Privigen

— THERAPEUTIC CATEGORIES —
  • Bleeding disorders
  • Miscellaneous immune disorders
  • Primary immune deficiency
PAGE CONTENTS
  • Jump to Section
  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Privigen Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Immune globulin (human) 0.1g/mL; soln for IV infusion; contains L-proline; sucrose-, preservative-, and latex-free.

    Pharmacological Class

    Immune globulin.

    How Supplied

    Single-use vial (50mL, 100mL, 200mL, 400mL)—1

    Storage

    When stored at room temperature (up to 25ºC [77ºF]), Privigen is stable for up to 36 months, as indicated by the expiration date printed on the outer carton and vial label. Do not freeze.

    Manufacturer

    CSL Behring, LLC

    Generic Availability

    NO

    Privigen Indications

    Indications

    Chronic immune thrombocytopenic purpura (ITP).

    Privigen Dosage and Administration

    Adults and Children

    <15yrs: not established. ≥15yrs: Give by IV infusion at an initial rate of 0.5mg/kg/min, if tolerated may increase to 4mg/kg/min. Renal dysfunction, thrombosis risk: give at the minimum infusion rate practicable. Usual dose: 1g/kg once daily for 2 consecutive days for a total dose of 2g/kg. Increased risk of thrombosis, hemolysis, acute renal injury, or volume overload: consider carefully the relative risks and benefits before prescribing high dose regimen (2g/kg).

    Privigen Contraindications

    Contraindications

    IgA-deficiency with antibodies against IgA and history of hypersensitivity. Privigen contains trace amounts of IgA (≤25mcg/mL). Hyperprolinemia (contains the stabilizer L-proline). Previous severe reaction to human immune globulin.

    Privigen Boxed Warnings

    Boxed Warning

    Thrombosis. Renal dysfunction. Acute renal failure.

    Boxed Warning

    Thrombosis may occur with immune globulin products.

    Renal dysfunction, acute renal failure, osmotic nephrosis, and death may occur with immune globulin intravenous (IGIV) products in predisposed patients (eg, pre-existing renal insufficiency, diabetes mellitus, age >65 years, volume depletion, sepsis, paraproteinemia, receiving nephrotoxic drugs).

    For patients at risk of thrombosis, renal dysfunction or failure: administer at the minimum dose and infusion rate practicable. Ensure adequate hydration and monitor for signs/symptoms of thrombosis. Assess blood viscosity in patients at risk for hyperviscosity.

    Privigen Warnings/Precautions

    Warnings/Precautions

    Advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling central vascular catheters, hyperviscosity, cardiovascular risk factors: increased risk of thrombosis. Monitor for signs/symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity. Pre-existing renal insufficiency, diabetes, >65yrs, obese, hypovolemia: increased risk of renal dysfunction and acute renal failure. Correct volume depletion; assess renal function, BUN, serum creatinine, urine output before and during therapy; discontinue if renal function deteriorates. Monitor for aseptic meningitis, hemolysis, delayed hemolytic anemia, transfusion-related acute lung injury (eg, respiratory distress, pulmonary edema, hypoxemia). History of hypertension. Monitor BP before, during and after infusions. Antibody formation. Risk of transmission of viral diseases. Have epinephrine inj available. Elderly. Pregnancy. Nursing mothers.

    Warnings/Precautions

    Hypersensitivity

    Infusion of Privigen should be discontinued immediately if hypersensitivity occurs. Epinephrine should be available to treat acute hypersensitivity reactions. 

    Privigen contains trace amounts of IgA (≤25mcg/mL). Individuals with IgA deficiency can develop anti-IgA antibodies and anaphylactic reactions (including anaphylaxis and shock) after administration of blood components containing IgA. Patients with known antibodies to IgA may have a greater risk of developing potentially severe hypersensitivity and anaphylactic reactions with administration of Privigen.

    Renal Dysfunction and Acute Renal Failure

    In predisposed patient (eg, pre-existing renal insufficiency, diabetes mellitus, hypovolemia, obese, concomitant nephrotoxic drugs, >65 years old), renal dysfunction, acute renal failure, osmotic nephrosis, and death may occur with immune globulin IV products. Acute renal failure may also occur as a result of Privigen-induced hemolysis.

    Before initial infusion of Privigen, ensure that patients are not volume depleted and assess renal function (eg, measure BUN and serum creatinine) at appropriate intervals thereafter. Consider discontinuing Privigen if renal function deteriorates. For those judged to be at risk of developing renal dysfunction, administer Privigen at the minimum rate of infusion practicable. 

    Thrombosis

    Thrombosis may occur with immune globulin products. Risk factors 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, though thrombosis may occur in the absence of these risk factors. For patients at risk of thrombosis, Privigen should be administered at the minimum dose and infusion rate practicable; ensure adequate hydration before administration.

    Patients at risk for hyperviscosity (eg, those with cryoglobulins, fasting chylomicronemia/markedly high triacylglycerols [triglycerides], or monoclonal gammopathies): consider baseline assessment of blood viscosity. 

    Hyperproteinemia, Increased Serum Viscosity, and Hyponatremia

    Hyponatremia is likely to be a pseudohyponatremia, as demonstrated by a decreased calculated serum osmolality or elevated osmolar gap. It is critical to distinguish true hyponatremia from pseudohyponatremia, as treatment aimed at decreasing serum free water in patients with pseudohyponatremia may lead to volume depletion, a further increase in serum viscosity, and a possible predisposition to thromboembolic events

    Aseptic Meningitis Syndrome

    Aseptic meningitis syndrome (AMS) may occur with Privigen though it is infrequent. It may occur more frequently in association with high doses (2g/kg) and/or rapid infusion of IGIV.

    AMS signs/symptoms: severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, nausea, and vomiting.

    AMS usually begins within several hours to 2 days after IGIV treatment. Discontinuation of treatment has resulted in remission within several days without sequelae.

    Hemolysis

    Privigen may contain blood group antibodies that can act as hemolysins and induce

    in vivo coating of red blood cells with immunoglobulin, causing a positive direct antiglobulin test (Coombs’ test) result and hemolysis. Delayed hemolytic anemia can develop subsequent to Privigen therapy. Cases of severe hemolysis-related renal dysfunction/failure or disseminated intravascular coagulation have been reported.

    High doses (eg, ≥2g/kg), given either as a single administration or divided over several days, and non-O blood group are risk factors associated with hemolysis development.

    Closely monitor for signs/symptoms of hemolysis, particularly in patients with risk factors and those with pre-existing anemia and/or cardiovascular or pulmonary compromise. In higher risk patients, consider lab testing (eg, hemoglobin/hematocrit measurement prior to infusion and within approximately 36 hours and again 7-10 days post infusion). If transfusion is indicated for patients who develop hemolysis with clinically compromising anemia after receiving IGIV, perform adequate cross-matching to avoid exacerbating on-going hemolysis.

    Hypertension

    Elevations of systolic blood pressure to ≥180 mm Hg and/or of diastolic blood pressure to >120 mm Hg (hypertensive urgency) have been observed during and/or shortly following infusion of Privigen; these elevations were reported more frequently in patients with a history of hypertension. Blood pressure should be monitored prior to, during, and following Privigen infusion.

    Transfusion-Related Acute Lung Injury (TRALI)

    TRALI is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever. Symptoms typically appear within 1 to 6 hours following treatment. 

    Monitor for pulmonary adverse reactions. Test for the presence of anti-neutrophil antibodies and anti-human leukocyte antigen antibodies in both the product and the patient’s serum if TRALI is suspected. May be managed with oxygen therapy with adequate ventilatory support.

    Volume Overload

    Carefully consider the relative risks and benefits before prescribing the high dose regimen in patients at increased risk of thrombosis, hemolysis, acute kidney injury, or volume overload.

    Transmissible Infectious Agents

    Because Privigen is made from human blood, it may carry a risk of transmitting infectious agents (eg, viruses, the variant Creutzfeldt Jakob disease agent and, theoretically, the Creutzfeldt Jakob disease agent).

    The risk of infectious agent transmission has been reduced by screening plasma donors for prior exposure to certain viruses, testing for the presence of certain current virus infections, and including virus inactivation/removal steps in the manufacturing process for Privigen.

    Interference with Laboratory Tests

    Various passively transferred antibodies in immunoglobulin preparations may lead to misinterpretation of the results of serological testing.

    Pregnancy Considerations

    No human data are available to indicate the presence or absence of drug-associated risk. Immune globulins cross the placenta from maternal circulation increasingly after 30 weeks of gestation. Give Privigen to pregnant patients only if clearly needed.

    Nursing Mother Considerations

    No human data are available to indicate the presence or absence of drug-associated risk. Consider the benefits to the mother vs the potential risks on the breastfed infant.

    Pediatric Considerations

    Safety and effectiveness of Privigen have not been established in pediatric patients with chronic ITP who are under the age of 15.

    Geriatric Considerations

    Clinical studies did not include sufficient numbers of patients age 65 and over to determine whether they respond differently from younger subjects. Use caution in patients age 65 and over who are judged to be at increased risk of developing acute renal insufficiency and thrombosis. Do not exceed recommended doses, and administer Priviegn at the minimum dose and infusion rate practicable.

    Privigen Pharmacokinetics

    See Literature

    Privigen Interactions

    Interactions

    Concomitant nephrotoxic drugs: increased risk of renal toxicity. May affect response to live virus vaccines. May interfere with serological test interpretation.

    Privigen Adverse Reactions

    Adverse Reactions

    Headache, fatigue, nausea, chills, vomiting, pain (back, pharyngolaryngeal, extremity), elevated body temperature, abdominal pain, diarrhea, cough, stomach discomfort, chest pain, joint swelling/effusion, influenza-like illness, urticaria, dizziness, hemolysis, anemia, asthenia, hypertension, leukopenia, rash; hypersensitivity, hyperproteinemia, increased serum viscosity, hyponatremia; rare: aseptic meningitis syndrome (esp. high dose of 2g/kg), TRALI, thrombosis.

    Privigen Clinical Trials

    Clinical Trials

    Prospective, open-label, single-arm, multicenter study.

    Efficacy, safety, and tolerability of Privigen was evaluated in 57 patients with chronic ITP and a platelet count of 20 x 109/L or less.

    Patients received a 2g/kg dosage of Privigen administered as 1g/kg (10mL/kg) intravenous infusion daily for 2 consecutive days, and were observed for 29 days.

    Primary endpoint: response rate defined as the percentage of patients with an increase in platelet counts to at least 50 x 109/L within 7 days after the first infusion (responders).

    Of the 57 patients in the efficacy analysis, 46 (80.7%) responded to Privigen with a rise in platelet counts to at least 50 x 109/L within 7 days after the first infusion.

    Privigen Note

    Not Applicable

    Privigen Patient Counseling

    Patient Counseling

    Inform patients of the early signs of hypersensitivity reactions to Privigen (including hives,

    generalized urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis).

    Report the following signs/symptoms immediately: 

    • Decreased urine output, sudden weight gain, fluid retention/edema, and/or shortness of breath (may suggest kidney problems).
    • Pain and/or swelling of an arm or leg with warmth over the affected area, discoloration of an arm or leg, unexplained shortness of breath, chest pain or discomfort that worsens on deep breathing, unexplained rapid pulse, numbness or weakness on one side of the body (may be symptoms of thrombosis).
    • Severe headache, neck stiffness, drowsiness, fever, sensitivity to light, painful eye movements, nausea, and vomiting (may be symptoms of aseptic meningitis syndrome).
    • Fatigue, increased heart rate, yellowing of skin or eyes, and dark-colored urine (may suggest hemolysis).
    • Severe breathing problems, lightheadedness, drops in blood pressure, and fever (may suggest TRALI).

    Though the risk is reduced, Privigen is made from human blood and may contain infectious agents that can cause disease.

    Administration of IgG may interfere with the response to live virus vaccines.

    Privigen Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Immune globulin (human) 0.1g/mL; soln for IV infusion; contains L-proline; sucrose-, preservative-, and latex-free.

    Pharmacological Class

    Immune globulin.

    How Supplied

    Single-use vial (50mL, 100mL, 200mL, 400mL)—1

    Storage

    When stored at room temperature (up to 25ºC [77ºF]), Privigen is stable for up to 36 months, as indicated by the expiration date printed on the outer carton and vial label. Do not freeze.

    Manufacturer

    CSL Behring, LLC

    Generic Availability

    NO

    Privigen Indications

    Indications

    Chronic inflammatory demyelinating polyneuropathy (CIDP) to improve neuromuscular disability and impairment.

    Limitations of Use

    Not studied for maintenance therapy longer than 6 months. Individualize the duration of any treatment beyond 6 months based on patient's response and demonstrated need for continued therapy.

    Privigen Dosage and Administration

    Adult

    ≥18yrs: Give by IV infusion at an initial rate of 0.5mg/kg/min, if tolerated may increase to 8mg/kg/min. Renal dysfunction, thrombosis risk, or volume overload: give at the minimum infusion rate practicable. Loading dose: 2g/kg in divided doses over 2–5 consecutive days. Maintenance: 1g/kg as a single infusion given in one day or divided into two infusions on 2 consecutive days, every 3 weeks.

    Children

    <18yrs: not established.

    Privigen Contraindications

    Contraindications

    IgA-deficiency with antibodies against IgA and history of hypersensitivity. Privigen contains trace amounts of IgA (≤25mcg/mL). Hyperprolinemia (contains the stabilizer L-proline). Previous severe reaction to human immune globulin.

    Privigen Boxed Warnings

    Boxed Warning

    Thrombosis. Renal dysfunction. Acute renal failure.

    Boxed Warning

    Thrombosis may occur with immune globulin products.

    Renal dysfunction, acute renal failure, osmotic nephrosis, and death may occur with immune globulin intravenous (IGIV) products in predisposed patients (eg, pre-existing renal insufficiency, diabetes mellitus, age >65 years, volume depletion, sepsis, paraproteinemia, receiving nephrotoxic drugs).

    For patients at risk of thrombosis, renal dysfunction or failure: administer at the minimum dose and infusion rate practicable. Ensure adequate hydration and monitor for signs/symptoms of thrombosis. Assess blood viscosity in patients at risk for hyperviscosity.

    Privigen Warnings/Precautions

    Warnings/Precautions

    Advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling central vascular catheters, hyperviscosity, cardiovascular risk factors: increased risk of thrombosis. Monitor for signs/symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity. Pre-existing renal insufficiency, diabetes, >65yrs, obese, hypovolemia: increased risk of renal dysfunction and acute renal failure. Correct volume depletion; assess renal function, BUN, serum creatinine, urine output before and during therapy; discontinue if renal function deteriorates. Monitor for aseptic meningitis, hemolysis, delayed hemolytic anemia, transfusion-related acute lung injury (eg, respiratory distress, pulmonary edema, hypoxemia). History of hypertension. Monitor BP before, during and after infusions. Antibody formation. Risk of transmission of viral diseases. Have epinephrine inj available. Elderly. Pregnancy. Nursing mothers.

    Warnings/Precautions

    Hypersensitivity

    Infusion of Privigen should be discontinued immediately if hypersensitivity occurs. Epinephrine should be available to treat acute hypersensitivity reactions. 

    Privigen contains trace amounts of IgA (≤25mcg/mL). Individuals with IgA deficiency can develop anti-IgA antibodies and anaphylactic reactions (including anaphylaxis and shock) after administration of blood components containing IgA. Patients with known antibodies to IgA may have a greater risk of developing potentially severe hypersensitivity and anaphylactic reactions with administration of Privigen.

    Renal Dysfunction and Acute Renal Failure

    In predisposed patient (eg, pre-existing renal insufficiency, diabetes mellitus, hypovolemia, obese, concomitant nephrotoxic drugs, >65 years old), renal dysfunction, acute renal failure, osmotic nephrosis, and death may occur with immune globulin IV products. Acute renal failure may also occur as a result of Privigen-induced hemolysis.

    Before initial infusion of Privigen, ensure that patients are not volume depleted and assess renal function (eg, measure BUN and serum creatinine) at appropriate intervals thereafter. Consider discontinuing Privigen if renal function deteriorates. For those judged to be at risk of developing renal dysfunction, administer Privigen at the minimum rate of infusion practicable. 

    Thrombosis

    Thrombosis may occur with immune globulin products. Risk factors 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, though thrombosis may occur in the absence of these risk factors. For patients at risk of thrombosis, Privigen should be administered at the minimum dose and infusion rate practicable; ensure adequate hydration before administration.

    Patients at risk for hyperviscosity (eg, those with cryoglobulins, fasting chylomicronemia/markedly high triacylglycerols [triglycerides], or monoclonal gammopathies): consider baseline assessment of blood viscosity. 

    Hyperproteinemia, Increased Serum Viscosity, and Hyponatremia

    Hyponatremia is likely to be a pseudohyponatremia, as demonstrated by a decreased calculated serum osmolality or elevated osmolar gap. It is critical to distinguish true hyponatremia from pseudohyponatremia, as treatment aimed at decreasing serum free water in patients with pseudohyponatremia may lead to volume depletion, a further increase in serum viscosity, and a possible predisposition to thromboembolic events

    Aseptic Meningitis Syndrome

    Aseptic meningitis syndrome (AMS) may occur with Privigen though it is infrequent. It may occur more frequently in association with high doses (2g/kg) and/or rapid infusion of IGIV.

    AMS signs/symptoms: severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, nausea, and vomiting.

    AMS usually begins within several hours to 2 days after IGIV treatment. Discontinuation of treatment has resulted in remission within several days without sequelae.

    Hemolysis

    Privigen may contain blood group antibodies that can act as hemolysins and induce

    in vivo coating of red blood cells with immunoglobulin, causing a positive direct antiglobulin test (Coombs’ test) result and hemolysis. Delayed hemolytic anemia can develop subsequent to Privigen therapy. Cases of severe hemolysis-related renal dysfunction/failure or disseminated intravascular coagulation have been reported.

    High doses (eg, ≥2g/kg), given either as a single administration or divided over several days, and non-O blood group are risk factors associated with hemolysis development.

    Closely monitor for signs/symptoms of hemolysis, particularly in patients with risk factors and those with pre-existing anemia and/or cardiovascular or pulmonary compromise. In higher risk patients, consider lab testing (eg, hemoglobin/hematocrit measurement prior to infusion and within approximately 36 hours and again 7-10 days post infusion). If transfusion is indicated for patients who develop hemolysis with clinically compromising anemia after receiving IGIV, perform adequate cross-matching to avoid exacerbating on-going hemolysis.

    Hypertension

    Elevations of systolic blood pressure to ≥180 mm Hg and/or of diastolic blood pressure to >120 mm Hg (hypertensive urgency) have been observed during and/or shortly following infusion of Privigen; these elevations were reported more frequently in patients with a history of hypertension. Blood pressure should be monitored prior to, during, and following Privigen infusion.

    Transfusion-Related Acute Lung Injury (TRALI)

    TRALI is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever. Symptoms typically appear within 1 to 6 hours following treatment. 

    Monitor for pulmonary adverse reactions. Test for the presence of anti-neutrophil antibodies and anti-human leukocyte antigen antibodies in both the product and the patient’s serum if TRALI is suspected. May be managed with oxygen therapy with adequate ventilatory support.

    Volume Overload

    Carefully consider the relative risks and benefits before prescribing the high dose regimen in patients at increased risk of thrombosis, hemolysis, acute kidney injury, or volume overload.

    Transmissible Infectious Agents

    Because Privigen is made from human blood, it may carry a risk of transmitting infectious agents (eg, viruses, the variant Creutzfeldt Jakob disease agent and, theoretically, the Creutzfeldt Jakob disease agent).

    The risk of infectious agent transmission has been reduced by screening plasma donors for prior exposure to certain viruses, testing for the presence of certain current virus infections, and including virus inactivation/removal steps in the manufacturing process for Privigen.

    Interference with Laboratory Tests

    Various passively transferred antibodies in immunoglobulin preparations may lead to misinterpretation of the results of serological testing.

    Pregnancy Considerations

    No human data are available to indicate the presence or absence of drug-associated risk. Immune globulins cross the placenta from maternal circulation increasingly after 30 weeks of gestation. Give Privigen to pregnant patients only if clearly needed.

    Nursing Mother Considerations

    No human data are available to indicate the presence or absence of drug-associated risk. Consider the benefits to the mother vs the potential risks on the breastfed infant.

    Pediatric Considerations

    Safety and effectiveness of Privigen have not been established in pediatric patients with CIDP who are under the age of 18 years.

    Geriatric Considerations

    Safety and effectiveness of Privigen in CIDP patients age 65 and over was similar to those under age 65. Use caution in patients age 65 and over who are judged to be at increased risk of developing acute renal insufficiency and thrombosis. Do not exceed recommended doses, and administer Priviegn at the minimum dose and infusion rate practicable.

    Privigen Pharmacokinetics

    See Literature

    Privigen Interactions

    Interactions

    Concomitant nephrotoxic drugs: increased risk of renal toxicity. May affect response to live virus vaccines. May interfere with serological test interpretation.

    Privigen Adverse Reactions

    Adverse Reactions

    Headache, fatigue, nausea, chills, vomiting, pain (back, pharyngolaryngeal, extremity), elevated body temperature, abdominal pain, diarrhea, cough, stomach discomfort, chest pain, joint swelling/effusion, influenza-like illness, urticaria, dizziness, hemolysis, anemia, asthenia, hypertension, leukopenia, rash; hypersensitivity, hyperproteinemia, increased serum viscosity, hyponatremia; rare: aseptic meningitis syndrome (esp. high dose of 2g/kg), TRALI, thrombosis.

    Privigen Clinical Trials

    Clinical Trials

    PRIMA trial

    • Prospective, open-label, single-arm, multicenter clinical study.
    • 28 patients with CIDP (13 IGIV-pretreated and 15 IGIV-untreated) received a Privigen loading dose of 2g/kg followed by Privigen maintenance doses of 1g/kg for up to 21 weeks with a 3 week follow up.
    • Primary endpoint: responder rate of Privigen vs historical control in the adjusted 10-point Inflammatory Neuropathy Cause and Treatment (INCAT) score.
    • Responder rate was defined as the proportion of subjects who demonstrated clinically meaningful improvement (at least 1 point decrease on adjusted INCAT score) between baseline and week 25, with a pre-specified threshold of 35% in the lower limit of the 2-sided 95% Wilson-Score CI.
    • Overall percentage of responders  was 61% (95% CI, 42.4-76.4). 
    • Response rates were 47% in IGIV-untreated and 77% in IGIV-pretreated patient subgroups.
    • Overall median time to first adjusted INCAT response was 7.5 weeks.

    PATH trial

    • Same Privigen dosing regimen as in the PRIMA study.
    • 207 IGIV-pretreated patients who had relapsed following withdrawal of IGIV prior to being administered Privigen.
    • Response rate was 73%.
    • Among the 151 patients in the PATH study who had deteriorated by 1 or more points in adjusted INCAT score following withdrawal of IGIV, 137 patients (90.7%) responded during the Privigen “restabilization” period with an increase of 1 or more adjusted INCAT score points.
    • Median time to first adjusted INCAT response was 3.7 weeks.

    Privigen Note

    Not Applicable

    Privigen Patient Counseling

    Patient Counseling

    Inform patients of the early signs of hypersensitivity reactions to Privigen (including hives,

    generalized urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis).

    Report the following signs/symptoms immediately: 

    • Decreased urine output, sudden weight gain, fluid retention/edema, and/or shortness of breath (may suggest kidney problems).
    • Pain and/or swelling of an arm or leg with warmth over the affected area, discoloration of an arm or leg, unexplained shortness of breath, chest pain or discomfort that worsens on deep breathing, unexplained rapid pulse, numbness or weakness on one side of the body (may be symptoms of thrombosis).
    • Severe headache, neck stiffness, drowsiness, fever, sensitivity to light, painful eye movements, nausea, and vomiting (may be symptoms of aseptic meningitis syndrome).
    • Fatigue, increased heart rate, yellowing of skin or eyes, and dark-colored urine (may suggest hemolysis).
    • Severe breathing problems, lightheadedness, drops in blood pressure, and fever (may suggest TRALI).

    Though the risk is reduced, Privigen is made from human blood and may contain infectious agents that can cause disease.

    Administration of IgG may interfere with the response to live virus vaccines.

    Privigen Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Immune globulin (human) 0.1g/mL; soln for IV infusion; contains L-proline; sucrose-, preservative-, and latex-free.

    Pharmacological Class

    Immune globulin.

    How Supplied

    Single-use vial (50mL, 100mL, 200mL, 400mL)—1

    Storage

    When stored at room temperature (up to 25ºC [77ºF]), Privigen is stable for up to 36 months, as indicated by the expiration date printed on the outer carton and vial label. Do not freeze.

    Manufacturer

    CSL Behring, LLC

    Generic Availability

    NO

    Privigen Indications

    Indications

    As replacement therapy for primary humoral immunodeficiency (eg, congenital agammaglobulinemia, X-linked agammaglobulinemia, common variable immunodeficiency, Wiskott-Aldrich syndrome, severe combined immunodeficiencies).

    Privigen Dosage and Administration

    Adults and Children

    <3yrs: not established. ≥3yrs: Give by IV infusion at an initial rate of 0.5mg/kg/min, if tolerated may increase to 8mg/kg/min. Renal dysfunction, thrombosis risk: give at the minimum infusion rate practicable. Usual dose: 200–800mg/kg every 3–4 weeks. Adjust subsequent dose based on serum IgG trough levels and clinical response.

    Adults and Children

    The proper amount of immune globulin therapy can be determined by monitoring clinical response. Dosage should be adjusted over time to achieve the desired serum IgG trough levels and clinical responses. 

    The recommended dose is 200-800mg/kg administered every 3-4 weeks. 

    Initial infusion rate: 0.5mg/kg/min.

    Maintenance infusion rate (as tolerated): increase to 8mg/kg/min. 

    Administer a missed dose as soon as possible and then resume the scheduled treatments every 3-4 weeks, as applicable.

    Measles exposure

    • An extra dose may be prudent as soon as possible and within 6 days of exposure. 
    • A dose of 400mg/kg should provide a serum level >240mIU/mL of measles antibodies for at least 2 weeks.
    • Patient at risk of future measles exposure and receives dose <530mg/kg every 3-4 weeks: increase dose to at least 530mg/kg; this should provide a serum level of 240mIU/mL of measles antibodies for at least 22 days after infusion.

    Privigen Contraindications

    Contraindications

    IgA-deficiency with antibodies against IgA and history of hypersensitivity. Privigen contains trace amounts of IgA (≤25mcg/mL). Hyperprolinemia (contains the stabilizer L-proline). Previous severe reaction to human immune globulin.

    Privigen Boxed Warnings

    Boxed Warning

    Thrombosis. Renal dysfunction. Acute renal failure.

    Boxed Warning

    Thrombosis may occur with immune globulin products.

    Renal dysfunction, acute renal failure, osmotic nephrosis, and death may occur with immune globulin intravenous (IGIV) products in predisposed patients (eg, pre-existing renal insufficiency, diabetes mellitus, age >65 years, volume depletion, sepsis, paraproteinemia, receiving nephrotoxic drugs).

    For patients at risk of thrombosis, renal dysfunction or failure: administer at the minimum dose and infusion rate practicable. Ensure adequate hydration and monitor for signs/symptoms of thrombosis. Assess blood viscosity in patients at risk for hyperviscosity.

    Privigen Warnings/Precautions

    Warnings/Precautions

    Advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling central vascular catheters, hyperviscosity, cardiovascular risk factors: increased risk of thrombosis. Monitor for signs/symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity. Pre-existing renal insufficiency, diabetes, >65yrs, obese, hypovolemia: increased risk of renal dysfunction and acute renal failure. Correct volume depletion; assess renal function, BUN, serum creatinine, urine output before and during therapy; discontinue if renal function deteriorates. Monitor for aseptic meningitis, hemolysis, delayed hemolytic anemia, transfusion-related acute lung injury (eg, respiratory distress, pulmonary edema, hypoxemia). History of hypertension. Monitor BP before, during and after infusions. Antibody formation. Risk of transmission of viral diseases. Have epinephrine inj available. Elderly. Pregnancy. Nursing mothers.

    Warnings/Precautions

    Hypersensitivity

    Infusion of Privigen should be discontinued immediately if hypersensitivity occurs. Epinephrine should be available to treat acute hypersensitivity reactions. 

    Privigen contains trace amounts of IgA (≤25mcg/mL). Individuals with IgA deficiency can develop anti-IgA antibodies and anaphylactic reactions (including anaphylaxis and shock) after administration of blood components containing IgA. Patients with known antibodies to IgA may have a greater risk of developing potentially severe hypersensitivity and anaphylactic reactions with administration of Privigen.

    Renal Dysfunction and Acute Renal Failure

    In predisposed patient (eg, pre-existing renal insufficiency, diabetes mellitus, hypovolemia, obese, concomitant nephrotoxic drugs, >65 years old), renal dysfunction, acute renal failure, osmotic nephrosis, and death may occur with immune globulin IV products. Acute renal failure may also occur as a result of Privigen-induced hemolysis.

    Before initial infusion of Privigen, ensure that patients are not volume depleted and assess renal function (eg, measure BUN and serum creatinine) at appropriate intervals thereafter. Consider discontinuing Privigen if renal function deteriorates. For those judged to be at risk of developing renal dysfunction, administer Privigen at the minimum rate of infusion practicable. 

    Thrombosis

    Thrombosis may occur with immune globulin products. Risk factors 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, though thrombosis may occur in the absence of these risk factors. For patients at risk of thrombosis, Privigen should be administered at the minimum dose and infusion rate practicable; ensure adequate hydration before administration.

    Patients at risk for hyperviscosity (eg, those with cryoglobulins, fasting chylomicronemia/markedly high triacylglycerols [triglycerides], or monoclonal gammopathies): consider baseline assessment of blood viscosity. 

    Hyperproteinemia, Increased Serum Viscosity, and Hyponatremia

    Hyponatremia is likely to be a pseudohyponatremia, as demonstrated by a decreased calculated serum osmolality or elevated osmolar gap. It is critical to distinguish true hyponatremia from pseudohyponatremia, as treatment aimed at decreasing serum free water in patients with pseudohyponatremia may lead to volume depletion, a further increase in serum viscosity, and a possible predisposition to thromboembolic events

    Aseptic Meningitis Syndrome

    Aseptic meningitis syndrome (AMS) may occur with Privigen though it is infrequent. It may occur more frequently in association with high doses (2g/kg) and/or rapid infusion of IGIV.

    AMS signs/symptoms: severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, nausea, and vomiting.

    AMS usually begins within several hours to 2 days after IGIV treatment. Discontinuation of treatment has resulted in remission within several days without sequelae.

    Hemolysis

    Privigen may contain blood group antibodies that can act as hemolysins and induce

    in vivo coating of red blood cells with immunoglobulin, causing a positive direct antiglobulin test (Coombs’ test) result and hemolysis. Delayed hemolytic anemia can develop subsequent to Privigen therapy. Cases of severe hemolysis-related renal dysfunction/failure or disseminated intravascular coagulation have been reported.

    High doses (eg, ≥2g/kg), given either as a single administration or divided over several days, and non-O blood group are risk factors associated with hemolysis development.

    Closely monitor for signs/symptoms of hemolysis, particularly in patients with risk factors and those with pre-existing anemia and/or cardiovascular or pulmonary compromise. In higher risk patients, consider lab testing (eg, hemoglobin/hematocrit measurement prior to infusion and within approximately 36 hours and again 7-10 days post infusion). If transfusion is indicated for patients who develop hemolysis with clinically compromising anemia after receiving IGIV, perform adequate cross-matching to avoid exacerbating on-going hemolysis.

    Hypertension

    Elevations of systolic blood pressure to ≥180 mm Hg and/or of diastolic blood pressure to >120 mm Hg (hypertensive urgency) have been observed during and/or shortly following infusion of Privigen; these elevations were reported more frequently in patients with a history of hypertension. Blood pressure should be monitored prior to, during, and following Privigen infusion.

    Transfusion-Related Acute Lung Injury (TRALI)

    TRALI is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever. Symptoms typically appear within 1 to 6 hours following treatment. 

    Monitor for pulmonary adverse reactions. Test for the presence of anti-neutrophil antibodies and anti-human leukocyte antigen antibodies in both the product and the patient’s serum if TRALI is suspected. May be managed with oxygen therapy with adequate ventilatory support.

    Volume Overload

    Carefully consider the relative risks and benefits before prescribing the high dose regimen in patients at increased risk of thrombosis, hemolysis, acute kidney injury, or volume overload.

    Transmissible Infectious Agents

    Because Privigen is made from human blood, it may carry a risk of transmitting infectious agents (eg, viruses, the variant Creutzfeldt Jakob disease agent and, theoretically, the Creutzfeldt Jakob disease agent).

    The risk of infectious agent transmission has been reduced by screening plasma donors for prior exposure to certain viruses, testing for the presence of certain current virus infections, and including virus inactivation/removal steps in the manufacturing process for Privigen.

    Interference with Laboratory Tests

    Various passively transferred antibodies in immunoglobulin preparations may lead to misinterpretation of the results of serological testing.

    Pregnancy Considerations

    No human data are available to indicate the presence or absence of drug-associated risk. Immune globulins cross the placenta from maternal circulation increasingly after 30 weeks of gestation. Give Privigen to pregnant patients only if clearly needed.

    Nursing Mother Considerations

    No human data are available to indicate the presence or absence of drug-associated risk. Consider the benefits to the mother vs the potential risks on the breastfed infant.

    Pediatric Considerations

    Privigen was evaluated in 31 pediatric subjects (19 children and 12 adolescents) with PI (prospective, open label, single arm, multicenter clinical study). There were no apparent differences in the safety and efficacy profiles as compared to those in adult patients. The safety and effectiveness of Privigen have not been studied in clinical trials in pediatric patients with PI who are under the age of 3 years.

     

    Geriatric Considerations

    Clinical studies did not include sufficient numbers of patients age 65 and over to determine whether they respond differently from younger subjects. Use caution in patients age 65 and over who are judged to be at increased risk of developing acute renal insufficiency and thrombosis. Do not exceed recommended doses, and administer Priviegn at the minimum dose and infusion rate practicable.

    Privigen Pharmacokinetics

    See Literature

    Privigen Interactions

    Interactions

    Concomitant nephrotoxic drugs: increased risk of renal toxicity. May affect response to live virus vaccines. May interfere with serological test interpretation.

    Privigen Adverse Reactions

    Adverse Reactions

    Headache, fatigue, nausea, chills, vomiting, pain (back, pharyngolaryngeal, extremity), elevated body temperature, abdominal pain, diarrhea, cough, stomach discomfort, chest pain, joint swelling/effusion, influenza-like illness, urticaria, dizziness, hemolysis, anemia, asthenia, hypertension, leukopenia, rash; hypersensitivity, hyperproteinemia, increased serum viscosity, hyponatremia; rare: aseptic meningitis syndrome (esp. high dose of 2g/kg), TRALI, thrombosis.

    Privigen Clinical Trials

    Clinical Trials

    Prospective, open-label, single-arm, multicenter study.

    Efficacy, safety, and pharmacokinetics of Privigen was evaluated in adult and pediatric patients with PI, who were treated for 12 months at a 3-week or 4-week dosing interval. 

    Efficacy analysis included 80 patients, 16 (20%) on the 3-week dosing interval (median dose was 428.3mg/kg per infusion) and 64 (80%) on the 4-week dosing interval (median dose was 440.6mg/kg per infusion).

    Primary endpoint: annual rate of acute serious bacterial infections (aSBI), defined as pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess, per patient per year.

    During the 12-month study period, the aSBI rate was 0.08 (with an upper 1-sided 99% CI of 0.203), which met the predefined success rate of less than 1 aSBI per patient per year.

    The rate of other infections was 3.55 infections per patient per year.

    Privigen Note

    Not Applicable

    Privigen Patient Counseling

    Patient Counseling

    Inform patients of the early signs of hypersensitivity reactions to Privigen (including hives,

    generalized urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis).

    Report the following signs/symptoms immediately: 

    • Decreased urine output, sudden weight gain, fluid retention/edema, and/or shortness of breath (may suggest kidney problems).
    • Pain and/or swelling of an arm or leg with warmth over the affected area, discoloration of an arm or leg, unexplained shortness of breath, chest pain or discomfort that worsens on deep breathing, unexplained rapid pulse, numbness or weakness on one side of the body (may be symptoms of thrombosis).
    • Severe headache, neck stiffness, drowsiness, fever, sensitivity to light, painful eye movements, nausea, and vomiting (may be symptoms of aseptic meningitis syndrome).
    • Fatigue, increased heart rate, yellowing of skin or eyes, and dark-colored urine (may suggest hemolysis).
    • Severe breathing problems, lightheadedness, drops in blood pressure, and fever (may suggest TRALI).

    Though the risk is reduced, Privigen is made from human blood and may contain infectious agents that can cause disease.

    Administration of IgG may interfere with the response to live virus vaccines.

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