Products made from human blood may contain infectious agents, such as viruses, that can cause disease. Vaccinia immune globulin intravenous (VIGIV) is a derivative of human plasma. As with other products derived from or purified with human blood components, the remote possibility of contamination or infection with bacteria or viruses exists in individuals receiving VIGIV. Screening plasma donors for prior exposure to certain viruses, testing for the presence of viruses, and inactivating and/or reducing viruses has reduced the risk of infectious agent transmission. Transmissibility of the Creutzfeldt-Jakob disease (CJD) virus by plasma-derived products is unknown. The manufacturing processes are designed to reduce the risk of transmitting viral infection. However, none of the processes are completely effective. There is also the possibility that unknown infectious agents may be present in this product. VIGIV should be given only if a benefit is expected. Report all infections thought by a health care provider to have been possibly transmitted by VIGIV to the manufacturer. Discuss the risks and benefits with the individual or the legal guardian of the individual receiving VIGIV.[48345]

During clinical trials, the safety of vaccinia immune globulin intravenous (VIGIV) was evaluated in 110 patients who received doses of either 6,000 Units per kg, 9,000 Units per kg, or 24,000 Units per kg. Most adverse reactions were mild in intensity, with no serious adverse reactions reported and no instances of treatment discontinuation due to an adverse reaction. The most commonly reported adverse reactions were headache (5% to 59%), nausea (up to 28.2%), rigors (up to 22.6%), dizziness (up to 17.9%), feeling cold (up to 15.4%), and pain (up to 12.8%). Other adverse reactions reported in at least 5% of drug recipients included feeling hot (up to 9.7%), increased sweating or hyperhidrosis (up to 9.7%), pallor (up to 7.7%), vomiting (up to 7.7%), fever (up to 6.5%), asthenia (up to 6.5%), decreased appetite or anorexia (up to 6.5%), muscle spasms and back pain (up to 6.5%), paresthesias (up to 6.5%), fatigue (up to 5.1%), tremor (up to 5.1%), and peripheral edema (up to 5%).[48345]

Vaccinia immune globulin intravenous (VIGIV) is a human immune globulin intravenous (IGIV) product. Acute renal failure, renal dysfunction, osmotic nephrosis, proximal tubular nephropathy, and death have been reported in patients receiving IGIV. Most cases of renal insufficiency associated with IGIV products have occurred in patients receiving total doses containing at least 400 mg/kg of sucrose; VIGIV does not contain sucrose. No prospective data are available in patients with risk factors for renal insufficiency to identify a maximum safe dose, concentration, or rate of infusion for VIGIV. Administer VIGIV at the minimum infusion rate practicable. Do not exceed the maximum recommended infusion rate and follow the infusion schedule closely. Additionally, ensure patients are adequately hydrated before initiating the infusion. Assess renal function before the initial infusion and at appropriate intervals thereafter. Periodic monitoring of renal function and urine output is especially important in patients determined to be at increased risk of developing acute renal failure. Consider discontinuing VIGIV if renal function deteriorates.[48345]

Vaccinia immune globulin intravenous (VIGIV) may contain blood group antibodies that can behave as hemolysins and induce in vivo coating of red blood cells (RBC) with immune globulin, resulting in a positive direct antiglobulin reaction and hemolysis. Acute hemolysis, consistent with intravascular hemolysis, has been reported, and hemolytic anemia can develop after exposure to human immune globulin intravenous (IGIV) due to enhanced RBC sequestration. Closely monitor VIGIV recipients for clinical signs and symptoms of hemolysis, particularly those with risk factors. Consider appropriate laboratory testing for higher risk individuals, including measuring hemoglobin or hematocrit at baseline and again within approximately 36 to 96 hours post-infusion. If signs or symptoms of hemolysis develop or a significant drop in hemoglobin or hematocrit is observed, perform additional confirmatory laboratory testing. If transfusion is indicated for individuals who develop hemolysis with clinically compromising anemia after receiving VIGIV, perform adequate cross-matching to avoid exacerbating ongoing hemolysis.[48345]

Vaccinia immune globulin intravenous (VIGIV) is a human immune globulin intravenous (IGIV) derived product. Noncardiogenic pulmonary edema [Transfusion-related acute lung injury (TRALI)] has been reported in individuals administered IGIV. Characteristics of TRALI include severe respiratory distress, pulmonary edema, hypoxia, normal left ventricular function, and fever and usually occurs within 1 to 6 hours after transfusion. Other respiratory adverse reactions reported during postapproval use of IGIV products include apnea, acute respiratory distress syndrome (ARDS), cyanosis, dyspnea, bronchospasm, and wheezing. Closely monitor individuals' vital signs and observe for any symptoms, including pulmonary adverse reactions, throughout the infusion period and immediately after the infusion. If TRALI is suspected, perform appropriate tests for the presence of anti-neutrophil antibodies in both the product and the individual's serum. Individuals with TRALI may be managed using oxygen therapy with adequate ventilatory support.[48345]

Vaccinia immune globulin intravenous (VIGIV) is a human immune globulin intravenous (IGIV) derived product. Treatment with IGIV has been associated with the development of aseptic meningitis syndrome (AMS). The syndrome usually begins within several hours to 2 days after IGIV treatment. It is characterized by signs and symptoms including severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements (ocular pain), nausea, and vomiting. Cerebrospinal fluid (CSF) studies are frequently positive with pleocytosis up to several thousand cells per mm³ (predominately from granulocytic series) and with elevated protein concentrations up to several hundred mg/dL, but culture results are negative. For drug recipients exhibiting the above symptoms, conduct a thorough neurological examination with CSF studies to rule out other causes of meningitis. Stopping IGIV treatment has resulted in remission within several days without sequelae.[48345]

Mild and transient chest pain (unspecified) has been reported on the same day as treatment with vaccinia immune globulin intravenous (VIGIV). VIGIV is a human immune globulin intravenous (IGIV) product. Cardiovascular adverse events reported during postapproval use of other IGIV products include cardiac arrest and sinus tachycardia. Due to the voluntary nature of postmarketing reports, neither a frequency nor a definitive causal relationship can be established.[48345]

Vaccinia immune globulin intravenous (VIGIV) is a human immune globulin intravenous (IGIV) product. Hematologic and lymphatic adverse events reported during postapproval use of other IGIV products include anemia, neutropenia, leukopenia, and lymphadenopathy. Due to the voluntary nature of postmarketing reports, neither a frequency nor a definitive causal relationship can be established.[48345]

Vaccinia immune globulin intravenous (VIGIV) is a human immune globulin intravenous (IGIV) product. Dermatologic adverse events reported during postapproval use of other IGIV products include Stevens-Johnson syndrome, epidermolysis, erythema multiforme, dermatitis (e.g., bullous dermatitis), urticaria, and other skin reactions. Due to the voluntary nature of postmarketing reports, neither a frequency nor a definitive causal relationship can be established.[48345]

Vaccinia immune globulin intravenous (VIGIV) is a human immune globulin intravenous (IGIV) product. Gastrointestinal adverse events reported during postapproval use of other IGIV products include abdominal pain, diarrhea, and hepatic dysfunction. Due to the voluntary nature of postmarketing reports, neither a frequency nor a definitive causal relationship can be established.[48345]

Vaccinia immune globulin intravenous (VIGIV) is a human immune globulin intravenous (IGIV) product. Neurologic adverse events reported during postapproval use of other IGIV products include coma, loss of consciousness, and seizures. Due to the voluntary nature of postmarketing reports, neither a frequency nor a definitive causal relationship can be established.[48345]

Vaccinia immune globulin intravenous (VIGIV) is a human immune globulin intravenous (IGIV) product. Musculoskeletal and general adverse events reported during postapproval use of other IGIV products include arthralgia, myalgia, malaise, and chest discomfort. Due to the voluntary nature of postmarketing reports, neither a frequency nor a definitive causal relationship can be established.[48345]

Although not observed during clinical trials, severe hypersensitivity reaction such as hypotension, anaphylactic shock, or anaphylactoid reactions are possible with vaccinia immune globulin intravenous (VIGIV). If anaphylaxis or hypotension occurs, discontinue the infusion and give supportive care as needed.[48345]

Vaccinia immune globulin intravenous (VIGIV) is a human immune globulin intravenous (IGIV) derived product. Thrombotic events (e.g., thrombosis, thromboembolism) have been associated with IGIV treatment. Before administering VIGIV, ensure individuals are adequately hydrated. Do not exceed a maximum daily dose of 12,000 Units per kg for individuals at risk for a thrombotic event and administer VIGIV at the minimum concentration available and at the minimum infusion rate practicable. Monitor for signs and symptoms of thrombosis and assess blood viscosity in individuals at risk for hyperviscosity.[48345]

Vaccinia immune globulin intravenous (VIGIV) contains maltose, and use may result in laboratory test interference, specifically falsely elevated glucose readings leading to unrecognized hypoglycemia or inappropriate insulin administration. When administering vaccinia immune globulin to patients with diabetes mellitus, measure blood glucose using a glucose-specific method. Do not use blood glucose monitors or strips using glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ) or glucose-dye-oxidoreductase (GDO) because the presence of maltose can interfere with their readings. Carefully review the product information of the blood glucose testing system to determine if the system is appropriate for use with maltose-containing parenteral products. If any uncertainty exists, contact the manufacturer of the system to ensure appropriate use. Additionally, antibodies present in VIGIV may interfere with some serological tests. After administration of immune globulins like VIGIV, a transitory increase of passively transferred antibodies in the individual's blood may result in positive results in serological testing (e.g., Coomb's test).[48345]

Vaccinia immune globulin intravenous (VIGIV) is contraindicated for use in individuals with a history of significant adverse event(s) associated with previous use of this or other human immunoglobulin preparations. It is also contraindicated in IgA deficiency with antibodies against IgA and a history of IgA hypersensitivity. Individuals with IgA deficiency with antibodies against IgA could have a severe hypersensitivity reaction to subsequent administration of blood products that contain IgA; VIGIV contains trace amounts of IgA (up to 40 mcg/mL).[48345]

Administer vaccinia immune globulin intravenous (VIGIV) with caution to individuals with preexisting renal impairment, including renal failure, and to individuals at increased risk for renal insufficiency (including, but not limited to those with diabetes mellitus, volume depletion or hypovolemia, sepsis, paraproteinemia or monoclonal gammopathy of undetermined significance, age greater than 65 years, and individuals receiving known nephrotoxic medications). Assess renal function before the initial infusion and at appropriate intervals thereafter. Periodic monitoring of renal function and urine output is especially important in individuals determined to be at increased risk of developing acute renal failure. Consider discontinuing VIGIV if renal function deteriorates.[48345]

Vaccinia immune globulin intravenous (VIGIV) contains maltose, and use may result in laboratory test interference, specifically falsely elevated glucose readings leading to unrecognized hypoglycemia or inappropriate insulin administration. When administering vaccinia immune globulin to patients with diabetes mellitus, measure blood glucose using a glucose-specific method. Do not use blood glucose monitors or strips using glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ) or glucose-dye-oxidoreductase (GDO) because the presence of maltose can interfere with their readings. Carefully review the product information of the blood glucose testing system to determine if the system is appropriate for use with maltose-containing parenteral products. If any uncertainty exists, contact the manufacturer of the system to ensure appropriate use. Additionally, antibodies present in VIGIV may interfere with some serological tests. After administration of immune globulins like VIGIV, a transitory increase of passively transferred antibodies in the individuals's blood may result in positive results in serological testing (e.g., Coomb's test).[48345]

Vaccinia immune globulin intravenous (VIGIV) may contain blood group antibodies which act as hemolysins and induce in vivo coating of red blood cells (RBCs) with immune globulin, resulting in a positive antiglobulin reaction and hemolysis. Risk factors that may be associated with the development of hemolysis after receipt of IGIV products include high doses given as a single administration or divided over several days and non-O blood group (i.e., blood group phenotype A, blood group phenotype AB, and blood group phenotype B). An underlying inflammatory state (as reflected by elevated C-reactive protein or erythrocyte sedimentation rate) is an individual patient factor hypothesized to increase the risk of hemolysis after administration of IGIV; however, the role is uncertain. Closely monitor VIGIV recipients for clinical signs and symptoms of hemolysis, particularly those with the above listed risk factors. Consider appropriate laboratory testing for higher risk individuals, including measuring hemoglobin or hematocrit at baseline and again within approximately 36 to 96 hours post-infusion.[48345]

Data on vaccinia immune globulin intravenous (VIGIV) use during human pregnancy are lacking, and no animal reproduction studies have been performed.[48345] According to the Advisory Committee on Immunization Practices, administration of immune globulin preparations to pregnant individuals results in no known risk to the fetus. Fetal vaccinia may occur if a pregnant person receives the smallpox vaccine; the likelihood of fetal vaccinia development is unknown but appears to be rare. No indication exists for the routine prophylactic use of VIGIV to prevent fetal vaccinia. Only use during pregnancy if clearly needed; however, if a pregnant individual develops a condition for which use of VIGIV is required, the product should not be withheld.[31173] [43236]

Thrombotic events may occur during or after treatment with immune globulin products. Cautious use of vaccinia immune globulin intravenous (VIGIV) is warranted in individuals with a history of thromboembolic or cardiovascular disease. Individuals at risk for thrombotic events are geriatric individuals, those with a history of cardiovascular risk factors, impaired cardiac output (heart failure), thrombophilia (hypercoagulable disorders), arterial or venous thromboembolism, estrogen use, an indwelling central venous catheter, immobility or prolonged periods of immobilization, and known or suspected hyperviscosity. Assessment of baseline blood viscosity may be warranted for individuals at risk for hyperviscosity such as those with cryoglobulinemia, fasting chylomicronemia, hypertriglyceridemia, or monoclonal gammopathies.[48345]

There are no data on the presence of vaccinia immune globulin intravenous (VIGIV) in human milk, its effects on the breast-fed child, or its effect on milk production.[48345] Case reports of 2 breast-feeding individuals receiving intravenous immune globulin therapy suggest transfer of IgG and IgM into the colostrum and breast milk.[48199] Consider the benefits of breast-feeding, the risk of potential drug exposure in the child, and the risk of an untreated or inadequately treated condition.