Human Botulinum Neurotoxin A/B Immune Globulin

5 WARNINGS AND PRECAUTIONS Only administer BabyBIGas an intravenous infusion, since other routes of administration have not been evaluated. Do not use BabyBIG if the reconstituted solution is turbid [ see DOSAGE AND ADMINISTRATION (2.1) ]. Assess renal function prior to and following administration ( 5.1 , 5.2 ). Anaphylaxis and hypersensitivity reactions may occur ( 5.4 ). This risk should be considered when an IgA-deficient patient is to receive subsequent administration of blood products containing IgA after previous treatment with BabyBIG ( 4 ). Hyperproteinemia, increased serum viscosity and hyponatremia may occur in patients receiving immune globulin intravenous (human) (IGIV) therapy ( 5.6 ). Thrombotic events have occurred in patients receiving IGIV products. Monitor patients with known risk factors for thrombotic events; consider baseline assessment of blood viscosity for those at risk of hyperviscosity ( 5.7 ). Hemolytic anemia can develop subsequent to IGIV therapy due to enhanced RBC sequestration ( 5.8 ). IGIV recipients should be monitored for pulmonary adverse reactions, such as Transfusion-Related Acute Lung Injury (TRALI) ( 5.9 ). Aseptic meningitis syndrome (AMS) has been reported with other IGIV treatment, especially with high doses or rapid infusion ( 5.5 ). The product is made from human plasma and may contain infectious agents, e.g. viruses and, theoretically, the Creutzfeldt-Jakob disease agent ( 5.3 ). 5.1 Patient Monitoring for Administration Patients should be well hydrated prior to the initiation of the BabyBIG infusion. Assess renal function, including the measurement of blood urea nitrogen (BUN) or serum creatinine prior to the initial infusion of BabyBIG [ see DOSAGE AND ADMINISTRATION (2) ]. Periodic monitoring of renal function tests and urine output is particularly important in patients judged to have a potential risk for developing acute renal failure. [1-6] Increases in serum creatinine and BUN have been observed as soon as one to two days following treatment with other IGIV products. During administration, monitor the patient's vital signs continuously and observe the patient carefully for any associated symptoms. DO NOT EXCEED THE RECOMMENDED INFUSION RATE of 1 mL/kg/hour (50 mg/kg/h), and follow the infusion schedule closely [ see DOSAGE AND ADMINISTRATION (2.3) ]. If a patient develops an infusion reaction, slow the rate of infusion immediately or temporarily interrupt the infusion. 5.2 Renal Adverse Reactions Other IGIV products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. [5, 6] While these reports of renal dysfunction and acute renal failure have been associated with the use of many licensed IGIV products, those that contained sucrose as a stabilizer and were administered at daily doses of 400 mg/kg or greater have accounted for a disproportionate share of the total number. [5, 7] BabyBIG contains sucrose as a stabilizer. Patients predisposed to acute renal failure include those patients with any degree of pre-existing renal insufficiency, diabetes mellitus, volume depletion, sepsis, paraproteinemia, or who are receiving known nephrotoxic drugs. Especially in such patients, BabyBIG should be administered at the minimum concentration available and at the minimum rate of infusion practicable. [1-4] 5.3 Transmission of Blood-Borne Infectious Agents BabyBIG is made from human plasma and, like other plasma products, carries the possibility for transmission of blood-borne viral agents and, theoretically, the Creutzfeldt-Jakob disease agent. The risk of transmission of recognized blood-borne viruses has been reduced by screening plasma donors for prior exposure to certain viruses, for the presence of certain viral infections, and by the viral inactivation and/or removal properties of the precipitation procedures used for the purification of BabyBIG [see DESCRIPTION (11) ]. Despite these measures, some as yet unrecognized blood-borne infectious agents may not be inactivated by the manufacturing process; therefore, BabyBIG, like any other blood product, should be given only if a benefit is expected [ see PATIENT COUNSELING INFORMATION (17) ]. 5.4 Anaphylaxis Severe reactions, such as angioedema and anaphylactic shock, although not observed during clinical trials with BabyBIG, are a possibility. [8, 9] Clinical anaphylaxis may occur even when the patient is not known to be sensitive to immune globulin products. A reaction may be related to the rate of infusion; therefore, carefully adhere to the infusion rates as outlined under "DOSAGE AND ADMINISTRATION (2.3)." If anaphylaxis or a drop in blood pressure occurs, discontinue the infusion and administer epinephrine. [1-4] Although acute systemic allergic reactions were not seen in clinical trials with BabyBIG, epinephrine should be available for treatment of acute allergic symptoms [ see ADVERSE REACTIONS (6.1) ]. If hypotension or anaphylaxis occurs, discontinue the administration of BabyBIG immediately and give supportive care as needed. 5.5 Aseptic Meningitis Syndrome An aseptic meningitis syndrome (AMS) has been reported to occur infrequently in association with IGIV administration. [10-13] The syndrome usually begins within several hours to two days following IGIV treatment. It is characterized by symptoms and signs that include the following: severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, and nausea and vomiting. Cerebrospinal fluid studies are frequently positive with pleocytosis up to several thousand cells per cubic millimeter, predominately from the granulocytic series, and with elevated protein levels up to several hundred mg/dL. Conduct a thorough neurological examination in patients exhibiting such symptoms and signs to rule out other causes of meningitis. [10-13] AMS may occur more frequently in association with high total doses (2 g/kg) of IGIV treatment. Discontinuation of IGIV treatment has resulted in remission of AMS within several days without sequelae. [1, 10-13] AMS was not observed in clinical trials of BabyBIG. 5.6 Hyperproteinemia, Hyponatremia, and Serum Viscosity Hyperproteinemia, hyponatremia, and increased serum viscosity have been observed following administration of IGIV products. It is clinically critical to distinguish true hyponatremia from pseudohyponatremia caused by 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. These adverse events have not been observed with BabyBIG. 5.7 Thrombotic Events Thrombotic events may occur following IGIV treatment. 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. 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 BabyBIG at the minimum rate of infusion practicable. 5.8 Hemolytic Anemia IGIV products may contain blood group antibodies, which can act as hemolysins and induce in vivo coating of red blood cells with immunoglobulin, causing a positive direct antiglobulin reaction and, rarely, hemolysis. Hemolytic anemia may develop subsequent to IGIV therapy due to enhanced red blood cell sequestration. Monitor patients for clinical signs and symptoms of hemolysis. If these are present after BabyBIG infusion, perform appropriate confirmatory laboratory testing. 5.9 Transfusion-Related Acute Lung Injury (TRALI) Non-cardiogenic pulmonary edema may occur in patients following IGIV treatment. [14] TRALI is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever. Symptoms typically occur within 1 to 6 hours following treatment [See PATIENT COUNSELING INFORMATION (17) ] . Monitor patients for pulmonary adverse reactions. If TRALI is suspected, perform appropriate tests for the presence of anti-neutrophil antibodies in both the product and patient serum. TRALI may be managed using oxygen therapy with adequate ventilatory support.