ADVERSE REACTIONS
In clinical trials involving the administration of 7918 doses of COMVAX to 3561 healthy infants 6 weeks to 15 months of age, COMVAX was generally well tolerated. In these studies, infants received COMVAX with licensed pediatric vaccines (n=1745) or investigational vaccines (n=1816). Serious adverse experience data were available for all 3561 infants and non-serious adverse experience data were available for a subset of 1678 infants. Pivotal Immunogenicity and Safety Study
In the pivotal, randomized, multicenter study, 882 infants were assigned in a 3:1 ratio to receive either COMVAX or PedvaxHIB plus RECOMBIVAX HB at separate injection sites at 2, 4, and 12-15 months of age. Children may have also received routine pediatric immunizations. The children were monitored daily for five days after each injection for injection-site and systemic adverse experiences. During this time, adverse experiences in infants who received COMVAX were generally similar in type and frequency to those observed in infants who received PedvaxHIB plus RECOMBIVAX HB.
The most frequently cited events were mild, transient signs and symptoms of inflammation at the injection site (i.e., pain/soreness, erythema, and swelling/induration), somnolence, and irritability, all of which were prompted for on report cards filled out by parents of vaccinated children. Table 3 summarizes the frequencies of injection-site and systemic adverse experiences within five days of vaccination that were reported among >/=1.0% of children in this pivotal trial.
Table 3
Local Reactions and Systemic Complaints Within 5 Days After Injection Reported to Occur in >/=1.0% **/* of Children
Given a 3-Dose Course of COMVAX Compared to These Events in Children Given Concomitant Injections of
PedvaxHIB and RECOMBIVAX HB
|
|
|
|
Injection 1 **/** |
|
|
Injection 2 **/** |
|
|
Injection 3
|
|
|
|
|
PedvaxHIB
and
RECOMBIVAX
|
|
|
PedvaxHIB
and
RECOMBIVAX
|
|
|
PedvaxHIB
and
RECOMBIVAX
|
|
Event
|
COMVAX®
(N=660)
%
|
HB ***
(N=221)
%
|
COMVAX®
(N=645)
%
|
HB ***
(N=213)
%
|
COMVAX®
(N=593)
%
|
HB ***
(N=193)
%
|
| Injection Site Reactions |
|
|
|
|
|
|
|
|
|
|
|
|
|
Pain/Soreness *
|
34.5
|
37.6
|
24.3
|
25.8
|
23.9
|
21.2
|
|
Erythema (>1 in.) *
|
22.4 (2.7) |
25.8 (2.7) |
25.7 (1.4) |
23.5 (3.3) |
27.2 (3.0) |
24.4 (1.6) |
|
Swelling/Induration (>1 in.) *
|
27.6 (3.0) |
33.5 (4.1) |
30.4 (2.9) |
31.0 (3.8) |
27.2 (3.2) |
29.5 (4.1) |
| Systemic Complaints |
|
|
|
|
|
|
|
|
|
|
|
|
|
Irritability *
|
57
|
.0
|
46
|
.6
|
50
|
.7
|
44
|
.1
|
32
|
.2
|
29
|
.0
|
|
Somnolence *
|
49
|
.5
|
47
|
.1
|
37
|
.4
|
31
|
.9
|
21
|
.1
|
22
|
.3
|
|
Crying--
|
|
|
|
|
|
|
|
|
|
|
|
|
|
unusual, high pitched *
|
10
|
.6
|
8
|
.6
|
6
|
.7
|
2
|
.3
|
2
|
.9
|
3
|
.6
|
|
not otherwise specified
|
2
|
.3
|
2
|
.3
|
1
|
.4
|
2
|
.3
|
0
|
.7
|
1
|
.6
|
|
prolonged (>4 hrs.) *
|
2
|
.4
|
2
|
.3
|
0
|
.8
|
1
|
.4
|
0
|
.2
|
0
|
|
|
Anorexia
|
3
|
.9
|
2
|
.3
|
2
|
.0
|
0
|
.9
|
0
|
.8
|
0
|
.5
|
|
Vomiting
|
2
|
.1
|
1
|
.8
|
2
|
.5
|
0
|
.9
|
1
|
.0
|
1
|
.6
|
|
Otitis media
|
0
|
.5
|
0
|
|
2
|
.0
|
1
|
.4
|
2
|
.7
|
1
|
.6
|
|
Fever (°F, rectal equiv.) **
|
|
|
|
|
|
|
|
|
|
|
|
|
|
101.0-102.9
|
14
|
.2
|
11
|
.9
|
13
|
.8
|
12
|
.2
|
10
|
.5
|
6
|
.4
|
|
>/=103.0
|
0
|
.8
|
0
|
|
1
|
.6
|
1
|
.4
|
2
|
.7
|
4
|
.3
|
|
Diarrhea
|
1
|
.7
|
1
|
.8
|
0
|
.8
|
0
|
.9
|
2
|
.2
|
0
|
.5
|
|
Upper respiratory infection
|
0
|
.5
|
0
|
.5
|
1
|
.1
|
0
|
.9
|
1
|
.3
|
0
|
.5
|
|
Rash
|
0
|
.8
|
0
|
|
0
|
.9
|
0
|
|
0
|
.8
|
0
|
.5
|
|
Rhinorrhea
|
0
|
.2
|
0
|
|
1
|
.1
|
0
|
.9
|
1
|
.3
|
2
|
.1
|
|
Respiratory congestion
|
0
|
.6
|
0
|
.5
|
1
|
.2
|
0
|
.9
|
0
|
.3
|
0
|
.5
|
|
Cough
|
0
|
.2
|
0
|
|
0
|
.9
|
0
|
.5
|
0
|
.2
|
1
|
.0
|
|
Candidiasis, oral
|
0
|
.3
|
0
|
.5
|
0
|
.8
|
0
|
|
0
|
.2
|
0
|
|
|
Rash, diaper
|
0
|
.5
|
0
|
.5
|
0
|
.5
|
0
|
.9
|
0
|
.2
|
0
|
|
|
**/* Overall frequency of each event listed above is >/=1% even though the frequency after a given dose may be <1%. |
|
**/** Most children received DTP and OPV concomitantly with the first two doses of COMVAX or PedvaxHIB and RECOMBIVAX HB.
|
|
* Events prompted for on Vaccination Report Card given to parents/guardians of vaccinees. |
|
** N for injections 1, 2, and 3 equals 655, 639, and 588, respectively, for COMVAX; N for injections 1, 2, and 3 equals 218, 213, and 187, respectively, for PedvaxHIB and RECOMBIVAX HB.
|
|
*** Injection site reactions for PedvaxHIB and RECOMBIVAX HB based on occurrence with either of the monovalent components. |
|
Infants Previously Vaccinated with Hepatitis B Vaccine
In a group of infants (N=126) given a three-dose course of COMVAX after previously receiving a dose of Hepatitis B Vaccine (Recombinant) at or shortly after birth, the type, frequency, and severity of adverse experiences did not appear to be greater than those observed in infants in the pivotal study who did not receive hepatitis B vaccine at birth.
Infants 6 Weeks to 15 Months of Age
In clinical trials, 3285 doses of COMVAX were administered to 1678 infants who were monitored for injection-site and systemic adverse experiences from Days 0 to 5 after each injection of vaccine. Of these, 855 infants had safety data following vaccination at approximately 2 months of age, 836 infants at approximately 4 months of age and 1573 infants at 12 to 15 months of age. The most frequently reported adverse experiences (>/=1% of subjects for at least one injection), without regard to causality are listed in decreasing order of frequency within each body system:
Injection Site Reactions: Pain/tenderness/soreness, swelling/induration, erythema; Body as a Whole: Fever; Digestive System: Anorexia, diarrhea, vomiting; Nervous System/Psychiatric: Irritability, somnolence, crying; Respiratory System: Upper respiratory infection, rhinorrhea, cough, rhinitis; Skin: Rash; Special Senses: Otitis media.
Post-Marketing Experience
As with any vaccine, there is the possibility that broad use of COMVAX could reveal adverse experiences not observed in clinical trials. The following additional adverse reactions have been reported with the use of the marketed vaccine.
Hypersensitivity
Anaphylaxis, angioedema, urticaria, erythema multiforme
Hematologic
Thrombocytopenia
Nervous System
Seizure, febrile seizures
Potential Adverse Effects
In addition, a variety of adverse effects have been reported with marketed use of either PedvaxHIB or RECOMBIVAX HB in infants and children through 71 months of age. These adverse effects are listed below. PedvaxHIB Hematologic/Lymphatic
Lymphadenopathy
Skin
Sterile injection-site abscess; pain at the injection site
RECOMBIVAX HB Hypersensitivity
Symptoms of hypersensitivity including reports of rash, pruritus, edema, arthralgia, dyspnea, hypotension, and ecchymoses
Cardiovascular System
Tachycardia; syncope
Digestive System
Elevation of liver enzymes
Hematologic
Increased erythrocyte sedimentation rate
Musculoskeletal System
Arthritis
Nervous System
Bell's Palsy; Guillain-Barré Syndrome
Psychiatric/Behavioral
Agitation; somnolence; irritability
Skin
Stevens-Johnson Syndrome; alopecia
Special Senses
Conjunctivitis; visual disturbances
Adverse Event Reporting
Patients, parents and guardians should be instructed to report any serious adverse reactions to their health-care provider who in turn should report such events to the U.S. Department of Health and Human Services through the Vaccine Adverse Event Reporting System (VAERS), 1-800-822-7967. The health-care provider should inform the parent or guardian of the National Vaccine Injury Compensation Program (NVICP), 1-888-338-2382 or http://www.hrsa.dhhs.gov/bhpr/vicp.
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