Introduction

Anthrax immune globulin IV (human) is a specific immune globulin (hyperimmune globulin) that contains immunoglobulin G (IgG) prepared from plasma of healthy donors immunized with anthrax vaccine adsorbed to achieve high titers of anti-anthrax antibody. The immune globulin contains polyclonal antibodies that bind the protective antigen (PA) component of Bacillus anthracis lethal and edema toxins.

Uses for Anthrax Immune Globulin IV (Human)

Anthrax immune globulin IV (human) has the following uses:

Anthrax immune globulin IV (human) is indicated for the treatment of inhalational anthrax in adult and pediatric patients in combination with appropriate antibacterial drugs.

Anthrax immune globulin IV (human) has the following limitations of use:

The effectiveness of anthrax immune globulin IV (human) is based solely on efficacy studies conducted in animal models of inhalational anthrax.

Anthrax immune globulin IV (human) does not have any direct antibacterial activity.

Anthrax immune globulin IV (human) does not cross the blood-brain barrier and does not prevent or treat meningitis.

There have been no studies of anthrax immune globulin IV (human) in pediatric, geriatric, or obese populations.

Anthrax Immune Globulin IV (Human) Dosage and Administration

General

Anthrax immune globulin IV (human) is available in the following dosage form(s) and strength(s):

Single-use vials containing a minimum potency of ≥60 units by toxin neutralization assay (TNA).

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

• For intravenous use only.

• Administer anthrax immune globulin IV (human) by slow intravenous infusion using an infusion pump and recommended adult or pediatric infusion rates (see Table 1).

• Maximum infusion rate in adults is 2 mL/min.

Select initial dose based on clinical severity; severe cases may warrant use of 14 vials (840 units) in adults or 2–14 vials (based on weight) in pediatric patients weighing >5 kg.

Adjust dose and consider redosing based on clinical severity and response to treatment.

Select initial dose based on clinical severity. Dose may be doubled for severe cases in pediatric patients weighing >5 kg.

Contraindications

• History of anaphylactic or severe systemic reaction to human immune globulins.

• IgA deficiency with antibodies against IgA and a history of IgA hypersensitivity.

Warnings/Precautions

Hypersensitivity Reactions

Hypersensitivity reactions may occur with anthrax immune globulin IV (human).

Administer anthrax immune globulin IV (human) in a setting where appropriate equipment, medication (including epinephrine) and personnel trained in the management of hypersensitivity, anaphylaxis, and shock are available.

Monitor all patients for signs and symptoms of acute allergic reactions (e.g., urticaria, pruritus, erythema, angioedema, bronchospasm with wheezing or cough, stridor, laryngeal edema, hypotension, tachycardia) during and following the anthrax immune globulin IV (human) infusion. In case of severe hypersensitivity reactions, discontinue the administration of anthrax immune globulin IV (human) immediately and administer appropriate emergency care.

Anthrax immune globulin IV (human) contains trace amounts of IgA (less than or equal to 40 mcg per mL). Patients with known antibodies to IgA may have greater risk of developing severe hypersensitivity and anaphylactic reactions. Anthrax immune globulin IV (human) is contraindicated in patients with antibodies against IgA and a history of hypersensitivity reaction.

Interference with Blood Glucose Testing

Anthrax immune globulin IV (human) contains maltose. Maltose has been shown to give falsely high blood glucose levels in certain types of blood glucose testing systems (for example, by systems based on glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ) or glucose-dye-oxidoreductase methods). Due to the potential for falsely elevated glucose readings (or falsely normal glucose readings when hypoglycemia is present), only use testing systems that are glucose-specific to test or monitor blood glucose levels in patients receiving anthrax immune globulin IV (human).

Review the product information of the blood glucose testing system, including that of the test strips, to determine if the system is appropriate for use with maltose-containing parenteral products. If any uncertainty exists, contact the manufacturer of the testing system to determine if the system is appropriate for use with maltose-containing parenteral products.

Thrombosis

Thrombosis may occur following treatment with immune globulin products, including anthrax immune globulin IV (human). Risk factors include cardiovascular risk factors, advanced age, impaired cardiac output, hypercoagulable disorders, prolonged periods of immobilization, history of arterial or venous thrombosis, estrogen use, indwelling central vascular catheters, and/or known or suspected hyperviscosity. Thrombosis may occur in the absence of known risk factors. Weigh the potential risks and benefits of anthrax immune globulin IV (human) against those of alternative therapies for all patients for whom anthrax immune globulin IV (human) administration is being considered.

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.

In patients with risk factors where the benefits of anthrax immune globulin IV (human) administration out-weigh the potential risks of thrombosis, administer anthrax immune globulin IV (human) at the minimum rate of infusion practicable. Ensure adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis.

Acute Renal Dysfunction/failure

Acute renal dysfunction, acute renal failure, osmotic nephropathy, acute tubular necrosis, proximal tubular nephropathy, and death may occur upon use of immune globulin intravenous products, including anthrax immune globulin IV (human). Use anthrax immune globulin IV (human) with caution in patients with any degree of pre-existing renal insufficiency and in patients at risk of developing renal insufficiency (including, but not limited to those with diabetes mellitus, age greater than 65 years, volume depletion, paraproteinemia, sepsis, and patients receiving known nephrotoxic drugs), administering at the minimum rate of infusion practicable. Ensure that patients are not volume depleted before anthrax immune globulin IV (human) infusion. Do not exceed the recommended infusion rate, and follow the infusion schedule closely. Periodic monitoring of renal function and urine output is important 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 anthrax immune globulin IV (human) and at appropriate intervals thereafter. If renal function deteriorates, consider discontinuing anthrax immune globulin IV (human).

Most cases of renal insufficiency following administration of immune globulin products have occurred in patients receiving total doses containing 400 mg per kg of sucrose or greater. Anthrax immune globulin IV (human) does not contain sucrose.

Infusion Rate Precautions

Adverse reactions (such as chills, fever, headache, nausea and vomiting) may be related to the rate of infusion. Closely follow recommended infusion rates (see Dosage and Administration). Closely monitor and carefully observe patients and their vital signs for any symptoms throughout the infusion period and immediately following an infusion.

Hemolysis

Hemolytic anemia and hemolysis may develop subsequent to anthrax immune globulin IV (human) administration. Anthrax immune globulin IV (human) may contain blood group antibodies that may act as hemolysins and induce in vivo coating of red blood cells with immune globulin, causing a positive direct antiglobulin reaction and hemolysis. Acute hemolysis, including intravascular hemolysis, has been reported following immune globulin administration and delayed hemolytic anemia can develop due to enhanced red blood cell sequestration. Severe hemolysis may lead to renal dysfunction/failure.

The following risk factors may be associated with the development of hemolysis: high doses (e.g., >2 g per kg), given either as a single administration or divided over several days, and non-O blood group). Other individual patient factors, such as an underlying inflammatory state (as may be reflected by, for example, elevated C-reactive protein or erythrocyte sedimentation rate), have been hypothesized to increase the risk of hemolysis), but their role is uncertain.

Monitor anthrax immune globulin IV (human) recipients 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 to 96 hours and again approximately seven to 10 days post infusion. If signs and/or symptoms of hemolysis or a significant drop in hemoglobin or hematocrit have been observed after infusion, perform additional confirmatory laboratory testing.

Aseptic Meningitis Symptom (AMS)

AMS may occur in association with administration of immune globulin products, including anthrax immune globulin IV (human). AMS usually is associated with high total doses (>2 g per kg) and begins within several hours to two days following treatment. Discontinuation of treatment has resulted in remission of AMS within several days without sequelae.

AMS is characterized by the following symptoms and signs: severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, and 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 per dL, but negative culture results. Conduct a detailed neurological examination in patients exhibiting such symptoms and signs, including CSF studies, to rule out other causes of meningitis (particularly anthrax meningitis).

Monitoring: Laboratory Tests

Consider 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 BUN and serum creatinine, before the initial infusion of anthrax immune globulin IV (human) and at appropriate intervals thereafter.

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.

If signs and/or symptoms of hemolysis are present after an infusion of anthrax immune globulin IV (human), perform appropriate laboratory testing for confirmation.

If transfusion-related acute lung injury (TRALI) is suspected, perform appropriate tests for the presence of anti-HLA and anti-neutrophil antibodies in the product.

Interference With Laboratory Tests

Anthrax immune globulin IV (human) contains maltose, which can be misinterpreted as glucose by certain types of blood glucose testing systems (for example, those based on the GDH-PQQ or glucose-dye-oxidoreductase methods). Due to the potential for falsely elevated glucose readings, use only testing systems that are glucose-specific to test or monitor blood glucose levels in patients receiving anthrax immune globulin (human). (See Interference with Blood Glucose Testing under Cautions: Warnings/Precautions.)

Antibodies present in anthrax immune globulin IV (human) may interfere with some serological tests. After administration of immune globulins like anthrax immune globulin IV (human), a transitory increase of passively transferred antibodies in the patient’s blood may result in positive results in serological testing (e.g. Coombs’ test). (See Hemolysis under Cautions: Warnings/Precautions.)

Urinalysis after anthrax immune globulin IV (human) administration may result in elevated glucose. As this is a known transient effect, testing should be repeated to determine if further action is warranted.

Transfusion-related Acute Lung Injury (TRALI)

Noncardiogenic pulmonary edema may occur in patients receiving immune globulin products, including anthrax immune globulin IV (human). TRALI is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever and typically occurs within one to six hours after transfusion.

Monitor recipients for pulmonary adverse reactions. If TRALI is suspected, perform tests for the presence of anti-HLA and anti-neutrophil antibodies in the product. TRALI may be managed using oxygen therapy with adequate ventilator support.

Transmission of Infectious Agents from Human Plasma

Because anthrax immune globulin IV (human) is made from human plasma, it may carry a risk of transmitting blood-borne infectious agents, including viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. No cases of transmission of viral diseases, vCJD, or CJD have been associated with the use of anthrax immune globulin IV (human).

All infections thought to have been possibly transmitted by this product should be reported by the physician or other health care provider to Emergent BioSolutions at 800-768-2304.

Specific Populations

Pregnancy

There are no human data to establish the presence or absence of risk associated with anthrax immune globulin IV (human).

Lactation

There are no data to assess the presence or absence of anthrax immune globulin IV (human) in human milk, the effects on the breast-fed child, or the effects on milk production/excretion.

Pediatric Use

Safety and effectiveness of anthrax immune globulin IV (human) in the pediatric population (≤16 years of age) have not been studied. Allometric scaling was used to derive dosing regimens to provide pediatric patients with exposure comparable to the observed exposure in adults receiving 420 units and 840 units. The dose for pediatric patients is based on body weight.

Geriatric Use

Safety and effectiveness of anthrax immune globulin IV (human) in the geriatric population (>65 years of age) have not been studied.

Renal Insufficiency

Use anthrax immune globulin IV (human) with caution in patients with any degree of preexisting renal insufficiency and in patients at risk of developing renal insufficiency (including, but not limited to those with diabetes mellitus, age greater than 65 years, volume depletion, paraproteinemia, sepsis, and patients receiving known nephrotoxic drugs) and administer at the minimum rate of infusion practicable.

Ensure that patients are not volume depleted before anthrax immune globulin IV (human) infusion. Do not exceed the recommended infusion rate, and follow the infusion schedule closely. (See Dosage and Administration.)

Use in Obese Populations

Safety and effectiveness of anthrax immune globulin IV (human) in the obese population have not been studied.

Common Adverse Effects

The most common adverse reactions to anthrax immune globulin IV (human) observed in >5% of healthy volunteers in clinical trials were headache, infusion site pain and swelling, nausea, and back pain.

General

Anthrax immune globulin IV (human) is available in the following dosage form(s) and strength(s):

Single-use vials containing a minimum potency of ≥60 units by toxin neutralization assay (TNA).

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

• For intravenous use only.

• Administer anthrax immune globulin IV (human) by slow intravenous infusion using an infusion pump and recommended adult or pediatric infusion rates (see Table 1).

• Maximum infusion rate in adults is 2 mL/min.

Select initial dose based on clinical severity; severe cases may warrant use of 14 vials (840 units) in adults or 2–14 vials (based on weight) in pediatric patients weighing >5 kg.

Adjust dose and consider redosing based on clinical severity and response to treatment.

Select initial dose based on clinical severity. Dose may be doubled for severe cases in pediatric patients weighing >5 kg.