BabyBIG
Generic: HUMAN BOTULINUM NEUROTOXIN A/B IMMUNE GLOBULIN
Basic Information
Manufacturer
CALIFORNIA DEPARTMENT OF PUBLIC HEALTH
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
INTRAVENOUS
FDA Set ID
9ec59262-35c1-4d8e-8451-a7cfbacb0675
Indications & Usage
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 ).
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 ).
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 113 (39) Rhonchi 100 (34) Pallor 83 (28) Loose stools 73 (25) Dermatitis contact 70 (24) Rash erythematous 64 (22) Vomiting 58 (20) Nasal congestion 54 (18) Edema 54 (18) Oxygen saturation decreased 51 (17) Pyrexia 51 (17) Body temperature decreased 48 (16) Blood pressure decreased 47 (16) Cardiac murmur 45 (15) Cough 39 (13) Rales 37 (13) Abdominal distension 33 (11) Breath sounds decreased 30 (10) Dehydration 30 (10) Agitation 29 (10) Hemoglobin decreased 27 (9) Stridor 26 (9) Lower respiratory tract infection 23 (8) Oral candidiasis 23 (8) Injection-site reaction 21 (7) Tachycardia NOS 20 (7) Peripheral coldness 19 (7) Dyspnea NOS 16 (6) Hyponatremia 16 (6) Injection-site erythema 15 (5) Intubation NOS 15 (5) Metabolic acidosis 15 (5) Neurogenic bladder 15 (5) Anemia 14 (5) Tachypnea 14 (5) Adverse event coding was used in the open label study to distinguish between minor clinical events that required no intervention and more significant events that required intervention.
For example, "increased blood pressure" or "decreased blood pressure" was assigned when transient changes in blood pressure were observed, whereas "hypertension" or "hypotension" was assigned when more prolonged or significant changes were observed.
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
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 113 (39) Rhonchi 100 (34) Pallor 83 (28) Loose stools 73 (25) Dermatitis contact 70 (24) Rash erythematous 64 (22) Vomiting 58 (20) Nasal congestion 54 (18) Edema 54 (18) Oxygen saturation decreased 51 (17) Pyrexia 51 (17) Body temperature decreased 48 (16) Blood pressure decreased 47 (16) Cardiac murmur 45 (15) Cough 39 (13) Rales 37 (13) Abdominal distension 33 (11) Breath sounds decreased 30 (10) Dehydration 30 (10) Agitation 29 (10) Hemoglobin decreased 27 (9) Stridor 26 (9) Lower respiratory tract infection 23 (8) Oral candidiasis 23 (8) Injection-site reaction 21 (7) Tachycardia NOS 20 (7) Peripheral coldness 19 (7) Dyspnea NOS 16 (6) Hyponatremia 16 (6) Injection-site erythema 15 (5) Intubation NOS 15 (5) Metabolic acidosis 15 (5) Neurogenic bladder 15 (5) Anemia 14 (5) Tachypnea 14 (5) Adverse event coding was used in the open label study to distinguish between minor clinical events that required no intervention and more significant events that required intervention.
For example, "increased blood pressure" or "decreased blood pressure" was assigned when transient changes in blood pressure were observed, whereas "hypertension" or "hypotension" was assigned when more prolonged or significant changes were observed.
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