warnings and cautions
WARNINGS AND PRECAUTIONS IgA deficient patients with antibodies against IgA are at greater risk of developing severe hypersensitivity and anaphylactic reactions Epinephrine should be available immediately to treat any acute severe hypersensitivity reactions. (5.1) Monitor renal function, including blood urea nitrogen and serum creatinine, and urine output in patients at risk of developing acute renal failure. (5.2) Falsely elevated blood glucose readings may occur during and after the infusion of Octagam 5% liquid with some glucometer and test strip systems (5.3) Hyperproteinemia, increased serum viscosity and hyponatremia occur in patients receiving IGIV therapy. (5.4) Thrombotic events have occurred in patients receiving IGIV therapy. Monitor patients with known risk factors for thrombotic events; consider baseline assessment of blood viscosity for those at risk of hyperviscosity. (5.5) Aseptic Meningitis Syndrome has been reported with Octagam 5% liquid and other IGIV treatments, especially with high doses or rapid infusion. (5.6) Hemolytic anemia can develop subsequent to IGIV therapy due to enhanced RBC sequestration (5.7) IGIV recipients should be monitored for pulmonary adverse reactions (TRALI) (5.8) The product is made from human plasma and may contain infectious agents, e.g. viruses and, theoretically, the Creutzfeldt-Jakob disease agent (5.9) Sensitivity Severe hypersensitivity reactions may occur [ 1 ] (See Contraindications [4.1]). In case of hypersensitivity, Octagam 5% liquid infusion should be immediately discontinued and appropriate treatment instituted. Epinephrine should be immediately available for treatment of acute severe hypersensitivity reaction. IgA deficient patients with antibodies against IgA are at greater risk of developing severe hypersensitivity and anaphylactoid reactions when administered Octagam 5% liquid (See Contraindications [4.2]). Patients known to have corn allergies should avoid using Octagam 5% liquid (See Contraindications [4.3]). Renal Failure Assure that patients are not volume depleted prior to the initiation of the infusion of Octagam 5% liquid. Periodic monitoring of renal function tests and urine output is particularly important in patients judged to have a potential increased risk of developing acute renal failure. Renal function, including a measurement of blood urea nitrogen (BUN)/serum creatinine, should be assessed prior to the initial infusion of Octagam 5% liquid and again at appropriate intervals thereafter. If renal function deteriorates, discontinuation of the product should be considered (See Patient Counselling Information [17]) For patients judged to be at risk for developing renal dysfunction and/or at risk of developing thrombotic events, it may be prudent to reduce the amount of product infused per unit time by infusing Octagam 5% liquid at a maximum rate less than 0.07 ml/kg (3.3 mg/kg)/minute (200 mg/kg/hour) (See Boxed Warning, and Dosage and Administration [2.4]). Blood Glucose Monitoring Blood Glucose Testing [ 2 ] :some types of blood glucose testing systems (for example, those based on the glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ) or glucose-dye-oxidoreductase methods) falsely interpret the maltose contained in Octagam 5% liquid as glucose. This has resulted in falsely elevated glucose readings and, consequently, in the inappropriate administration of insulin, resulting in life-threatening hypoglycemia. Also, cases of true hypoglycemia may go untreated if the hypoglycemic state is masked by falsely elevated glucose readings. Accordingly, when administering Octagam 5% liquid, the measurement of blood glucose must be done with a glucose-specific method. The product information of the blood glucose testing system, including that of the test strips, should be carefully reviewed to determine if the system is appropriate for use with maltose-containing parenteral products. If any uncertainty exists, contact the manufacturer of the testing system to determine if the system is appropriate for use with maltose-containing parenteral products. Hyperproteinemia Hyperproteinemia, increased serum viscosity and hyponatremia may occur in patients receiving IGIV therapy. The hyponatremia is likely to be a pseudohyponatremia as demonstrated by a decreased calculated serum osmolality or elevated osmolar gap. Distinguishing true hyponatremia from pseudohyponatremia is clinically critical, 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 disposition to thromboembolic events [ 3 ]. Thrombotic events Thrombotic events have been reported in association with IGIV therapy [ 4 ],[ 5 ],[ 6 ]. Patients at risk may include those with a history of atherosclerosis, multiple cardiovascular risk factors, advanced age, impaired cardiac output, coagulation disorders, prolonged periods of immobilization and/or known or suspected hyperviscosity. The potential risks and benefits of IGIV should be weighed against those of alternative therapies for all patients for whom IGIV administration is being considered. Baseline assessment of blood viscosity should be considered in patients at risk for hyperviscosity, including those with cryoglobulins, fasting chylomicronemia / markedly high triacylglycerols (triglycerides), or monoclonal gammopathies. Aseptic meningitis syndrome Aseptic meningitis syndrome (AMS) has been reported to occur infrequently in association with IGIV treatment. Discontinuation of IGIV treatment has resulted in remission of AMS within several days without sequelae. The syndrome usually begins within several hours to two days following IGIV treatment and rapid infusion. 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 are frequently positive with pleocytosis up to several thousand cells per cu mm, predominantly from the granulocytic series, and elevated protein levels up to several hundred mg/dl. Patients exhibiting such symptoms and signs should receive a thorough neurological examination, including CSF studies, to rule out other causes of meningitis. It appears that patients with a history of migraine may be more susceptible. [ 7 ] (See Patient Counselling Information [17]). Hemolysis IGIV products can contain blood group antibodies which may act as hemolysins and induce in vivo coating of red blood cells with immunoglobulin, causing a positive direct antiglobulin reaction and, rarely, hemolysis [ 8 ]. Hemolytic anemia can develop subsequent to IGIV therapy due to enhanced RBC sequestration [See ADVERSE REACTIONS] [ 9 ]. IGIV recipients should be monitored for clinical signs and symptoms of hemolysis. If signs and/or symptoms of hemolysis are present after IGIV infusion, appropriate confirmatory laboratory testing should be done (See Patient Counseling Information [17]). Transfusion-Related Acute Lung Injury (TRALI) There have been reports of noncardiogenic pulmonary edema [Transfusion-Related Acute Lung Injury (TRALI)] in patients administered IGIV [ 10 ]. TRALI is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever and typically occurs within 1-6 hours after transfusion. Patients with TRALI may be managed using oxygen therapy with adequate ventilatory support. IGIV recipients should be monitored for pulmonary adverse reactions (See Patient Counseling Information [17]). If TRALI is suspected, appropriate tests should be performed for the presence of anti-neutrophil antibodies in both the product and patient serum. General Because this product is made from human blood, it may carry a risk of transmitting infectious agents, e.g., viruses and theoretically, the Creutzfeldt-Jakob disease (CJD) agent. All infections thought by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Octapharma. The physician should discuss the risks and benefits of this product with the patient, before prescribing or administering it to the patient (See Patient Counseling Information [17]). Laboratory Tests If signs and/or symptoms of hemolysis are present after IGIV infusion, appropriate confirmatory laboratory testing should be done. If TRALI is susppected, appropriate tests should be performed for the presence of anti-neutrophil antibodies in both the product and patient serum. Because of the potentially increased risk of thrombosis, baseline assessment of blood viscosity should be considered in patients at risk for hyperviscosity, including those with cryoglobulins, fasting chylomicronemia/markedly high triacylglycerols (triglycerides), or monoclonal gammopathies.