FDA label b7445298-f6fe-4f8c-bb27-9fc73aa6a2f2

WARNING: ACUTE RENAL DYSFUNCTION/FAILURE Use of Immune Globulin Intravenous (IGIV) products, particularly those containing sucrose, have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephropathy, and death. 1 Patients at risk of acute renal failure include those with any degree of pre-existing renal insufficiency, diabetes mellitus, advanced age (above 65 years of age), volume depletion, sepsis, paraproteinemia, or receiving known nephrotoxic drugs ( see Warnings and Precautions [5.2] ). Privigen does not contain sucrose. For patients at risk of renal dysfunction or failure, administer Privigen at the minimum infusion rate practicable ( see Dosage and Administration [2.3] , Warnings and Precautions [5.2] ). WARNING: ACUTE RENAL DYSFUNCTION/FAILURE See full prescribing information for complete boxed warning. Renal dysfunction, acute renal failure, osmotic nephropathy, and death may occur with the administration of human immune globulin intravenous (IGIV) products. Renal dysfunction and acute renal failure occur more commonly in patients receiving IGIV products that contain sucrose. Privigen does not contain sucrose. For patients at risk of renal dysfunction or renal failure, administer Privigen at the minimum infusion rate practicable.

5 WARNINGS AND PRECAUTIONS IgA-deficient patients with antibodies to IgA are at greater risk of developing severe hypersensitivity and anaphylactic 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 ). Hyperproteinemia, increased serum viscosity, and hyponatremia may occur ( 5.3 ). Thrombotic events may occur. Monitor patients with known risk factors for thrombotic events; consider baseline assessment of blood viscosity for those at risk of hyperviscosity ( 5.4 ). Aseptic meningitis syndrome (AMS) may occur, especially with high doses or rapid infusion ( 5.5 ). Hemolysis can develop subsequent to Privigen treatments due to enhanced red blood cell sequestration. Monitor patients for hemolysis and hemolytic anemia ( 5.6 ). Monitor patients for pulmonary adverse reactions (transfusion-related acute lung injury [TRALI]) ( 5.7 ). Avoid use of the high-dose regimen (for chronic ITP) in patients with expanded fluid volume or where fluid volume is of concern ( 5.8 ). Privigen is made from human blood and may contain infectious agents, e.g., viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent ( 5.9 ). 5.1 Hypersensitivity Severe hypersensitivity reactions may occur ( see Contraindications [4] ). In case of hypersensitivity, discontinue the Privigen infusion immediately and institute appropriate treatment. Medications such as epinephrine should be available for immediate treatment of acute hypersensitivity reactions. Privigen contains trace amounts of IgA (≤25 mcg/mL) ( see Description [11] ) . 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 Privigen. Privigen is contraindicated in patients with antibodies against IgA and a history of hypersensitivity. 5.2 Renal Dysfunction/Failure Acute renal dysfunction/failure, osmotic nephropathy, and death may occur with the use of IGIV products, including Privigen. 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 Privigen and at appropriate intervals thereafter. Periodic monitoring of renal function and urine output is particularly important in patients judged to be at increased risk of developing acute renal failure. 1 If renal function deteriorates, consider discontinuing Privigen. 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, those who use concomitant nephrotoxic medicinal products, or those who are over 65 years of age), administer Privigen at the minimum rate of infusion practicable ( see Boxed Warning , Dosage and Administration [2.3] ). 5.3 Hyperproteinemia, Increased Serum Viscosity, and Hyponatremia Hyperproteinemia, increased serum viscosity, and hyponatremia may occur following treatment with IGIV products, including Privigen. The hyponatremia is likely to be a pseudohyponatremia, as demonstrated by a decreased calculated serum osmolality or elevated osmolar gap. It is critical to distinguish true hyponatremia from pseudohyponatremia, 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 possible predisposition to thromboembolic events. 2 5.4 Thrombotic Events Thrombotic events may occur following treatment with IGIV products, including Privigen. 3-5 Patients at risk 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/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 Privigen at the minimum rate of infusion practicable ( see Dosage and Administration [2.3] ). 5.5 Aseptic Meningitis Syndrome (AMS) AMS may occur infrequently following treatment with Privigen ( see Adverse Reactions [6] ) and other human immune globulin products. Discontinuation of treatment has resulted in remission of AMS within several days without sequelae. 6 AMS usually begins within several hours to 2 days following IGIV 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 are frequently positive with pleocytosis up to several thousand cells per cubic millimeter, predominantly from the granulocytic series, and with elevated protein levels up to several hundred mg/dL, but negative culture results. Conduct a thorough neurological examination on patients exhibiting such signs and symptoms, including CSF studies, to rule out other causes of meningitis. AMS may occur more frequently in association with high doses (2 g/kg) and/or rapid infusion of IGIV. 5.6 Hemolysis Privigen 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. 7-9 Delayed hemolytic anemia can develop subsequent to Privigen therapy due to enhanced RBC sequestration, and acute hemolysis, consistent with intravascular hemolysis, has been reported. 10 Hemolysis, possibly intravascular, occurred in two subjects treated with Privigen in the ITP study ( see Adverse Reactions [6] ). These cases resolved uneventfully. Six other subjects experienced hemolysis in the ITP study as documented from clinical laboratory data. Monitor patients for clinical signs and symptoms of hemolysis. If these are present after a Privigen infusion, perform appropriate 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. 5.7 Transfusion-Related Acute Lung Injury (TRALI) Noncardiogenic pulmonary edema may occur following treatment with IGIV products, including Privigen. 11 TRALI is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever. Symptoms typically appear within 1 to 6 hours following treatment. Monitor patients for pulmonary adverse reactions. If TRALI is suspected, perform appropriate tests for the presence of anti-neutrophil antibodies and anti-human leukocyte antigen (HLA) antibodies in both the product and the patient's serum. TRALI may be managed using oxygen therapy with adequate ventilatory support. 5.8 Volume Overload The high-dose regimen (1 g/kg/day for 2 days) used to treat patients with chronic ITP is not recommended for individuals with expanded fluid volumes or where fluid volume may be of concern ( see Dosage and Administration [2.2] ). 5.9 Transmissible Infectious Agents Because Privigen 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). 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 Privigen. Report any infection thought to be possibly transmitted by Privigen to CSL Behring Pharmacovigilance at 1-866-915-6958 . 5.10 Interference with Laboratory Tests Various passively transferred antibodies in immunoglobulin preparations may lead to misinterpretation of the results of serological testing.

6 ADVERSE REACTIONS The most serious adverse reactions observed in clinical study subjects receiving Privigen for PI was hypersensitivity in one subject. The most common adverse reactions observed in >5% of clinical study subjects with PI were headache, pain, nausea, fatigue, chills, vomiting, joint swelling/effusion, pyrexia, and urticaria. The most serious adverse reactions observed in clinical study subjects receiving Privigen for chronic ITP were aseptic meningitis syndrome in one subject and hemolysis in two subjects. Six other subjects in the ITP study experienced hemolysis as documented from clinical laboratory data. The most common adverse reactions observed in >5% of clinical study subjects with chronic ITP were headache, pyrexia/hyperthermia, positive DAT, anemia, vomiting, nausea, hyperthermia, bilirubin conjugated increased, bilirubin unconjugated increased, hyperbilirubinemia, and blood lactate dehydrogenase increased. PI – The most common adverse reactions, observed in >5% of study subjects, were headache, pain, nausea, fatigue, chills, vomiting, joint swelling/effusion, pyrexia, and urticaria. Serious adverse reactions were hypersensitivity, chills, fatigue, dizziness, and increased body temperature ( 6 ). Chronic ITP – The most common adverse reactions, observed in >5% of study subjects, were headache, pyrexia/hyperthermia, positive direct antiglobulin test (DAT), anemia, vomiting, nausea, bilirubin conjugated increased, bilirubin unconjugated increased, hyperbilirubinemia, and blood lactate dehydrogenase increased. A serious adverse reaction was aseptic meningitis ( 6 ). To report SUSPECTED ADVERSE REACTIONS, contact CSL Behring Pharmacovigilance at 1-866-915-6958 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because different clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Treatment of Primary Humoral Immunodeficiency In a prospective, open-label, single-arm, multicenter clinical study (pivotal study), 80 subjects with PI (with a diagnosis of XLA or CVID) received Privigen every 3 or 4 weeks for up to 12 months ( see Clinical Studies [14.1] ). All subjects had been on regular IGIV replacement therapy for at least 6 months prior to participating in the study. Subjects ranged in age from 3 to 69; 46 (57.5%) were male and 34 (42.5%) were female. The safety analysis included all 80 subjects, 16 (20%) on the 3-week schedule and 64 (80%) on the 4-week schedule. The median dose of Privigen administered was 428.3 mg/kg (3-week schedule) or 440.6 mg/kg (4-week schedule) and ranged from 200 to 888 mg/kg. A total of 1038 infusions of Privigen were administered, 272 in the 3-week schedule and 766 in the 4-week schedule Routine premedication was not allowed. However, subjects who experienced two consecutive infusion-related adverse events (AEs) that were likely to be prevented by premedication were permitted to receive antipyretics, antihistamines, NSAIDs, or antiemetic agents. During the study, 8 (10%) subjects received premedication prior to 51 (4.9%) of the 1038 infusions administered. Temporally associated AEs are those occurring during an infusion or within 72 hours after the end of an infusion, irrespective of causality . In this study, the upper bound of the 1-sided 97.5% confidence interval for the proportion of Privigen infusions temporally associated with one or more AEs was 23.8% (actual proportion: 20.8%). The total number of temporally associated AEs was 397 (a rate of 0.38 AEs per infusion), reflecting that some subjects experienced more than one AE during the observation period. Table 2 lists the temporally associated AEs that occurred in >5% of subjects, irrespective of causality . Table 2: PI Pivotal Study – Adverse Events Excluding infections. Occurring in >5% of Subjects During a Privigen Infusion or Within 72 Hours After the End of an Infusion, Irrespective of Causality Adverse Event Number (%) of Subjects [n=80] Number (Rate) of Infusions with Adverse Event [n=1038] Headache 35 (43.8) 82 (0.079) Pain 20 (25.0) 44 (0.042) Fatigue 13 (16.3) 27 (0.026) Nausea 10 (12.5) 19 (0.018) Chills 9 (11.3) 15 (0.014) Vomiting 7 (8.8) 13 (0.013) Pyrexia 6 (7.5) 10 (0.010) Cough 5 (6.3) 5 (0.005) Diarrhea 5 (6.3) 5 (0.005) Stomach discomfort 5 (6.3) 5 (0.005) Of the 397 temporally associated AEs reported for the 80 subjects with PI, the investigators judged 192 to be at least possibly related to the infusion of Privigen (including 5 serious, severe AEs described below). Of these, 91 were mild, 81 were moderate, 19 were severe, and 1 was of unknown severity. Table 3 lists the adverse reactions (AEs at least possibly related to the infusion of Privigen) that occurred in >5% of subjects with PI, irrespective of time of occurrence. Table 3: PI Pivotal Study – Adverse Reactions Occurring in >5% of Subjects, Irrespective of Time of Occurrence Adverse Reaction Number (%) of Subjects [n=80] Number (Rate) of Infusions with Adverse Reaction [n=1038] Headache 24 (30.0) 62 (0.060) Pain, all types Includes abdominal pain lower, abdominal tenderness, arthralgia, back pain, chest pain, infusion-site pain, injection-site pain, neck pain, pain, pain in extremity, and pharyngolaryngeal pain. 12 (15.0) Some subjects experienced more than one type of pain. 26 (0.025) Nausea 10 (12.5) 18 (0.017) Fatigue 9 (11.3) 16 (0.015) Chills 9 (11.3) 15 (0.014) Vomiting 6 (7.5) 11 (0.011) Sixteen (20%) subjects experienced 41 serious AEs. Five of these AEs (hypersensitivity, chills, fatigue, dizziness, and increased body temperature, all severe) were related to Privigen, occurred in one subject, and resulted in the subject's withdrawal from the study. Two other subjects withdrew from the study due to AEs related to Privigen treatment (chills and headache in one subject; vomiting in the other). Seventy-seven of the 80 subjects enrolled in this study had a negative DAT at baseline. Of these 77 subjects, 36 (46.8%) developed a positive DAT at some time during the study. However, no subjects showed evidence of hemolytic anemia. During this study, no subjects tested positive for infection due to human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), or B19 virus (B19V). An extension of the pivotal study was conducted in 55 adult and pediatric subjects with PI to collect additional efficacy, safety, and tolerability data. This study included 45 subjects from the pivotal study who were receiving Privigen and 10 new subjects who were receiving another IGIV product prior to enrolling in the extension study. Subjects ranged in age from 4 to 81 years; 26 (47.3%) were male and 29 (52.7%) were female. Subjects were treated with Privigen at median doses ranging from 286 to 832 mg/kg per infusion over a treatment period ranging from 1 to 27 months. Twelve (21.8%) subjects were on a 3-week treatment schedule with the number of infusions per subject ranging from 4 to 38 (median: 8 infusions); 43 (78.2%) subjects were on a 4-week schedule with the number of infusions ranging from 1 to 31 (median: 15 infusions). A total of 771 infusions were administered in this study. In this study, subjects who continued from the pivotal study were permitted to receive infusions of Privigen at a rate up to 12 mg/kg/min (as opposed to the maximum of 8 mg/kg/min allowed in the pivotal study) at the discretion of the investigator based on individual tolerability. Twenty-three (51%) of the 45 subjects from the pivotal study (41.8% of the 55 subjects in the extension study) received 265 (38.4%) infusions at a maximum rate greater than the recommended rate of 8 mg/kg/min ( see Dosing and Administration [2.3] ). The median of the maximum infusion rate in this subset was 12 mg/kg/min. However, because the study was not designed to compare infusion rates, no definitive conclusions regarding tolerability could be drawn for infusion rates higher than the recommended rate of 8 mg/kg/min. In this study, the proportion of infusions temporally associated with one or more AEs occurring during a Privigen infusion or within 72 hours after the end of an infusion was 15%. The total number of temporally associated AEs, irrespective of causality , was 206 (a rate of 0.27 AEs per infusion), reflecting that some subjects experienced more than one AE during the observation period. Table 4 lists the temporally associated AEs that occurred in >5% of subjects, irrespective of causality . Table 4: PI Extension Study – Adverse Events Excluding infections. Occurring in >5% of Subjects During a Privigen Infusion or Within 72 Hours After the End of an Infusion, Irrespective of Causality Adverse Event Number (%) of Subjects [n=55] Number (Rate) of Infusions with Adverse Event [n=771] Note: The AE rates in this study cannot be compared directly to the rates in other IGIV studies, including the original pivotal study described earlier in this section, because (1) the extension study used an enriched population and (2) the selective use of higher infusion rates at the investigators' discretion in a subset of subjects may have introduced bias. Headache 18 (32.7) 56 (0.073) Pain, all types Includes abdominal pain, abdominal pain upper, arthralgia, back pain, chest pain, fibromyalgia, injection-site pain, myalgia, pain, pain in extremity, painful respiration, pharyngolaryngeal pain, and toothache. 14 (25.5) Some subjects experienced more than one type of pain. 31 (0.040) Abdominal pain Also includes abdominal pain, upper. 3 (5.5) 4 (0.005) Chest pain 3 (5.5) 4 (0.005) Pharyngolaryngeal pain 3 (5.5) 4 (0.005) Nausea 6 (10.9) 10 (0.013) Pyrexia 4 (7.3) 9 (0.012) Chills 3 (5.5) 7 (0.009) Influenza-like illness 3 (5.5) 4 (0.005) Of the 206 temporally associated AEs reported for the 55 subjects with PI, the investigators judged 125 to be at least possibly related to the infusion of Privigen. Of these, 76 were mild, 40 were moderate, and 9 were severe. Table 5 lists the adverse reactions that occurred in >5% of subjects, irrespective of time of occurrence. Table 5: PI Extension Study – Adverse Reactions Occurring in >5% of Subjects, Irrespective of Time of Occurrence Adverse Reaction Number (%) of Subjects [n=55] Number (Rate) of Infusions With Adverse Reaction [n=771] Headache 16 (29.1) 53 (0.069) Pain, all types Includes abdominal pain, abdominal pain lower, abdominal pain upper, arthralgia, back pain, chest pain, injection-site pain, musculoskeletal pain, myalgia, pain, and painful respiration. 11 (20.0) Some subjects experienced more than one type of pain. 26 (0.034) Abdominal pain Includes abdominal pain, lower and abdominal pain, upper. 4 (7.3) 6 (0.008) Chest pain 3 (5.5) 4 (0.005) Chills 3 (5.5) 7 (0.009) Fatigue 3 (5.5) 5 (0.006) Joint swelling/effusion 3 (5.5) 7 (0.009) Pyrexia 3 (5.5) 10 (0.013) Urticaria 3 (5.5) 4 (0.005) Eleven (20%) subjects experienced 17 serious AEs, none of which were considered to be related to Privigen. Three subjects experienced AEs that were considered to be at least possibly related to Privigen: dyspnea and pancytopenia in one subject, a transient ischemic attack 16 days after the infusion in one subject, and mild urticaria in one subject, resulting in the subject's withdrawal from the study. Treatment of Chronic Immune Thrombocytopenic Purpura In a prospective, open-label, single-arm, multicenter clinical study, 57 subjects with chronic ITP and a platelet count of 20 x 10 9 /L or less received a total of 2 g/kg dose of Privigen administered as 1 g/kg infusions daily for 2 consecutive days ( see Clinical Studies [14.2] ). Subjects ranged in age from 15 to 69; 23 (40.4%) were male and 34 (59.6%) were female. Concomitant medications affecting platelets or other treatments for chronic ITP were not allowed. Thirty-two (56.1%) subjects received premedication with acetaminophen and/or an antihistamine. Table 6 lists the temporally associated AEs that occurred in >5% of subjects with chronic ITP during a Privigen infusion or within 72 hours after the end of a treatment cycle (two consecutive infusions) with Privigen, irrespective of causality . Table 6: Chronic ITP Study – Adverse Events Occurring in >5% of Subjects During a Privigen Infusion or Within 72 hours After the End of a Treatment Cycle Two consecutive daily infusions. , Irrespective of Causality Adverse Event Number (%) of Subjects [n=57] Number (Rate) of Infusions With Adverse Event [n=114] Headache 37 (64.9) 41 (0.360) Pyrexia/hyperthermia 21 (36.8) 22 (0.193) Nausea 6 (10.5) 6 (0.053) Epistaxis 6 (10.5) 6 (0.053) Vomiting 6 (10.5) 6 (0.053) Blood unconjugated bilirubin increased 6 (10.5) 6 (0.053) Blood conjugated bilirubin increased 5 (8.8) 5 (0.044) Blood total bilirubin increased 4 (7.0) 4 (0.035) Hematocrit decreased 3 (5.3) 3 (0.026) Table 7 lists the adverse reactions that occurred in >5% of subjects, irrespective of time of occurrence . Table 7: Chronic ITP Study – Adverse Reactions Occurring in >5% of Subjects, Irrespective of Time of Occurrence Adverse Reaction Number (%) of Subjects [n=57] Number (Rate) of Infusions With Adverse Reaction [n=114] Headache 37 (64.9) 52 (0.456) Pyrexia/hyperthermia 19 (33.3) 21 (0.184) Positive DAT 6 (10.5) 7 (0.061) Anemia 6 (10.5) 6 (0.053) Vomiting 5 (8.8) 6 (0.053) Nausea 5 (8.8) 7 (0.061) Bilirubin conjugated, increased 5 (8.8) 5 (0.044) Bilirubin unconjugated, increased 5 (8.8) 5 (0.044) Hyperbilirubinemia 3 (5.3) 3 (0.026) Blood lactate dehydrogenase increased 3 (5.3) 3 (0.026) Hematocrit decreased 3 (5.3) 3 (0.026) Of the 149 non-serious AEs related to Privigen, 103 were mild, 37 were moderate, and 9 were severe. Three subjects experienced three serious AEs, one of which (aseptic meningitis) was related to the infusion of Privigen. One subject withdrew from the study due to gingival bleeding that was not related to Privigen. Eight subjects, all of whom had a positive DAT, experienced transient drug-related hemolytic reactions, which were associated with elevated bilirubin, elevated lactate dehydrogenase, and a decrease in hemoglobin level within two days after the infusion of Privigen. Two of the eight subjects were clinically anemic but did not require clinical intervention; these cases resolved uneventfully. Four other subjects with active bleeding were reported to have developed anemia without evidence of hemolysis. In this study, there was a decrease in hemoglobin after the first Privigen infusion (median decrease of 1.2 g/dL by Day 8) followed by a return to near baseline by Day 29. Fifty-six of the 57 subjects in this study had a negative DAT at baseline. Of these 56 subjects, 12 (21.4%) developed a positive DAT during the 29-day study period. 6.2 Postmarketing Experience Because adverse reactions are reported voluntarily post-approval from a population of uncertain size, it is not always possible to reliably estimate the frequency of these reactions or establish a causal relationship to product exposure. The following adverse reactions have been identified and reported during the post-approval use of IGIV products. 12 Infusion Reactions: Hypersensitivity (e.g., anaphylaxis), headache, diarrhea, tachycardia, fever, fatigue, dizziness, malaise, chills, flushing, urticaria or other skin reactions, wheezing or other chest discomfort, nausea, vomiting, rigors, back pain, myalgia, arthralgia, and changes in blood pressure Renal : Acute renal dysfunction/failure, osmotic nephropathy Respiratory : Apnea, Acute Respiratory Distress Syndrome (ARDS), TRALI, cyanosis, hypoxemia, pulmonary edema, dyspnea, bronchospasm Cardiovascular: Cardiac arrest, thromboembolism, vascular collapse, hypotension Neurological: Coma, loss of consciousness, seizures, tremor, aseptic meningitis syndrome Integumentary: Stevens-Johnson syndrome, epidermolysis, erythema multiforme, bullous dermatitis Hematologic: Pancytopenia, leukopenia, hemolysis, positive DAT (Coombs' test) Musculoskeletal: Back pain Gastrointestinal: Hepatic dysfunction, abdominal pain General/Body as a Whole: Pyrexia, rigors

<table width="80%" ID="table2"> <caption>Table 2: PI Pivotal Study &#x2013; Adverse Events<footnote>Excluding infections.</footnote> Occurring in &gt;5% of Subjects During a Privigen Infusion or Within 72 Hours After the End of an Infusion, Irrespective of Causality</caption> <col width="33%" align="left" valign="top"/> <col width="34%" align="center" valign="top"/> <col width="33%" align="center" valign="top"/> <thead> <tr> <th styleCode="Lrule Rrule">Adverse Event</th> <th styleCode="Rrule">Number (%) of Subjects [n=80]</th> <th styleCode="Rrule">Number (Rate) of Infusions with Adverse Event [n=1038]</th> </tr> </thead> <tbody> <tr> <td styleCode="Lrule Rrule">Headache</td> <td styleCode="Rrule">35 (43.8)</td> <td styleCode="Rrule">82 (0.079)</td> </tr> <tr> <td styleCode="Lrule Rrule">Pain</td> <td styleCode="Rrule">20 (25.0)</td> <td styleCode="Rrule">44 (0.042)</td> </tr> <tr> <td styleCode="Lrule Rrule">Fatigue</td> <td styleCode="Rrule">13 (16.3)</td> <td styleCode="Rrule">27 (0.026)</td> </tr> <tr> <td styleCode="Lrule Rrule">Nausea</td> <td styleCode="Rrule">10 (12.5)</td> <td styleCode="Rrule">19 (0.018)</td> </tr> <tr> <td styleCode="Lrule Rrule">Chills</td> <td styleCode="Rrule">9 (11.3)</td> <td styleCode="Rrule">15 (0.014)</td> </tr> <tr> <td styleCode="Lrule Rrule">Vomiting</td> <td styleCode="Rrule">7 (8.8)</td> <td styleCode="Rrule">13 (0.013)</td> </tr> <tr> <td styleCode="Lrule Rrule">Pyrexia</td> <td styleCode="Rrule">6 (7.5)</td> <td styleCode="Rrule">10 (0.010)</td> </tr> <tr> <td styleCode="Lrule Rrule">Cough</td> <td styleCode="Rrule">5 (6.3)</td> <td styleCode="Rrule">5 (0.005)</td> </tr> <tr> <td styleCode="Lrule Rrule">Diarrhea</td> <td styleCode="Rrule">5 (6.3)</td> <td styleCode="Rrule">5 (0.005)</td> </tr> <tr> <td styleCode="Lrule Rrule">Stomach discomfort</td> <td styleCode="Rrule">5 (6.3)</td> <td styleCode="Rrule">5 (0.005)</td> </tr> </tbody> </table>

<table width="80%" ID="table3"> <caption>Table 3: PI Pivotal Study &#x2013; Adverse Reactions Occurring in &gt;5% of Subjects, Irrespective of Time of Occurrence</caption> <col width="33%" align="left" valign="top"/> <col width="34%" align="center" valign="top"/> <col width="33%" align="center" valign="top"/> <thead> <tr> <th styleCode="Lrule">Adverse Reaction</th> <th styleCode="Lrule">Number (%) of Subjects [n=80]</th> <th styleCode="Lrule Rrule">Number (Rate) of Infusions with Adverse Reaction [n=1038]</th> </tr> </thead> <tbody> <tr> <td styleCode="Lrule">Headache</td> <td styleCode="Lrule">24 (30.0)</td> <td styleCode="Lrule Rrule">62 (0.060)</td> </tr> <tr> <td styleCode="Lrule">Pain, all types<footnote>Includes abdominal pain lower, abdominal tenderness, arthralgia, back pain, chest pain, infusion-site pain, injection-site pain, neck pain, pain, pain in extremity, and pharyngolaryngeal pain.</footnote> </td> <td styleCode="Lrule">12 (15.0)<footnote>Some subjects experienced more than one type of pain.</footnote> </td> <td styleCode="Lrule Rrule">26 (0.025)</td> </tr> <tr> <td styleCode="Lrule">Nausea</td> <td styleCode="Lrule">10 (12.5)</td> <td styleCode="Lrule Rrule">18 (0.017)</td> </tr> <tr> <td styleCode="Lrule">Fatigue</td> <td styleCode="Lrule">9 (11.3)</td> <td styleCode="Lrule Rrule">16 (0.015)</td> </tr> <tr> <td styleCode="Lrule">Chills</td> <td styleCode="Lrule">9 (11.3)</td> <td styleCode="Lrule Rrule">15 (0.014)</td> </tr> <tr> <td styleCode="Lrule">Vomiting</td> <td styleCode="Lrule">6 (7.5)</td> <td styleCode="Lrule Rrule">11 (0.011)</td> </tr> </tbody> </table>

<table width="90%" ID="table4"> <caption>Table 4: PI Extension Study &#x2013; Adverse Events<footnote ID="t41">Excluding infections.</footnote> Occurring in &gt;5% of Subjects During a Privigen Infusion or Within 72 Hours After the End of an Infusion, Irrespective of Causality</caption> <col width="40%" align="left" valign="top"/> <col width="30%" align="center" valign="top"/> <col width="30%" align="center" valign="top"/> <thead> <tr> <th styleCode="Lrule">Adverse Event<footnoteRef IDREF="t41"/> </th> <th styleCode="Lrule">Number (%) of Subjects [n=55]</th> <th styleCode="Lrule Rrule">Number (Rate) of Infusions with Adverse Event [n=771]</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="3">Note: The AE rates in this study cannot be compared directly to the rates in other IGIV studies, including the original pivotal study described earlier in this section, because (1) the extension study used an enriched population and (2) the selective use of higher infusion rates at the investigators&apos; discretion in a subset of subjects may have introduced bias.</td> </tr> </tfoot> <tbody> <tr> <td styleCode="Lrule">Headache</td> <td styleCode="Lrule">18 (32.7)</td> <td styleCode="Lrule Rrule">56 (0.073)</td> </tr> <tr> <td styleCode="Lrule">Pain, all types<footnote>Includes abdominal pain, abdominal pain upper, arthralgia, back pain, chest pain, fibromyalgia, injection-site pain, myalgia, pain, pain in extremity, painful respiration, pharyngolaryngeal pain, and toothache. </footnote> </td> <td styleCode="Lrule">14 (25.5)<footnote>Some subjects experienced more than one type of pain.</footnote> </td> <td styleCode="Lrule Rrule">31 (0.040)</td> </tr> <tr> <td styleCode="Lrule"> Abdominal pain<footnote>Also includes abdominal pain, upper.</footnote> </td> <td styleCode="Lrule">3 (5.5)</td> <td styleCode="Lrule Rrule">4 (0.005)</td> </tr> <tr> <td styleCode="Lrule"> Chest pain </td> <td styleCode="Lrule">3 (5.5)</td> <td styleCode="Lrule Rrule">4 (0.005)</td> </tr> <tr> <td styleCode="Lrule"> Pharyngolaryngeal pain</td> <td styleCode="Lrule">3 (5.5)</td> <td styleCode="Lrule Rrule">4 (0.005)</td> </tr> <tr> <td styleCode="Lrule">Nausea</td> <td styleCode="Lrule">6 (10.9)</td> <td styleCode="Lrule Rrule">10 (0.013)</td> </tr> <tr> <td styleCode="Lrule">Pyrexia</td> <td styleCode="Lrule">4 (7.3)</td> <td styleCode="Lrule Rrule">9 (0.012)</td> </tr> <tr> <td styleCode="Lrule">Chills</td> <td styleCode="Lrule">3 (5.5)</td> <td styleCode="Lrule Rrule">7 (0.009)</td> </tr> <tr> <td styleCode="Lrule">Influenza-like illness</td> <td styleCode="Lrule">3 (5.5)</td> <td styleCode="Lrule Rrule">4 (0.005)</td> </tr> </tbody> </table>