Botulism Immune Globulin (Intravenous-Human)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, powder for reconstitution [preservative free]:

BabyBIG: ~ 100 mg [contains albumin (human), sucrose; supplied with diluent]

Pharmacology

Mechanism of Action

BIG-IV is purified immunoglobulin derived from the plasma of adults immunized with botulinum toxoid types A and B. BIG-IV provides antibodies to neutralize circulating toxins.

Pharmacokinetics/Pharmacodynamics

Duration of Action

Protective neutralizing antibody levels: ~6 months

Half-Life Elimination

Infants: 28 days

Use: Labeled Indications

Treatment of infant botulism caused by toxin type A or B

Contraindications

Hypersensitivity to human immune globulin preparations or any component of the formulation; selective immunoglobulin A deficiency

Dosage and Administration

Dosing: Pediatric

Infant botulism: Dosage is specific to the manufactured lot; refer to product-specific labeling.

Infants: IV: 50 mg/kg as a single IV infusion; begin as soon as diagnosis of infant botulism is made.

Storage

Prior to reconstitution, store between 2°C to 8°C (36°F to 46°F). Infusion should begin within 2 hours of reconstitution and be completed within 4 hours of reconstitution.

Drug Interactions

Vaccines (Live): Immune Globulins may diminish the therapeutic effect of Vaccines (Live). Management: Consult full interaction monograph for dose interval recommendations. This interaction does not apply to oral Ty21a typhoid vaccine or others listed as exceptions. Exceptions: Adenovirus (Types 4, 7) Vaccine; Cholera Vaccine; Influenza Virus Vaccine (Live/Attenuated); Poliovirus Vaccine (Live/Bivalent/Oral); Poliovirus Vaccine (Live/Trivalent/Oral); Rotavirus Vaccine; Yellow Fever Vaccine; Zoster Vaccine (Live/Attenuated). Consider therapy modification

Adverse Reactions

Frequency not always defined. Percentages reported in open-label study except where otherwise noted; may reflect pathophysiology of infant botulism.

>10%:

Cardiovascular: Increased blood pressure (transient, 75%), edema (18%), decreased blood pressure (transient, 16%), heart murmur (15%)

Central nervous system: Irritability (41%), decreased body temperature (16%)

Dermatologic: Pallor (28%), contact dermatitis (24%), erythematous rash (22%, reported as 14% vs 8% in placebo-controlled study)

Gastrointestinal: Dysphagia (65%), loose stools (25%), vomiting (20%), abdominal distension (11%)

Otic: Otitis media (11%, reported in placebo-controlled study)

Respiratory: Atelectasis (39%), rhonchi (34%), nasal congestion (18%), oxygen saturation decreased (17%), cough (13%), rales (13%)

Miscellaneous: Fever (17%)

1% to 10%:

Cardiovascular: Cold extremities (7%), tachycardia (7%)

Central nervous system: Agitation (10%), neurologic abnormality (neurogenic bladder)

Endocrine & metabolic: Dehydration (10%), hyponatremia (6%), metabolic acidosis (5%)

Gastrointestinal: Oral candidiasis (8%)

Hematologic & oncologic: Decreased hemoglobin (9%), anemia (5%)

Local: Injection site reaction (7%), erythema at injection site (5%)

Respiratory: Abnormal breath sounds (decreased: 10%), stridor (9%), lower respiratory tract infection (8%), dyspnea (6%), tachypnea (5%)

Miscellaneous: Infusion related reaction (related to rate: <5%, includes back pain, chills, fever, muscle cramps, nausea, vomiting, wheezing)

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylaxis/hypersensitivity reactions: Hypersensitivity and anaphylactic reactions can occur (some severe); patients with known antibodies to IgA are at greater risk; a severe fall in blood pressure may rarely occur with anaphylactic reaction; discontinue therapy and institute immediate treatment (including epinephrine 1 mg/mL) should be available.
• Aseptic meningitis: Aseptic meningitis syndrome (AMS) has been reported with immune globulin administration; may occur with rapid infusion and/or high doses of intravenous immune globulin (IGIV, ≥1 g/kg). Syndrome usually appears within several hours to 2 days following treatment; usually resolves within several days after product is discontinued. Female patients or patients with a migraine history may be at higher risk for AMS.
• Hemolysis: IGIV has been associated with antiglobulin hemolysis (acute or delayed). Cases of hemolysis-related renal impairment/failure or disseminated intravascular coagulation (DIC) have been reported. Risk factors associated with hemolysis include high doses (≥2 g/kg) given either as a single administration or divided over several days, underlying associated inflammatory conditions, and non-O blood type (FDA 2012). An underlying inflammatory state (eg, elevated C-reactive protein or erythrocyte sedimentation rate) may also increase the risk. Closely monitor patients for signs of hemolytic anemia, particularly in patients with preexisting anemia and/or cardiovascular or pulmonary compromise.
• Hyperproteinemia: Hyperproteinemia, increased serum viscosity, and hyponatremia may occur; distinguish hyponatremia from pseudohyponatremia to prevent volume depletion, a further increase in serum viscosity and a higher risk of thrombotic events.
• Infusion reactions: Patients should be monitored for adverse events during and after the infusion. Stop administration with signs of infusion reaction (fever, chills, nausea, vomiting, and rarely shock). With other immune globulin products, risk may be increased with initial treatment, when switching brands of immune globulin, and with treatment interruptions of >8 weeks.
• Pulmonary edema: Monitor for transfusion-related acute lung injury (TRALI); noncardiogenic pulmonary edema has been reported with IGIV use. TRALI is characterized by severe respiratory distress, pulmonary edema, hypoxemia, and fever in the presence of normal left ventricular function. Usually occurs within 1 to 6 hours after infusion.
• Renal impairment: Acute renal dysfunction (increased serum creatinine, oliguria, acute renal failure, osmotic nephrosis) can rarely occur and has been associated with fatalities in predisposed patients. Patients predisposed to renal dysfunction include patients with renal disease, diabetes mellitus, hypovolemia, volume depletion, sepsis, paraproteinemia, and nephrotoxic medications due to risk of renal dysfunction. Renal dysfunction and acute renal failure occur more commonly in patients receiving IGIV products containing sucrose. In patients at risk of renal dysfunction or acute renal failure, ensure adequate hydration prior to administration; the dose, rate of infusion, and concentration of solution should be minimized. Assess renal function prior to treatment and periodically thereafter. Discontinue if renal function deteriorates.
• Thrombotic events: Thrombosis may occur with immune globulin products even in the absence of risk factors for thrombosis. For patients at risk of thrombosis (eg, hypercoagulable conditions, history of venous or arterial thrombosis, indwelling central vascular catheters, hyperviscosity, cardiovascular risk factors, use of estrogens, prolonged immobilization, and advanced age), administer at the minimum dose and infusion rate practicable. Ensure adequate hydration before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity, such as those with cryoglobulins, fasting chylomicronemia/severe hypertriglyceridemia, or monoclonal gammopathies.

Disease-related concerns:

• Renal impairment: Use with caution; ensure adequate hydration prior to administration; the rate of infusion and concentration of solution should be minimized.

Special populations:

• Adults: Not indicated for use in adults.

Dosage form specific issues:

• Human plasma: Product of human plasma; may potentially contain infectious agents (eg, viruses, the variant Creutzfeldt Jakob disease [vCJD] agent and, theoretically, the Creutzfeldt Jakob disease [CJD] agent) that could transmit disease, including unknown or emerging viruses and other pathogens. Screening of donors, as well as testing and/or inactivation or removal of certain viruses, reduces the risk. Infections thought to be transmitted by this product should be reported to the manufacturer.

Other warnings/precautions:

• Administration: For IV infusion only; do not exceed recommended rate of administration.

Monitoring Parameters

Renal function (BUN, serum creatinine, urinary output); vital signs (continuously during infusion); signs and/or symptoms of allergic reaction (continuously during infusion); aseptic meningitis syndrome (may occur hours to days following IGIV therapy); signs of relapse (may occur up to 1 month following recovery)

Pregnancy

Pregnancy Considerations

Botulism immune globulin is only indicated for use in infants <1 year of age.

Patient Education

What is this drug used for?

• It is used to treat botulism.

Frequently reported side effects of this drug

• Irritability
• Diarrhea
• Vomiting
• Stuffy nose

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Blood clots like numbness or weakness on one side of the body; pain, redness, tenderness, warmth, or swelling in the arms or legs; change in color of an arm or leg; chest pain; shortness of breath; fast heartbeat; or coughing up blood
• Meningitis like headache with fever, stiff neck, nausea, confusion, or sensitivity to light
• Kidney problems like not able to pass urine, blood in your urine, change in amount of urine passed, or weight gain
• Fluid and electrolyte problems like mood changes, confusion, muscle pain or weakness, abnormal heartbeat, severe dizziness, passing out, fast heartbeat, increased thirst, seizures, loss of strength and energy, lack of appetite, not passing urine or change in amount of urine passed, dry mouth, dry eyes, or nausea or vomiting
• Lactic acidosis like fast breathing, fast heartbeat, abnormal heartbeat, vomiting, fatigue, shortness of breath, severe loss of strength and energy, severe dizziness, feeling cold, or muscle pain or cramps
• Severe pulmonary disorder like lung or breathing problems like trouble breathing, shortness of breath, or a cough that is new or worse
• Severe headache
• Severe dizziness
• Passing out
• Vision changes
• Severe loss of strength and energy
• Chills
• Cough
• Thrush
• Ear pain
• Pale skin
• Swelling
• Feeling cold
• Abdominal swelling
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.