FDA label 7f4ae7dc-958f-49e4-ab4d-95816a98d7ed

Immune Globulin Intravenous (Human) (IGIV) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. 31–36 Patients predisposed to acute renal failure include patients with: any degree of pre-existing renal insufficiency diabetes mellitus age greater than 65 volume depletion sepsis paraproteinemia patients receiving known nephrotoxic drugs In such patients, IGIV products should be administered at the minimum concentration available and the minimum rate of infusion practicable. While these reports of renal dysfunction and acute renal failure have been associated with the use of many of the licensed IGIV products, those containing sucrose as a stabilizer accounted for a disproportionate share of the total number. See PRECAUTIONS and DOSAGE AND ADMINISTRATION sections for important information intended to reduce the risk of acute renal failure.

WARNINGS Immune Globulin Intravenous (Human) (IGIV) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. 31–36 Patients predisposed to acute renal failure include patients with: any degree of pre-existing renal insufficiency diabetes mellitus age greater than 65 volume depletion sepsis paraproteinemia patients receiving known nephrotoxic drugs In such patients, IGIV products should be administered at the minimum concentration available and the minimum rate of infusion practicable. While these reports of renal dysfunction and acute renal failure have been associated with the use of many of the licensed IGIV products, those containing sucrose as a stabilizer accounted for a disproportionate share of the total number. See PRECAUTIONS and DOSAGE AND ADMINISTRATION sections for important information intended to reduce the risk of acute renal failure. IgA deficient patients, especially those with known antibodies against IgA, are at greater risk of developing severe hypersensitivity and anaphylactic reactions. Carimune ® NF is made from human plasma. Products made from human plasma may contain infectious agents, such as viruses, that can cause disease. The risk that such products will transmit an infectious agent has been reduced by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections, and through the application of viral elimination/reduction steps such as alcohol fractionation in the presence of filter aids, nanofiltration and pH 4/pepsin treatment 5-7 (see Table 1 ). Despite these measures, such products may carry a risk of transmitting infectious agents, e.g., viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent. There is also the possibility that unknown infectious agents may be present in such products. 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 CSL Behring Pharmacovigilance at 1-866-915-6958. The physician should discuss the risks and benefits of this product with the patient. Patients with agamma- or extreme hypogammaglobulinemia who have never before received immunoglobulin substitution treatment or whose time from last treatment is greater than 8 weeks, may be at risk of developing inflammatory reactions on rapid infusion (greater than 2 mg/kg/min) of Carimune ® NF. These reactions are manifested by a rise in temperature, chills, nausea, and vomiting. The patient's vital signs should be monitored continuously. The patient should be carefully observed throughout the infusion, since these reactions on rare occasions may lead to shock. Epinephrine and other appropriate resuscitative drugs and equipment should be available for treatment of an acute anaphylactic reaction.

ADVERSE REACTIONS Increases in creatinine and blood urea nitrogen (BUN) have been observed as soon as one to two days following infusion. Progression to oliguria or anuria, requiring dialysis has been observed. Types of severe renal adverse events that have been seen following IGIV therapy include: acute renal failure, acute tubular necrosis, proximal tubular nephropathy and osmotic nephrosis. 31–36,64,71–73 Inflammatory adverse reactions have been described in agammaglobulinemic and hypogammaglobulinemic patients who have never received immunoglobulin substitution therapy before or in patients whose time from last treatment is greater than 8 weeks and whose initial infusion rate exceeds 2 mg/kg/min. This occurs in approximately 10% of such cases. Such reactions may also be observed in some patients during chronic substitution therapy. Reactions, which may become apparent only 30 minutes to 1 hour after the beginning of the infusion, are as follows: flushing of the face, feelings of tightness in the chest, chills, fever, dizziness, nausea, diaphoresis, and hypotension or hypertension. In such cases, the infusion should be slowed or temporarily stopped until the symptoms subside. The infusion may then be resumed at a lower rate that is comfortable for the patient. If anaphylaxis or other severe reactions occur, the infusion should be stopped immediately. Arthralgia, myalgia, and transient skin reactions (such as rash, erythema, pruritus, urticaria, eczema or dermatitis) have also been reported. Immediate anaphylactoid and hypersensitivity reactions due to previous sensitization of the recipient to certain antigens, most commonly IgA, may be observed in exceptional cases, described under CONTRAINDICATIONS . 16,17,65 In patients with ITP, who receive higher doses (0.4 g/kg/day or greater), 2.9% of infusions may result in adverse reactions. 21 Headache, generally mild, is the most common symptom noted, occurring during or following 2% of infusions. A few cases of usually mild hemolysis have been reported after infusion of intravenous immunoglobulin products. 51–53 These were attributed to transferal of blood group (e.g., anti-D) antibodies. Postmarketing The following adverse reactions have been identified and reported during the post-approval use of IGIV products: Respiratory Apnea, Acute Respiratory Distress Syndrome (ARDS), Transfusion-Related Acute Lung Injury (TRALI), cyanosis, hypoxemia, pulmonary edema, dyspnea, bronchospasm Cardiovascular Cardiac arrest, thromboembolism, vascular collapse, hypotension Neurological Coma, loss of consciousness, seizures, tremor Integumentary Stevens-Johnson syndrome, epidermolysis, erythema multiforme, bullous dermatitis Hematologic Pancytopenia, leukopenia, hemolysis, positive direct antiglobulin (Coombs) test General/Body as a Whole Pyrexia, rigors Musculoskeletal Back pain Gastrointestinal Hepatic dysfunction, abdominal pain Because postmarketing reporting of these reactions is voluntary and the at-risk populations are of uncertain size, it is not always possible to reliably estimate the frequency of the reaction or establish a causal relationship to exposure to the product. Such is also the case with literature reports authored independently. 66