antihemophilic factor recombinant (Rx)

Brand and Other Names:Helixate FS, Xyntha, more...Kogenate FS, NovoEight, Recombinate, Advate, Eloctate, Factor VIII (Recombinant), turoctocog alfa, Obizur, Nuwiq, Adynovate, Kovaltry, Afstyla, Jivi, Esperoct
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injection, lyophilized powder for reconstitution

  • Eloctate
    • 250 IU, 500 IU, 750 IU, 1000 IU, 1500 IU, 2000 IU, 3000 IU, 4000 IU, 5000 IU, 6000 IU
  • Kogenate FS
    • 250 IU, 500 IU, 1000 IU, 2000 IU, 3000 IU
  • Nuwiq
    • 250 IU, 500 IU, 1000 IU, 2000 IU, 2500 IU, 3000 IU, 4000 IU
  • NovoEight
    • 250 IU, 500 IU, 1000 IU, 1500 IU, 2000 IU, 3000 IU
  • Recombinate
    • 220-400 IU, 401-800 IU, 801-1240 IU, 1241-1800 IU, 1801-2400 IU
  • pegylated (Adynovate)
    • 250 IU, 500 IU, 750 IU, 1000 IU, 1500 IU, 2000 IU, 3000 IU
  • pegylated-aucl (Jivi)
    • 500 IU, 1000 IU, 2000 IU, 3000 IU
  • glycopegylated-exei (Esperoct)
    • 500 IU, 1000 IU, 1500 IU, 2000 IU, 3000 IU
  • single-chain (Afstyla)
    • 250 IU, 500 IU, 1000 IU, 1500 IU, 2000 IU, 2500 IU, 3000 IU
  • plasma/albumin free
    • 250 IU, 500 IU, 1000 IU, 2000 IU (Xyntha)
    • 250 IU, 500 IU, 1000 IU, 2000 IU, 3000 IU (Xyntha Solofuse)
    • 250 IU, 500 IU, 1000 IU, 2000 IU, 3000 IU (Kovaltry)
    • 250 IU, 500 IU, 1000 IU, 1500 IU, 2000 IU, 3000 IU, 4000 IU (Advate)
  • porcine sequence (Obizur)
    • 500 IU

Hemophilia A, Congenital

Indicated for prevention and control of bleeding episodes, perioperative management, and routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A (congenital Factor VIII deficiency)

Dosage (IU) = Body Weight (kg) × Desired Factor VIII level increase (IU/dL or % normal) × 0.5 (IU/kg per IU/dL)

Bleeding episodes

  • Mild/moderate hemorrhage
    • Eloctate: 20-30 IU/kg IV to achieve factor VIII level of 40% to 60% of normal for the treatment of joint, superficial muscle/no neurovascular compromise (except iliopsoas), deep laceration and renal, superficial soft tissue, or mucous membrane bleeding; repeat q24-48hr until resolved
    • Advate, Helixate FS, Kogenate FS (initial): 10-20 units/kg IV to achieve factor VIII level of 20-40% of normal for the treatment of early hemarthrosis and minor muscle or oral bleed; may repeat dose q12-24hr x1-3 days if evidence of further bleeding
    • Recombinate, Xyntha: A dose sufficient to achieve factor VIII level of 20-40% of normal for the treatment of early hemarthrosis, muscle bleeding, or oral bleeding episode; may repeat dose q12-24hr x1-3 days if evidence of further bleeding
    • Nuwiq (mild): A dose sufficient to achieve factor VIII activity of 20-40% of normal for superficial muscle or soft tissue and oral bleeds; may repeat dose q12-24hr for at least 1 day, until bleeding episode resolved
    • Adynovate (mild): 10-20 IU/kg IV to achieve factor VIII activity of 20-40% of normal for superficial muscle or soft tissue and minor oral bleeds; may repeat dose q12-24hr for at least 1 day, until bleeding episode resolved
    • Kovaltry (mild): A dose sufficient to achieve factor VIII activity of 20-40% of normal for early hemarthrosis, minor muscle bleeding, or oral bleeds; may repeat dose q12-24hr for at least 1 day, until bleeding episode resolved
    • Afstyla (mild): A dose sufficient to achieve factor VIII activity of 20-40% of normal for early hemarthrosis, minor muscle bleeding, or oral bleeds; may repeat dose q12-24hr for at least 1 day, until bleeding episode resolved
    • Jivi (mild): 10-20 IU/kg IV to achieve factor VIII activity of 20-40% of normal for early hemarthrosis, superficial muscle or soft tissue and minor oral bleeds; may repeat dose q24-48hr until bleeding episode resolved
    • Esperoct (mild): 40 IU/kg; 1 dose is typically sufficient
  • Moderate hemorrhage
    • Advate: 15-30 units/kg IV to achieve factor VIII level of 30-60% of normal for the treatment of moderate bleeding into muscles, bleeding into the oral cavity, definite hemarthroses, and known trauma; may repeat dose q12-24hr x1-3 days if evidence of further bleeding
    • Eloctate: 20-30 IU/kg IV to achieve factor VIII level of 40-60% of normal for the treatment of joint, superficial muscle/no neurovascular compromise (except iliopsoas), deep laceration and renal, superficial soft tissue, or mucous membrane bleeding; repeat q24-48hr until resolved
    • Helixate FS, Kogenate FS (initial): 15-20 units/kg IV to achieve factor VIII level of 30-60% of normal for the treatment of moderate bleeding into muscles, bleeding into the oral cavity, definite hemarthroses, and known trauma; may repeat dose q12-24hr x1-3 days if evidence of further bleeding
    • Recombinate: A dose sufficient to achieve factor VIII level of 30-60% of normal for the treatment of more extensive hemarthrosis, muscle bleeding, or hematoma; repeat q12-24hr x3 days or more
    • Xyntha: A dose sufficient to achieve factor VIII level of 30-60% of normal for the treatment of hemorrhages into muscles, mild head trauma, and hemorrhages into oral cavity; repeat q12-24hr x3-4 days or until adequate local hemostasis is achieved
    • Nuwiq: A dose sufficient to achieve factor VIII activity of 30-60% of normal for hemorrhage into muscles, into oral cavity, hemarthrosis, or known trauma; may repeat dose q12-24hr for at least 3-4 day, until bleeding episode resolved
    • Adynovate: 15-30 IU/kg IV to achieve factor VIII activity of 30-60% of normal for moderate hemorrhage in oral cavity, definite hemarthroses, and known trauma; may repeat dose q12-24hr until bleeding episode resolved
    • Kovaltry: A dose sufficient to achieve factor VIII activity of 30-60% of normal for more extensive hemarthrosis, muscle bleeding or hematoma; may repeat dose q12-24hr for at least 3-4 day, until bleeding episode resolved
    • Afstyla: A dose sufficient to achieve factor VIII activity of 30-60% of normal for more extensive hemarthrosis, muscle bleeding or hematoma; may repeat dose q12-24hr for at least 3-4 day, until bleeding episode resolved
    • Jivi: 15-30 IU/kg IV to achieve factor VIII activity of 30-60% of normal for more extensive hemarthrosis, muscle bleeding, or hematoma; may repeat dose q24-48hr until bleeding episode resolved
    • Esperoct: 40 IU/kg; an additional dose may be administered after 24 hr
  • Severe hemorrhage
    • Advate: 30-50 units/kg IV to achieve factor VIII plasma level of 60-100% of normal for treatment of significant GI bleeding; intracranial, intra-abdominal, or intrathoracic bleeding; CNS bleeding; bleeding in the retropharyngeal or retroperitoneal spaces; or iliopsoas sheath, factures, and head trauma; repeat q8-24hr until bleeding episode resolved
    • Eloctate: 40-50 IU/kg IV to achieve factor VIII level of 80-100% of normal for the treatment of life or limb threatening hemorrhage, iliopsoas and deep muscle with neurovascular injury, and retroperitoneum, intracranial, or GI bleeding; repeat q12-24hr until bleeding resolved (typically 7-10 days)
    • Helixate FS, Kogenate FS: 40-50 units/kg IV to achieve factor VIII level of 80-100% of normal for the treatment of intracranial, intra-abdominal, or intrathoracic bleeding; GI bleeding; CNS bleeding; bleeding in the retroperitoneal or retropharyngeal spaces or iliopsoas sheath; fractures; and head trauma; repeat with 20-25 units/kg q8-12hr until bleeding episode resolved
    • Recombinate: A dose sufficient to achieve factor VIII level of 60-100% of normal for the treatment of life-threatening bleeding episodes, such as head injury, throat bleeding, or severe abdominal pain; repeat q8-24hr until bleeding episode resolved
    • Xyntha: A dose sufficient to achieve factor VIII level of 60-100% of normal for GI bleeding; intracranial, intra-abdominal, or intrathoracic hemorrhages; and fractures; repeat q8-24hr until bleeding episode resolved
    • Nuwiq: A dose sufficient to achieve factor VIII activity of 60-100% of normal for Intracranial, intraabdominal, GI, or intrathoracic bleeds, central nervous system bleeds, bleeding in retropharyngeal spaces or iliopsoas sheath, eyes/retina, fractures or head trauma; may repeat dose 8-24 hr until bleeding risk resolved
    • Adynovate: 30-50 IU/kg IV to achieve factor VIII activity of 60-100% of normal for severe hemorrhage including GI bleeding, intracranial, intraabdominal or intrathoracic, CNS, bleeding in the retropharyngeal or retroperitoneal spaces or iliopsoas sheath, fractures, head trauma; may repeat dose q8-24hr until bleeding episode resolved
    • Kovaltry: A dose sufficient to achieve factor VIII activity of 60-100% of normal for intracranial, intraabdominal, GI, or intrathoracic bleeds, central nervous system bleeds, bleeding in retropharyngeal spaces or iliopsoas sheath, life or limb threatening hemorrhage; may repeat dose 8-24 hr until bleeding risk resolved
    • Afstyla: A dose sufficient to achieve factor VIII activity of 60-100% of normal for intracranial, intraabdominal, GI, or intrathoracic bleeds, central nervous system bleeds, bleeding in retropharyngeal spaces or iliopsoas sheath, life or limb threatening hemorrhage; may repeat dose 8-24 hr until bleeding risk resolved
    • Jivi: 30-50 IU/kg IV to achieve factor VIII activity of 60-100% of normal for major hemorrhage including GI bleeding, intracranial, intraabdominal or intrathoracic, CNS, bleeding in the retropharyngeal or retroperitoneal spaces or iliopsoas sheath, live- or limb-threatening hemorrhage; may repeat dose q8-24hr until bleeding episode resolved
    • Esperoct: 50 IU/kg; additional doses may be administered ~q24hr

Perioperative management

  • Minor surgery
    • Advate: 30-50 units/kg IV as a single IV bolus infusion beginning within 1 hr of the operation to achieve factor VIII level of 60-100% of normal for minor surgery, including tooth extraction; may repeat dosage q12-24hr as needed to control bleeding (for dental procedures, adjunctive therapy may be considered)
    • Eloctate: 25-40 units/kg IV to achieve factor VIII level of 50-80% of normal for minor surgery, including tooth extraction; may repeat dosage q24hr for at least 1 day until healing is achieved
    • Helixate FS, Kogenate FS: 15-30 units/kg IV to achieve factor VIII level of 30-60% of normal for minor surgery, including tooth extraction; may repeat dosage q12-24hr until bleeding is resolved
    • Recombinate: 60-80 units/kg IV to achieve adequate factor VIII level for minor surgery, including tooth extraction; a single infusion plus oral antifibrinolytic therapy within 1 hr is sufficient in ~70% of cases
    • Xyntha: An IV dose sufficient to achieve Factor VIII activity within 30-60% of normal q12-24hr for 3-4 days or until adequate local hemostasis is achieved; for tooth extraction, a single infusion plus oral antifibrinolytic therapy within 1 hr may be sufficient
    • Nuwiq: An IV dose sufficient to achieve Factor VIII activity within 80-100% of normal pre- and postoperatively; may repeat q24hr for least 1 day until healing is achieved
    • Kovaltry: An IV dose sufficient to achieve Factor VIII activity within 30-60% of normal pre- and postoperatively; may repeat q24hr for least 1 day until healing is achieved
    • Afstyla: An IV dose sufficient to achieve Factor VIII activity within 30-60% of normal pre- and postoperatively; may repeat q24hr for least 1 day until healing is achieved
    • Jivi: 15-30 IU/kg IV to achieve factor VIII level of 30-60% of normal for minor surgery (eg, tooth extraction); may repeat dosage q24hr for at least 1 day until healing is achieved
    • Esperoct: 50 IU/kg; additional dose(s) may be administered after 24 hr if necessary
  • Major surgery
    • Advate: 40-60 units/kg IV preoperatively to achieve factor VIII level of 80-120% of normal pre- and postoperatively for major surgery, including intracranial, intra-abdominal, or intrathoracic surgery, and joint replacement surgery; repeat q8-24hr, depending on the desired level of factor VIII and state of wound healing
    • Eloctate: 40-60 units/kg IV preoperatively to achieve factor VIII level of 80-120% of normal pre- and postoperatively for major surgery, including intracranial, intra-abdominal, and joint replacement surgery; repeat dose of 40-50 units/kg after 8-24hr and then q24hr until adequate wound healing, then continue therapy for at least 7 days to maintain a Factor VIII activity within the target range
    • Helixate FS, Kogenate FS: 50 units/kg IV preoperatively to achieve factor VIII level of 100% of normal perioperatively for major surgery, including tonsillectomy, inguinal herniotomy, synovectomy, total knee replacement, craniotomy, osteosynthesis, trauma; repeat dose q6-12hr to maintain a Factor VIII activity within the target range until healing is complete
    • Recombinate: 80-100 units/kg IV preoperatively and postoperatively for major surgery; repeat dose q8-24hr depending on the state of healing
    • Xyntha: An IV dose sufficient to achieve Factor VIII activity within 60-100% of normal q8-24hr until threat is resolved, or in the case of surgery, until adequate local hemostasis and wound healing are achieved
    • Nuwiq: An IV dose sufficient to achieve Factor VIII activity within 30-60% of normal pre- and postoperatively for major surgery including intracranial, intraabdominal, or joint replacement therapy; may repeat q8-24hr until adequate wound healing, then continue therapy for at least another 7 days to maintain a Factor VIII activity of 30-60% (IU/dL)
    • Kovaltry: An IV dose sufficient to achieve Factor VIII activity within 80-100% of normal pre- and postoperatively for major surgery including intracranial, intraabdominal, intrathoracic, or joint replacement therapy; may repeat q8-24hr until adequate wound healing, then continue therapy for at least another 7 days to maintain a Factor VIII activity of 30-60% (IU/dL)
    • Afstyla: An IV dose sufficient to achieve Factor VIII activity within 80-100% of normal pre- and postoperatively for major surgery including intracranial, intraabdominal, intrathoracic, or joint replacement therapy; may repeat q8-24hr until adequate wound healing, then continue therapy for at least another 7 days to maintain a Factor VIII activity of 30-60% (IU/dL)
    • Jivi: 40-50 IU/kg IV to achieve factor VIII level of 80-100% of normal for major surgery (eg, intracranial, intra-abdominal, or joint replacement); may repeat dosage q12-24hr for at least 1 day until adequate wound healing complete, then continue therapy for at least another 7 days to maintain Factor VIII activity of 30-60% (IU/dL)
    • Esperoct: 50 IU/kg; additional doses can be administered ~q24hr for the first week and then ~q48hr until wound healing has occurred

Routine prophylaxis dose

  • NovoEight: 20-50 IU/kg IV 3x/week, OR 20-4 IU/kg IV every other day
  • Kogenate FS: 25 IU/kg IV 3x/week
  • Advate: 20-50 IU/kg IV every other day, OR every 3rd day dosing targeted to maintain FVIII trough levels ≥1%
  • Eloctate: 50 IU/kg IV q4days; adjust based on patient response (range: 24-65 IU/kg at 3-5 day intervals)
  • Nuwiq: 30-40 IU/kg IV every other day
  • Adynovate: 40-50 IU/kg IV 2x/week; adjust dose based on clinical response
  • Kovaltry (adults and adolescents): 20-40 IU/kg IV 2-3 x/week
  • Afstyla (adults and adolescents): 20-50 IU/kg IV 2-3 times per week
  • Jivi: 30-40 IU/kg IV 2x/week; based on bleeding episodes, may adjust to 45-60 IU/kg q5days; may further individually adjust to less or more frequent dosing
  • Esperoct: 50 IU/kg IV q4days; may further individually adjust to less or more frequent dosing
  • Xyntha: 30 IU/kg IV 3x/week; adjust dose based on clinical response

Hemophilia A, Acquired

Obizur: Porcine sequence product indicated for treatment of bleeding episodes in adults with acquired hemophilia

Initial: 200 units/kg; infuse IV at rate of 1-2 mL/min

Subsequent dosing

  • May repeat q4-12hr
  • Titrate dose and frequency of administration based on factor VIII recovery levels and individual clinical response
  • Maintain the factor VIII activity within the target range; plasma levels of factor VIII should not exceed 200% of normal or 200 units/dL

FVIII level required

  • Minor/moderate, superficial muscle, no neurovascular compromise, and joint: 50-100 U/dL
  • Major, moderate to severe IM bleeding, retroperitoneal, GI, intracranial:
  • -Acute major bleed: 100-200 U/dL
  • -After acute major bleed controlled (if required): 50-100 U/dL

Limitations of use

  • Safety and efficacy not established in patients with a baseline antiporcine factor VIII inhibitor titer >20 BU
  • Not indicated for the treatment of congenital hemophilia A or von Willebrand disease

Dosing Considerations

Advate, Kovaltry, Xyntha: Recombinant, plasma/albumin-free method products

Obizur: Recombinant, porcine sequence product

Nuwiq: B-domain deleted recombinant FVIII derived from a human cell-line, not chemically modified or fused with another protein

Jivi: Not indicated for previously untreated patients or for treating von Willebrand disease

The amount of recombinant Factor VIII (in international units [IU]) is specified on each vial for the various products

Dosage Forms & Strengths

injection, lyophilized powder for reconstitution

  • Eloctate
    • 250 IU, 500 IU, 750 IU, 1000 IU, 1500 IU, 2000 IU, 3000 IU, 4000 IU, 5000 IU, 6000 IU
  • Kogenate FS
    • 250 IU, 500 IU, 1000 IU, 2000 IU, 3000 IU
  • Nuwiq
    • 250 IU, 500 IU, 1000 IU, 2000 IU, 2500 IU, 3000 IU, 4000 IU
  • NovoEight
    • 250 IU, 500 IU, 1000 IU, 1500 IU, 2000 IU, 3000 IU
  • Recombinate
    • 220-400 IU, 401-800 IU, 801-1240 IU, 1241-1800 IU, 1801-2400 IU
  • pegylated (Adynovate)
    • 250 IU, 500 IU, 750 IU, 1000 IU, 1500 IU, 2000 IU, 3000 IU
  • pegylated-aucl (Jivi)
    • 500 IU, 1000 IU, 2000 IU, 3000 IU
  • glycopegylated-exei (Esperoct)
    • 500 IU, 1000 IU, 1500 IU, 2000 IU, 3000 IU
  • single-chain (Afstyla)
    • 250 IU, 500 IU, 1000 IU, 1500 IU, 2000 IU, 2500 IU, 3000 IU
  • plasma/albumin free
    • 250 IU, 500 IU, 1000 IU, 2000 IU (Xyntha)
    • 250 IU, 500 IU, 1000 IU, 2000 IU, 3000 IU (Xyntha Solofuse)
    • 250 IU, 500 IU, 1000 IU, 2000 IU, 3000 IU (Kovaltry)
    • 250 IU, 500 IU, 1000 IU, 1500 IU, 2000 IU, 3000 IU, 4000 IU (Advate)
  • porcine sequence (Obizur)
    • 500 IU

Hemophilia A, Congenital

Indicated for prevention and control of bleeding episodes, perioperative management, and routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A (congenital Factor VIII deficiency)

Dosage (IU) = Body Weight (kg) × Desired Factor VIII Increase (IU/dL or % normal) × 0.5 (IU/kg per IU/dL)

Bleeding episodes, FVIII level required

  • Mild hemorrhage: 20-40 IU/dL peak (700-1400 IU for 70 kg); begin infusions q12-24hr x 1-3 days until resolved
  • Moderate hemorrhage: 30-60 IU/dL peak (1050-2100 IU for 70 kg); repeat infusions q12-24hr x 3 days or more until resolved
  • Severe/life-threatening hemorrhage: 60-100 IU/dL peak (2100-3500 IU for 70 kg); repeat infusions q8-24hr until resolved

Bleeding episodes (Eloctate)

  • Mild/moderate hemorrhage: 20-30 IU/kg IV; repeat q24-48hr (age <6 yr give q12-24hr) until resolved; 40-60 IU/dL FVIII level required
  • Severe hemorrhage: 40-50 IU/kg IV; repeat q12-24hr (age <6 yr give q8-24hr) until resolved (~7-10 days); 80-100 IU/dL FVIII level required

Bleeding episodes (Nuwiq)

  • Aged 2-17 years
    • Mild hemorrhage: A dose sufficient to achieve factor VIII activity of 20-40% of normal for superficial muscle or soft tissue and oral bleeds; may repeat dose q12-24hr for at least 1 day, until bleeding episode resolved
    • Moderate hemorrhage: A dose sufficient to achieve factor VIII activity of 30-60% of normal for hemorrhage into muscles, into oral cavity, hemarthrosis, or known trauma; may repeat dose q12-24hr for at least 3-4 day, until bleeding episode resolved
    • Severe hemorrhage: A dose sufficient to achieve factor VIII activity of 60-100% of normal for Intracranial, intraabdominal, GI, or intrathoracic bleeds, central nervous system bleeds, bleeding in retropharyngeal spaces or iliopsoas sheath, eyes/retina, fractures or head trauma; may repeat dose 8-24 hr until bleeding risk resolved

Bleeding episodes (Adynovate)

  • Children (<12 years) have demonstrated higher clearance, a shorter half-life, and lower incremental recovery of factor VIII compared to adults; dose adjustment or more frequent dosing based on per kg body weight may be needed in this population
  • Mild hemorrhage: 10-20 IU/kg to achieve factor VIII activity of 20-40% of normal for superficial muscle or soft tissue and minor oral bleeds; may repeat dose q12-24hr for at least 1 day, until bleeding episode resolved
  • Moderate hemorrhage: 15-30 IU/kg to achieve factor VIII activity of 30-60% of normal for moderate hemorrhage in oral cavity, definite hemarthroses, and known trauma; may repeat dose q12-24hr until bleeding episode resolved
  • Severe hemorrhage: 30-50 IU/kg to achieve factor VIII activity of 60-100% of normal for severe hemorrhage including GI bleeding, intracranial, intraabdominal or intrathoracic, CNS, bleeding in the retropharyngeal or retroperitoneal spaces or iliopsoas sheath, fractures, head trauma; may repeat dose q8-24hr until bleeding episode resolved

Bleeding episodes (Kovaltry)

  • Aged ≤12 years
    • Mild hemorrhage: A dose sufficient to achieve factor VIII activity of 20-40% of normal for early hemarthrosis, minor muscle bleeding, or oral bleeds; may repeat dose q12-24hr for at least 1 day, until bleeding episode resolved
    • Moderate hemorrhage: A dose sufficient to achieve factor VIII activity of 30-60% of normal for more extensive hemarthrosis, muscle bleeding or hematoma; may repeat dose q12-24hr for at least 3-4 day, until bleeding episode resolved
    • Severe hemorrhage: A dose sufficient to achieve factor VIII activity of 60-100% of normal for intracranial, intraabdominal, GI, or intrathoracic bleeds, central nervous system bleeds, bleeding in retropharyngeal spaces or iliopsoas sheath, life or limb threatening hemorrhage; may repeat dose 8-24 hr until bleeding risk resolved

Bleeding episodes (Afstyla)

  • All ages
    • Mild hemorrhage: A dose sufficient to achieve factor VIII activity of 20-40% of normBal for early hemarthrosis, minor muscle bleeding, or oral bleeds; may repeat dose q12-24hr for at least 1 day, until bleeding episode resolved
    • Moderate hemorrhage: A dose sufficient to achieve factor VIII activity of 30-60% of normal for more extensive hemarthrosis, muscle bleeding or hematoma; may repeat dose q12-24hr for at least 3-4 day, until bleeding episode resolved
    • Severe hemorrhage: A dose sufficient to achieve factor VIII activity of 60-100% of normal for intracranial, intraabdominal, GI, or intrathoracic bleeds, central nervous system bleeds, bleeding in retropharyngeal spaces or iliopsoas sheath, life or limb threatening hemorrhage; may repeat dose 8-24 hr until bleeding risk resolved

Bleeding episodes (Jivi)

  • <12 years: Safety and efficacy not established
  • There is a higher rate of hypersensitivity in children aged <12 years owing to immune response to PEG
  • ≥12 years
    • Mild hemorrhage: 10-20 IU/kg IV to achieve factor VIII activity of 20-40% of normal for early hemarthrosis, superficial muscle or soft tissue and minor oral bleeds; may repeat dose q24-48hr until bleeding episode resolved
    • Moderate hemorrhage: 15-30 IU/kg IV to achieve factor VIII activity of 30-60% of normal for more extensive hemarthrosis, muscle bleeding, or hematoma; may repeat dose q24-48hr until bleeding episode resolved
    • Severe hemorrhage: 30-50 IU/kg IV to achieve factor VIII activity of 60-100% of normal for major hemorrhage including GI bleeding, intracranial, intraabdominal or intrathoracic, CNS, bleeding in the retropharyngeal or retroperitoneal spaces or iliopsoas sheath, live- or limb-threatening hemorrhage; may repeat dose q8-24hr until bleeding episode resolved

Bleeding episodes (Esperoct)

  • Aged ≤12 years
    • Mild hemorrhage: 65 IU/kg; 1 dose is typically sufficient
    • Moderate hemorrhage: 65 IU/kg; an additional dose may be administered after 24 hr
    • Severe hemorrhage: 65 IU/kg; additional doses may be administered ~q24hr

Perioperative management, FVIII level required

  • Minor surgery: Target of 60-100 IU/dL peak (2100-3500 IU for 70 kg); single bolus within 1 hr of operation; additional dosing q12-24hr PRN for bleeding
  • Major surgery: Target of 80-100 IU/dL peak (2800-4200 IU for 70 kg) preop and postop; repeat infusion q6-12hr PRN for wound healing

Perioperative management (Eloctate)

  • Minor surgery: 25-40 IU/kg IV; repeat q24hr (age <6 yr q12-24hr) for at least 1 day until healing is achieved; 50-80 IU/dL FVIII level required
  • Major surgery: 40-60 IU/kg IV preop; repeat 40-50 IU/kg after 8-24 hr (age <6 yr q6-24hr), and then qDay until adequate wound healing, then continue for at least 7 days; 80-120 IU/dL FVIII level required

Perioperative management (Nuwiq)

  • Aged 2-17 years
    • Minor surgery: An IV dose sufficient to achieve Factor VIII activity within 80-100% of normal pre- and postoperatively; may repeat q24hr for least 1 day until healing is achieved
    • Major surgery: An IV dose sufficient to achieve Factor VIII activity within 30-60% of normal pre- and postoperatively for major surgery including intracranial, intraabdominal, or joint replacement therapy; may repeat q8-24hr until adequate wound healing, then continue therapy for at least another 7 days to maintain a Factor VIII activity of 30-60% (IU/dL)

Perioperative management (Adynovate)

  • Children (<12 years) have demonstrated higher clearance, a shorter half-life, and lower incremental recovery of factor VIII compared to adults; dose adjustment or more frequent dosing based on per kg body weight may be needed in this population
  • Minor surgery: An IV dose of 30-50 IU/kg sufficient to achieve Factor VIII activity within 60-100% of normal pre- and postoperatively; may repeat q24hr for least 1 day until healing is achieved
  • Major surgery: An IV dose of 40-60 IU/kg sufficient to achieve Factor VIII activity within 80-120% of normal pre- and postoperatively within 1 hr before operation for major surgery including intracranial, intraabdominal, or joint replacement therapy; may repeat q8-24hr (q6-24 hr for children <12 yr) until adequate wound healing

Perioperative management (Kovaltry)

  • Aged ≤12 years
    • Minor surgery: An IV dose sufficient to achieve Factor VIII activity within 30-60% of normal pre- and postoperatively; may repeat q24hr for least 1 day until healing is achieved
    • Major surgery: An IV dose sufficient to achieve Factor VIII activity within 80-100% of normal pre- and postoperatively for major surgery including intracranial, intraabdominal, intrathoracic, or joint replacement therapy; may repeat q8-24hr until adequate wound healing, then continue therapy for at least another 7 days to maintain a Factor VIII activity of 30-60% (IU/dL)

Perioperative management (Afstyla)

  • Any age
    • Minor surgery: An IV dose sufficient to achieve Factor VIII activity within 30-60% of normal pre- and postoperatively; may repeat q24hr for least 1 day until healing is achieved
    • Major surgery: An IV dose sufficient to achieve Factor VIII activity within 80-100% of normal pre- and postoperatively for major surgery including intracranial, intraabdominal, intrathoracic, or joint replacement therapy; may repeat q8-24hr until adequate wound healing, then continue therapy for at least another 7 days to maintain a Factor VIII activity of 30-60% (IU/dL)

Perioperative management (Jivi)

  • <12 years: Safety and effiacy not established
  • There is a higher rate of hypersensitivity in children aged <12 years owing to immune response to PEG
  • ≥12 years
    • Minor surgery: 15-30 IU/kg IV to achieve factor VIII level of 30-60% of normal for minor surgery (eg, tooth extraction); may repeat dosage q24hr for at least 1 day until healing is achieved
    • Major surgery: 40-50 IU/kg IV to achieve factor VIII level of 80-100% of normal for major surgery (eg, intracranial, intra-abdominal, or joint replacement); may repeat dosage q12-24hr for at least 1 day until adequate wound healing complete, then continue therapy for at least another 7 days to maintain Factor VIII activity of 30-60% (IU/dL)

Perioperative management (Esperoct)

  • Aged ≤12 years
    • Minor surgery: 65 IU/kg; additional dose(s) may be administered after 24 hr if necessary
    • Major surgery: 65 IU/kg; additional doses can be administered ~q24hr for the first week and then ~q48hr until wound healing has occurred

Routine prophylaxis dose

  • Children have higher factor VIII clearance compared with adults and may require larger or more frequent dosing
  • NovoEight (<12 years): 25-60 IU/kg IV 3x/week, OR 25-50 IU/kg IV every other day
  • NovoEight (≥12 years): 20-50 IU/kg IV 3x/week, OR 20-40 IU/kg IV every other day
  • Kogenate FS, Helixate FS: 25 IU/kg IV every other day
  • Advate: 20-50 IU/kg IV every other day
  • Eloctate: 50 IU/kg IV q4days; adjust based on patient response (range: 24-65 IU/kg at 3-5 day intervals); more frequent or higher doses up to 80 IU/kg may be required for children aged <6 years
  • Nuwiq (2-11 years): 30-50 IU/kg IV every other day or 3x/week
  • Nuwiq (12-17 years): 30-40 IU/kg IV every other day
  • Adynovate (≥12 years): 40-50 IU/kg IV 2x/week; adjust dose based on clinical response
  • Adynovate (<12 years): 55 IU/kg IV 2x/week; adjust dose based on clinical response, not to exceed 70 IU/kg
  • Kovaltry (≤12 years): 25-50 IU/kg IV 2-3 x/week or every other day according to individual requirements
  • Afstyla (<12 years): 30-50 IU/kg IV 2-3 times per week Afstyla (≥12 years): 20-50 IU/kg IV 2-3 times per week
  • Jivi (≥12 years): 30-40 IU/kg IV 2x/week; based on bleeding episodes, may adjust to 45-60 IU/kg q5days; may further individually adjust to less or more frequent dosing
  • Esperoct (≤12 years): 65 IU/kg IV 2 x/week; may further individually adjust to less or more frequent dosing
  • Xyntha (≥12 years): 30 IU/kg IV 3x/week; adjust dose based on clinical response
  • Xyntha (<12 years): 25 IU/kg IV every other day; adjust dose based on clinical response

Dosing Considerations

Advate, Kovaltry, Xyntha: Recombinant, plasma/albumin free method products

Nuwiq: B-domain deleted recombinant FVIII derived from a human cell-line, not chemically modified or fused with another protein

Jivi: Not indicated for previously untreated patients, treating von Willebrand disease, or children aged <12 years

The amount of recombinant Factor VIII (in international units [IU]) is specified on each vial for the various products

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Adverse Effects

>10%

Factor VIII inhibitor disorder (31.7%)

1-10%

Pyrexia (5.9%)

Nausea (1-4.4%)

Dizziness (3.5%)

Headache (3.5%)

Taste disorder (2.7%)

Dyspnea (1.8%)

Hypotension (1%)

Pruritus (1%)

Rash (1%)

Swelling or redness at injection site (1%)

Frequency Not Defined

Arthralgia

Asthenia

Somnolence

Chills

Vasodilation

Hemorrhage

Rhinitis

Sore throat

Stuffy nose

Vomiting

Diarrhea

Joint pain/swelling

Urticaria

Postmarketing Reports

Reports of less than expected or lack of effect following antihemophilic factor VIII infusions which has resulted in unexpected bleeding into target joints and bleeding into new joints, due to formation of activity-neutralizing antibodies in patients previously receiving antihemophilic factor VIII

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Warnings

Contraindications

Hypersensitivity to mouse or hamster protein, or intolerance or allergic reaction to any components, including hamster proteins

Cautions

Use serial Factor VIII assays during treatment whenever possible to assure adequate Factor VIII levels are achieved and maintained

Some products may contain Willebrand factor for stabilization; efficacy not established for treatment of Willebrand disease

Clinical response to antihemophilic factor administration may vary; dosage must be individualized based on clinical response and coagulation studies, performed prior to treatment and regular intervals during treatment

May form antibodies to mouse or hamster protein

Monitoring laboratory tests

  • Use individual factor VIII values for recovery and, if clinically indicated, other pharmacokinetic characteristics to guide dosing and administration
  • Monitor plasma factor VIII activity levels by the one-stage clotting assay to confirm that adequate factor VIII levels have been achieved and are maintained, when clinically indicated
  • Monitor for development of factor VIII inhibitors; perform assay to determine if factor VIII inhibitor is present when expected factor VIII activity plasma levels are not attained, or when bleeding is not controlled with expected dose
  • Use Bethesda Units (BU) to titer inhibitors

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Pregnancy & Lactation

Pregnancy

No data are available in pregnant women

Lactation

No data are available regarding the presence in human milk, the effects on the breastfed infant, or the effects on milk production

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

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Pharmacology

Mechanism of Action

Recombinant human antihemophilic factor

Temporarily replaces missing clotting factor VIII which corrects &/or prevents bleeding

Pharmacokinetics

Peak plasma concentration: 120±26 IU/dL

AUC: 1534±436 IU•hr/dL

Vd: 0.60±0.15 dL/kg

Half-life: 13-15 hr

Total body clearance: 0.03±0.01 dL/kg/hr

Eloctate

  • Peak plasma concentration: 109 IU/dL
  • AUC: 54.1 IU•hr/dL
  • Vd: 49.5 mL/kg
  • Half-life: 19.7 hr
  • Total body clearance: 2.06 mL/hr/kg

Nuwiq

  • Peak plasma concentration: 0.022 IU/mL
  • AUC: 18 IU•hr/dL
  • Vd: 59.8 mL/kg
  • Half-life: 17.1 hr
  • Total body clearance: 3 mL/hr/kg

Kovaltry

  • Peak plasma concentration: 91.7-99.7 IU/dL
  • AUC: 1013-1601 IU•hr/dL
  • Vd: 0.63-0.85 dL/kg
  • Half-life: 11.7-14.3 hr
  • Total body clearance: 0.035-0.053 dL/hr/kg

Jivi

  • Ranges based on 24-60 IU/kg doses
  • Peak plasma concentration: 64.2-167 IU/dL
  • AUC: 1640-4060 IU•hr/dL
  • Vd: 39.4-42.8 mL/kg
  • Half-life: 17.9-18.6 hr
  • Total body clearance: 1.63-1.68 mL/hr/kg
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Administration

IV Administration

Total dose may be administered over 5-10 min

Maximum IV infusion rate: 10 mL/min; reduce rate or temporarily halt injection if significant increase in pulse rate

Specific product infusion rates

  • Nuwiq: Not to exceed infusion rate of 4 mL/min
  • Obizur: Infuse at rate of 1-2 mL/min
  • Esperoct: Infuse over ~2 min
  • Kovaltry: Infuse IV over 1-15 minutes
  • Jivi: Infuse IV over 1-15 minutes; not to exceed 2.5 mL/min
  • Adapt infusion rate based on patient response

Storage

Unopened vials

  • Refrigerate at 2-8°C (36-46°F); avoid freezing and store in original carton to protect from light
  • Kogenate FS and Helixate FS: May store at room temperature for up to 3 months; do not return product to refrigerator
  • Jivi: May store at room temperature for up to 6 months; do not return product to refrigerator
  • Esperoct: May store at room temperature for up to 12 months; do not return product to refrigerator

Reconstituted vials

  • Use within 3 hr of preparation; discard unused product
  • Afstyla, Esperoct: Use within 4 hr of preparation if stored at room temperature; protect from direct sunlight
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Images

BRAND FORM. UNIT PRICE PILL IMAGE
Recombinate intravenous
-
1,500 (+/-) unit vial
Recombinate intravenous
-
2,000 (+/-) unit vial
Recombinate intravenous
-
1,000 (+/-) unit vial
Recombinate intravenous
-
500 (+/-) unit vial
Recombinate intravenous
-
250 (+/-) unit vial

Copyright © 2010 First DataBank, Inc.

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Patient Handout

Patient Education
antihemophilic factor (recombinant) intravenous

ANTIHEMOPHILIC FACTOR (FACTOR VIII), RECOMBINANT - INJECTION

(AN-tye-HEE-moe-FIL-ik FAK-tor, ree-KOM-bi-nant)

COMMON BRAND NAME(S): Advate, Adynovate, Kogenate, Obizur, Recombinate

USES: This medication is used to control and prevent bleeding episodes in people with low levels of factor VIII (hemophilia A). It is also used in these patients before surgery to prevent bleeding. People with low factor VIII levels are at risk for bleeding longer after an injury/surgery and for bleeding inside the body (especially into the joints and muscles). This product contains a man-made form of factor VIII, also called antihemophilic factor. This product is used to temporarily replace the missing factor VIII, a protein (clotting factor) that is normally in the blood, so that the blood can clot and the bleeding can stop.This medication should not be used to treat von Willebrand disease.

HOW TO USE: This medication is given by injection into a vein as directed by your doctor. The medication may need to be given more slowly over a longer time depending on your dose and how you respond to it.After first receiving this medication in a hemophilia treatment center or hospital, some patients may be able to give this medication to themselves at home. If your doctor directs you to give this medication at home, read the Patient Information Leaflet available from your pharmacist before you start using this medication and each time you get a refill. Learn all preparation and usage instructions in the product package. Learn how to store and discard needles and medical supplies safely. If you have any questions, ask your health care professional.If the medication and the solution used to mix it were refrigerated, bring both to room temperature before combining. After adding the solution to the powder, gently swirl the mixture to completely dissolve the powder. Do not shake. Before using this product, check it visually for particles or discoloration. If either is present, do not use the liquid. Use right away according to the product instructions.The dosage is based on your medical condition, weight, blood test results, and response to treatment. Follow your doctor's instructions closely.Tell your doctor if your condition does not improve or if it worsens.

SIDE EFFECTS: Flushing of the face, headache, nausea, and fast heartbeat may sometimes occur and can be lessened by giving this medication more slowly. Burning/redness/irritation at the injection site, fever, and chills may also occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing, chest discomfort/tightness.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using this medication, tell your doctor or pharmacist if you are allergic to any antihemophilic factor (factor VIII) products; or if you have any other allergies. Some brands may also contain polyethylene glycol (PEG), or inactive ingredients (such as natural rubber/latex), which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history.Manufacturers of some brands of this medication recommend that you monitor your heartbeat during treatment. If your heart starts to beat faster, it is recommended that you give this medication more slowly or temporarily stop the infusion until your heart rate returns to normal. Consult your doctor for more details.During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.It is not known whether this drug passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use.Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others.Laboratory blood tests (e.g., factor VIII levels) should be performed frequently to determine your dosage and to check how well this medication is working. Consult your doctor for more details.

MISSED DOSE: It is important to follow the dosing schedule as directed by your doctor. If you miss a dose, ask your doctor or pharmacist right away for a new dosing schedule. Do not double the dose to catch up.

STORAGE: Store the medication according to the manufacturer's instructions. Ask your pharmacist if you have any questions. Do not freeze this product or store it in the bathroom. Protect the product from light. After mixing, use the product within the time frame stated in the manufacturer's instructions and throw away any unused portion. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-888-633-4298 (US) or 1-800-668-1507 (Canada).

Information last revised August 2021. Copyright(c) 2021 First Databank, Inc.

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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Formulary

FormularyPatient Discounts

Adding plans allows you to compare formulary status to other drugs in the same class.

To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

Adding plans allows you to:

  • View the formulary and any restrictions for each plan.
  • Manage and view all your plans together – even plans in different states.
  • Compare formulary status to other drugs in the same class.
  • Access your plan list on any device – mobile or desktop.

The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL Quantity Limits
Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST Step Therapy
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR Other Restrictions
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.