Bivigam

• Thrombosis may occur with immune globulin (IGIV) products, including BIVIGAM. 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
  

  5.1 Thrombosis

  Thrombosis may occur following treatment with immune globulin products (IGIV), including BIVIGAM.^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 those with cryoglobulins, fasting chylomicronemia/markedly high triacylglycerols (triglycerides), or monoclonal gammopathies. For patients at risk of thrombosis, administer BIVIGAM 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 [2.3], Patient Counseling Information [17.2]

  ).

  ,
  

  17.2 Thrombosis

  Instruct patients to immediately report symptoms of thrombosis. These symptoms may include: 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 Warnings and Precautions [5.1]

  ).

  ).
  
• Use of Immune Globulin Intravenous (IGIV) products, particularly those containing sucrose, has been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death
  ^1,2. Patients at risk of acute renal failure include those with any degree of pre-existing renal insufficiency, diabetes mellitus, advanced age (above 65 years of age), volume depletion, sepsis, paraproteinemia, or receiving known nephrotoxic drugs (
  

  see
  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 BIVIGAM. Periodic monitoring of renal function and urine output is particularly important in patients judged to be at increased risk of developing acute renal failure². Assess renal function, including measurement of blood urea nitrogen (BUN) and serum creatinine, before the initial infusion of BIVIGAM and at appropriate intervals thereafter. If renal function deteriorates, consider discontinuing BIVIGAM (

  see Patient Counseling Information [17.1]

  ). 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 BIVIGAM at the minimum infusion rate practicable (

  see Dosage and Administration [2.3]

  ).
  )
  .
  
• Renal dysfunction and acute renal failure occur more commonly in patients receiving IGIV products containing sucrose. BIVIGAM does not contain sucrose.
• For patients at risk of thrombosis, renal dysfunction or renal failure, administer BIVIGAM 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
  2.2 Recommended Dose

  As there are significant differences in the half-life of IgG among patients with primary humoral immunodeficiency, the frequency and amount of immunoglobulin therapy may vary from patient to patient. The proper amount can be determined by monitoring clinical response.

  The recommended dose of BIVIGAM for replacement therapy in primary humoral immunodeficiency in adults and children 2 years of age and older, is 300 to 800 mg/kg body weight administered every 3 to 4 weeks. The dosage may be adjusted over time to achieve the desired trough levels and clinical response.

  BIVIGAM 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, the dose will be adjusted proportionally, targeting a trough of ≥ 600 mg/dL, based on the previous trough and the associated dose.

  ,
  

  2.3 Administration

  It has been reported that the frequency of adverse drug reactions to IGIV increases with the infusion rate. Initial infusion rates should be slow. If there are no adverse drug reactions, the infusion rate for subsequent infusions can be slowly increased to the maximum rate. For patients experiencing adverse drug reactions, it is advisable to reduce the infusion rate in subsequent infusions.

  Table 1: Recommended Infusion Rates for BIVIGAM

  Indication	Initial Infusion Rate (for first 10 minutes)	Maintenance Infusion Rate (if tolerated)
  PI	0.5 mg/kg/min (0.005 mL/kg/min)	Increase every 20 minutes (if tolerated) by 0.8 mg/kg/min up to 6 mg/kg/min.

  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 lower rate that 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 BIVIGAM at the minimum infusion rate practicable, and consider discontinuation of administration if renal function deteriorates (

  see Boxed Warning, Warnings and Precautions [5.1, 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 BIVIGAM. Periodic monitoring of renal function and urine output is particularly important in patients judged to be at increased risk of developing acute renal failure². Assess renal function, including measurement of blood urea nitrogen (BUN) and serum creatinine, before the initial infusion of BIVIGAM and at appropriate intervals thereafter. If renal function deteriorates, consider discontinuing BIVIGAM (

  see Patient Counseling Information [17.1]

  ). 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 BIVIGAM at the minimum infusion rate practicable (

  see Dosage and Administration [2.3]

  ).
  ).

Indications and Usage, Primary Humoral Immunodeficiency (

Dosage and Administration, Recommended Dose (

BIVIGAM is an Immune Globulin Intravenous (Human), 10% Liquid, indicated for the treatment of adults and pediatric patients 2 years of age and older with primary humoral immunodeficiency (PI).

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

• Pregnancy: Use in pregnant women has not been evaluated. Use BIVIGAM in pregnant women only if clearly needed.
  
  8.1 Pregnancy

  No human data are available to indicate the presence or absence of drug-associated risk. Animal reproductive studies have not been conducted with BIVIGAM. It is not known whether BIVIGAM can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Immune globulins cross the placenta from maternal circulation increasingly after 30 weeks of gestation. BIVIGAM should be given to pregnant women only if clearly needed. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
• 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 BIVIGAM at the minimum infusion rate practicable.
  
  8.5 Geriatric Use

  BIVIGAM should be used with caution in patients age 65 and over who are judged to be at increased risk of developing renal insufficiency or thrombotic events

  (see Boxed Warning, Warnings and Precautions [5.1, 5.3]

  ). Do not exceed recommended doses and administer BIVIGAM at the minimum infusion rate practicable.

  BIVIGAM was evaluated in 9 patients age 65 and older with PI. This number of geriatric patients is not sufficient to determine whether they respond differently from younger patients (

  see Clinical Studies [14]

  ).