Panzyga

— 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

    • Panzyga Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Immune globulin (human) - ifas 10% (100mg/mL); soln for IV infusion; preservative-free.

    Pharmacological Class

    Immune globulin.

    How Supplied

    Single-use bottle (10mL, 25mL, 50mL, 100mL, 200mL, 300mL)—1

    How Supplied

    Panzyga is supplied in 1 g, 2.5 g, 5 g, 10 g, 20 g, and 30 g single-use bottles.

    Panzyga is available as:

    • 10 mL size for 1 g

    • 25 mL size for 2.5 g

    • 50 mL size for 5 g

    • 100 mL size for 10 g

    • 200 mL size for 20 g

    • 300 mL size for 30 g

    Panzyga is not supplied with an infusion set. If a filtered infusion set is used (not mandatory), choose a filter size of 0.2-200 microns. Components used in the packaging of Panzyga are not made with natural rubber latex. Panzyga contains no preservatives. 

    Storage

    Store Panzyga for 36 months at +2°C to +8°C (36°F to 46°F) from the date of manufacture. Within its shelf-life, the product may be stored at ≤ +25°C (77°F) for up to 12 months. After storage at ≤ +25°C (77°F), either use immediately or discard the product. Do not use after expiration date. Do not freeze. Do not use frozen product.

    The Panzyga bottle is for single use only. Use promptly any bottle that has been entered or opened, and discard partially used bottles.

    Manufacturer

    Octapharma

    Generic Availability

    NO

    Panzyga Indications

    Indications

    Chronic immune thrombocytopenia (ITP) to raise platelet counts to control or prevent bleeding.

    Panzyga Dosage and Administration

    Adult

    Give by IV infusion at an initial rate of 1mg/kg/min for first 30mins; if tolerated, may gradually increase every 15‒30mins up to max 8mg/kg/min. 2g/kg divided into 2 daily doses of 1g/kg given on 2 consecutive days. Renal dysfunction, thrombosis risk: give at the minimum infusion rate practicable; max 3.3mg/kg/min.

    Children

    Not established.

    Panzyga Contraindications

    Contraindications

    IgA deficiency with antibodies against IgA and history of hypersensitivity. Previous severe reaction to human immunoglobulin.

    Panzyga Boxed Warnings

    Boxed Warning

    Thrombosis. Renal dysfunction. Acute renal failure.

    Boxed Warning

    Thrombosis, Renal Dysfunction, and Acute Renal Failure

    • Thrombosis may occur with immune globulin products.

    • 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. 

    • 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.

     

    Panzyga 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 disorders: increased risk of thrombosis. Ensure adequate hydration. Monitor for signs/symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity. Pre-existing renal insufficiency, diabetes, >65yrs, hypovolemia, sepsis, paraproteinemia: 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 (esp. in those with a history of migraine), hemolysis, delayed hemolytic anemia. Consider lab testing including measurement of hemoglobin or hematocrit at baseline and approx. 36–96hrs post-infusion in patients with higher risk for hemolysis. Monitor for pulmonary dysfunction; perform tests for anti-HLA and anti-neutrophil antibodies if transfusion-related acute lung injury (TRALI) is suspected. History of hypertension. Monitor BP before, during, and after infusion. Risk of transmission of viral diseases. Have epinephrine inj available. Elderly. Pregnancy. Nursing mothers.

    Warnings/Precautions

    Hypersensitivity

    • Discontinued Panzyga infusion immediately if hypersensitivity reactions occur, and institute appropriate treatment. Epinephrine should be available to treat acute hypersensitivity reactions.

    • Panzyga contains trace amounts of IgA (on average 100 mcg/mL in a 10% solution). Individuals with IgA deficiency with antibodies may have a greater risk of developing potentially severe hypersensitivity and anaphylactic reactions with administration of Panzyga.

    Renal Failure

    • Renal dysfunction, acute renal failure, osmotic nephropathy, and death may occur upon use of Panzyga in predisposed patients. 

    • Prior to initiation, ensure that patients are not volume depleted. 

    • Administer Panzyga at the minimum infusion rate practicable for patients at risk of renal dysfunction because of pre-existing renal insufficiency or predisposition to acute renal failure (such as individuals with diabetes mellitus, age greater than 65 years, volume depletion, sepsis, paraproteinemia, or those receiving known nephrotoxic drugs). 

    • Monitor periodically renal function tests and urine output in patients at risk of developing acute renal failure. Prior to initial infusion and again at appropriate intervals thereafter, assess renal function (including blood urea nitrogen [BUN]/serum creatinine). Consider discontinuing if renal function deteriorates. 

    Hyperproteinemia, Increased Serum Viscosity and Hyponatremia

    • Hyperproteinemia, increased serum viscosity and hyponatremia may occur.

    • 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.

    Thrombotic Events

    • Thrombosis may occur following treatment with immune globulin products, including Panzyga. 

    • 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. 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 thrombotic events, administer Panzyga 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.

    Aseptic Meningitis Syndrome

    • Aseptic meningitis syndrome (AMS) may occur with Panzyga 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. History of migraine may be more susceptible.

    • Consider thorough neurological examination if signs and symptoms of AMS develop.

    Hemolysis

    • Panzyga 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 IGIV 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. In higher risk patients, consider lab testing (eg, hemoglobin/hematocrit measurement prior to infusion and within approximately 36 to 96 hours 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.

    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.

    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 IGIV; these elevations were reported more frequently in patients with a history of hypertension. Blood pressure should be monitored prior to, during, and following Panzyga infusion.

    Volume Overload

    • Carefully consider the relative risks and benefits before prescribing the high dose regimen in patients at increased risk of volume overload.

    Transmissible Infectious Agents

    • Because Panzyga 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 Panzyga.

    Monitoring Laboratory Tests

    • After infusion of immunoglobulin, may yield positive serological testing results with the potential for misleading interpretation. 

    • Passive transmission of antibodies to erythrocyte antigens (e.g., A, B, and D) may cause a positive direct or indirect antiglobulin (Coombs’) test. Clinically assess patients with known renal dysfunction, diabetes mellitus, age greater than 65 years, volume depletion, sepsis, paraproteinemia, orthose receiving nephrotic agents, and monitor as appropriate (BUN; serum creatinine, urine output) during therapy with Panzyga.

    • Consider baseline assessment of blood viscosity in patients at risk for hyperviscosity. Consider measuring hemoglobin or hematocrit at baseline and approximately 36 to 96 hours post-infusion in patients at higher risk of hemolysis. Obtain laboratory testing for confirmation if signs and symptoms of hemolysis are present after infusion.

    • Perform appropriate tests for the presense of anti-neutrophil antibodies in both the product and patient’s serum if TRALI is suspected.

    Pregnancy Considerations

    Risk Summary

    • 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. It is not known whether Panzyga can cause fetal harm.

    Nursing Mother Considerations

    Risk Summary

    • 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

    Primary Humoral Immunodeficiency

    • Panzyga was evaluated in 25 pediatric subjects with PI. Pharmacokinetics, efficacy and safety were similar to those in adults. No specific dose requirements were necessary to achieve the targeted serum IgG levels in the pediatric subjects.

    Chronic Immune Thrombocytopenic Purpura

    • Safety and effectiveness of Panzyga have not been established in pediatric patients with ITP.

    Chronic Inflammatory Demyelinating Polyneuropathy

    • Safety and effectiveness of Panzyga have not been established in pediatric patients with CIDP.

     

    Geriatric Considerations

    Clinical studies of Panzyga in PID and ITP did not include sufficient numbers of subjects older than 65 years to determine whether they respond differently from younger subjects.

    In the clinical study the safety and effectiveness of Panzyga in subjects with CIDP older than 65 years was similar to those 65 years of age and younger. A total of 36 subjects older than 65 years were included in the clinical trial. 

    Patients older than 65 years of age may be at increased risk for developing adverse reactions such as thromboembolic events and acute renal failure. Do not exceed recommended doses in this population, and apply the minimum practicable infusion rate. 

    Panzyga Pharmacokinetics

    See Literature

    Panzyga Interactions

    Interactions

    May affect response to live viral vaccines; defer immunization for ≥3 months. Concomitant nephrotoxic drugs: increased risk of renal dysfunction. May interfere with serological testing (eg, false [+] Treponema pallidum test may result).

    Panzyga Adverse Reactions

    Adverse Reactions

    Headache, fever, nausea, fatigue, abdominal pain, vomiting, dizziness, anemia, dermatitis, increased BP; hypersensitivity, renal dysfunction, hyperproteinemia, hyponatremia, hemolytic anemia, aseptic meningitis syndrome (esp. with high doses ≥2g/kg and/or rapid infusion), TRALI, thrombosis.

    Panzyga Clinical Trials

    Clinical Trials

    Treatment of Chronic Immune Thrombocytopenia (ITP) in Adults

    The approval was based on data from a prospective, open-label, single-arm, multicenter study that evaluated the efficacy, safety, and tolerability of Panzyga in 40 subjects with chronic ITP and a platelet count of 20 x 109 /L or less. Patients received Panzyga 2 g/kg administered as 2 daily 1 g/kg intravenous doses, given on 2 consecutive days. Platelet counts were measured on Days 1 to 8, 15, and 22.

    The study was designed to determine the response rate, defined as the percentage of subjects with an increase in platelet count to at least 50 x 109 /L within 7 days after the first infusion (responders). Additionally, maximum platelet count, the time to reach a platelet count of at least 50 x 109 /L within the first 7 days, the duration of that response (i.e., the number of days the platelet count remained in excess of 50 x 109 /L), and the regression of hemorrhages in subjects who had bleeding at baseline were observed. 

    Among 36 patients in the full analysis set, 29 (81% [95% CI, 64%-92%]) responded to Panzyga with a rise in platelet count to at least 50 x 109 /L within 7 days after the first infusion. The lower bound of the overall 95% confidence interval for the response rate in all 36 subjects (64%) is above the predefined response rate of 60%. 

    Of the 36 subjects, 23 (64%) subjects had bleeding at baseline. Bleeding was minor in 14 subjects (39%), mild in 2 subjects (6%) and moderate in 7 subjects (19%). On Day 7, only 14% of subjects were bleeding (5/36). Persistent bleeding was mild in 1 and minor in 2 subjects. Information regarding bleeding resolution was missing in 2 subjects with moderate bleeding.  

    Panzyga Note

    Not Applicable

    Panzyga Patient Counseling

    Patient Counseling

    Inform patients of the early signs of hypersensitivity reactions to Panzyga (including urticaria, 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, Panzyga 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.

    Panzyga Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Immune globulin (human) - ifas 10% (100mg/mL); soln for IV infusion; preservative-free.

    Pharmacological Class

    Immune globulin.

    How Supplied

    Single-use bottle (10mL, 25mL, 50mL, 100mL, 200mL, 300mL)—1

    How Supplied

    Panzyga is supplied in 1 g, 2.5 g, 5 g, 10 g, 20 g, and 30 g single-use bottles.

    Panzyga is available as:

    • 10 mL size for 1 g

    • 25 mL size for 2.5 g

    • 50 mL size for 5 g

    • 100 mL size for 10 g

    • 200 mL size for 20 g

    • 300 mL size for 30 g

    Panzyga is not supplied with an infusion set. If a filtered infusion set is used (not mandatory), choose a filter size of 0.2-200 microns. Components used in the packaging of Panzyga are not made with natural rubber latex. Panzyga contains no preservatives. 

    Storage

    Store Panzyga for 36 months at +2°C to +8°C (36°F to 46°F) from the date of manufacture. Within its shelf-life, the product may be stored at ≤ +25°C (77°F) for up to 12 months. After storage at ≤ +25°C (77°F), either use immediately or discard the product. Do not use after expiration date. Do not freeze. Do not use frozen product.

    The Panzyga bottle is for single use only. Use promptly any bottle that has been entered or opened, and discard partially used bottles.

    Manufacturer

    Octapharma

    Generic Availability

    NO

    Panzyga Indications

    Indications

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

    Panzyga Dosage and Administration

    Adult

    Give by IV infusion at an initial rate of 1mg/kg/min for first 30mins; if tolerated, may gradually increase every 15‒30mins up to max 12mg/kg/min. Loading dose: 2g/kg divided into 2 daily doses of 1g/kg given on 2 consecutive days. Maintenance dose: 1‒2g/kg divided into 2 daily doses given on 2 consecutive days every 3 weeks. Renal dysfunction, thrombosis risk: give at the minimum infusion rate practicable; max 3.3mg/kg/min.

    Children

    Not established.

    Panzyga Contraindications

    Contraindications

    IgA deficiency with antibodies against IgA and history of hypersensitivity. Previous severe reaction to human immunoglobulin.

    Panzyga Boxed Warnings

    Boxed Warning

    Thrombosis. Renal dysfunction. Acute renal failure.

    Boxed Warning

    Thrombosis, Renal Dysfunction, and Acute Renal Failure

    • Thrombosis may occur with immune globulin products.

    • 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. 

    • 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.

     

    Panzyga 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 disorders: increased risk of thrombosis. Ensure adequate hydration. Monitor for signs/symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity. Pre-existing renal insufficiency, diabetes, >65yrs, hypovolemia, sepsis, paraproteinemia: 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 (esp. in those with a history of migraine), hemolysis, delayed hemolytic anemia. Consider lab testing including measurement of hemoglobin or hematocrit at baseline and approx. 36–96hrs post-infusion in patients with higher risk for hemolysis. Monitor for pulmonary dysfunction; perform tests for anti-HLA and anti-neutrophil antibodies if transfusion-related acute lung injury (TRALI) is suspected. History of hypertension. Monitor BP before, during, and after infusion. Risk of transmission of viral diseases. Have epinephrine inj available. Elderly. Pregnancy. Nursing mothers.

    Warnings/Precautions

    Hypersensitivity

    • Discontinued Panzyga infusion immediately if hypersensitivity reactions occur, and institute appropriate treatment. Epinephrine should be available to treat acute hypersensitivity reactions.

    • Panzyga contains trace amounts of IgA (on average 100 mcg/mL in a 10% solution). Individuals with IgA deficiency with antibodies may have a greater risk of developing potentially severe hypersensitivity and anaphylactic reactions with administration of Panzyga.

    Renal Failure

    • Renal dysfunction, acute renal failure, osmotic nephropathy, and death may occur upon use of Panzyga in predisposed patients. 

    • Prior to initiation, ensure that patients are not volume depleted. 

    • Administer Panzyga at the minimum infusion rate practicable for patients at risk of renal dysfunction because of pre-existing renal insufficiency or predisposition to acute renal failure (such as individuals with diabetes mellitus, age greater than 65 years, volume depletion, sepsis, paraproteinemia, or those receiving known nephrotoxic drugs). 

    • Monitor periodically renal function tests and urine output in patients at risk of developing acute renal failure. Prior to initial infusion and again at appropriate intervals thereafter, assess renal function (including blood urea nitrogen [BUN]/serum creatinine). Consider discontinuing if renal function deteriorates. 

    Hyperproteinemia, Increased Serum Viscosity and Hyponatremia

    • Hyperproteinemia, increased serum viscosity and hyponatremia may occur.

    • 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.

    Thrombotic Events

    • Thrombosis may occur following treatment with immune globulin products, including Panzyga. 

    • 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. 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 thrombotic events, administer Panzyga 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.

    Aseptic Meningitis Syndrome

    • Aseptic meningitis syndrome (AMS) may occur with Panzyga 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. History of migraine may be more susceptible.

    • Consider thorough neurological examination if signs and symptoms of AMS develop.

    Hemolysis

    • Panzyga 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 IGIV 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. In higher risk patients, consider lab testing (eg, hemoglobin/hematocrit measurement prior to infusion and within approximately 36 to 96 hours 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.

    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.

    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 IGIV; these elevations were reported more frequently in patients with a history of hypertension. Blood pressure should be monitored prior to, during, and following Panzyga infusion.

    Volume Overload

    • Carefully consider the relative risks and benefits before prescribing the high dose regimen in patients at increased risk of volume overload.

    Transmissible Infectious Agents

    • Because Panzyga 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 Panzyga.

    Monitoring Laboratory Tests

    • After infusion of immunoglobulin, may yield positive serological testing results with the potential for misleading interpretation. 

    • Passive transmission of antibodies to erythrocyte antigens (e.g., A, B, and D) may cause a positive direct or indirect antiglobulin (Coombs’) test. Clinically assess patients with known renal dysfunction, diabetes mellitus, age greater than 65 years, volume depletion, sepsis, paraproteinemia, orthose receiving nephrotic agents, and monitor as appropriate (BUN; serum creatinine, urine output) during therapy with Panzyga.

    • Consider baseline assessment of blood viscosity in patients at risk for hyperviscosity. Consider measuring hemoglobin or hematocrit at baseline and approximately 36 to 96 hours post-infusion in patients at higher risk of hemolysis. Obtain laboratory testing for confirmation if signs and symptoms of hemolysis are present after infusion.

    • Perform appropriate tests for the presense of anti-neutrophil antibodies in both the product and patient’s serum if TRALI is suspected.

    Pregnancy Considerations

    Risk Summary

    • 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. It is not known whether Panzyga can cause fetal harm.

    Nursing Mother Considerations

    Risk Summary

    • 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

    Primary Humoral Immunodeficiency

    • Panzyga was evaluated in 25 pediatric subjects with PI. Pharmacokinetics, efficacy and safety were similar to those in adults. No specific dose requirements were necessary to achieve the targeted serum IgG levels in the pediatric subjects.

    Chronic Immune Thrombocytopenic Purpura

    • Safety and effectiveness of Panzyga have not been established in pediatric patients with ITP.

    Chronic Inflammatory Demyelinating Polyneuropathy

    • Safety and effectiveness of Panzyga have not been established in pediatric patients with CIDP.

     

    Geriatric Considerations

    Clinical studies of Panzyga in PID and ITP did not include sufficient numbers of subjects older than 65 years to determine whether they respond differently from younger subjects.

    In the clinical study the safety and effectiveness of Panzyga in subjects with CIDP older than 65 years was similar to those 65 years of age and younger. A total of 36 subjects older than 65 years were included in the clinical trial. 

    Patients older than 65 years of age may be at increased risk for developing adverse reactions such as thromboembolic events and acute renal failure. Do not exceed recommended doses in this population, and apply the minimum practicable infusion rate. 

    Panzyga Pharmacokinetics

    See Literature

    Panzyga Interactions

    Interactions

    May affect response to live viral vaccines; defer immunization for ≥3 months. Concomitant nephrotoxic drugs: increased risk of renal dysfunction. May interfere with serological testing (eg, false [+] Treponema pallidum test may result).

    Panzyga Adverse Reactions

    Adverse Reactions

    Headache, fever, nausea, fatigue, abdominal pain, vomiting, dizziness, anemia, dermatitis, increased BP; hypersensitivity, renal dysfunction, hyperproteinemia, hyponatremia, hemolytic anemia, aseptic meningitis syndrome (esp. with high doses ≥2g/kg and/or rapid infusion), TRALI, thrombosis.

    Panzyga Clinical Trials

    Clinical Trials

    Treatment of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) in Adults

    The approval was based on data from a prospective, double-blind, multicenter study that compared 2 different maintenance dosages of Panzyga in 142 adults (ages 18 to 83 years) with CIDP. Patients were randomly assigned 1:2:1 to receive first a loading dose of 2g/kg, and then 0.5g/kg, 1 g/kg or 2 g/kg according to their respective dose arm for 7 maintenance infusions at 3-week intervals during the 24-week dose-evaluation phase; those in the 0.5g/kg and 1g/kg arms had the option of rescue treatment with 2 consecutive infusions of 2g/kg at 3-week intervals if criteria were met.

    The primary efficacy outcome was based on the proportion of responders, defined as a patient with a decrease of at least 1 point in the adjusted 10-point Inflammatory Neuropathy Cause and Treatment (INCAT) disability score.

    Results showed that almost 80% (55/69) of patients in the 1g/kg arm responded to treatment. Findings also showed a dose-dependent response based on the proportion of responders in the 2g/kg dose arm in the adjusted INCAT disability score (91.7%; 33/36), and the proportion of responders in the 1 g/kg and 2 g/kg dose arms in the grip strength (65.2% and 83.3%, respectively), inflammatory Rasch-built Overall Disability Scale (55.1% and 72.2%, respectively) and Medical Research Council sum score (72.5% and 86.1%, respectively).

    Panzyga Note

    Not Applicable

    Panzyga Patient Counseling

    Patient Counseling

    Inform patients of the early signs of hypersensitivity reactions to Panzyga (including urticaria, 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, Panzyga 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.

    Panzyga Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Immune globulin (human) - ifas 10% (100mg/mL); soln for IV infusion; preservative-free.

    Pharmacological Class

    Immune globulin.

    How Supplied

    Single-use bottle (10mL, 25mL, 50mL, 100mL, 200mL, 300mL)—1

    How Supplied

    Panzyga is supplied in 1 g, 2.5 g, 5 g, 10 g, 20 g, and 30 g single-use bottles.

    Panzyga is available as:

    • 10 mL size for 1 g

    • 25 mL size for 2.5 g

    • 50 mL size for 5 g

    • 100 mL size for 10 g

    • 200 mL size for 20 g

    • 300 mL size for 30 g

    Panzyga is not supplied with an infusion set. If a filtered infusion set is used (not mandatory), choose a filter size of 0.2-200 microns. Components used in the packaging of Panzyga are not made with natural rubber latex. Panzyga contains no preservatives. 

    Storage

    Store Panzyga for 36 months at +2°C to +8°C (36°F to 46°F) from the date of manufacture. Within its shelf-life, the product may be stored at ≤ +25°C (77°F) for up to 12 months. After storage at ≤ +25°C (77°F), either use immediately or discard the product. Do not use after expiration date. Do not freeze. Do not use frozen product.

    The Panzyga bottle is for single use only. Use promptly any bottle that has been entered or opened, and discard partially used bottles.

    Manufacturer

    Octapharma

    Generic Availability

    NO

    Panzyga Indications

    Indications

    Primary humoral immunodeficiency (eg, congenital agammaglobulinemia, common variable immunodeficiency, X-linked agammaglobulinemia, Wiskott-Aldrich syndrome, severe combined immunodeficiencies).

    Panzyga Dosage and Administration

    Adults and Children

    <2yrs: not established. ≥2yrs: Give by IV infusion 300‒600mg/kg every 3‒4 weeks at an initial rate of 1mg/kg/min for first 30mins; if tolerated, may gradually increase every 15‒30mins up to max 14mg/kg/min. Renal dysfunction, thrombosis risk: give at the minimum infusion rate practicable; max 3.3mg/kg/min. Adjust subsequent dose based on serum IgG trough levels and clinical response. Measles exposure: see full labeling.

    Panzyga Contraindications

    Contraindications

    IgA deficiency with antibodies against IgA and history of hypersensitivity. Previous severe reaction to human immunoglobulin.

    Panzyga Boxed Warnings

    Boxed Warning

    Thrombosis. Renal dysfunction. Acute renal failure.

    Boxed Warning

    Thrombosis, Renal Dysfunction, and Acute Renal Failure

    • Thrombosis may occur with immune globulin products.

    • 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. 

    • 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.

    Panzyga 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 disorders: increased risk of thrombosis. Ensure adequate hydration. Monitor for signs/symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity. Pre-existing renal insufficiency, diabetes, >65yrs, hypovolemia, sepsis, paraproteinemia: 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 (esp. in those with a history of migraine), hemolysis, delayed hemolytic anemia. Consider lab testing including measurement of hemoglobin or hematocrit at baseline and approx. 36–96hrs post-infusion in patients with higher risk for hemolysis. Monitor for pulmonary dysfunction; perform tests for anti-HLA and anti-neutrophil antibodies if transfusion-related acute lung injury (TRALI) is suspected. History of hypertension. Monitor BP before, during, and after infusion. Risk of transmission of viral diseases. Have epinephrine inj available. Elderly. Pregnancy. Nursing mothers.

    Warnings/Precautions

    Hypersensitivity

    • Discontinued Panzyga infusion immediately if hypersensitivity reactions occur, and institute appropriate treatment. Epinephrine should be available to treat acute hypersensitivity reactions.

    • Panzyga contains trace amounts of IgA (on average 100 mcg/mL in a 10% solution). Individuals with IgA deficiency with antibodies may have a greater risk of developing potentially severe hypersensitivity and anaphylactic reactions with administration of Panzyga.

    Renal Failure

    • Renal dysfunction, acute renal failure, osmotic nephropathy, and death may occur upon use of Panzyga in predisposed patients. 

    • Prior to initiation, ensure that patients are not volume depleted. 

    • Administer Panzyga at the minimum infusion rate practicable for patients at risk of renal dysfunction because of pre-existing renal insufficiency or predisposition to acute renal failure (such as individuals with diabetes mellitus, age greater than 65 years, volume depletion, sepsis, paraproteinemia, or those receiving known nephrotoxic drugs). 

    • Monitor periodically renal function tests and urine output in patients at risk of developing acute renal failure. Prior to initial infusion and again at appropriate intervals thereafter, assess renal function (including blood urea nitrogen [BUN]/serum creatinine). Consider discontinuing if renal function deteriorates. 

    Hyperproteinemia, Increased Serum Viscosity and Hyponatremia

    • Hyperproteinemia, increased serum viscosity and hyponatremia may occur.

    • 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.

    Thrombotic Events

    • Thrombosis may occur following treatment with immune globulin products, including Panzyga. 

    • 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. 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 thrombotic events, administer Panzyga 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.

    Aseptic Meningitis Syndrome

    • Aseptic meningitis syndrome (AMS) may occur with Panzyga 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. History of migraine may be more susceptible.

    • Consider thorough neurological examination if signs and symptoms of AMS develop.

    Hemolysis

    • Panzyga 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 IGIV 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. In higher risk patients, consider lab testing (eg, hemoglobin/hematocrit measurement prior to infusion and within approximately 36 to 96 hours 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.

    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.

    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 IGIV; these elevations were reported more frequently in patients with a history of hypertension. Blood pressure should be monitored prior to, during, and following Panzyga infusion.

    Volume Overload

    • Carefully consider the relative risks and benefits before prescribing the high dose regimen in patients at increased risk of volume overload.

    Transmissible Infectious Agents

    • Because Panzyga 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 Panzyga.

    Monitoring Laboratory Tests

    • After infusion of immunoglobulin, may yield positive serological testing results with the potential for misleading interpretation. 

    • Passive transmission of antibodies to erythrocyte antigens (e.g., A, B, and D) may cause a positive direct or indirect antiglobulin (Coombs’) test. Clinically assess patients with known renal dysfunction, diabetes mellitus, age greater than 65 years, volume depletion, sepsis, paraproteinemia, orthose receiving nephrotic agents, and monitor as appropriate (BUN; serum creatinine, urine output) during therapy with Panzyga.

    • Consider baseline assessment of blood viscosity in patients at risk for hyperviscosity. Consider measuring hemoglobin or hematocrit at baseline and approximately 36 to 96 hours post-infusion in patients at higher risk of hemolysis. Obtain laboratory testing for confirmation if signs and symptoms of hemolysis are present after infusion.

    • Perform appropriate tests for the presense of anti-neutrophil antibodies in both the product and patient’s serum if TRALI is suspected.

    Pregnancy Considerations

    Risk Summary

    • 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. It is not known whether Panzyga can cause fetal harm.

    Nursing Mother Considerations

    Risk Summary

    • 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

    Primary Humoral Immunodeficiency

    • Panzyga was evaluated in 25 pediatric subjects with PI. Pharmacokinetics, efficacy and safety were similar to those in adults. No specific dose requirements were necessary to achieve the targeted serum IgG levels in the pediatric subjects.

    Chronic Immune Thrombocytopenic Purpura

    • Safety and effectiveness of Panzyga have not been established in pediatric patients with ITP.

    Chronic Inflammatory Demyelinating Polyneuropathy

    • Safety and effectiveness of Panzyga have not been established in pediatric patients with CIDP.

    Geriatric Considerations

    Clinical studies of Panzyga in PID and ITP did not include sufficient numbers of subjects older than 65 years to determine whether they respond differently from younger subjects.

    In the clinical study the safety and effectiveness of Panzyga in subjects with CIDP older than 65 years was similar to those 65 years of age and younger. A total of 36 subjects older than 65 years were included in the clinical trial. 

    Patients older than 65 years of age may be at increased risk for developing adverse reactions such as thromboembolic events and acute renal failure. Do not exceed recommended doses in this population, and apply the minimum practicable infusion rate. 

    Panzyga Pharmacokinetics

    See Literature

    Panzyga Interactions

    Interactions

    May affect response to live viral vaccines; defer immunization for ≥3 months. Concomitant nephrotoxic drugs: increased risk of renal dysfunction. May interfere with serological testing (eg, false [+] Treponema pallidum test may result).

    Panzyga Adverse Reactions

    Adverse Reactions

    Headache, fever, nausea, fatigue, abdominal pain, vomiting, dizziness, anemia, dermatitis, increased BP; hypersensitivity, renal dysfunction, hyperproteinemia, hyponatremia, hemolytic anemia, aseptic meningitis syndrome (esp. with high doses ≥2g/kg and/or rapid infusion), TRALI, thrombosis.

    Panzyga Clinical Trials

    Clinical Trials

    Treatment of Primary Humoral Immunodeficiency (PI)

    The approval was based on data from a prospective, open-label, single-arm, multicenter study that evaluated Panzyga in 51 children and adults with PI. Patients received Panzyga at a dose between 200 to 800 mg/kg body weigh every 3 or 4 weeks. In the study, patients received Panzyga for a mean of 360 days. The primary endpoint was the number of episodes of serious bacterial infections per patient per year.

    Results showed that the observed rate was 0.08 serious bacterial infections per patient per year (4 infections over 50.2 patient-years). There was 1 adult patients hospitalized due to an infection for 4 days (overall rate of days in hospital per person-year: 0.080. The mean resolution time was 14 days for serious bacterial infections and 18 days for other infections.

    Panzyga Note

    Not Applicable

    Panzyga Patient Counseling

    Patient Counseling

    Inform patients of the early signs of hypersensitivity reactions to Panzyga (including urticaria, 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, Panzyga 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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