BabyBIG

Your baby should not receive this medicine if he or she has immune globulin A (IgA) deficiency with antibody to IgA.

Your baby should not receive a "live" vaccine (measles, mumps, rubella, polio, rotavirus, yellow fever, varicella) for at least 3 months after receiving botulism immune globulin.

Your baby will remain under constant supervision during treatment with botulism immune globulin.

Get emergency medical help if your baby has any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if the baby has:

• tenderness, redness, warmth, cold feeling, or blue/purple appearance in the arms or legs;

• fussiness, trouble breathing, blue lips, pale skin;

• little or no urinating, fewer wet diapers than usual;

• yellowed skin, dark colored urine;

• low levels of sodium in the body--confusion, severe weakness, vomiting, loss of coordination or motor skills; or

• swelling around the brain or spinal cord--fever, neck stiffness, sensitivity to light, weakness, sleepiness, vomiting.

Common side effects may include:

• mild skin rash or redness on the baby's face, chest, back, or stomach;

• chills, body aches;

• wheezing; or

• vomiting.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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

Infant Botulism

Treatment of infant botulism caused by toxin types A or B in infants <1 year of age;1 designated an orphan drug by FDA for this indication.2

Infant botulism occurs when young infants ingest spores of Clostridium botulinum; spores then germinate, colonize GI tract, and produce botulinum toxin.5 7 9 10 12 In some cases, source of C. botulinum spores identified as honey;7 9 12 source usually unknown and may be environmental (e.g., soil or dust particles).7 12 Most cases occur in infants ≤6 months of age; usually caused by C. botulinum toxin types A and B,3 4 5 7 12 but disease caused by toxin type E from C. butyricum or toxin type F from C. baratii reported rarely.3 7 12 Botulinum toxins are neurotoxins that cause generalized weakness and loss of muscle tone.7 9 10 12 Fatalities can occur as result of rapidly progressing muscle weakness, paralysis, and respiratory arrest.4 7

BIG-IV in conjunction with supportive care measures is standard of care in US.3 4 7 10 12

Anti-infectives not effective and should not be used.7 9

Botulinum antitoxin (equine) (available from CDC) is used for treatment of foodborne and wound botulism, but it is not used for treatment of infant botulism because it has serious adverse effects (e.g., sensitivity reactions).5 7

BabyBIG®, Botulism Immune Globulin Intravenous (Human), is indicated for the treatment of infant botulism caused by toxin type A or B in patients below one year of age.

Only administer BabyBIG as an intravenous infusion, since other routes of administration have not been evaluated. Do not use BabyBIG if the reconstituted solution is turbid [see DOSAGE AND ADMINISTRATION (2.1)].

Patient Monitoring for Administration

• Patients should be well hydrated prior to the initiation of the BabyBIG infusion.
• Assess renal function, including the measurement of blood urea nitrogen (BUN) or serum creatinine prior to the initial infusion of BabyBIG [see DOSAGE AND ADMINISTRATION (2)]. Periodic monitoring of renal function tests and urine output is particularly important in patients judged to have a potential risk for developing acute renal failure.[1-4] Increases in serum creatinine and BUN have been observed as soon as one to two days following treatment with other IGIV products.
• During administration, monitor the patient's vital signs continuously and observe the patient carefully for any associated symptoms.
• DO NOT EXCEED THE RECOMMENDED INFUSION RATE of 1 mL/kg/hour (50 mg/kg/h), and follow the infusion schedule closely [see DOSAGE AND ADMINISTRATION (2.3)]. If a patient develops an infusion reaction, slow the rate of infusion immediately or temporarily interrupt the infusion.

Renal Adverse Reactions

Other IGIV products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death.[5-6] While these reports of renal dysfunction and acute renal failure have been associated with the use of many licensed IGIV products, those that contained sucrose as a stabilizer and were administered at daily doses of 400 mg/kg or greater have accounted for a disproportionate share of the total number.[7] BabyBIG contains sucrose as a stabilizer. Patients predisposed to acute renal failure include those patients with any degree of pre-existing renal insufficiency, diabetes mellitus, volume depletion, sepsis, paraproteinemia, or who are receiving known nephrotoxic drugs. Especially in such patients, BabyBIG should be administered at the minimum concentration available and at the minimum rate of infusion practicable.[1]

Transmission of Blood-Borne Infectious Agents

BabyBIG is made from human plasma and, like other plasma products, carries the possibility for transmission of blood-borne viral agents and, theoretically, the Creutzfeldt-Jakob disease agent. The risk of transmission of recognized blood-borne viruses has been reduced by screening plasma donors for prior exposure to certain viruses, for the presence of certain viral infections, and by the viral inactivation and/or removal properties of the precipitation procedures used for the purification of BabyBIG [see DESCRIPTION (11)]. Despite these measures, some as yet unrecognized blood-borne infectious agents may not be inactivated by the manufacturing process; therefore, BabyBIG, like any other blood product, should be given only if a benefit is expected [see PATIENT COUNSELING INFORMATION (17)].

Anaphylaxis

• Severe reactions, such as angioedema and anaphylactic shock, although not observed during clinical trials with BabyBIG, are a possibility.[8,9] Clinical anaphylaxis may occur even when the patient is not known to be sensitive to immune globulin products. A reaction may be related to the rate of infusion; therefore, carefully adhere to the infusion rates as outlined under "DOSAGE AND ADMINISTRATION (2.3)." If anaphylaxis or a drop in blood pressure occurs, discontinue the infusion and administer epinephrine.[1-4]
• Although acute systemic allergic reactions were not seen in clinical trials with BabyBIG, epinephrine should be available for treatment of acute allergic symptoms [see ADVERSE REACTIONS (6.1)]. If hypotension or anaphylaxis occurs, discontinue the administration of BabyBIG immediately and give supportive care as needed.

Aseptic Meningitis Syndrome

An aseptic meningitis syndrome (AMS) has been reported to occur infrequently in association with IGIV administration.[10-13] The syndrome usually begins within several hours to two days following IGIV treatment. It is characterized by symptoms and signs that include the following: severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, and nausea and vomiting. Cerebrospinal fluid studies are frequently positive with pleocytosis up to several thousand cells per cubic millimeter, predominately from the granulocytic series, and with elevated protein levels up to several hundred mg/dL. Conduct a thorough neurological examination in patients exhibiting such symptoms and signs to rule out other causes of meningitis.[10-13] AMS may occur more frequently in association with high total doses (2 g/kg) of IGIV treatment. Discontinuation of IGIV treatment has resulted in remission of AMS within several days without sequelae.[1] AMS was not observed in clinical trials of BabyBIG.

Hyperproteinemia, Hyponatremia, and Serum Viscosity

Hyperproteinemia, hyponatremia, and increased serum viscosity have been observed following administration of IGIV products. It is clinically critical to distinguish true hyponatremia from pseudohyponatremia caused by decreased calculated serum osmolality or elevated osmolar gap, because treatment aimed at decreasing serum free water in patients with pseudohyponatremia may lead to volume depletion, a further increase in serum viscosity and a higher risk of thromboembolic events. These adverse events have not been observed with BabyBIG.

Thrombotic Events

Thrombotic events may occur following IGIV treatment. Patients at risk may include those with a history of atherosclerosis, multiple cardiovascular risk factors, advanced age, impaired cardiac output, coagulation disorders, prolonged periods of immobilization, and/or known or suspected hyperviscosity. 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. For patients judged to be at risk of developing thrombotic events, administer BabyBIG at the minimum rate of infusion practicable.

Hemolytic Anemia

IGIV products may contain blood group antibodies, which can act as hemolysins and induce in vivo coating of red blood cells with immunoglobulin, causing a positive direct antiglobulin reaction and, rarely, hemolysis. Hemolytic anemia may develop subsequent to IGIV therapy due to enhanced red blood cell sequestration.

Monitor patients for clinical signs and symptoms of hemolysis. If these are present after BabyBIG infusion, perform appropriate confirmatory laboratory testing.

Transfusion-Related Acute Lung Injury (TRALI)

Non-cardiogenic pulmonary edema may occur in patients following IGIV treatment.[31] TRALI is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever. Symptoms typically occur within 1 to 6 hours following treatment [See PATIENT COUNSELING INFORMATION (17)].

Monitor patients for pulmonary adverse reactions. If TRALI is suspected, perform appropriate tests for the presence of anti-neutrophil antibodies in both the product and patient serum.

TRALI may be managed using oxygen therapy with adequate ventilatory support.

• NDC 68403-1100-6, 100 mg ± 20 mg lyophilized immunoglobulin single-dose vial individually packaged in a carton, supplied with 2 mL Sterile Water for Injection USP for reconstitution.
• Store the vial containing the lyophilized product between 2° and 8°C (35.6° to 46.4°F). Do not store BabyBIG in the reconstituted state.
• Use reconstituted BabyBIG within 2 hours.
• Do not use beyond expiration date, and dispose unused product in accordance with local requirements.

• Discuss the risks and benefits of BabyBIG use with the patient's legal guardians, including the possibility of adverse reactions, e.g., hypersensitivity reactions such as anaphylaxis, as well as aseptic meningitis, TRALI, hemolysis, renal failure, and thrombosis [see WARNINGS AND PRECAUTIONS (5)].
• Inform patient's legal guardians that BabyBIG is made from human plasma and may contain infectious agents that can cause disease. While the risk of transmitting an infection has been reduced by screening plasma donors for prior exposure, testing donated plasma, and inactivating or removing certain viruses during manufacturing, the patient's guardian should report any symptoms that concern them [see WARNINGS AND PRECAUTIONS (5.3)].
• Inform patient's legal guardians that BabyBIG may interfere with immune response to live viral vaccines (e.g., MMR) and instruct them to notify the healthcare provider of this potential interaction when the patient is to receive vaccinations [see DRUG INTERACTIONS (7)].

For additional information concerning BabyBIG, contact:

Infant Botulism Treatment and Prevention Program
California Department of Public Health
850 Marina Bay Parkway, Room E-361
Richmond, California 94804
Telephone: 510-231-7600
US Govt. License No. 1797

Manufactured by:
Baxter Healthcare Corporation
Westlake Village, CA 91362, USA
US Govt. License No. 140; and

Cangene Corporation
Winnipeg, Manitoba, R3T 5Y3, Canada
US Govt. License No. 1201

Distributed by:
FFF Enterprises
Temecula, California 92591, USA

Distributed for:
Infant Botulism Treatment and Prevention Program
California Department of Public Health
850 Marina Bay Parkway, Room E-361
Richmond, California 94804

Revised October 2011

PRINCIPAL DISPLAY PANEL - 2 mL Vial Label

Botulism Immune Globulin Intravenous
(Human) (BIG-IV)

BabyBIG®

DO NOT SHAKE VIAL
AFTER RECONSTITUTION;
AVOID FOAMING.
See package insert for
reconstitution, dosage, and
administration. Rx only.
Single use container.

Manufactured for:
California Department of
Public Health
by: Baxter Healthcare
Corporation and
Cangene Corporation

LOT
EXP.

PRINCIPAL DISPLAY PANEL - 1 Single Use Vial Carton

NDC 68403-1100-6

Rx Only

100 mg IgG, 100 mg Sucrose
20 mg Albumin (Human)
Lyophilized
Solvent Detergent Treated

Botulism Immune Globulin
Intravenous (Human) (BIG-IV)

BabyBIG®

Store between 2°C and 8°C (35.6°F and 46.4°F).

>10%

Transient increase in blood pressure

Pallor Edema

Transient decrease in blood pressure

Cardiac murmur

Irritability

Pyrexia

Decrease in body temperature

Contact dermatitis

Erythematous rash

Dysphagia

Loose stools

Vomiting

Abdominal distension

Otitis media

Atelectasis

Rhonchi

Nasal congestion

Decrease in oxygen saturation

Cough

Rales

1-10%

Tachycardia

Peripheral coldness

Central nervous system agitation

Dehydration

Hyponatremia

Metabolic acidosis

Decrease in hemoglobin

Local injection site reaction

Injection site erythema

Neurogenic bladder

Decrease in breath sounds

Stridor

Lower respiratory tract infection

Dyspnea

Tachypnea

Oral candidiasis

Infusion rate reactions

Postmarketing Reports

Retrospective publications have shown safety-related information consistent with the safety-related information in the approved product labeling, and no new safety-related information has been presented for BabyBIG.

Contraindications

Documented hypersensitivity; selective immunoglobulin A deficiency

Cautions

Aseptic meningitis syndrome reported

Acute renal dysfunction may occur

Assess renal function prior to and following administration

Hyperproteinemia, increased serum viscosity and hyponatremia may occur in patients receiving IGIV therapy

Hemolytic anemia can develop subsequent to IGIV therapy due to enhanced RBC sequestration

The product is made from human plasma and may contain infectious agents, e.g. viruses and, theoretically, the Creutzfeldt-Jakob disease agent

Patients should not be volume depleted (hypovolemic) prior to therapy

For IV infusion only; do not exceed recommended rate of administration