HUMAN IMMUNOGLOBULIN G: 70,701 Adverse Event Reports & Safety Profile

QIVIGY (immune globulin intravenous, human-kthm) is a ready-to-use, sterile, non-pyrogenic liquid solution of human immune globulin (IgG) for intravenous administration. QIVIGY is clear or slightly opalescent, colorless or pale yellow. QIVIGY consists of immune globulin of which IgG represents at least 96% of the total protein. It consists of 9 - 11% protein in 0.20 - 0.28 M glycine. In the solution, the IgG proteins are present by more than 97% (at lot release) and 93% (by expiration date) in monomeric and dimeric forms. Minimum value for osmolality is: 240 mOsmol/Kg. pH of the solution is in the range of 4.0 - 4.5. It contains trace levels of IgA (not more than 50 mg/L). The main component of QIVIGY is IgG (≥ 96%) with a sub-class distribution compatible with native human plasma. QIVIGY contains no carbohydrate stabilizers (e.g., sucrose, maltose) and no preservative. To specifically reduce the anti-A and anti-B titers in the drug product (isoagglutinins A and B), donor plasma is screened for isoagglutinin titer using a validated assay, and plasma units with high agglutination scores are excluded from further processing. All donors of plasma are carefully screened by history and laboratory testing to reduce the risk of transmitting blood-borne pathogens from infected donors. All plasma units used in the manufacture of QIVIGY are tested and approved for manufacture using FDA-licensed serological assays for Hepatitis B surface antigen (HBsAg), Human immunodeficiency virus 1/2 antibodies (anti-HIV-1/2), and Hepatitis C antibodies (anti-HCV). In addition, donations are screened for Hepatitis C virus (HCV), Human immunodeficiency virus 1 (HIV-1), Hepatitis B virus (HBV), Hepatitis A virus (HAV) and Parvovirus B19 (B19V) by NAT. Further testing is performed on the manufacturing pools for HBsAg and antibodies to HIV-1/2; plasma pools are also tested for HCV, HIV-1, HBV, HAV and B19V by NAT with the limit for B19V set to not exceed 10 4 IU B19V DNA per mL plasma. QIVIGY is made from large pools of human plasma by a combination of cold alcohol fractionation, caprylate precipitation and filtration, anion-exchange chromatography, nanofiltration and ultrafiltration/diafiltration (UF/DF). QIVIGY is incubated in the final container at the low pH of 4.0 – 4.5. The product is intended for intravenous administration. The capacity of the manufacturing process to remove and/or inactivate enveloped and non-enveloped viruses has been validated by spiking studies at laboratory scale with a validated model of the manufacturing processes, using the following enveloped and non-enveloped viruses: HIV-1 as the relevant virus for HIV-1 and HIV–2; Bovine Viral Diarrhea virus (BVDV) as a model for HCV; Pseudorabies virus (PRV) as a model for large enveloped DNA viruses (e.g., Herpes viruses and HBV); HAV as relevant non-enveloped virus, Encephalomyocarditis virus (EMCV) as a model for HAV, and Porcine Parvovirus (PPV) as a model for human parvovirus B19. The viral clearance capacity of QIVIGY manufacturing process has been evaluated by summing logarithmic reduction factors from single steps with significant reduction factors more than 1 log, obtaining overall log reduction factors (LRFs) reported in Table 3. The manufacturing process for QIVIGY includes four steps to reduce the risk of virus transmission. Two of these are dedicated virus clearance steps: sodium caprylate incubation to inactivate enveloped viruses and virus filtration to remove, by size exclusion, both enveloped and non-enveloped viruses as small as approximately 20 nanometers. In addition, caprylate precipitation and filtration step and low pH treatment step contributes to the virus reduction capacity. Overall virus reduction was calculated only from steps that were orthogonal in mechanisms of removal/inactivation. In addition, each step was verified to provide robust virus reduction across the production range for key operating parameters.

Table

3: Viral Inactivation/Removal Capacity of the QIVIGY Manufacturing Process LRF Enveloped Viruses LRF Non-Enveloped Viruses Step BVDV HIV-1 PsRV HAV PPV EMCV NI: not investigated. NA: Not applicable. 1 st Caprylate (precipitation+depth filtration)

3.35 NI NI > 5.93

2.69 NI 2 nd Caprylate (inactivation) > 5.37 > 4.54 >

6.79 NA NA NA Nanofiltration > 5.26

2.27 NI Due to the low pH condition at which nanofiltration was performed, PsRV was immediately inactivated and it was not possible to properly evaluate virus removal by nanofiltration. > 4.85 > 6.19 >

4.28 Inactivation by Low pH 2.45 6.17

6.65 NI NI

3.43 Overall Viral Reduction > 16.43 > 12.98 > 13.44 > 10.78 > 8.88 >

7.71 Concerning vCJD risk, donor exclusion criteria are in accordance with the relevant FDA Guidance for Industry (Recommendations to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease (vCJD) by Blood and Blood Components, current edition).

AND USAGE ASCENIV (immune globulin intravenous, human – slra) is a 10% immune globulin liquid for intravenous injection, indicated for the treatment of primary humoral immunodeficiency (PI) in adults and adolescents (12 to 17 years of age). PI includes, but is not limited to, the humoral immune defect in congenital agammaglobulinemia, common variable immunodeficiency (CVID), X-linked agammaglobulinemia, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies (SCID). ASCENIV (immune globulin intravenous, human – slra) is a 10% immune globulin liquid for intravenous injection, indicated for the treatment of primary humoral immunodeficiency (PI) in adults and adolescents (12 to 17 years of age). [1]

AND ADMINISTRATION Intravenous Administration Only.

Dose

Infusion number Initial Infusion Rate Maintenance Infusion Rate (as tolerated) 300 - 800 mg/kg every 3-4 weeks For the 1 st infusion 1 mg/kg/min (0.01 mL/kg/min) for 30 minutes Increase every 30 minutes to a maximum of 8 mg/kg/min (0.08 mL/kg/min) 300 - 800 mg/kg every 3-4 weeks From the 2 nd infusion 2 mg/kg/min (0.02 mL/kg/min) for 15 minutes Increase every 15 minutes to a maximum of 8 mg/kg/min (0.08 mL/kg/min)

2.1 Recommended Dosage Table 1.

Recommended

Dosage for QIVIGY Dose Infusion number Initial Infusion Rate Maintenance Infusion Rate (as tolerated) 300 - 800 mg/kg every 3-4 weeks For the 1 st infusion 1 mg/kg/min (0.01 mL/kg/min) for 30 minutes Increase every 30 minutes to a maximum of 8 mg/kg/min (0.08 mL/kg/min) 300 - 800 mg/kg every 3-4 weeks From the 2 nd infusion 2 mg/kg/min (0.02 mL/kg/min) for 15 minutes Increase every 15 minutes to a maximum of 8 mg/kg/min (0.08 mL/kg/min) Adjust frequency and dosage overtime to achieve target serum IgG levels and clinical response. If a patient misses a dose, administer the missed dose as soon as possible, and then resume scheduled treatments every 3 or 4 weeks, as applicable. In patients judged to have a potential increased risk for developing acute renal failure or thrombosis, QIVIGY should be administered at the minimum rate of infusion and dose practicable. In case of renal impairment, IGIV discontinuation should be considered [see Administration and Warnings and Precautions (2.3 , 5.3) ]. Measles pre-/post exposure prophylaxis Post-exposure prophylaxis If a patient has been exposed to measles, a dose of 400 mg/kg (4 mL/kg) of QIVIGY should be administered as soon as possible after exposure. Pre-exposure prophylaxis If a patient routinely receives a dose of less than 400 mg/kg of QIVIGY every 3 to 4 weeks (less than 4 mL/kg) and is at risk of measles exposure (i.e. traveling to a measles endemic area), administer a dose of at least 400 mg/kg (4 mL/kg) just prior to the expected measles exposure.

2.2 Preparation and Handling QIVIGY is a clear or slightly opalescent and colorless or pale-yellow solution. Inspect QIVIGY visually for particulate matter and discoloration prior to administration, whenever the solution and container permit. Do not use if the solution is cloudy, turbid, or if it contains particulate matter or deposits. Do not shake. Do not dilute. QIVIGY should be brought to room temperature before use (up to 25 °C [77 °F]). Keep the vial in the outer carton. If the packaging shows any signs of tampering, do not use the product and notify Kedrion Biopharma Inc. immediately at 1-855-3KDRION (1-855-353-7466). The QIVIGY vial is for single use only. Any vial that has been opened must be used immediately. QIVIGY contains no preservative. For administration of large doses, pool multiple vials using aseptic technique Infuse QIVIGY using a separate infusion line. At the end of the infusion flush tubing with saline solution or Dextrose 5% in water (D5W) to ensure that the entire dose is administered. Do not mix QIVIGY with other IGIV products or other intravenous medications (including normal saline) Do not use after expiration date. Record the batch number every time QIVIGY is administered to a patient. Dispose partially used or unused product or waste material in accordance with local requirements.

2.3 Administration Intravenous administration only . Hydrate the patient adequately prior to the initiation of infusion. Infuse QIVIGY intravenously using an intravenous infusion set.

See Table

1 for recommended infusion rates. Monitor patient vital signs throughout the infusion. The rate of infusion can be related to certain severe adverse drug reactions. Slow or stop infusion if adverse reactions occur. If symptoms subside promptly, resume infusion at a lower rate as tolerated by the patient. The observation time of patients after QIVIGY administration may vary. If the patient (a) has not received QIVIGY or another IgG product, (b) is switched from an alternative IGIV product or (c) has had a long interval since the previous infusion, prolong the observation time for adverse reactions after QIVIGY infusion. Ensure that patients with pre-existing renal insufficiency are not volume depleted. For patients at risk of renal dysfunction or thrombosis, administer QIVIGY at the minimum dose and infusion rate practicable and discontinue QIVIGY if renal function deteriorates [see Boxed Warning , Warnings and Precautions (5.2 , 5.3) ] .

QIVIGY is contraindicated in patients who have had an anaphylactic or severe systemic reaction to the administration of human immune globulin. QIVIGY is contraindicated in IgA deficient patients with antibodies against IgA and history of hypersensitivity [see Warnings and Precautions (5.1) ] . Patients with history of anaphylactic or severe systemic reactions to human immune globulins. ( 4 ) IgA deficient patients with antibodies against IgA and a history of hypersensitivity. ( 4 )

REACTIONS Serious adverse reactions observed in clinical trial subjects receiving BIVIGAM were vomiting and dehydration in one subject. The most common adverse reactions to BIVIGAM (reported in ≥5% of clinical study subjects) were headache, fatigue, infusion site reaction, nausea, sinusitis, blood pressure increased, diarrhea, dizziness, and lethargy. The most common adverse reactions to BIVIGAM (reported in ≥5% of clinical study subjects) were headache, fatigue, infusion site reaction, nausea, sinusitis, blood pressure increased, diarrhea, dizziness, and lethargy. [6] To report SUSPECTED ADVERSE REACTIONS, contact ADMA Biologics at (800) 458-4244 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials cannot be directly compared to rates in the clinical trials of another product and may not reflect the rates observed in clinical practice. In a multicenter, open-label, non-randomized clinical trial, 63 subjects with PI, on regular IGIV replacement therapy, received doses of BIVIGAM ranging from 254 to 1029 mg/kg (median dose 462.8 mg/kg) every 3 weeks or 4 weeks for up to 12 months (mean 317.3 days; range 66 – 386 days) ( see Clinical Studies [ 14 ] ). The use of pre-medication was discouraged; however, if subjects required pre-medication (antipyretic, antihistamine, or antiemetic agent) for recurrent reactions to immune globulins, they were allowed to continue those medications for this trial. Of the 746 infusions administered, 41 (65%) subjects received premedication prior to 415 (56%) infusions. Fifty-nine subjects (94%) had an adverse reaction at some time during the study. The proportion of subjects who had at least one adverse reaction was the same for both the 3- and 4-week cycles. The most common adverse reactions observed in this clinical trial were headache (32 subjects, 51%), sinusitis (24 subjects, 38%), fatigue (18 subjects, 29%), upper respiratory tract infection (16 subjects, 25%), diarrhea (13 subjects, 21%), cough (14 subjects, 22%), bronchitis (12 subjects, 19%), pyrexia (12 subjects, 19%), and nausea (9 subjects, 14%). Adverse reactions (ARs) are those occurring during or within 72 hours after the end of an infusion. In this study, the upper bound of the 1-sided 95% confidence interval for the proportion of BIVIGAM infusions with one or more temporally associated adverse reactions was 31%. The total number of adverse reactions was 431 (a rate of

0.58 ARs per infusion).

Table

2: Adverse Reactions (ARs) (within 72 hours after the end of a BIVIGAM infusion) in ≥5% of Subjects ARs No.

Subjects

Reporting ARs (% of Subjects) [n=63] No.

Infusions

With ARs (% of Infusions) [n=746]

Headache

27 (43%) 115 (15.4%)

Fatigue

15 (24%) 59 (7.9%)

Infusion Site Reaction

5 (8%) 5 (0.7%)

Nausea

5 (8%) 8 (1.1%)

Sinusitis

5 (8%) 5 (0.7%)

Blood Pressure Increased

4 (6%) 5 (0.7%)

Diarrhea

4 (6%) 4 (0.5%)

Dizziness

4 (6%) 4 (0.5%)

Lethargy

4 (6%) 4 (0.5%)

Back Pain

3 (5%) 3 (0.4%)

Blood Pressure Diastolic Decreased

3 (5%) 5 (0.7%) Fibromyalgia a 3 (5%) 17 (2.3%)

Migraine

3 (5%) 8 (1.1%)

Myalgia

3 (5%) 4 (0.5%)

Pharyngolaryngeal Pain

3 (5%) 3 (0.4%) a Symptoms occurring under pre-existing fibromyalgia Seven subjects (11.1%) experienced 11 serious ARs. Two of these were related serious ARs (vomiting and dehydration) that occurred in one subject. One subject withdrew from the study due to ARs related to BIVIGAM (lethargy, headache, tachycardia and pruritus).

All

63 subjects enrolled in this study had a negative direct antiglobulin (Coombs’) test at baseline. During the study, no subjects showed clinical evidence of hemolytic anemia. No cases of transmission of viral diseases or CJD have been associated with the use of BIVIGAM. During the clinical trial no subjects tested positive for infection due to human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). There was a single positive finding for parvovirus (B19 virus) during the study. This subject came in contact with acute B19 virus from working at a school, greeting children, where a child was reported to have symptomatic Fifth's disease. There was no cluster (no other cases in other subjects) of B19 virus transmission with the IGIV batch concerned.

Pediatric Only

Study In a prospective, open-label, single-arm, multi-center study, 16 children and adolescents with PI received doses of BIVIGAM ranging from 300 to 800 mg/kg every 3-weeks (±7 days) days (actual doses ranged from 350 mg/kg to 1077 mg/kg) or 4-weeks (±7 days) (actual doses ranged from 312 mg/kg to 693 mg/kg), for up to 5 months. In this study, four subjects (25.0%) experienced a total of 9 adverse reactions. Adverse reactions (ARs) are those occurring during or within 72 hours after the end of an infusion. All ARs were of mild (3 events) or moderate severity (6 events). No infusion site reactions occurred during the study. No deaths and no treatment-related SAEs occurred during the study. Seven of the 96 (7.3%) BIVIGAM infusions administered were temporally associated with an adverse reaction. Two infusions were associated with more than one AR.

Table

3: Adverse Reactions (ARs) within 72 hours after the end of a BIVIGAM Infusion Adverse Reaction (AR) Number of Subjects Reporting AR (n=16) % of Subjects Reporting AR (n=16) Number of Infusions with AR (n=96) % of Infusions with AR (n=96)

Fatigue

1 6 2 2 Headache 3 19 5 5 Nausea 1 6 1 1 Rash 1 6 1 1

6.2 Postmarketing Experience Because postmarketing reporting of adverse reactions is voluntary and 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: Respiratory: Apnea, Acute Respiratory Distress Syndrome (ARDS), Transfusion Associated 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.

AND PRECAUTIONS Hypersensitivity Reactions: In case of a severe hypersensitivity reaction, discontinue QIVIGY infusion, and manage as appropriate. IgA deficient patients with antibodies against IgA are at greater risk of developing severe hypersensitivity and anaphylactic reactions. ( 5.1 ) Thrombotic events: Monitor patients with known risk factors for thrombotic events; consider baseline assessment of blood viscosity for patients at risk of hyperviscosity. ( 5.2 ) Hyperproteinemia, hyperviscosity, hyponatremia, or pseudohyponatremia may occur in patients receiving IGIV therapy. ( 5.4 )

Renal

Injury: Ensure patients are not volume depleted before administering QIVIGY. Monitor renal function, including blood urea nitrogen, serum creatinine, and urine output in patients receiving QIVIGY prior to initial infusion and at appropriate intervals thereafter. ( 5.3 )

Aseptic Meningitis

Syndrome (AMS) may occur, more frequently in association with high doses of IGIV or rapid infusion. ( 5.5 ) Hemolysis: Risk factors include high doses and non-O blood group. Monitor patients for hemolysis and hemolytic anemia. ( 5.6 ) Transfusion-related acute lung injury (TRALI): Monitor patients for symptoms of TRALI and manage using oxygen therapy with adequate ventilatory support as appropriate. ( 5.7 ) Transmission of infectious agents: QIVIGY is made from human plasma and may carry a risk of transmitting infectious agents. ( 5.8 )

5.1 Hypersensitivity Severe hypersensitivity reactions, including anaphylaxis, may occur with QIVIGY <span class="opacity-50 text-xs">[see Adverse Reactions (6) ]</span> In case of hypersensitivity, discontinue QIVIGY infusion immediately and institute appropriate treatment. Medications such as epinephrine should be available for immediate treatment of acute hypersensitivity reactions. QIVIGY contains IgA (≤ 50 mg/L) <span class="opacity-50 text-xs">[see Description (11) ]</span> . Patients with known antibodies to IgA may have a greater risk of developing potentially severe hypersensitivity and anaphylactic reactions. QIVIGY is contraindicated in IgA deficient patients with antibodies against IgA and patients with a history of hypersensitivity reaction <span class="opacity-50 text-xs">[see Contraindications (4) ]</span> .

5.2 Thrombosis Thrombosis may occur following treatment with immune globulin products, including QIVIGY. Risk factors may include advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling central vascular catheters, hyperviscosity, and cardiovascular risk factors. Thrombosis may occur in the absence of known risk factors. Consider baseline assessment of blood viscosity in patients at risk for hyperviscosity, including those with cryoglobulins, fasting chylomicronemia, high triacylglycerols (triglycerides), or monoclonal gammopathies. For patients at risk of thrombosis, administer QIVIGY at the minimum dose and infusion rate practicable. Ensure adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis <span class="opacity-50 text-xs">[see Boxed Warning , Dosage and Administration (2) ]</span> .

5.3 Renal Injury Renal injury including acute renal dysfunction, acute renal failure, acute tubular necrosis, proximal tubular nephropathy, and, osmotic nephrosis may occur after treatment with immune globulin products including QIVIGY. Ensure that patients are not volume depleted prior to the initiation of the infusion of QIVIGY. For patients judged to be at risk for developing renal dysfunction because of pre-existing renal insufficiency or predisposition to acute renal failure (such as diabetes mellitus, hypovolemia, overweight, use of concomitant nephrotoxic drugs, or age over 65 years), administer QIVIGY at the minimum infusion rate practicable <span class="opacity-50 text-xs">[see Dosage and Administration (2) ]</span> . The risk of renal dysfunction and acute renal failure is greater in products that contain sucrose, though may still occur in products without sucrose. QIVIGY does not contain sucrose. Conduct periodic monitoring of renal function and urine output in patients judged to be at increased risk of developing acute renal failure. Assess renal function, including measurement of blood urea nitrogen (BUN) and serum creatinine, before the initial infusion of QIVIGY and at appropriate intervals thereafter. If renal function deteriorates, consider discontinuing QIVIGY <span class="opacity-50 text-xs">[see Dosage and Administration (2) ]</span>.

5.4 Hyperproteinemia, Increased Serum Viscosity, and Hyponatremia Hyperproteinemia, hyperviscosity, and hyponatremia may occur in patients receiving immune globulin treatment, including QIVIGY. It is critical to clinically distinguish true hyponatremia from a pseudohyponatremia that is associated with or causally related to hyperproteinemia with concomitant 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 possible predisposition to thromboembolic events.

5.5 Aseptic Meningitis Syndrome Aseptic meningitis syndrome (AMS) may occur in patients following immune globulin treatment, including QIVIGY. The risk of AMS may be higher with high doses (2 g/kg) and/or rapid infusion of immune globulin products. AMS usually begins within several hours to two days following immune globulin treatment and is characterized by the following symptoms and signs: severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, nausea and vomiting. Cerebrospinal fluid (CSF) studies frequently reveal pleocytosis up to several thousand cells per cubic millimeter, predominantly from the granulocytic series, and elevated protein levels up to several hundred mg/dL, but negative culture results. Conduct a thorough neurological examination on patients exhibiting symptoms and signs of AMS, 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.

5.6 Hemolysis Hemolysis may occur after administration of immune globulin products, including QIVIGY due to the presence of blood group antibodies that can act as hemolysins and induce in vivo coating of red blood cells (RBCs) with immune globulin, causing a positive direct antiglobulin test and hemolysis. Delayed hemolytic anemia can develop after immune globulin treatment due to enhanced RBC sequestration, and acute hemolysis consistent with intravascular hemolysis has been reported. The risk factors for hemolysis include high doses (e.g., ≥ 2 g/kg) given either as a single administration or divided over several days, non-O blood group, and an underlying inflammatory disease condition. Monitor patients for clinical signs and symptoms of hemolysis. Consider appropriate laboratory testing in higher risk patients, including measurement of hemoglobin or hematocrit prior to infusion and within approximately 36 hours and again 7 to 10 days post infusion. If clinical signs and symptoms of hemolysis or a significant drop in hemoglobin or hematocrit are observed after QIVIGY infusion, perform confirmatory laboratory testing.

5.7 Transfusion-related Acute Lung Injury Transfusion-Related Acute Lung Injury (TRALI) may occur in patients following immune globulin treatment, including QIVIGY. TRALI is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever. Symptoms typically appear within 1 to 6 hours after treatment. Monitor patients for pulmonary adverse reactions. If TRALI is suspected, immediately stop QIVIGY infusion, and perform appropriate tests for the presence of anti-neutrophil antibodies and anti-human leukocyte antigen (HLA) antibodies in both the product and patient&apos;s serum. Manage patients using oxygen therapy with adequate ventilatory support as appropriate.

5.8 Transmissible Infectious Agents There is risk of transmission of infectious disease or agents including viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and the Creutzfeldt-Jakob disease agent with QIVIGY administration because it is manufactured using human blood. The risk of infectious agent transmission is minimized by plasma donor screening, donation testing, and manufacturing steps proven to inactivate and remove bloodborne pathogens. Any infection suspected to have been transmitted by this product should be reported by the physician or other healthcare provider to Kedrion Biopharma Inc. at 1-855-3KDRION (1-855-353-7466) .

5.9 Monitoring Laboratory Tests Assess renal function, including measurement of BUN and serum creatinine, before the initial infusion of QIVIGY and at appropriate intervals thereafter <span class="opacity-50 text-xs">[see Warnings and Precautions (5.3) ]</span>. 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, because of the potentially increased risk of thrombosis <span class="opacity-50 text-xs">[see Warnings and Precautions (5.2) ]</span>. If signs and/or symptoms of hemolysis are present after an infusion of QIVIGY, perform appropriate laboratory testing for confirmation <span class="opacity-50 text-xs">[see Warnings and Precautions (5.6) ]</span>. If TRALI is suspected, perform appropriate tests for the presence of anti-neutrophil antibodies and anti-HLA antibodies in both the product and the patient&apos;s serum <span class="opacity-50 text-xs">[see Warnings and Precautions (5.7) ]</span>.

5.10 Interference with Laboratory Tests After the administration of immune globulin, the transitory rise of the various passively transferred antibodies in the patients&apos; blood may result in misleading positive results in serological testing. Passive transmission of antibodies to erythrocyte antigens, e.g. A, B, D may interfere with some serological tests for red cell antibodies for example the direct or indirect antiglobulin test (Coombs test).

INTERACTION The passive transfer of antibodies may: Interfere with the response to live virus vaccines, such as measles, rubella, mumps and varicella. ( 7 ) Result in misleading positive results in serological testing. ( 5.9 , 7 )

7.1 Effect of QIVIGY on Live attenuated virus vaccines Immune globulin administration may transiently impair the efficacy of live attenuated virus vaccines such as measles, mumps, rubella, s and varicella because the continued presence of high levels of passively acquired antibody may interfere with an active antibody response. Inform the immunizing physician of recent therapy with QIVIGY so that appropriate measures may be taken.

7.2 Effect of QIVIGY on Serological Testing Passive transmission of antibodies through immune globulin administration may interfere with some serological testing <span class="opacity-50 text-xs">[see Warnings and Precautions (5.10) ]</span>.

7.3 Effect of Loop diuretics on QIVIGY The use of loop diuretics should be avoided. Concomitant use of loop diuretics with IGIV may contribute to an increased blood viscosity and subsequently increase the risk of thromboembolic events.