Prescription Drug Information: BabyBIG (Page 3 of 5)

6.2 Postmarketing Experience

Because postmarketing reporting of adverse reactions is voluntary and from a population of uncertain size, it is not always possible to reliably estimate the frequency of these reactions or establish a causal relationship to product exposure.

Experience with BabyBIG. No adverse reactions have been identified or reported that are ascribed to the use of BabyBIGduring postapproval use. 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.[19, 20]

Experience with Other IGIV Products. Some classes of adverse reactions that have not been reported in BabyBIG clinical studies or postmarketing experience have been observed with the overall post-approval use of other IGIV products, as shown in the following table.

Respiratory Apnea, Acute Respiratory Distress Syndrome (ARDS), Transfusion Related Acute Lung Injury (TRALI), cyanosis, hypoxemia, pulmonary edema, dyspnea, bronchospasm
Cardiovascular Cardiac arrest, thromboembolism, vascular collapse, hypotension
Neurological Coma, loss of consciousness, seizures, tremor
Integumentary Steven-Johnson syndrome, epidermolysis, erythema multiforme, bullous dermatitis
Hematologic Pancytopenia, leukopenia, hemolysis, positive direct antiglobulin (Coombs’) test
General /Body as a Whole Pyrexia, rigors
Musculoskeletal Back pain
Gastrointestinal Hepatic dysfunction, abdominal pain

7 DRUG INTERACTIONS

  • 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 such as MMR (measles, mumps, and rubella), MMRV (measles, mumps, rubella, and varicella), and monovalent varicella vaccines should be deferred until six months after administration of BabyBIG. This interval may be shortened if exposure to measles is likely. If such vaccinations were given shortly before or after BabyBIG administration, revaccination may be necessary.[21]

8 USE IN SPECIFIC POPULATIONS

8.4 Pediatric Use

BabyBIG has been studied for safety and efficacy only in patients below one year of age [see ADVERSE REACTIONS (6) and CLINICAL STUDIES (14)]. It has not been tested in other populations.

10 OVERDOSAGE

Although limited data are available, clinical experience with other immunoglobulin preparations suggests that the major manifestations would be those related to volume overload.[1]

11 DESCRIPTION

BabyBIG, Botulism Immune Globulin Intravenous (Human) (BIG-IV), is a solvent-detergent-treated, sterile, lyophilized powder of immunoglobulin G (IgG), stabilized with 5% sucrose and 1% albumin (human). It contains no preservative. The purified immunoglobulin is derived from pooled adult plasma from persons who were immunized with recombinant botulinum vaccine for serotypes A and B (rBV A/B) and selected for their high titers of neutralizing antibody against botulinum neurotoxins type A and B. All donors were tested and their sera found to be negative for antibodies against the human immunodeficiency virus and the hepatitis B and hepatitis C viruses.

The pooled plasma was fractionated by cold ethanol precipitation of the proteins according to the Cohn/Oncley method, modified to yield a product suitable for intravenous administration.[22, 23] Several steps in the manufacturing process have been validated for their ability to inactivate or remove viruses that may not have been detected in the Source Plasma.[1, 24-27] These include Cohn/Oncley fractionation (Fraction I through Supernatant III Filtrate); nanofiltration through one 75-nm and two 35-nm filters; and solvent/detergent viral inactivation. These viral reduction steps have been validated in a series of in vitro experiments for their capacity to inactivate and/or remove Human Immunodeficiency Virus type 1 (HIV-1) and the following model viruses: bovine viral diarrhea virus (BVDV) as a model for hepatitis C virus; mouse encephalomyelitis virus (MEMV) as a model for hepatitis A virus; and pseudorabies virus (PRV), feline calicivirus (FCV), and Sindbis virus to cover a wide range of physicochemical properties in the model viruses studied. Total mean log10 reductions range from 4.63 to greater than 16 log10 as shown in the following table.

Process Step Mean Reduction Factor (log10 )
Enveloped Viruses(size in nm) Non-Enveloped Viruses(size in nm)
Sindbis(60-70) HIV-1(80-100) PRV(120-200) BVDV(40-60) MEMV(22-30) FCV(35-39)
*
Included hydrophobic chromatography after solvent/detergent treatment.
Cohn/Oncley fractionation 6.6 > 9.44 > 10.37 6.25 4.06 Not done
Nanofiltration ≥ 6.84 Not done Not done ≥ 5.4 Not done ≥ 6.92
Solvent/detergent treatment Not done > 4.51 > 5.53 > 4.85 0.57* Not done
Cumulative Reduction Factor (log10 ) ≥ 13.44 > 13.95 > 15.9 ≥ 16.5 4.63 ≥ 6.92

Additional testing performed with bovine parvovirus (as a model for parvovirus B19) showed a mean cumulative reduction factor of greater than 7.34 log10 for Cohn/Oncley fractionation and solvent/detergent treatment followed by hydrophobic chromatography. A mean cumulative reduction factor of 2.55 log10 was observed for removal of porcine parvovirus by nanofiltration.

When reconstituted with Sterile Water for Injection USP, each cubic centimeter (milliliter) contains approximately 50 ± 10 mg immunoglobulin, primarily IgG, and trace amounts of IgA and IgM; 50 mg sucrose; 10 mg albumin (human); and approximately 20 × 10-3 mEq sodium. The reconstituted solution should appear colorless and translucent [see DOSAGE AND ADMINISTRATION (2.1), WARNINGS AND PRECAUTIONS (5)].

12 CLINICAL PHARMACOLOGY

BabyBIG contains IgG antibodies from the immunized donors who contributed to the plasma pool from which the product was derived. The titer of antibodies in the reconstituted product against type A botulinum toxin is at least 15 IU/mL and against type B toxin is at least 4.0 IU/mL. For toxin types A and B, by definition, 1 IU of botulinum antitoxin neutralizes 10,000 intraperitoneal mouse LD50 of botulinum toxin. The titers of antibody against botulinum neurotoxins C, D, and E have not been determined. In the case of infants who may be exposed to botulinum neurotoxin type A or B, this product is expected to provide the relevant antibodies at levels sufficient to neutralize the expected levels of circulating neurotoxin.[16, 28]

12.1 Mechanism of Action

BabyBIG contains antibodies specific for botulinum neurotoxin types A and B that bind to and neutralize circulating toxin types A and B in the patient.

12.2 Pharmacodynamics

Formal studies on pharmacodynamics have not been conducted with BabyBIG.

12.3 Pharmacokinetics

Traditional pharmacokinetic studies of BabyBIG have not been performed. However, the following table summarizes the mean serum titer of the anti-A component of BabyBIG following administration.

Time BabyBIG Lot 1 Anti-A Titer(mean ± S.D.) BabyBIG Lot 2 Anti-A Titer(mean ± S.D.)
mIU/mL
NOTE: 1 IU of anti-type A or anti-type B antibody neutralizes, by definition, 104 mouse LD50 of botulinum toxin.
Day 1 Not done 537.1 ± 213.4
Week 2 106.7 ± 44.6 192.2 ± 71.2
Week 4 90.0 ± 39.2 155.5 ± 56.7
Week 8 54.9 ± 22.8 96.0 ± 33.2
Week 12 26.0 ± 20.5 61.4 ± 32.3
Week 16 15.6 ± 10.4 33.0 ± 22.3
Week 20 7.6 ± 6.6 19.3 ± 14.1

The half-life of injected BabyBIG has been shown to be approximately 28 days in infants,[16] which is in agreement with existing data for other immunoglobulin preparations.[2, 16]

RxDrugLabels.com provides trustworthy package insert and label information about marketed prescription drugs as submitted by manufacturers to the U.S. Food and Drug Administration. Package information is not reviewed or updated separately by RxDrugLabels.com. Every individual prescription drug label and package insert entry contains a unique identifier which can be used to secure further details directly from the U.S. National Institutes of Health and/or the FDA.

As a leading independent provider of trustworthy medication information, we source our database directly from the FDA's central repository of drug labels and package inserts under the Structured Product Labeling standard. RxDrugLabels.com provides the full prescription-only subset of the FDA's repository. Medication information provided here is not intended as a substitute for direct consultation with a qualified health professional.

Terms of Use | Copyright © 2023. All Rights Reserved.