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.
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 )
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'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'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' 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).