A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Acthib Side Effects, and Drug Interactions - Haemophilus b Conjugate Vaccine
Acthib Side Effects, and Drug Interactions - Haemophilus b Conjugate Vaccine
NOTE: Haemophilus b Conjugate Vaccine (Tetanus Toxoid Conjugate)
- ActHIB® is
identical to Haemophilus
b Conjugate Vaccine (Tetanus Toxoid Conjugate) - OmniHIB®
(distributed by SmithKline Beecham Pharmaceuticals); and is manufactured
by Pasteur Mérieux Sérums Vaccins S.A.
More than 7,000 infants and young children (<2 years of age)
have received at least one dose
of ActHIB®
during US clinical trials.
Of these, 1,064 subjects 12 to 24 months of age who received ActHIB®
alone reported no serious or life
threatening adverse reactions.
Adverse reactions commonly associated with a first ActHIB®
immunization of children 12 to 15 months of age
who were previously unimmunized with any Haemophilus
b conjugate vaccine,
include local pain,
redness and swelling at the injection
site. Systemic reactions include fever,
irritability and lethargy. 14,18
In a multicenter trial, ActHIB®
was administered to US infants at 2, 4, and 6 months of age
concomitantly, at separate sites, with CLI D.P.
The adverse events observed are summarized in Table 5.
TABLE 5 14
|
PERCENTAGE
OF INFANTS PRESENTING WITH LOCAL OR
SYSTEMIC REACTIONS
AT 6,
24, AND 48 HOURS OF IMMUNIZATION WITH ActHIB® ADMINISTERED
SIMULTANEOUSLY,
AT SEPARATE SITES, WITH CLI DTP VACCINE
|
|
AGE AT
IMMUNIZATION
|
| REACTION
|
2 Months
(n= 365)
|
4 Months
(n= 364)
|
6 Months
(n= 365)
|
|
6 Hrs.
|
24 Hrs.
|
48 Hrs.
|
6 Hrs.
|
24 Hrs.
|
48 Hrs.
|
6 Hrs.
|
24 Hrs.
|
48 Hrs.
|
| Local
§ |
| Tenderness
|
46.3%
|
11.5%
|
2.2%
|
23.4%
|
7.4%
|
1.1%
|
19.2%
|
6.0%
|
1.1%
|
| Erythema
|
14.3%
|
4.1%
|
0.3%
|
8.8%
|
5.8%
|
0.6%
|
11.5%
|
6.9%
|
1.6%
|
| Induration
|
22.5%
|
6.3%
|
1.9%
|
12.4%
|
4.7%
|
0.8%
|
9.6%
|
3.8%
|
1.1%
|
| Systemic* |
| Fever>100.8°
F† |
20.1%
|
1.3%
|
0.6%
|
14.6%
|
6.6%
|
1.4%
|
15.7%
|
8.8%
|
0.8%
|
| Irritability
|
72.6%
|
21.9%
|
12.6%
|
48.4%
|
25.0%
|
13.2%
|
44.1%
|
25.2%
|
10.1%
|
| Drowsiness
|
57.5%
|
29.9%
|
10.4%
|
44.2%
|
18.1%
|
7.4%
|
32.6%
|
13.4%
|
2.5%
|
| Anorexia
|
15.3%
|
5.8%
|
4.9%
|
8.0%
|
5.0%
|
3.0%
|
5.5%
|
4.9%
|
2.2%
|
| Diarrhea
|
4.4%
|
6.6%
|
5.2%
|
5.0%
|
4.7%
|
4.7%
|
4.7%
|
6.3%
|
3.6%
|
| Vomiting
|
2.7%
|
4.1%
|
2.7%
|
2.5%
|
3.3%
|
2.8%
|
2.2%
|
2.7%
|
1.9%
|
| Persistent
Crying |
Percentage
of infants within 72 hours after immunization
was 1.6% after dose one,
0.6%
after dose
two, and 0.3% after dose
three.
|
§ Local
reactions were evaluated at the ActHIB®
injection site.
* The adverse reaction
profile is defined by the
concomitant use of CLI DTP vaccine.
† The
number of individuals observed at each time
point for fever
varied from 357 to 363.
In general, the rates of minor
systemic reactions after
ActHIB®
and DTP immunization
were comparable to those usually reported after DTP vaccine alone. 30,31,32,33
When ActHIB®
reconstituted with CLI whole-cell DTP was administered in infants at 2,
4, and 6 months of age, the systemic
adverse experience profile
(Table 6) was comparable to that observed when the two vaccines were given
separately (Table 5). An increase
in the rates of local reactions
was observed within the 24- hour period
after immunization. 18
TABLE 6 18
|
PERCENTAGE
OF INFANTS PRESENTING WITH LOCAL OR
SYSTEMIC REACTIONS
AT 6,
24, AND 48 HOURS OF IMMUNIZATION WITH ActHIB®
COMBINED
WITH CLI
DTP VACCINE BY RECONSTITUTION
|
|
AGE AT
IMMUNIZATION
|
| REACTION
|
2 Months
(n= 204)
|
4 Months
(n= 199)
|
6 Months
(n= 200)
|
|
6 Hrs.
|
24 Hrs.
|
48 Hrs.
|
6 Hrs.
|
24 Hrs.
|
48 Hrs.
|
6 Hrs.
|
24 Hrs.
|
48 Hrs.
|
| Local
|
| Tenderness
|
47.1%
|
18.6%
|
3.4%
|
33.2%
|
17.6%
|
4.0%
|
25.0%
|
17.0%
|
3.5%
|
| Erythema
> 1" |
11.8%
|
2.5%
|
0.0%
|
11.6%
|
9.1%
|
2.5%
|
10.5%
|
13.5%
|
3.5%
|
| Induration
|
31.4%
|
17.2%
|
3.9%
|
26.1%
|
20.1%
|
7.5%
|
28.5%
|
22.5%
|
10.0%
|
| Systemic
|
| Fever
> 100.4° F |
24.6%
|
2.0%
|
0.5%
|
15.8%
|
6.1%
|
3.6%
|
13.0%
|
10.3%
|
3.1%
|
| Irritability
|
70.6%
|
22.1%
|
12.8%
|
56.8%
|
31.2%
|
19.1%
|
40.5%
|
28.2%
|
15.9%
|
| Drowsiness
|
60.3%
|
23.5%
|
11.3%
|
42.2%
|
20.6%
|
9.6%
|
30.3%
|
12.3%
|
5.6%
|
| Anorexia
|
17.7%
|
6.4%
|
2.9%
|
10.1%
|
7.5%
|
5.5%
|
5.1%
|
4.6%
|
4.1%
|
| Diarrhea
|
2.5%
|
5.4%
|
1.5%
|
3.5%
|
3.5%
|
2.5%
|
2.6%
|
4.1%
|
5.6%
|
| Vomiting
|
2.9%
|
5.4%
|
2.9%
|
3.0%
|
5.0%
|
3.0%
|
3.6%
|
3.6%
|
1.5%
|
| Persistent
Crying |
Percentage
of infants within 72 hours after immunization
was 0.0% after dose one,
0.0%
after dose
two, and 0.005% after dose
three.
|
In a third US trial when ActHIB®
was combined with DTP by reconstitution, approximately 1,450 doses were
administered to infants starting at 2 months of age. Adverse reactions
observed at 6 and 24 hours respectively after the first immunization
(n=498) were tenderness
66.9% and 30.7%; erythema
(>1") 8.6% and 2.2%; induration 38.2% and 21.7%; irritability
77.9% and 35.7%; drowsiness
63.7% and 34.1%; anorexia
26.1% and 12.9%; diarrhea
6.8% and 9.0%; and vomiting 3.4% and 3.8%. 18 One
hypotonic hyporesponsive episode (HHE) was seen in an infant
following the second dose in
this trial. This is consistent with the HHE incidence
rate observed with DTP vaccination
alone. 4
Adverse reactions associated with ActHIB®
generally subsided after 24 hours and usually do not persist beyond 48
hours after immunization.
No data are available on the safety of a booster
dose of ActHIB®
combined with CLI DTP vaccine
by reconstitution given
in 15 to 20 month old children.
In a US trial, safety of TriHIBitTM,ActHIB®
combined with Tripedia®
by reconstitution, in 110 children aged
15 to 20 months was compared to ActHIB®
given with Tripedia®
at separate sites to 110 children. All children received three doses of
Haemophilus b conjugate
vaccine (ActHIB®
or HibTITER®
)and three doses of whole-cell DTP at approximately 2, 4 and 6 months
of age.
TABLE 7 18
|
PERCENTAGE
OF 15 TO 20-MONTH-OLD
CHILDREN PRESENTING WITH LOCAL
OR SYSTEMIC
REACTIONS AT 6, 24 AND 48 HOURS OF IMMUNIZATION WITH TriHIBitTM
COMPARED
TO ActHIB® AND
TRIPEDIA®
GIVEN CONCOMITANTLY AT SEPARATE SITES
|
| |
6 Hrs.
Post- dose
|
24 Hrs.
Post- dose
|
48 Hrs.
Post- dose
|
| REACTION
|
Separate
Injections*
|
TriHIBitTM
|
Separate
Injections*
|
TriHIBitTM
|
Separate
Injections*
|
TriHIBitTM
|
| |
| Local |
n= 110
|
n= 110
|
n= 110
|
n= 110
|
n= 110
|
n= 110
|
| Tenderness
|
17.3/ 20.0
|
19.1
|
8.2/ 8.2
|
10.0
|
1.8/ 0.9
|
1.8
|
| Erythema
> 1" |
0.9/ 0.0
|
3.6
|
2.7/ 0.9
|
3.6
|
0.9/ 0.0
|
1.8
|
| Induration**
|
3.6/ 5.5
|
2.7
|
2.7/ 3.6
|
8.2
|
4.5/ 0.9
|
3.6
|
| Swelling
|
3.6/ 3.6
|
3.6
|
2.7/ 1.8
|
5.5
|
0.9/ 0.0
|
4.5
|
| Systemic
|
n= 103-110
|
n= 102-109
|
n= 105-110
|
n= 103-108
|
n= 104-110
|
n= 103-109
|
| Fever
> 102.2° F |
0
|
2.0
|
1.0
|
1.9
|
1.9
|
0
|
| Irritability
|
27.3
|
22.9
|
20.9
|
17.6
|
12.7
|
10.1
|
| Drowsiness
|
36.4
|
30.3
|
17.3
|
13.9
|
12.7
|
11.0
|
| Anorexia
|
12.7
|
9.2
|
10.0
|
6.5
|
6.4
|
2.8
|
| Vomiting
|
0.9
|
1.8
|
0.9
|
1.9
|
0.9
|
2.8
|
| Persistent
Cry |
0
|
0
|
0
|
0
|
0
|
0
|
| Unusual
Cry |
0
|
0
|
0
|
0
|
0
|
0.9
|
* Tripedia injection
site ActHIB®
injection site.
** Induration is defined as hardness
with or without swelling.
TriHIBitTM ActHIB®
combined with Tripedia®
by reconstitution, was administered to approximately 850 children, aged
15 to 20 months. All children received three doses of a Haemophilus
b conjugate vaccine (ActHIB®
or HibTITER®)and
three doses of whole-cell DTP at approximately 2, 4 and 6 months of age
.Local reactions were typically mild and usually resolved within the 24
to 48 hour period after immunization.
The most common local reactions
were pain and tenderness
at the injection site. Systemic
reactions occurring were usually mild and resolved within 72 hours of
immunization. The reaction rates were similar to those observed in Table
7 when TriHIBitTM ,ActHIB®
reconstituted with Tripedia®
was administered and when Tripedia®
was administered alone as a booster. 18
In a randomized, double-blind US clinical
trial, ActHIB®
was given concomitantly with DTP to more than 5,000 infants and hepatitis
B vaccine was given with DTP
to a similar number. In this large
study, deaths due to sudden infant
death syndrome
(SIDS) and other causes were observed but were not different in the two
groups. In the first 48 hours following
immunization, two definite
and three possible seizures were observed after ActHIB and DTP in comparison
with none after hepatitis
B vaccine and DTP 18 This rate
of seizures following ActHIB®
and DTP was not greater than previously reported in infants receiving
DTP alone. (Refer to product
insert for CLI DTP.) Other adverse reactions reported with administration
of other Haemophilus b
conjugate vaccines include urticaria,
seizures, hives, renal
failure and Guillain-Barré
syndrome (GBS). 18,34 A cause
and effect relationship among any of these events and the vaccination
has not been established.
When ActHIB®
was given with DTP and inactivated poliovirus
vaccine to more than 100,000
Finnish infants, the rate and
extent of serious adverse reactions were not different from those seen
when other Haemophilus
b conjugate vaccines were
evaluated in Finland (i.e. HibTITER®,ProHIBiT®)18
However, the number of subjects
studied with TriHIBitTM,ActHIB®
combined with Tripedia®
by reconstitution was
inadequate to detect rare serious adverse events.
Reporting of Adverse Events
Reporting by the parent or
guardian of all adverse events occurring after vaccine
administration should
be encouraged. Adverse events following immunization with vaccine
should be reported by the health-care provider to the US Department of
Health and Human Services (DHHS) Vaccine Adverse Event Reporting System
(VAERS). Reporting forms and information about reporting requirements
or completion of the form can
be obtained from VAERS through a toll-free number
1-800-822-7967. 26,27,28
Health-care providers also should report
these events to the Director of Medical Affairs, Connaught Laboratories,
Inc., Route 611, PO Box 187, Swiftwater, PA
18370 or call 1-800-822-2463.
DRUG INTERACTIONS
When CLI DTP is used to reconstitute ActHIB®or
Tripedia®
is used to reconstitute ActHIB®
(TriHIBitTM
)and administered to immunosuppressed persons or persons receiving immunosuppressive
therapy, the expected antibody
response may not be obtained.
Immunosuppressive therapies, including irradiation, antimetabolites,
alkylating agents, cytotoxic
drugs, and corticosteroids (used in greater than physiologic doses), may
reduce the immune
response to vaccines. Short-term
(< 2 weeks) corticosteroid
therapy or intra-articular,
bursal, or tendon injections with corticosteroids should not be immunosuppressive.
Although no specific studies
with pertussis vaccine
are available, if immunosuppressive therapy will
be discontinued shortly, it is reasonable to defer vaccination until the
patient has been off therapy
for one month; otherwise, the patient should be vaccinated while still
on therapy. 23
If ActHIB®
reconstituted with CLI DTP or ActHIB®
reconstituted with Tripedia®
(TriHIBitTM
) has been administered to persons receiving immunosuppressive therapy,
a recent injection of immunoglobulin
or having an immunodeficiency
disorder, an adequate immunologic response
may not be obtained.
In clinical trials, ActHIB®
was administered, at separate sites, concomitantly with one or more of
the following vaccines: D.P.
DTaP, Poliovirus Vaccine Live Oral (OPV), Measles, Mumps and Rubella vaccine
(MMR), Hepatitis B vaccine
and occasionally Inactivated Poliovirus Vaccine (IPV). No
impairment of the antibody
response to the individual antigens, diphtheria, tetanus
and pertussis was demonstrated
when ActHIB®
was given at the same time, at separate sites, with IPV or MMR. 18
In addition, more than 47,000 infants in Finland have received a third
dose of ActHIB®
concomitantly with MMR vaccine
with no increase in serious or
unexpected adverse events. 18
No significant impairment
of antibody response
to Measles, Mumps and Rubella was noted in 15 - 20 month-old children
who received TriHIBitTM
, ActHIB®
reconstituted with Tripedia®
concomitantly with MMR. No data
are available to the manufacturer concerning the effects on immune
response of OPV, IPV or Hepatitis
B vaccine when given concurrently
with ActHIB®
reconstituted with 0.4% Sodium Chloride or CLI DTP or ActHIB®
reconstituted with Tripedia®
TriHIBit TM.18
As with other intramuscular
injections, use with caution in patients on anticoagulant
therapy.
CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY
ActHIB®
reconstituted with CLI DTP or ActHIB®
reconstituted with Tripedia®
(TriHIBitTM)
has not been evaluated for its carcinogenic,
mutagenic potential or impairment
of fertility.)
PREGNANCY
REPRODUCTIVE STUDIES - PREGNANCY CATEGORY C
Animal reproduction
studies have not been conducted with ActHIB®
reconstituted with CLI DTP or ActHIB®
reconstituted with Tripedia®
(TriHIBitTM)
or saline diluent
(0.4% Sodium Chloride). It is also not known whether ActHIB®
reconstituted with CLI DTP or ActHIB®
reconstituted with Tripedia®
(TriHIBitTM)
or saline diluent
(0.4% Sodium Chloride) can cause
fetal harm when administered
to a pregnant woman
or can affect reproduction
capacity. ActHIB®
reconstituted with CLI DTP or ActHIB®
reconstituted with Tripedia®
(TriHIBitTM)
or saline diluent
(0.4% Sodium Chloride) is NOT recommended for use in a pregnant
woman and is not approved for
use in children 5 years of age or older.
PEDIATRIC
USE SAFETY AND EFFECTIVENESS OF TriHIBitTM,
ActHIB®
RECONSTITUTED WITH Tripedia®,
IN INFANTS BELOW THE AGE OF 15 MONTHS HAVE NOT BEEN ESTABLISHED. (See
DOSAGE AND ADMINISTRATION section.)
SAFETY AND EFFECTIVENESS OF ActHIB®
RECONSTITUTED WITH CLI DTP OR SALINE
DILUENT (0.4% SODIUM CHLORIDE) IN INFANTS BELOW THE AGE OF SIX WEEKS HAVE
NOT BEEN ESTABLISHED. (See DOSAGE AND ADMINISTRATION
section.)
top
