Human Botulinum Neurotoxin A/B Immune Globulin
FDA Drug Information • Also known as: Babybig
- Brand Names
- Babybig
- Drug Class
- Human Immunoglobulin G [EPC]
- Route
- INTRAVENOUS
- Dosage Form
- INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
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 log 10 reductions range from 4.63 to greater than 16 log 10 as shown in the following table. Process Step Mean Reduction Factor (log 10 ) Enveloped Viruses (size in nm) Non-Enveloped Viruses (size in nm) Sindbis (60-70) HIV-1 (80-100) PRV (120-200)...
What Is Human Botulinum Neurotoxin A/B Immune Globulin Used For?
1 INDICATIONS AND USAGE 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. BabyBIG is an immune globulin intravenous (human) indicated for: Treatment of infant botulism caused by toxin types A or B in patients below one year of age ( 1 ).
Dosage and Administration
2 DOSAGE AND ADMINISTRATION For Intravenous Use Only Intravenous use only ( 2 ) Recommended dose is 1.0 mL/kg (50 mg/kg) given as a single intravenous infusion ( 2 ). Reconstitute in 2 mL Sterile Water for Injection USP and initiate infusion within 2 hours of reconstitution ( 2.1 ). Administer BabyBIG through a separate intravenous line ( 2.3 ). Begin infusion slowly (0.5 mL/kg/h); if no untoward reaction in 15 minutes, increase rate to 1.0 mL/kg/h ( 2.2 , 2.3 ). DO NOT EXCEED THE RECOMMENDED DOSE, CONCENTRATION, AND RATE OF INFUSION ( 2.3 ). 2.1 Preparation for Administration BabyBIG does not contain a preservative. After reconstitution of the lyophilized product, the vial should be entered only once for the purpose of administration, and the infusion should begin within 2 hours of reconstitution. Remove the tab portion of the vial cap and clean the rubber stopper with 70% alcohol or equivalent. Reconstitute the lyophilized powder with 2 mL of Sterile Water for Injection USP, to obtain a 50 mg/mL BabyBIG solution. A double-ended transfer needle or large syringe is suitable for adding the water for reconstitution. When using a double-ended transfer needle, insert one end first into the vial of water. The lyophilized powder is supplied in an evacuated vial; therefore, the water should transfer by suction (the jet of water should be aimed to the side of the vial). After the water is transferred into the evacuated vial, the residual vacuum should be released to hasten the dissolution. Rotate the container gently to wet all the powder. An approximately 30-minute interval should be allowed for dissolving the powder. DO NOT SHAKE THE VIAL, AS THIS WILL CAUSE FOAMING. Inspect BabyBIG visually for particulate matter and discoloration prior to administration. Infuse the solution only if it is colorless, free of particulate matter, and not turbid [ see WARNINGS AND PRECAUTIONS (5) ]. To prevent the transmission of hepatitis viruses or other infectious agents from one person to another, use sterile disposable syringes and needles. Never reuse syringes and needles. 2.2 Treatment of Infant Botulism Caused by Toxin Type A or B The recommended total dosage of BabyBIG is 1.0 mL/kg (50 mg/kg), given as a single intravenous infusion as soon as the clinical diagnosis of infant botulism is made. BabyBIG should be used with caution in patients with pre-existing renal insufficiency and in patients judged to be at increased risk of developing renal insufficiency (including, but not limited to, those with diabetes mellitus, volume depletion, paraproteinemia, sepsis, or who are receiving known nephrotoxic drugs) [ see WARNINGS AND PRECAUTIONS (5.1) ]. 2.3 Administration Do not pre-dilute BabyBIG before infusion. Begin infusion within 2 hours after reconstitution is complete and conclude within 4 hours of reconstitution, unless infusion is temporarily interrupted for adverse reaction. Monitor vital signs continuously during infusion. Administer BabyBIG intravenously...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS Serious adverse reactions were not observed in clinical trials using BabyBIG. The most common adverse reaction observed with BabyBIG treatment during clinical trials (>5%) was skin rash. Other reactions such as chills, muscle cramps, back pain, fever, nausea, vomiting, and wheezing were the most frequent adverse reactions observed during the clinical trials of similarly-prepared human IGIV products. [15] The incidence of these reactions was less than 5% of all infusions in BabyBIG clinical trials, and these reactions were most often related to infusion rates. [7] The most common adverse reaction occurring in at least 5% of the patients treated with BabyBIG in a controlled clinical study was mild and transient erythematous rash of the face or trunk ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact the California Department of Public Health at 1-510-231-7600 and http://www.infantbotulism.org/ or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Two clinical studies of BabyBIG were performed: (1) an adequate and well-controlled study to evaluate safety and efficacy of BabyBIG, which used BabyBIG Lot 1, and (2) an open label study to collect additional safety data and confirm efficacy, which used BabyBIG Lot 2 [ see CLINICAL STUDIES (14) ]. [16, 17] Different methodologies were used to collect adverse events in the controlled study and open label study. Minor clinical events that were not recorded as adverse events in the controlled study were recorded as adverse events in the open label study. The only adverse event considered possibly related to BabyBIG administration was a mild, transient erythematous rash of the face or trunk. The following table summarizes the occurrence of rash by day of study relative to day of treatment for the randomized, controlled clinical trial (RCT) and for the open label study (OLS). Day of Study Relative to Treatment RCT OLS Placebo Both Gammagard 5% and Gammagard S/D 5% were used as placebo in this study. (N=64) BabyBIG (N=65) BabyBIG (N=293) n (%) Day -5 0 (0) 1 (2) 6 (2) Day -4 2 (3) 1 (2) 5 (2) Day -3 3 (5) 4 (6) 6 (2) Day -2 5 (8) 2 (3) 22 (8) Day -1 4 (6) 11 (17) 28 (10) Day 0 Day 0 is the day of treatment. Before In reference to treatment. 5 (8) 9 (14) 32 (11) During & After 2 (3) 9 (14) 39 (13) Day +1 2 (3) 1 (2) 18 (6) Day +2 1 (2) 2 (3) 13 (4) Day +3 3 (5) 0 (0) 7 (2) Day +4 1 (2) 2 (3) 11 (4) Day +5 2 (3) 0 (0) 5 (2) In the controlled study, when only treatment emergent events are considered, 14% of the BabyBIG-treated patients experienced erythematous rash during or after study infusion. Eight percent of placebo-treated patients also experienced erythematous rash in this study. A similar rash is known to occur both in infant botulism patients who have not received any IGIV products [18] and in patients treated with other IGIVs, [2, 3] making it difficult to ascertain the causality of the rash. In the controlled study only, the following adverse events occurred in at least 5% of the patients receiving BabyBIG or placebo: Adverse Event BabyBIG N=65 Placebo Both Gammagard 5% and Gammagard S/D 5% were used as placebo in this study. N=64 n (%) N (%) of Patients with any AE 20 (31) 29 (45) Rash erythematous 9 (14) 5 (8) Otitis media 7 (11) 5 (8) Pneumonia 7 (11) 9 (14) Anemia 3 (5) 9 (14) Hyponatremia 3 (5) 9 (14) Hypertension 1 (2) 3 (5) Respiratory arrest 1 (2) 6 (9) Urinary tract infection 1 (2) 8 (13) Convulsions 0 3 (5) In the open label study only, the following adverse events occurred in at least 5% of the patients: Adverse Event BabyBIG N=293 N (%) Patients with Any AE 285 (97) Blood pressure increased 221 (75) Dysphagia 190 (65) Irritability 121 (41) Atelectasis...
Drug Interactions
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] The passive transfer of antibodies may interfere with the response to live viral vaccines ( 7 ).
Contraindications
4 CONTRAINDICATIONS 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. Prior history of severe reaction to other human immunoglobulin preparations ( 4 ) Selective immunoglobulin A deficiency with anti-IgA antibodies ( 4 )
Overdosage
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]
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING NDC 68403-1100-6, 100 mg ± 20 mg lyophilized immunoglobulin single-dose vial individually packaged in a carton. 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.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.