hemoglobin level was available ( or an investigator ’ s opinion that the hemoglobin level would fall to ≤8 g / dL )
IDELVION ® [ Coagulation Factor IX ( Recombinant ), Albumin Fusion Protein ] Lyophilized Powder for Solution for Intravenous Injection Initial U . S . Approval : 2016
BRIEF SUMMARY OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use IDELVION safely and effectively . See full prescribing information for IDELVION .
----------------------------INDICATIONS AND USAGE--------------------------- IDELVION , Coagulation Factor IX ( Recombinant ), Albumin Fusion Protein ( rIX- FP ), a recombinant human blood coagulation factor , is indicated in children and adults with hemophilia B ( congenital Factor IX deficiency ) for :
• On-demand control and prevention of bleeding episodes
• Perioperative management of bleeding
• Routine prophylaxis to prevent or reduce the frequency of bleeding episodes Limitations of Use : IDELVION is not indicated for immune tolerance induction in patients with Hemophilia B .
------------------------DOSAGE AND ADMINISTRATION------------------------ For intravenous use after reconstitution only . Each vial of IDELVION is labeled with the actual Factor IX potency in international units ( IU ).
• One IU of IDELVION per kg body weight is expected to increase the circulating activity of Factor IX as follows :
° Adolescents and adults : 1 . 3 IU / dL per IU / kg ° Pediatrics (< 12 years ): 1 IU / dL per IU / kg
• Administer intravenously . Do not exceed infusion rate of 10 mL per minute . Control and prevention of bleeding episodes and perioperative management :
• Dosage and duration of treatment with IDELVION depends on the severity of the Factor IX deficiency , the location and extent of bleeding , and the patient ’ s clinical condition , age and recovery of Factor IX .
• Determine the initial dose using the following formula :
• Required Dose ( IU ) = Body Weight ( kg ) x Desired Factor IX rise (% of normal or IU / dL ) x ( reciprocal of recovery ( IU / kg per IU / dL ))
• Adjust dose based on the patient ’ s clinical condition and response .
Routine prophylaxis :
• Patients ≥12 years of age : 25-40 IU / kg body weight every 7 days . ( 2.1 ) Patients who are well-controlled on this regimen may be switched to a 14-day interval at 50-75 IU / kg body weight .
• Patients < 12 years of age : 40-55 IU / kg body weight every 7 days .
-------------------------DOSAGE FORMS AND STRENGTHS---------------------- IDELVION is available as a lyophilized powder in single-use vials containing nominally 250 , 500 , 1000 or 2000 IU .
-----------------------------CONTRAINDICATIONS ------------------------------- Do not use in patients who have had life-threatening hypersensitivity reactions to IDELVION or its components , including hamster proteins .
--------------------------WARNINGS AND PRECAUTIONS-----------------------
• Hypersensitivity reactions , including anaphylaxis , are possible . Should symptoms occur , discontinue IDELVION and administer appropriate treatment .
• Development of neutralizing antibodies ( inhibitors ) to IDELVION may occur . If expected Factor IX plasma recovery in patient plasma is not attained , or if bleeding is not controlled with an appropriate dose , perform an assay that measures Factor IX inhibitor concentration .
• Thromboembolism ( e . g ., pulmonary embolism , venous thrombosis , and arterial thrombosis ) may occur when using Factor IX-containing products .
• Nephrotic syndrome has been reported following immune tolerance induction with Factor IX-containing products in hemophilia B patients with Factor IX inhibitors and a history of allergic reactions to Factor IX .
• Factor IX activity assay results may vary with the type of activated partial thromboplastin time reagent used .
----------------------------ADVERSE REACTIONS--------------------------------- The most common adverse reaction ( incidence ≥1 %) reported in clinical trials was headache .
To report SUSPECTED ADVERSE REACTIONS , contact CSL Behring Pharmacovigilance Department at 1-866-915-6958 or FDA at 1-800- FDA-1088 or www . fda . gov / medwatch .
----------------------USE IN SPECIFIC POPULATIONS---------------------------
• Pediatric : Higher dose per kilogram body weight or more frequent dosing may be needed .
Based on March 2016 version .
• acute symptomatic bleeding in a critical area or organ ( e . g ., retroperitoneal , intra-articular , pericardial , intracranial , or intramuscular with the compartment syndrome )
Patients were excluded from the study if they had surgery scheduled within 12 hours after presentation ; a major thrombotic event within two weeks prior to enrollment ; or had received a vitamin K antagonist , dabigatran , prothrombin complex concentrate , or whole blood or plasma within seven days prior to screening .
Patients received an andexanet bolus for 15 to 30 minutes followed by a twohour infusion of andexanet . Doses were adjusted based on the anticoagulant used :
• For patients receiving apixaban or rivaroxaban > 7 hours before andexanet , the bolus was 500 mg and the infusion was 480 mg .
• For those who received enoxaparin , edoxaban , or rivaroxaban ≤7 hours before andexanet or at an unknown time , the bolus was 800 mg and the infusion was 960 mg .
Dr . Connolly and investigators assessed patients at three hours and at 15 minutes prior to administration of andexanet ( baseline ); at the end of bolus administration ( 15-30 minutes after initiation ); at the end of the two-hour infusion ; at four , eight , and 12 hours after infusion ; and at three and 30 days thereafter .
The mean patient age was 77 years , and all patients had a history of thrombotic events and cardiovascular disease . Thirty-two patients received rivaroxaban ( median daily dose = 20 mg ), 31 patients received apixaban ( median daily dose = 5 mg ), and four patients received enoxaparin ( median daily dose = 90 mg ).
The site of bleeding was most often gastrointestinal ( n = 33 ; 49 %) or intracranial ( n = 28 ; 42 %); other bleeding sites included nasal , pericardial , pleural or retroperitoneal , genital or urinary , or articular . The mean time from presentation in the emergency department to initiation of andexanet bolus was 4.8 hours .
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November 2016