Asceniv

• Thrombosis may occur with immune globulin (IGIV) products, including ASCENIV. Risk factors may include: advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling central vascular catheters, hyperviscosity, and cardiovascular risk factors. Thrombosis may occur in the absence of known risk factors (see
  
  
  

  5.2 Thrombosis

  Thrombosis may occur following treatment with immune globulin products, including ASCENIV.^4,5,6Risk factors may include: advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling central vascular catheters, hyperviscosity and cardiovascular risk factors. Thrombosis may occur in the absence of known risk factors.

  Consider baseline assessment of blood viscosity in patients at risk for hyperviscosity, including patients with cryoglobulins, fasting chylomicronemia/markedly high triacylglycerols (triglycerides), or monoclonal gammopathies. For patients at risk of thrombosis, administer ASCENIV at the minimum dose and infusion rate practicable. Ensure adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity (see

  Boxed Warning, Dosage and Administration [2], Patient Counseling Information [17]

  ).

  17 PATIENT COUNSELING INFORMATION

  Instruct patients taking ASCENIV to immediately report symptoms of:

  • Thrombosis
    which includes pain and/or swelling of an arm or legs/feet with warmth over the affected area, discoloration of an arm or leg, unexplained shortness of breath, acute chest pain or discomfort that worsens on deep breathing, unexplained rapid pulse, numbness or weakness on one side of the body (see Warning and Precaution [5.2]).
  • Acute Renal Dysfunction and Acute Renal Failure
    which includes decreased urine output, sudden weight gain, fluid retention/edema, and/or shortness of breath. Such symptoms may suggest kidney damage (see Boxed Warning, Warnings and Precautions [5.3]).
  • Aseptic Meningitis Syndrome (AMS)
    which includes severe headache, neck stiffness, drowsiness, fever, sensitivity to light, painful eye movements, nausea and vomiting (see Warnings and Precautions [5.5]).
  • Hemolysis
    which includes fatigue, increased heart rate, yellowing of skin or eyes, dark- colored urine (see Warnings and Precautions [5.5]).
  • Transfusion-Related Acute Lung Injury (TRALI)
    which includes trouble breathing, chest pain, blue lips or extremities, fever (see Warnings and Precautions [5.7])

  Inform patients that ASCENIV:

  • Is made from human plasma and may contain infectious agents that can cause disease. While the risk that ASCENIV can transmit an infection has been reduced by screening plasma donors for prior exposure, testing donated plasma, and inactivating or removing certain viruses during manufacturing, patients should report any symptoms that concern them (see Description [11]and Warnings and Precautions [5]).
  • Can interfere with their immune response to live viral vaccines (e.g., measles, mumps, rubella, and varicella). Instruct patients to notify their healthcare professional of this potential interaction when they are receiving vaccinations (see Drug Interactions [7]).

  Manufactured by ADMA Biologics
  
  
  
  Boca Raton, FL 33487 USA
  
  
  
  U.S. License No. 2019
  
  
  
  
  
  
  
  RM-5640 Rev.003
• Renal dysfunction, acute renal failure, osmotic nephrosis, and death may occur with the administration of IGIV products in predisposed patients.
• Renal dysfunction and acute renal failure occur more commonly in patients receiving IGIV products containing sucrose. ASCENIV does not contain sucrose.
• For patients at risk of thrombosis, renal dysfunction or renal failure, administer ASCENIV at the
  minimum dose and infusion rate practicable. Ensure adequate hydration in patients before administration. Monitor for signs and
  symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity (
  
  
  

  see
  
  
  

  2.1 Dose

  The recommended dose of ASCENIV for replacement therapy in primary humoral immunodeficiency (PI) is 300 to 800 mg/kg body
  weight administered every 3 to 4 weeks. The dose may be adjusted over time to achieve the desired trough levels and clinical
  response.

  ASCENIV dose adjustments may be required in patients who fail to maintain trough total IgG concentrations of at least 500 mg/ dL with a target of 600 mg/dL. Starting with the second infusion, adjust the dose proportionally, targeting a trough of ≥ 600 mg/dL, based on the previous trough and the associated dose.

  For intravenous use only.

  Table 1

  Dose	Initial Infusion Rate	Maintenance Infusion Rate (if tolerated)
  300-800 mg/kg every 3-4 weeks	0.5 mg/kg/min (0.005 mL/kg/min) for the first 15 minutes	Increase gradually every 15 minutes (if tolerated) up to 8 mg/kg/min (0.08 mL/kg/min)

  2.3 Administration

  Begin with an initial infusion rate of 0.5 mg/kg/min. If there are no adverse reactions, the infusion rate for subsequent infusions can be slowly increased to the maximum rate.

  Monitor patient vital signs throughout the infusion. Slow or stop the infusion if adverse reactions occur. If symptoms subside promptly, the infusion may be resumed at a slower rate which is comfortable for the patient.

  Ensure that patients with pre-existing renal insufficiency are not volume-depleted. For patients judged to be at risk for
  renal dysfunction or thrombotic events, administer ASCENIV at the minimum infusion rate practicable, and consider discontinuation
  of administration if renal function deteriorates (

  see Boxed Warning, Warnings and Precautions [5.2, 5.3]

  ).

  ,
  
  
  

  5.3 Acute Renal Dysfunction and Acute Renal Failure

  Acute renal dysfunction/failure, osmotic nephrosis, and death^1,2may occur upon use of human IGIV products. Ensure that patients are not volume depleted before administering ASCENIV. Periodic monitoring of renal function and urine output is particularly important in patients judged to be at increased risk of developing acute renal failure.²Assess renal function, including measurement of blood urea nitrogen (BUN) and serum creatinine, before the initial infusion of ASCENIV and at appropriate intervals thereafter. If renal function deteriorates, consider discontinuing ASCENIV (see Patient Counseling Information [17]). In patients who are at risk of developing renal dysfunction, because of pre-existing renal insufficiency or predisposition to acute renal failure (such as diabetes mellitus, hypovolemia, overweight, use of concomitant nephrotoxic medicinal products or age of >65 years), administer ASCENIV at the minimum infusion rate practicable (see

  Dosage and Administration [2]

  ).

  ).
  
  
  

ASCENIV (immune globulin intravenous, human – slra) is a 10% immune globulin liquid for intravenous injection, indicated for the
treatment of primary humoral immunodeficiency (PI) in adults and adolescents (12 to 17 years of age). PI includes, but is not limited to,
the humoral immune defect in congenital agammaglobulinemia, common variable immunodeficiency (CVID), X-linked agammaglobulinemia,
Wiskott-Aldrich syndrome, and severe combined immunodeficiencies (SCID).

• Ensure that patients with pre-existing renal insufficiency are not volume depleted; discontinue ASCENIV if renal function
  deteriorates.
  
  
  
  5.3 Acute Renal Dysfunction and Acute Renal Failure

  Acute renal dysfunction/failure, osmotic nephrosis, and death^1,2may occur upon use of human IGIV products. Ensure that patients are not volume depleted before administering ASCENIV. Periodic monitoring of renal function and urine output is particularly important in patients judged to be at increased risk of developing acute renal failure.²Assess renal function, including measurement of blood urea nitrogen (BUN) and serum creatinine, before the initial infusion of ASCENIV and at appropriate intervals thereafter. If renal function deteriorates, consider discontinuing ASCENIV (see Patient Counseling Information [17]). In patients who are at risk of developing renal dysfunction, because of pre-existing renal insufficiency or predisposition to acute renal failure (such as diabetes mellitus, hypovolemia, overweight, use of concomitant nephrotoxic medicinal products or age of >65 years), administer ASCENIV at the minimum infusion rate practicable (see

  Dosage and Administration [2]

  ).
• For patients at risk of renal dysfunction or thrombotic events, administer ASCENIV at the minimum infusion rate practicable.
  
  
  
  
  5.2 Thrombosis

  Thrombosis may occur following treatment with immune globulin products, including ASCENIV.^4,5,6Risk factors may include: advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling central vascular catheters, hyperviscosity and cardiovascular risk factors. Thrombosis may occur in the absence of known risk factors.

  Consider baseline assessment of blood viscosity in patients at risk for hyperviscosity, including patients with cryoglobulins, fasting chylomicronemia/markedly high triacylglycerols (triglycerides), or monoclonal gammopathies. For patients at risk of thrombosis, administer ASCENIV at the minimum dose and infusion rate practicable. Ensure adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity (see

  Boxed Warning, Dosage and Administration [2], Patient Counseling Information [17]

  ).
  5.3 Acute Renal Dysfunction and Acute Renal Failure

  Acute renal dysfunction/failure, osmotic nephrosis, and death^1,2may occur upon use of human IGIV products. Ensure that patients are not volume depleted before administering ASCENIV. Periodic monitoring of renal function and urine output is particularly important in patients judged to be at increased risk of developing acute renal failure.²Assess renal function, including measurement of blood urea nitrogen (BUN) and serum creatinine, before the initial infusion of ASCENIV and at appropriate intervals thereafter. If renal function deteriorates, consider discontinuing ASCENIV (see Patient Counseling Information [17]). In patients who are at risk of developing renal dysfunction, because of pre-existing renal insufficiency or predisposition to acute renal failure (such as diabetes mellitus, hypovolemia, overweight, use of concomitant nephrotoxic medicinal products or age of >65 years), administer ASCENIV at the minimum infusion rate practicable (see

  Dosage and Administration [2]

  ).

ASCENIV is a liquid solution containing 10% IgG (100 mg/mL) for intravenous infusion.

Geriatric Use: In patients over age 65 or in any patient at risk of developing renal insufficiency, do not exceed the recommended dose, and infuse ASCENIV at the minimum infusion rate practicable.