Octagam 10%

— THERAPEUTIC CATEGORIES —
  • Bleeding disorders
  • Miscellaneous immune disorders
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

    • Octagam 10% Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Immune globulin (human) 2g/20mL, 5g/50mL, 10g/100mL, 20g/200mL, 30g/300mL; liq for IV infusion; contains maltose; sucrose-, preservative-, and latex-free.

    Pharmacological Class

    Immune globulin.

    How Supplied

    Single-use bottle—1

    Storage

    Store Octagam 10% for 36 months at +2° C to +8° C (36° F to 46° F) from the date of manufacture. Within this shelf-life, the product may be stored up to 9 months at ≤ +25° C (77° F). After storage at ≤ +25° C (77° F) the product must be used or discarded.

    Do not use after the expiration date.

    Do not freeze. 

    Do not use frozen product.

    Manufacturer

    Octapharma

    Generic Availability

    NO

    Octagam 10% Indications

    Indications

    Chronic immune thrombocytopenic purpura (ITP).

    Octagam 10% Dosage and Administration

    Adult

    Individualize. Total dose of 2g/kg, divided into equal doses given on 2 consecutive days by IV infusion at a rate of 1mg/kg/min, if tolerated may increase up to max 12mg/kg/min. Risk of renal dysfunction/failure or thrombosis: give at the minimum practicable infusion rate; max: <3.3mg/kg/min. See full labeling.

    Children

    Not established.

    Octagam 10% Contraindications

    Contraindications

    IgA deficiency with antibodies against IgA. Previous severe reaction to human immune globulin.

    Octagam 10% Boxed Warnings

    Boxed Warning

    Thrombosis. Renal dysfunction and acute renal failure.

    Boxed Warning

    Thrombosis, Renal Dysfunction and Acute Renal Failure

    • Thrombosis, Renal Dysfunction and Acute Renal Failure
      Thrombosis may occur with immune globulin intravenous (IGIV) products, including Octagam 10%. 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 in predisposed patients who receive IGIV products, including Octagam 10%. Patients predisposed to renal dysfunction include those with a degree of pre-existing renal insufficiency, diabetes mellitus, age >65, volume depletion, sepsis, paraproteinemia, or patients receiving known nephrotoxic drugs. Renal dysfunction and acute renal failure occur more commonly in patients receiving IGIV product containing sucrose. Octagam 10% does not contain sucrose.
    • For patients at risk of thrombosis, renal dysfunction or acute renal failure, administer Octagam 10% 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.

    Octagam 10% 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. Ensure adequate hydration. Pre-existing renal insufficiency, diabetes, >65yrs, hypovolemia, sepsis, paraproteinemia: increased risk of renal dysfunction or acute renal failure. Correct volume depletion prior to initiation. Assess renal function, BUN, serum creatinine, urine output before and during therapy; discontinue if renal function deteriorates. Discontinue if hypersensitivity reactions occur; have epinephrine available. Corn allergy. Hyperproteinemia, increased serum viscosity and hyponatremia may occur. Risk of aseptic meningitis syndrome esp. in those with a history of migraine, high doses (2g/kg), and/or rapid infusion. Monitor for hemolysis and delayed hemolytic anemia; consider measuring baseline hemoglobin or hematocrit and approx. 36–96hrs post-infusion if patients are high risk. Monitor for pulmonary adverse reactions; perform test for anti-neutrophil antibodies if transfusion-related acute lung injury (TRALI) suspected. Antibody formation. Risk of transmission of blood-borne diseases. Elderly. Pregnancy. Nursing mothers.

    Warnings/Precautions

    Hypersensitivity 

    Severe hypersensitivity reactions may occur. In case of hypersensitivity, discontinue Octagam 10% infusion immediately and institute appropriate treatment. Epinephrine should be immediately available for treatment of severe acute hypersensitivity reactions. 

    Octagam 10% contains trace amounts of IgA (average 106 µg/mL in a 10% solution). IgA-deficient patients with antibodies against IgA are at greater risk of developing severe hypersensitivity and anaphylactoid reactions when administered Octagam 10%. 

    Octagam 10% may cause hypersensitivity reactions in patients with corn allergy. Octagam 10% contains maltose, a disaccharide sugar which is derived from corn.

    Renal Dysfunction/Failure 

    Renal dysfunction, acute renal failure, osmotic nephropathy, and death may occur upon use of Octagam 10% in predisposed patients. Ensure that patients are not volume depleted prior to the initiation of the infusion of Octagam 10%. 

    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, volume depletion, sepsis, paraproteinemia, or those receiving known nephrotoxic drugs), administer Octagam 10% at the minimum infusion rate practicable, not to exceed 3.3mg/kg/min (0.03mL/kg/min). 

    Periodic monitoring of renal function tests and urine output is particularly important in patients judged to be at risk of developing acute renal failure. Assess renal function, including a measurement of blood urea nitrogen (BUN)/serum creatinine, prior to the initial infusion of Octagam 10% and again at appropriate intervals thereafter. If renal function deteriorates, consider discontinuation of the product. 

    Blood Glucose Monitoring 

    Some glucose monitoring systems give falsely elevated glucose readings because they interpret the maltose in Octagam 10% as glucose.[ 2 ] This occurs in systems that use glucose dehydrogenase pyrroloquinoline quinone (GDH-PQQ) or glucose-dyeoxidoreductase methods for detecting blood glucose. Inaccurate glucose readings can cause inappropriate administration of insulin and resultant potentially life-threatening hypoglycemia. Also, true hypoglycemia may go undetected when masked by a falsely elevated glucose reading. 

    Monitor glucose levels in diabetic patients with a glucose-specific method only. Review the product information of blood glucose testing systems, including the test strips, to determine if the system is appropriate to use with maltose-containing parenteral products. Contact the manufacturer if there is any uncertainty about the system. 

    Hyperproteinemia, Increased Serum Viscosity and Hyponatremia 

    Hyperproteinemia, increased serum viscosity and hyponatremia may occur in patients receiving Octagam 10% therapy. It is clinically critical to distinguish true hyponatremia from pseudohyponatremia related to hyperproteinemia with concomitant decreased calculated serum osmolality or elevated osmolar gap, because treatment aimed at decreasing serum free water in patients with pseudohyponatremia may lead to volume depletion, a further increase in serum viscosity and a higher risk of thromboembolic events.

    Thrombosis 

    Thrombosis may occur following treatment with immune globulin products, including Octagam 10%. 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. 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 Octagam 10% 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.

    Hemolysis 

    Octagam 10% may contain blood group antibodies that can act as hemolysins and induce in vivo coating of red blood cells (RBCs) with immunoglobulin, causing a positive direct antiglobulin test (DAT) (Coombs’ test) result and hemolysis. Delayed hemolytic anemia can develop subsequent to IGIV therapy due to enhanced RBC sequestration and acute hemolysis, consistent with intravascular hemolysis, has been reported. Cases of severe hemolysis-related renal dysfunction/failure or disseminated intravascular coagulation have occurred following infusion of IGIV. 

    The following risk factors may be associated with the development of hemolysis following IGIV administration: high doses (eg, ≥ 2 g/kg), given either as a single administration or divided over several days, and non-O blood group. Other individual patient factors, such as an underlying inflammatory state (as may be reflected by, for example, elevated C-reactive protein or erythrocyte sedimentation rate), have been hypothesized to increase the risk of hemolysis following administration of IGIV, but their role is uncertain. Hemolysis has been reported following administration of IGIV for a variety of indications, including ITP. 

    Closely monitor patients for clinical signs and symptoms of hemolysis, particularly patients with risk factors noted above. Consider appropriate laboratory testing in higher risk patients, including measurement of hemoglobin or hematocrit prior to infusion and within approximately 36-96 hours post infusion. If clinical signs and symptoms of hemolysis or a significant drop in hemoglobin or hematocrit have been observed, perform confirmatory laboratory testing. 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.

    Aseptic Meningitis Syndrome 

    Aseptic meningitis syndrome (AMS) may occur with Octagam treatment. Discontinuation of treatment has resulted in remission of AMS within several days without sequelae. The syndrome usually begins within several hours to two days following rapid infusion with Octagam treatment. It is characterized by symptoms and signs including severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, nausea and vomiting. Cerebrospinal fluid (CSF) studies frequently reveal pleocytosis up to several thousand cells per cubic millimeter, predominantly from the granulocytic series, and elevated protein levels up to several hundred mg/dl, but negative culture results. Conduct a thorough neurological examination in patients exhibiting such symptoms and signs, including CSF studies, to rule out other causes of meningitis. It appears that patients with a history of migraine may be more susceptible. 

    AMS may occur more frequently following high doses (≥2 g/kg) and/or rapid infusion of IGIV.

    Transfusion-Related Acute Lung Injury (TRALI) 

    Noncardiogenic pulmonary edema [Transfusion-Related Acute Lung Injury (TRALI)] may occur in patients administered IGIV.  TRALI is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever. Signs and symptoms typically appear within 1 to 6 hours after transfusion. Patients with TRALI may be managed using oxygen therapy with adequate ventilatory support. 

    Monitor recipients of Octagam 10% for pulmonary adverse reactions. If TRALI is suspected, perform appropriate tests for the presence of anti-HLA and anti-neutrophil antibodies in the product.

    Transmission of Infectious Agents 

    Because Octagam 10% is made from human blood, it may carry a risk of transmitting infectious agents, eg, viruses and theoretically, the Creutzfeldt-Jakob disease (CJD) agent. 

    Pregnancy Considerations

    No human data are available to indicate the presence or absence of drug-associated risk. Animal reproduction studies have not been conducted with Octagam 10%. It is not known whether Octagam 10% can cause foetal harm when administered to a pregnant woman or can affect reproduction capacity. Immunoglobulins cross the placenta from maternal circulation increasingly after 30 weeks of gestation. Octagam 10% should be given to pregnant women only if clearly needed.

    Nursing Mother Considerations

    No human data are available to assess the presence or absence of Octagam 10% in human milk, the effects of Octagam 10% on the breastfed child, and the effects of Octagam 10% on milk production/excretion. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Octagam 10% liquid and any potential adverse effects on the breastfed infant from Octagam 10% liquid or from the underlying maternal condition. Immunoglobulins are excreted into the milk and may contribute to the transfer of protective antibodies to the neonate.

    Pediatric Considerations

    The safety and effectiveness of Octagam 10% has not been established in pediatric patients with ITP or DM.

    Geriatric Considerations

    Patients > 65 years of age may be at increased risk for developing certain adverse reactions such as thromboembolic events and acute renal failure. 

    Do not exceed recommended doses in this population, and the applied infusion rate should be the minimum practicable. Clinical studies of Octagam 10% did not include sufficient numbers of subjects >65 years to determine whether they respond differently from younger subjects.

    Octagam 10% Pharmacokinetics

    See Literature

    Octagam 10% Interactions

    Interactions

    Avoid live viral vaccines for ≥3 months. Concomitant nephrotoxic drugs: increased risk of acute renal failure. Falsely elevated results with some blood glucose tests (eg, GDH-PQQ based or glucose-dye-oxidoreductase methods); use glucose-specific method only. May lead to a positive direct or indirect antiglobulin (Coombs) test due to passive transmission of antibodies to erythrocyte antigens.

    Interactions

    It is recommended that Octagam 10% be administered separately from other drugs or medications which the patient may be receiving. Do not mix the product. 

    Do not mix Octagam 10% with IGIVs from other manufacturers. 

    Passively transferred antibodies in immunoglobulin preparations can confound the results of serological testing. 

    Antibodies in Octagam 10% may interfere with the response to live viral vaccines, such as measles, mumps, and rubella. Inform physicians of recent therapy with Octagam 10%, so that administration of live viral vaccines, if indicated, can be appropriately delayed for 3 or more months from the time of Octagam 10% administration.

    Octagam 10% Adverse Reactions

    Adverse Reactions

    ITP: headache, fever, increased heart rate; also with DM: nausea, vomiting, increased BP, chills, musculoskeletal pain, dyspnea, infusion site reactions; thrombosis, renal dysfunction (may be fatal); rare: hemolytic anemia, aseptic meningitis syndrome, TRALI.

    Octagam 10% Clinical Trials

    Clinical Trials

    Treatment of Chronic Immune Thrombocytopenic Purpura 

    A prospective, open-label, single-arm, multicenter study assessed the efficacy, safety, and tolerability of Octagam 10% in 116 patients with tentative newly diagnosed or chronic ITP and a platelet count of 20x109 /L or less. Patients ranged in age from 17 to 88; 64% were female and 36% were male. 

    Patients received a 2 g/kg dose of Octagam 10% administered as two daily 1 g/kg intravenous doses, given on 2 consecutive days. Pre-medication to alleviate potential adverse drug reactions was allowed but only given to 1 (0.9%) of 116 patients. In the initial study phase, the infusion rate allowed for Octagam 10% administration was up to 6 mg/kg/min [0.06 mL/kg/min], which was achieved in 24 of 26 patients (92%). Subsequently, the maximum infusion rate allowed was 12 mg/kg/min [0.12mL/kg/min], which was achieved in 54 of 90 patients (60%). Platelet counts were measured on Days 1 to 7, 14, 21, and 63. 

    The study was designed to determine the response rate defined as the percentage of patients with an increase in platelet count to at least 50x109 /L within 7 days after the first infusion (responders). Additionally, maximum platelet count, the time to reach a platelet count of at least 50x109 /L within the first 7 days, the duration of that response (ie, the number of days the platelet count remained in excess of 50x109 /L), and the regression of hemorrhages in patients who had bleeding at baseline were observed. 

    Of the 66 patients with chronic ITP in the efficacy analysis, 54 (82%) responded to Octagam 10% with a rise in platelet counts to at least 50x109 /L within 7 days after the first infusion. The lower bound of the overall 95% confidence interval for the response rate (73%) is above the predefined response rate of 70%. The mean maximum platelet count achieved in the 66 patients with chronic ITP was 227x109 /L.

    The median time to reach a platelet response of at least 50x109 /L was 2 days after the first infusion. The duration of platelet response was analyzed for the 54 subjects with chronic ITP who achieved a response within 7 days after the first infusion: the median duration of platelet response in these subjects was 12 days (range: 1 to 79 days). 

    In 35 of the 45 subjects with chronic ITP (78%) who had bleeding at baseline, the hemorrhages had completely resolved by Day 7. A decrease in the severity of hemorrhage from baseline to Day 7 was observed in 38 of 45 subjects (84%) with chronic ITP.

    Treatment of Dermatomyositis 

    In a prospective, double-blind, randomized, placebo-controlled, multicenter study, 95 adults with dermatomyositis were enrolled and randomized. Forty-seven patients received Octagam and 48 patients received placebo in an initial 16week, double-blind First Period, followed by a 6-month, open-label Extension Period, during which all patients who were eligible to continue, received Octagam 10% every 4 weeks. Forty-five patients in the initial Octagam group and 46 patients in the placebo group entered the Extension Period.

    Efficacy in this study was based on the proportion of responders at week 16. A responder was defined as a patient with a minimal improvement of ≥20 points on the Total Improvement Score (TIS). TIS is based on six Core Set Measures (CSM) which include: Manual Muscle Testing MMT-8, Physician Global Disease Activity (GDA) as part of Myositis Disease Activity Assessment Tool (MDAAT) assessed by the Investigator on a Visual Analog Scale (VAS), Extramuscular Activity as part of MDAAT assessed by the Investigator on a VAS, Patient GDA assessed by the Patient on a VAS, Health Assessment Questionnaire (HAQ) assessed by the Patient, and Muscle Enzymes: aldolase, creatine kinase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH).

    At week 16, results showed that patients with a minimal improvement of ≥20 points on the TIS in the Octagam 10% group was 37 (78.7%) compared to 21 (43.8%) in the placebo group; difference in responder proportion was 35% [95% CI: 16.7%, 53.2%], P= 0.0008.

    The median time to response was 35 days in the Octagam 10% group. In addition, there was a greater proportion of patients in the Octagam 10% group compared to placebo with at least moderate improvement defined as ≥40 points on the TIS and major improvement defined as ≥60 points on the TIS (see full labeling for data).

    Efficacy was further supported by an improvement in the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) total activity score, with a mean decrease of 9.4 (SD: 10.5) points from baseline to week 16 in the Octagam 10% group versus 1.2 (SD: 7.0) point in the placebo group. 

    The Octagam 10% group maintained their improvement in TIS (32/45, 71.1%) during the 6-month Extension Period. Among the 46 patients who switched from placebo to Octagam 10% in the Extension Period, 69.6% (32/46) were classified as responders at the end of the 6-month Extension Period.

    Octagam 10% Note

    Not Applicable

    Octagam 10% Patient Counseling

    Patient Counseling

    Inform patients of the signs and symptoms of hypersensitivity reactions including urticaria, generalized urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis, and to contact their physicians immediately if allergic symptoms occur. 

    Inform patients to immediately report the signs and symptoms of the following conditions to their physician:

    • renal failure, such as decreased urine output, sudden weight gain, fluid retention/edema, and/or shortness of breath.
    • aseptic meningitis, such as headache, neck stiffness, drowsiness, fever, sensitivity to light, painful eye movements, nausea, and vomiting.
    • hemolysis, such as fatigue, increased heart rate, yellowing of the skin or eyes, and dark-colored urine.
    • TRALI, such as troubled breathing, chest pain, blue lips or extremities, and fever. TRALI typically occurs within 1 to 6 hours following transfusion.

    Thrombosis 

    Instruct patients to immediately report symptoms of thrombosis. These symptoms may include: 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. 

    Inform patients that Octagam 10% is made from human plasma and may contain infectious agents that can cause disease (eg, viruses, and, theoretically, the CJD agent), and that the risk of infectious agent transmission has been reduced by (a) screening plasma donors for prior exposure to certain viruses, (b) testing the donated plasma for certain viral infections and (c) inactivating and/or removing certain viruses during manufacture. 

    Inform patients that administration of Octagam 10% may interfere with the response to live viral vaccines such as measles, mumps and rubella, and to notify their immunizing physician of their therapy with Octagam 10%.

    Octagam 10% Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Immune globulin (human) 2g/20mL, 5g/50mL, 10g/100mL, 20g/200mL, 30g/300mL; liq for IV infusion; contains maltose; sucrose-, preservative-, and latex-free.

    Pharmacological Class

    Immune globulin.

    How Supplied

    Single-use bottle—1

    Storage

    Store Octagam 10% for 36 months at +2° C to +8° C (36° F to 46° F) from the date of manufacture. Within this shelf-life, the product may be stored up to 9 months at ≤ +25° C (77° F). After storage at ≤ +25° C (77° F) the product must be used or discarded.

    Do not use after the expiration date.

    Do not freeze. 

    Do not use frozen product.

    Manufacturer

    Octapharma

    Generic Availability

    NO

    Octagam 10% Indications

    Indications

    Dermatomyositis (DM).

    Octagam 10% Dosage and Administration

    Adult

    Individualize. Total dose of 2g/kg, divided into equal doses given on 2–5 consecutive days every 4 weeks by IV infusion at a rate of 1mg/kg/min, if tolerated may increase up to max 4mg/kg/min (increased risk of thromboembolic events if >4mg/kg/min). Risk of renal dysfunction/failure or thrombosis: give at the minimum practicable infusion rate; max: <3.3mg/kg/min. See full labeling.

    Children

    Not established.

    Octagam 10% Contraindications

    Contraindications

    IgA deficiency with antibodies against IgA. Previous severe reaction to human immune globulin.

    Octagam 10% Boxed Warnings

    Boxed Warning

    Thrombosis. Renal dysfunction and acute renal failure.

    Boxed Warning

    Thrombosis, Renal Dysfunction and Acute Renal Failure

    • Thrombosis, Renal Dysfunction and Acute Renal Failure
      Thrombosis may occur with immune globulin intravenous (IGIV) products, including Octagam 10%. 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 in predisposed patients who receive IGIV products, including Octagam 10%. Patients predisposed to renal dysfunction include those with a degree of pre-existing renal insufficiency, diabetes mellitus, age >65, volume depletion, sepsis, paraproteinemia, or patients receiving known nephrotoxic drugs. Renal dysfunction and acute renal failure occur more commonly in patients receiving IGIV product containing sucrose. Octagam 10% does not contain sucrose.
    • For patients at risk of thrombosis, renal dysfunction or acute renal failure, administer Octagam 10% 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.

    Octagam 10% 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. Ensure adequate hydration. Pre-existing renal insufficiency, diabetes, >65yrs, hypovolemia, sepsis, paraproteinemia: increased risk of renal dysfunction or acute renal failure. Correct volume depletion prior to initiation. Assess renal function, BUN, serum creatinine, urine output before and during therapy; discontinue if renal function deteriorates. Discontinue if hypersensitivity reactions occur; have epinephrine available. Corn allergy. Hyperproteinemia, increased serum viscosity and hyponatremia may occur. Risk of aseptic meningitis syndrome esp. in those with a history of migraine, high doses (2g/kg), and/or rapid infusion. Monitor for hemolysis and delayed hemolytic anemia; consider measuring baseline hemoglobin or hematocrit and approx. 36–96hrs post-infusion if patients are high risk. Monitor for pulmonary adverse reactions; perform test for anti-neutrophil antibodies if transfusion-related acute lung injury (TRALI) suspected. Antibody formation. Risk of transmission of blood-borne diseases. Elderly. Pregnancy. Nursing mothers.

    Warnings/Precautions

    Hypersensitivity 

    Severe hypersensitivity reactions may occur. In case of hypersensitivity, discontinue Octagam 10% infusion immediately and institute appropriate treatment. Epinephrine should be immediately available for treatment of severe acute hypersensitivity reactions. 

    Octagam 10% contains trace amounts of IgA (average 106 µg/mL in a 10% solution). IgA-deficient patients with antibodies against IgA are at greater risk of developing severe hypersensitivity and anaphylactoid reactions when administered Octagam 10%. 

    Octagam 10% may cause hypersensitivity reactions in patients with corn allergy. Octagam 10% contains maltose, a disaccharide sugar which is derived from corn.

    Renal Dysfunction/Failure 

    Renal dysfunction, acute renal failure, osmotic nephropathy, and death may occur upon use of Octagam 10% in predisposed patients. Ensure that patients are not volume depleted prior to the initiation of the infusion of Octagam 10%. 

    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, volume depletion, sepsis, paraproteinemia, or those receiving known nephrotoxic drugs), administer Octagam 10% at the minimum infusion rate practicable, not to exceed 3.3mg/kg/min (0.03mL/kg/min). 

    Periodic monitoring of renal function tests and urine output is particularly important in patients judged to be at risk of developing acute renal failure. Assess renal function, including a measurement of blood urea nitrogen (BUN)/serum creatinine, prior to the initial infusion of Octagam 10% and again at appropriate intervals thereafter. If renal function deteriorates, consider discontinuation of the product. 

    Blood Glucose Monitoring 

    Some glucose monitoring systems give falsely elevated glucose readings because they interpret the maltose in Octagam 10% as glucose.[ 2 ] This occurs in systems that use glucose dehydrogenase pyrroloquinoline quinone (GDH-PQQ) or glucose-dyeoxidoreductase methods for detecting blood glucose. Inaccurate glucose readings can cause inappropriate administration of insulin and resultant potentially life-threatening hypoglycemia. Also, true hypoglycemia may go undetected when masked by a falsely elevated glucose reading. 

    Monitor glucose levels in diabetic patients with a glucose-specific method only. Review the product information of blood glucose testing systems, including the test strips, to determine if the system is appropriate to use with maltose-containing parenteral products. Contact the manufacturer if there is any uncertainty about the system. 

    Hyperproteinemia, Increased Serum Viscosity and Hyponatremia 

    Hyperproteinemia, increased serum viscosity and hyponatremia may occur in patients receiving Octagam 10% therapy. It is clinically critical to distinguish true hyponatremia from pseudohyponatremia related to hyperproteinemia with concomitant decreased calculated serum osmolality or elevated osmolar gap, because treatment aimed at decreasing serum free water in patients with pseudohyponatremia may lead to volume depletion, a further increase in serum viscosity and a higher risk of thromboembolic events.

    Thrombosis 

    Thrombosis may occur following treatment with immune globulin products, including Octagam 10%. 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. 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 Octagam 10% 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.

    Hemolysis 

    Octagam 10% may contain blood group antibodies that can act as hemolysins and induce in vivo coating of red blood cells (RBCs) with immunoglobulin, causing a positive direct antiglobulin test (DAT) (Coombs’ test) result and hemolysis. Delayed hemolytic anemia can develop subsequent to IGIV therapy due to enhanced RBC sequestration and acute hemolysis, consistent with intravascular hemolysis, has been reported. Cases of severe hemolysis-related renal dysfunction/failure or disseminated intravascular coagulation have occurred following infusion of IGIV. 

    The following risk factors may be associated with the development of hemolysis following IGIV administration: high doses (eg, ≥ 2 g/kg), given either as a single administration or divided over several days, and non-O blood group. Other individual patient factors, such as an underlying inflammatory state (as may be reflected by, for example, elevated C-reactive protein or erythrocyte sedimentation rate), have been hypothesized to increase the risk of hemolysis following administration of IGIV, but their role is uncertain. Hemolysis has been reported following administration of IGIV for a variety of indications, including ITP. 

    Closely monitor patients for clinical signs and symptoms of hemolysis, particularly patients with risk factors noted above. Consider appropriate laboratory testing in higher risk patients, including measurement of hemoglobin or hematocrit prior to infusion and within approximately 36-96 hours post infusion. If clinical signs and symptoms of hemolysis or a significant drop in hemoglobin or hematocrit have been observed, perform confirmatory laboratory testing. 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.

    Aseptic Meningitis Syndrome 

    Aseptic meningitis syndrome (AMS) may occur with Octagam treatment. Discontinuation of treatment has resulted in remission of AMS within several days without sequelae. The syndrome usually begins within several hours to two days following rapid infusion with Octagam treatment. It is characterized by symptoms and signs including severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, nausea and vomiting. Cerebrospinal fluid (CSF) studies frequently reveal pleocytosis up to several thousand cells per cubic millimeter, predominantly from the granulocytic series, and elevated protein levels up to several hundred mg/dl, but negative culture results. Conduct a thorough neurological examination in patients exhibiting such symptoms and signs, including CSF studies, to rule out other causes of meningitis. It appears that patients with a history of migraine may be more susceptible. 

    AMS may occur more frequently following high doses (≥2 g/kg) and/or rapid infusion of IGIV.

    Transfusion-Related Acute Lung Injury (TRALI) 

    Noncardiogenic pulmonary edema [Transfusion-Related Acute Lung Injury (TRALI)] may occur in patients administered IGIV.  TRALI is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever. Signs and symptoms typically appear within 1 to 6 hours after transfusion. Patients with TRALI may be managed using oxygen therapy with adequate ventilatory support. 

    Monitor recipients of Octagam 10% for pulmonary adverse reactions. If TRALI is suspected, perform appropriate tests for the presence of anti-HLA and anti-neutrophil antibodies in the product.

    Transmission of Infectious Agents 

    Because Octagam 10% is made from human blood, it may carry a risk of transmitting infectious agents, eg, viruses and theoretically, the Creutzfeldt-Jakob disease (CJD) agent. 

    Pregnancy Considerations

    No human data are available to indicate the presence or absence of drug-associated risk. Animal reproduction studies have not been conducted with Octagam 10%. It is not known whether Octagam 10% can cause foetal harm when administered to a pregnant woman or can affect reproduction capacity. Immunoglobulins cross the placenta from maternal circulation increasingly after 30 weeks of gestation. Octagam 10% should be given to pregnant women only if clearly needed.

    Nursing Mother Considerations

    No human data are available to assess the presence or absence of Octagam 10% in human milk, the effects of Octagam 10% on the breastfed child, and the effects of Octagam 10% on milk production/excretion. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Octagam 10% liquid and any potential adverse effects on the breastfed infant from Octagam 10% liquid or from the underlying maternal condition. Immunoglobulins are excreted into the milk and may contribute to the transfer of protective antibodies to the neonate.

    Pediatric Considerations

    The safety and effectiveness of Octagam 10% has not been established in pediatric patients with ITP or DM.

    Geriatric Considerations

    Patients > 65 years of age may be at increased risk for developing certain adverse reactions such as thromboembolic events and acute renal failure. 

    Do not exceed recommended doses in this population, and the applied infusion rate should be the minimum practicable. Clinical studies of Octagam 10% did not include sufficient numbers of subjects >65 years to determine whether they respond differently from younger subjects.

    Octagam 10% Pharmacokinetics

    See Literature

    Octagam 10% Interactions

    Interactions

    Avoid live viral vaccines for ≥3 months. Concomitant nephrotoxic drugs: increased risk of acute renal failure. Falsely elevated results with some blood glucose tests (eg, GDH-PQQ based or glucose-dye-oxidoreductase methods); use glucose-specific method only. May lead to a positive direct or indirect antiglobulin (Coombs) test due to passive transmission of antibodies to erythrocyte antigens.

    Interactions

    It is recommended that Octagam 10% be administered separately from other drugs or medications which the patient may be receiving. Do not mix the product. 

    Do not mix Octagam 10% with IGIVs from other manufacturers. 

    Passively transferred antibodies in immunoglobulin preparations can confound the results of serological testing. 

    Antibodies in Octagam 10% may interfere with the response to live viral vaccines, such as measles, mumps, and rubella. Inform physicians of recent therapy with Octagam 10%, so that administration of live viral vaccines, if indicated, can be appropriately delayed for 3 or more months from the time of Octagam 10% administration.

    Octagam 10% Adverse Reactions

    Adverse Reactions

    ITP: headache, fever, increased heart rate; also with DM: nausea, vomiting, increased BP, chills, musculoskeletal pain, dyspnea, infusion site reactions; thrombosis, renal dysfunction (may be fatal); rare: hemolytic anemia, aseptic meningitis syndrome, TRALI.

    Octagam 10% Clinical Trials

    Clinical Trials

    Treatment of Chronic Immune Thrombocytopenic Purpura 

    A prospective, open-label, single-arm, multicenter study assessed the efficacy, safety, and tolerability of Octagam 10% in 116 patients with tentative newly diagnosed or chronic ITP and a platelet count of 20x109 /L or less. Patients ranged in age from 17 to 88; 64% were female and 36% were male. 

    Patients received a 2 g/kg dose of Octagam 10% administered as two daily 1 g/kg intravenous doses, given on 2 consecutive days. Pre-medication to alleviate potential adverse drug reactions was allowed but only given to 1 (0.9%) of 116 patients. In the initial study phase, the infusion rate allowed for Octagam 10% administration was up to 6 mg/kg/min [0.06 mL/kg/min], which was achieved in 24 of 26 patients (92%). Subsequently, the maximum infusion rate allowed was 12 mg/kg/min [0.12mL/kg/min], which was achieved in 54 of 90 patients (60%). Platelet counts were measured on Days 1 to 7, 14, 21, and 63. 

    The study was designed to determine the response rate defined as the percentage of patients with an increase in platelet count to at least 50x109 /L within 7 days after the first infusion (responders). Additionally, maximum platelet count, the time to reach a platelet count of at least 50x109 /L within the first 7 days, the duration of that response (ie, the number of days the platelet count remained in excess of 50x109 /L), and the regression of hemorrhages in patients who had bleeding at baseline were observed. 

    Of the 66 patients with chronic ITP in the efficacy analysis, 54 (82%) responded to Octagam 10% with a rise in platelet counts to at least 50x109 /L within 7 days after the first infusion. The lower bound of the overall 95% confidence interval for the response rate (73%) is above the predefined response rate of 70%. The mean maximum platelet count achieved in the 66 patients with chronic ITP was 227x109 /L.

    The median time to reach a platelet response of at least 50x109 /L was 2 days after the first infusion. The duration of platelet response was analyzed for the 54 subjects with chronic ITP who achieved a response within 7 days after the first infusion: the median duration of platelet response in these subjects was 12 days (range: 1 to 79 days). 

    In 35 of the 45 subjects with chronic ITP (78%) who had bleeding at baseline, the hemorrhages had completely resolved by Day 7. A decrease in the severity of hemorrhage from baseline to Day 7 was observed in 38 of 45 subjects (84%) with chronic ITP.

    Treatment of Dermatomyositis 

    In a prospective, double-blind, randomized, placebo-controlled, multicenter study, 95 adults with dermatomyositis were enrolled and randomized. Forty-seven patients received Octagam and 48 patients received placebo in an initial 16week, double-blind First Period, followed by a 6-month, open-label Extension Period, during which all patients who were eligible to continue, received Octagam 10% every 4 weeks. Forty-five patients in the initial Octagam group and 46 patients in the placebo group entered the Extension Period.

    Efficacy in this study was based on the proportion of responders at week 16. A responder was defined as a patient with a minimal improvement of ≥20 points on the Total Improvement Score (TIS). TIS is based on six Core Set Measures (CSM) which include: Manual Muscle Testing MMT-8, Physician Global Disease Activity (GDA) as part of Myositis Disease Activity Assessment Tool (MDAAT) assessed by the Investigator on a Visual Analog Scale (VAS), Extramuscular Activity as part of MDAAT assessed by the Investigator on a VAS, Patient GDA assessed by the Patient on a VAS, Health Assessment Questionnaire (HAQ) assessed by the Patient, and Muscle Enzymes: aldolase, creatine kinase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH).

    At week 16, results showed that patients with a minimal improvement of ≥20 points on the TIS in the Octagam 10% group was 37 (78.7%) compared to 21 (43.8%) in the placebo group; difference in responder proportion was 35% [95% CI: 16.7%, 53.2%], P= 0.0008.

    The median time to response was 35 days in the Octagam 10% group. In addition, there was a greater proportion of patients in the Octagam 10% group compared to placebo with at least moderate improvement defined as ≥40 points on the TIS and major improvement defined as ≥60 points on the TIS (see full labeling for data).

    Efficacy was further supported by an improvement in the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) total activity score, with a mean decrease of 9.4 (SD: 10.5) points from baseline to week 16 in the Octagam 10% group versus 1.2 (SD: 7.0) point in the placebo group. 

    The Octagam 10% group maintained their improvement in TIS (32/45, 71.1%) during the 6-month Extension Period. Among the 46 patients who switched from placebo to Octagam 10% in the Extension Period, 69.6% (32/46) were classified as responders at the end of the 6-month Extension Period.

    Octagam 10% Note

    Not Applicable

    Octagam 10% Patient Counseling

    Patient Counseling

    Inform patients of the signs and symptoms of hypersensitivity reactions including urticaria, generalized urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis, and to contact their physicians immediately if allergic symptoms occur. 

    Inform patients to immediately report the signs and symptoms of the following conditions to their physician:

    • renal failure, such as decreased urine output, sudden weight gain, fluid retention/edema, and/or shortness of breath.
    • aseptic meningitis, such as headache, neck stiffness, drowsiness, fever, sensitivity to light, painful eye movements, nausea, and vomiting.
    • hemolysis, such as fatigue, increased heart rate, yellowing of the skin or eyes, and dark-colored urine.
    • TRALI, such as troubled breathing, chest pain, blue lips or extremities, and fever. TRALI typically occurs within 1 to 6 hours following transfusion.

    Thrombosis 

    Instruct patients to immediately report symptoms of thrombosis. These symptoms may include: 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. 

    Inform patients that Octagam 10% is made from human plasma and may contain infectious agents that can cause disease (eg, viruses, and, theoretically, the CJD agent), and that the risk of infectious agent transmission has been reduced by (a) screening plasma donors for prior exposure to certain viruses, (b) testing the donated plasma for certain viral infections and (c) inactivating and/or removing certain viruses during manufacture. 

    Inform patients that administration of Octagam 10% may interfere with the response to live viral vaccines such as measles, mumps and rubella, and to notify their immunizing physician of their therapy with Octagam 10%.

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