BabyBIG

Your baby should not receive botulism immune globulin if he or she has ever had an allergic reaction to an immune globulin, or if the child has immune globulin A (IgA) deficiency with antibody to IgA.

To make sure botulism immune globulin is safe for your baby, tell the doctor if your baby has:

• kidney disease;

• diabetes;

• if the baby has recently received any vaccination;

• if the baby is dehydrated; or

• if the baby is being treated with any medicines that weaken the immune system.

Botulism immune globulin is made from human plasma (part of the blood) which may contain viruses and other infectious agents. Donated plasma is tested and treated to reduce the risk of it containing infectious agents, but there is still a small possibility it could transmit disease. Talk with your doctor about the risks and benefits of using this medication.

Since this medicine is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

Your baby should not receive a "live" vaccine for at least 3 months after receiving botulism immune globulin. Live vaccines include measles, mumps, rubella, polio, rotavirus, yellow fever, and varicella. The vaccine may not work as well during this time, and may not fully protect your baby from disease.

Other drugs may interact with botulism immune globulin, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your baby's doctor about all medicines your baby receives.

General

• Administer BIG-IV as soon as possible after clinical diagnosis of infant botulism; do not wait for confirmatory diagnostic testing (e.g., toxin assay and culture of stool or enema specimens).3 4 7 10 12

• Prior to administration, ensure that patient is adequately hydrated and assess renal function (e.g., BUN or Scr).1 During administration, continuously monitor patient’s vital signs and closely observe for adverse effects.1 (See Administration Precautions under Cautions.)

• Patients with infant botulism may excrete C. botulinum and botulinum toxin in feces for up to 3 months after symptom onset.9 Use meticulous handwashing after diaper changes; properly dispose of soiled diapers (e.g., bag and autoclave).9 Individuals with open cuts or wounds on hands should wear gloves while handling soiled diapers.9 Avoid close contact between the infant and other infants or young children (e.g., sharing crib or toys) during time the organism or toxin may be excreted.9

Administration

IV Administration

Administer only by IV infusion;1 other routes not evaluated.1

Use inline or syringe filter (pore size 18 mcm), low-volume tubing, and controlled-infusion device (e.g., IVAC pump or equivalent) to control flow rate.1

Administer via a separate IV infusion line.1 If necessary, may be piggybacked into a preexisting line containing 0.9% sodium chloride injection or 2.5, 5, 10, or 20% dextrose injection (with or without sodium chloride), provided dilution of BIG-IV with such fluids does not exceed 1:2.1

Admixtures with other drugs not evaluated.1

Reconstitute single-dose vial by adding 2 mL of sterile water for injection diluent provided by the manufacturer to provide solution containing 50 mg of immunoglobulin per mL.1

After adding diluent to powder, gently swirl vial.1 Do not shake; avoid foam formation.1 Complete dissolution may take 30 minutes.1 Consult manufacturer’s information for additional directions regarding reconstitution.1

Do not dilute reconstituted solution.1

Following reconstitution, initiate IV infusion within 2 hours and complete infusion within 4 hours.1

Does not contain a preservative;1 administer only if reconstituted solution is colorless, free of particulate matter, and not turbid.1

Initiate IV infusion at a rate of 25 mg/kg (0.5 mL/kg) per hour; if no adverse reactions have occurred after 15 minutes, may increase rate to 50 mg/kg (1 mL/kg) per hour.1

Do not exceed infusion rate of 50 mg/kg (1 mL/kg) per hour.1

If relatively minor adverse effects (e.g., flushing) occur, slow infusion rate or temporarily interrupt infusion.1 If more severe reaction (e.g., anaphylaxis, substantial decrease in BP) occurs, discontinue infusion and administer appropriate therapy (e.g., epinephrine).1 (See Administration Precautions under Cautions.)

Dosage

Pediatric Patients

100 mg/kg (2 mL/kg) administered as a single IV infusion.1

Prescribing Limits

Pediatric Patients

Maximum dose 100 mg/kg (2 mL/kg).1

Special Populations

Renal Impairment

Do not exceed recommended dosage, concentration, and rate of IV infusion.1 (See Renal Impairment under Cautions.)

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

Absorption

Bioavailability

Pharmacokinetics not fully elucidated.1

Elimination

Half-life

Approximately 28 days in infants.1 4

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.

• As with other immunoglobulin preparations, BabyBIG should not be used in individuals with a prior history of severe reaction to other human immunoglobulin preparations.[1-4]
• Individuals with selective immunoglobulin A deficiency have the potential for developing antibodies to immunoglobulin A and could have anaphylactic reactions to the subsequent administration of blood products that contain immunoglobulin A.

• Admixtures of BabyBIG with other drugs have not been evaluated. It is recommended that BabyBIG be administered separately from other drugs or medications that the patient may be receiving [see DOSAGE AND ADMINISTRATION (2)].
• Antibodies present in immune globulin preparations may interfere with the immune response to live virus vaccines such as polio, measles, mumps, and rubella; THEREFORE, VACCINATION WITH LIVE VIRUS VACCINES SHOULD BE DEFERRED UNTIL APPROXIMATELY THREE OR MORE MONTHS AFTER ADMINISTRATION OF BabyBIG. If such vaccinations were given shortly before or after BabyBIG administration, revaccination may be necessary.