warnings and cautions
5 WARNINGS AND PRECAUTIONS IgA-deficient patients with anti-IgA antibodies are at greater risk of severe hypersensitivity and anaphylactic reactions. Discontinue use if hypersensitivity reaction occurs ( 5.1 ). Aseptic meningitis syndrome has been reported to occur with IGIV or IGSC treatment ( 5.2 ). Monitor patients for reactions reported to occur with IGIV treatment that may occur with Hizentra, including renal dysfunction/failure, thrombotic events, hemolysis, and transfusion-related acute lung injury (TRALI) ( 5.3 ). Products made from human plasma can contain infectious agents, e.g., viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent ( 5.4 ). 5.1 Hypersensitivity Severe hypersensitivity reactions may occur to human immune globulin or components of Hizentra, such as polysorbate 80. In case of hypersensitivity, discontinue the Hizentra infusion immediately and institute appropriate treatment. Individuals with IgA deficiency can develop anti-IgA antibodies and anaphylactic reactions (including anaphylaxis and shock) after administration of blood components containing IgA. Patients with known antibodies to IgA may have a greater risk of developing potentially severe hypersensitivity and anaphylactic reactions with administration of Hizentra. Hizentra contains ≤50 mcg/mL IgA ( see Description [11] ). 5.2 Aseptic Meningitis Syndrome (AMS) AMS has been reported with use of IGIV 1 or IGSC. The syndrome usually begins within several hours to 2 days following immune globulin treatment. AMS is characterized by the following signs and symptoms: severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, nausea, and vomiting. Cerebrospinal fluid (CSF) studies frequently show pleocytosis up to several thousand cells per cubic millimeter, predominantly from the granulocytic series, and elevated protein levels up to several hundred mg/dL. AMS may occur more frequently in association with high doses (≥2 g/kg) and/or rapid infusion of immune globulin product. Patients exhibiting such signs and symptoms should receive a thorough neurological examination, including CSF studies, to rule out other causes of meningitis. Discontinuation of immune globulin treatment has resulted in remission of AMS within several days without sequelae. 5.3 Reactions Reported to Occur With IGIV Treatment The following reactions have been reported to occur with IGIV treatment and may occur with IGSC treatment. Renal Dysfunction/Failure Renal dysfunction/failure, osmotic nephropathy, and death may occur with use of human immune globulin products. Ensure that patients are not volume depleted and assess renal function, including measurement of blood urea nitrogen (BUN) and serum creatinine, before the initial infusion of Hizentra and at appropriate intervals thereafter. Periodic monitoring of renal function and urine output is particularly important in patients judged to have a potential increased risk of developing acute renal failure. 2 If renal function deteriorates, consider discontinuing Hizentra. For patients judged to be at risk of developing renal dysfunction because of pre-existing renal insufficiency or predisposition to acute renal failure (such as those with diabetes mellitus or hypovolemia, those who are overweight or use concomitant nephrotoxic medicinal products, or those who are over 65 years of age), administer Hizentra at the minimum rate practicable. Thrombotic Events Thrombotic events may occur with use of human immune globulin products 3-5 . Patients at increased risk may include those with a history of atherosclerosis, multiple cardiovascular risk factors, advanced age, impaired cardiac output, hypercoagulable disorders, prolonged periods of immobilization, and/or known or suspected hyperviscosity. Because of the potentially increased risk of thrombosis, 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 judged to be at risk of developing thrombotic events, administer Hizentra at the minimum rate practicable. Hemolysis Hizentra can contain blood group antibodies that may act as hemolysins and induce in vivo coating of red blood cells (RBCs) with immunoglobulin, causing a positive direct antiglobulin (Coombs') test result and hemolysis. 6-8 Delayed hemolytic anemia can develop subsequent to immune globulin therapy due to enhanced RBC sequestration, and acute hemolysis, consistent with intravascular hemolysis, has been reported. 9 Monitor recipients of Hizentra for clinical signs and symptoms of hemolysis. If these are present after a Hizentra infusion, perform appropriate confirmatory laboratory testing. If transfusion is indicated for patients who develop hemolysis with clinically compromising anemia after receiving Hizentra, perform adequate cross-matching to avoid exacerbating on-going hemolysis. Transfusion-Related Acute Lung Injury (TRALI) Noncardiogenic pulmonary edema may occur in patients administered human immune globulin products. 10 TRALI is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever. Typically, it occurs within 1 to 6 hours following transfusion. Patients with TRALI may be managed using oxygen therapy with adequate ventilatory support. Monitor Hizentra recipients for pulmonary adverse reactions. If TRALI is suspected, perform appropriate tests for the presence of anti-neutrophil antibodies in both the product and patient's serum. 5.4 Transmissible Infectious Agents Because Hizentra is made from human plasma, it may carry a risk of transmitting infectious agents (e.g., viruses, and theoretically, the Creutzfeldt-Jakob disease [CJD] 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 Hizentra. Report all infections thought to be possibly transmitted by Hizentra to CSL Behring Pharmacovigilance at 1-866-915-6958. 5.5 Laboratory Tests Various passively transferred antibodies in immunoglobulin preparations may lead to misinterpretation of the results of serological testing.