Botulism immune globulin

Usual Pediatric Dose for Botulism:

Less than one year of age with infant botulism caused by toxin type A or B:

2 mL/kg (100 mg/kg), given as a single intravenous infusion as soon as the clinical diagnosis of infant botulism is made. Add 2 mL sterile water for injection to the 100 mg vial, resulting in 50 mg/mL solution. Infusion should begin within 2 hours after reconstitution is complete and should be concluded within 4 hours of reconstitution. The infusion should begin slowly. Administration should start at 0.5 mL per kg body weight per hr (25 mg/kg/hr). If no untoward reactions occur after 15 minutes, the rate may be increased to the maximum infusion rate of 1 mL/kg/hr (50 mg/kg/hr). At the recommended rates, infusion of the indicated dose should take 127.5 minutes total elapsed time.

Specific immune globulin (hyperimmune globulin).6 7 Botulism immune globulin IV (BIG-IV) contains IgG prepared from plasma of adults immunized with pentavalent botulinum toxoid and is capable of neutralizing botulinum toxin types A and B.1

Contraindications

• History of severe reaction to any immune globulin preparation.1

• Selective IgA deficiency.1 (See IgA Deficiency under Cautions.)

Warnings/Precautions

Sensitivity Reactions

Mild, transient, erythematous rash on face or trunk reported in 9–14% of infants receiving BIG-IV in clinical studies.1 4

Acute or severe systemic allergic reactions (e.g., anaphylaxis, angioedema) not reported in clinical studies, but such reactions are possible.1 Anaphylaxis can occur in patients with no known sensitivity to immune globulin preparations.1 Reactions may also be related to rate of infusion.1 (See Administration Precautions under Cautions.)

Epinephrine should be available to treat acute allergic symptoms.1

If anaphylaxis or hypotension occurs, immediately discontinue BIG-IV infusion and initiate appropriate treatment (e.g., epinephrine) as indicated.1

Individuals with IgA deficiency may develop antibodies to IgA; anaphylaxis could occur following administration of BIG-IV or other blood products containing IgA.1

BIG-IV contains trace amounts of IgA.1

Renal Effects

Renal dysfunction, acute renal failure, osmotic nephrosis, and death reported in patients receiving IGIV.1 Increases in BUN and Scr have been observed as soon as 1–2 days following IGIV treatment.1

Available data indicate that IGIV preparations stabilized with sucrose and administered at daily dosages ≥400 mg/kg are associated with a greater risk of developing IGIV-associated renal dysfunction.1 BIG-IV contains 5% sucrose as a stabilizer.1

Administer BIG-IV at the minimum concentration available and minimum IV infusion rate practicable, especially in patients predisposed to acute renal failure (e.g., those with any degree of preexisting renal insufficiency, diabetes mellitus, volume depletion, sepsis, paraproteinemia, receiving nephrotoxic drugs).1

Prior to administration, ensure that patient is adequately hydrated and assess renal function (e.g., BUN or Scr).1 Monitor renal function and urine output periodically, particularly in patients at risk of acute renal failure.1 (See Renal Impairment under Cautions.)

Administration Precautions

Adverse effects that appear to be related to infusion rate (e.g., chills, muscle cramps, back pain, fever, nausea, vomiting, wheezing) reported with immune globulin preparations, including BIG-IV.1

Do not exceed recommended infusion rate.1 (See Dosage and Administration: Administration.)

If relatively minor adverse effect (e.g., flushing) occurs, immediately decrease infusion rate or temporarily discontinue infusion.1 If anaphylaxis or substantial decrease in BP occurs, discontinue infusion and initiate appropriate therapy (e.g., epinephrine).1 (See Sensitivity Reactions under Cautions.)

Risk of Transmissible Infectious Agents in Plasma-derived Preparations

Because BIG-IV is prepared from pooled human plasma, it is a potential vehicle for transmission of human viruses and theoretically may carry a risk of transmitting the causative agent of Creutzfeldt-Jakob disease (CJD).1

Although donors are screened for certain viruses (e.g., HIV, HBV, HCV) and BIG-IV undergoes certain procedures (cold ethanol fractionation, nanofiltration, solvent/detergent viral inactivation) that reduce viral infectious potential, some unrecognized blood-borne infectious agents may not be inactivated and a risk for transmission of infectious agents still remains.1 Administer only when a benefit is expected.1

Aseptic Meningitis Syndrome

Aseptic meningitis syndrome reported rarely in patients receiving IGIV;1 occurs more frequently in patients receiving high total doses of IGIV (e.g., 2 g/kg).1 Not reported in clinical trials of BIG-IV.1

Symptoms include severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, nausea, and vomiting; usually evident within several hours to 2 days after administration of IGIV.1

Perform complete neurologic examination in patients exhibiting such symptoms to rule out other causes of meningitis.1 CSF analysis frequently reveals pleocytosis (up to several thousand cells per mm3), predominantly from the granulocytic series, and protein concentrations up to several hundred mg/dL.1

Syndrome generally resolved within several days without sequelae following IGIV discontinuance.1

Hyperproteinemia, Hyponatremia, and Increased Serum Viscosity

Hyperproteinemia, hyponatremia, and increased serum viscosity reported in patients receiving IGIV;1 not reported to date with BIG-IV.1

If hyponatremia occurs, it is critical to distinguish true hyponatremia from pseudohyponatremia caused by decreased calculated serum osmolality or elevated osmolar gap.1 Treatment aimed at decreasing serum free water in patients with pseudohyponatremia may lead to volume depletion, a further increase in serum viscosity, and increased risk of thromboembolic events.1

Thrombotic Events

Thrombotic events reported in patients receiving IGIV;1 not reported to date with BIG-IV.1

Patients at risk of thrombotic events include those with history of atherosclerosis, multiple cardiovascular risk factors, advanced age, impaired cardiac output, coagulation disorders, prolonged periods of immobilization, and/or known or suspected hyperviscosity.1

Consider baseline assessment of blood viscosity in patients at risk for hyperviscosity (e.g., those with cryoglobulins, fasting chylomicronemia/markedly high triacylglycerols [triglycerides], monoclonal gammopathies).1

In patients judged to be at risk of developing thrombotic events, administer BIG-IV at slowest infusion rate considered practicable.1

Hemolysis and Hemolytic Anemia

Immune globulin preparations may contain blood group antibodies that can act as hemolysins and induce in vivo coating of RBCs with immunoglobulin, causing a positive direct antiglobulin reaction and, rarely, hemolysis.1

Hemolytic anemia also can develop subsequent to immune globulin therapy due to enhanced RBC sequestration.1

Monitor for clinical signs and symptoms of hemolysis and, if necessary, perform appropriate confirmatory laboratory testing.1

Transfusion-related Acute Lung Injury

Transfusion-related acute lung injury (TRALI; noncardiogenic pulmonary edema) reported in patients receiving IGIV;1 not reported to date with BIG-IV.1

Typically occurs within 1–6 hours after IGIV infusion and is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever.1

Monitor for adverse pulmonary reactions.1 If TRALI is suspected, perform appropriate tests to determine whether antineutrophil antibodies are present in the product or patient serum.1

Manage using oxygen therapy with adequate ventilatory support.1

Improper Storage and Handling

Improper storage or handling of immune globulins may affect efficacy.6

Do not administer BIG-IV that has been mishandled or has not been stored at the recommended temperature.6 (See Storage under Stability.)

Inspect all immune globulins upon delivery and monitor during storage to ensure that the appropriate temperature is maintained.6 If there are concerns about mishandling, contact the manufacturer or state or local health departments for guidance on whether BIG-IV is usable.6

Specific Populations

Safety and efficacy not evaluated in adults, including pregnant women.1

Safety and efficacy established only in children <1 year of age.1

Safety and efficacy not evaluated in older pediatric patients.1

Safety and efficacy not evaluated in adults, including geriatric adults.1

Use with caution in patients with preexisting renal impairment and in patients judged to be at increased risk of developing renal impairment (e.g., those with diabetes mellitus, volume depletion, paraproteinemia, sepsis, receiving nephrotoxic drugs).1

Do not exceed recommended dosage, concentration, and IV infusion rate in patients with or at increased risk for renal impairment.1 (See Dosage and Administration.)

Common Adverse Effects

Erythematous rash.1

• Advise patient’s parent or legal guardian of the risks and benefits of BIG-IV.1 Discuss the possibility of adverse reactions, including hypersensitivity reactions (e.g., anaphylaxis), renal failure, aseptic meningitis syndrome, hemolysis, thrombosis, and TRALI.1 (See Cautions.)

• Advise patient’s parent or guardian that BIG-IV is prepared from pooled human plasma.1 Although improved donor screening and viral-inactivating and purification procedures used in manufacture of plasma-derived preparations have reduced the risk of pathogen transmission, BIG-IV is a potential vehicle for transmission of infectious agents.1 Importance of reporting any concerning adverse effects.1

• Advise patient’s parent or guardian that BIG-IV may interfere with the immune response to certain live virus vaccines (e.g., MMR, varicella vaccines); importance of informing clinicians administering vaccines about recent use of BIG-IV.1 6 (See Interactions.)

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

• Importance of informing patient’s parent or legal guardian of other important precautionary information.1 (See Cautions.)

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.