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
Prevnar Side Effects, and Drug Interactions - Pneumococcal 7-valent Conjugate
Prevnar Side Effects, and Drug Interactions - Pneumococcal 7-valent Conjugate
SIDE EFFECTS
Pre-Licensure Clinical Trial Experience
The majority of the safety experience with Prevnar®comes
from the NCKP Efficacy Trial in which 17,066 infants received 55,352 doses of
Prevnar®, along with other routine childhood vaccines through
April 1998 (see CLINICAL PHARMACOLOGY section).
The number of Prevnar®recipients in the safety analysis differs
from the number included in the efficacy analysis due to the different lengths
of follow-up for these study endpoints. Safety was monitored in this study using
several modalities. Local reactions and systemic events occurring within 48
hours of each dose of vaccine were ascertained by scripted telephone interview
on a randomly selected subset of approximately 3,000 children in each vaccine
group. The rate of relatively rare events requiring medical attention was evaluated
across all doses in all study participants using automated databases. Specifically,
rates of hospitalizations within 3, 14, 30, and 60 days of immunization, and
of emergency room visits within 3, 14, and 30 days of immunization were assessed
and compared between vaccine groups for each diagnosis. Seizures within 3 and
30 days of immunization were ascertained across multiple settings (hospitalizations,
emergency room or clinic visits, telephone interviews). Deaths and SIDS were
ascertained through April 1999. Hospitalizations due to diabetes, autoimmune
disorders, and blood disorders were ascertained through August 1999.
In Tables 8 and 9 the rate of local reactions at the Prevnar®injection
site is compared at each dose to the DTP or DTaP injection site in the same
children.
|
TABLE 8 Percentage of Subjects Reporting Local Reactions
Within 2 Days Following Immunization With Prevnar®and
DTP-HbOC* Vaccines at 2, 4, 6, and 12-15 Months of Age 24,25
|
|
Reaction
|
Dose 1
|
Dose 2
|
Dose 3
|
Dose 4
|
|
Prevnar® Site
|
DTP-HbOC Site
|
Prevnar®Site
|
DTP-HbOC Site
|
Prevnar®Site
|
DTP- HbOC Site
|
Prevnar®Site
|
DTP- HbOC Site
|
| |
N=2890
|
N=2890
|
N=2725
|
N=2725
|
N=2538
|
N=2538
|
N=599
|
N=599
|
| Erythema |
|
Any
|
12.4
|
21.9
|
14.3
|
25.1
|
15.2
|
26.5
|
12.7
|
23.4
|
|
>2.4 cm
|
1.2
|
4.6
|
1.0
|
2.9
|
2.0
|
4.4
|
1.7
|
6.4
|
|
Induration
|
|
Any
|
10.9
|
22.4
|
12.3
|
23.0
|
12.8
|
23.3
|
11.4
|
20.5
|
|
>2.4 cm
|
2.6
|
7.2
|
2.4
|
5.6
|
2.9
|
6.7
|
2.8
|
7.2
|
|
Tenderness
|
|
Any
|
28.0
|
36.4
|
25.2
|
30.5
|
25.6
|
32.8
|
36.5
|
45.1
|
|
Interfered with limb movement
|
7.9
|
10.7
|
7.4
|
8.4
|
7.8
|
10.0
|
18.5
|
22.2
|
|
* If Hep B vaccine was administered simultaneously, it
was administered into the same limb as the DTP-HbOC vaccine. If reactions
occurred at either or both sites on that limb, the more severe reaction
was recorded.
|
|
p<0.05 when
Prevnar®site compared to the DTP-HbOC site using the sign
test.
|
|
TABLE 9 Percentage of Subjects Reporting Local Reactions
Within 2 Days Following Immunization With Prevnar®*
and DTaP Vaccines at 2, 4, 6, and 12-15 Months of Age24,25
|
|
Reaction
|
Dose 1
|
Dose 2
|
Dose 3
|
Dose 4
|
| |
|
Prevnar®Site
|
DtaP Site
|
Prevnar®Site
|
DtaP Site
|
Prevnar®Site
|
DtaP Site
|
Prevnar®Site
|
DtaP Site
|
| |
|
| |
|
N=693
|
N=693
|
N=526
|
N=526
|
N=422
|
N=422
|
N=165
|
N=165
|
|
Erythema
|
| |
Any
|
10.0
|
6.7§
|
11.6
|
10.5
|
13.8
|
11.4
|
10.9
|
3.6§
|
| |
2.4 cm
|
1.3
|
0.4§
|
0.6
|
0.6
|
1.4
|
1.0
|
3.6
|
0.6
|
|
Induration
|
|
|
|
|
|
|
|
|
| |
Any
|
9.8
|
6.6§
|
12.0
|
10.5
|
10.4
|
10.4
|
12.1
|
5.5§
|
| |
2.4 cm
|
1.6
|
0.9
|
1.3
|
1.7
|
2.4
|
1.9
|
5.5
|
1.8
|
|
Tenderness
|
| |
Any
|
17.9
|
16.0
|
19.4
|
17.3
|
14.7
|
13.1
|
23.3
|
18.4
|
| |
Interfered with limb movement
|
3.1
|
1.8§
|
4.1
|
3.3
|
2.9
|
1.9
|
9.2
|
8.0
|
|
* HbOC was administered in the same limb as Pneumococcal
7-valent Conjugate Vaccine (Diphtheria CRM197 Protein), Prevnar®.
If reactions occurred at either or both sites on that
limb, the more severe reaction was recorded.
|
|
If Hep B vaccine was administered simultaneously,
it was administered into the same limb as DTaP. If reactions occurred
at either or both sites on that limb, the more severe reaction was recorded.
|
|
Subjects may have received DTP or a mixed
DTP/DTaP regimen for the primary series. Thus, this is the 4th dose
of a pertussis vaccine, but not a 4th dose of DTaP.
|
|
§ p<0.05 when
Prevnar ®site compared to DTaP site using the sign test.
|
Table 10 presents the rates of local reactions in previously
unvaccinated older infants and children.
|
TABLE 10 Percentage of Subjects Reporting Local Reactions
Within 3 Days of Immunization With Prevnar® in Infants
and Children from 7 Months Through 9 Years of Age 35
|
|
Age at 1st Vaccination
|
7 - 11 Mos.
|
12 - 23 Mos.
|
24-35 Mos.
|
36 - 59 Mos.
|
5 - 9 Yrs.
|
|
Study No.
|
118-12
|
118-16
|
118-9* 118-18
|
118-18
|
118-18
|
118-18
|
|
Dose Number
|
1
|
2
|
3
|
1
|
2
|
3
|
1
|
1
|
2
|
1
|
1
|
1
|
|
Number of Subjects
|
54
|
51
|
24
|
81
|
76
|
50
|
60
|
114
|
117
|
46
|
48
|
49
|
|
Reaction
|
|
Erythema
|
| |
Any
|
16.7
|
11.8
|
20.8
|
7.4
|
7.9
|
14.0
|
48.3
|
10.5
|
9.4
|
6.5
|
29.2
|
24.2
|
| |
>2.4 cm
|
1.9
|
0.0
|
0.0
|
0.0
|
0.0
|
0.0
|
6.7
|
1.8
|
1.7
|
0.0
|
8.3
|
7.1
|
|
Induration
|
|
|
|
|
|
|
|
|
|
|
|
|
| |
Any
|
16.7
|
11.8
|
8.3
|
7.4
|
3.9
|
10.0
|
48.3
|
8.8
|
6.0
|
10.9
|
22.9
|
25.5
|
| |
>2.4 cm
|
3.7
|
0.0
|
0.0
|
0.0
|
0.0
|
0.0
|
3.3
|
0.9
|
0.9
|
2.2
|
6.3
|
9.3
|
|
Tenderness
|
| |
Any
|
13.0
|
11.8
|
12.5
|
8.6
|
10.5
|
12.0
|
46.7
|
25.7
|
26.5
|
41.3
|
58.3
|
82.8
|
| |
Interfered with limb movement§
|
1.9
|
2.0
|
4.2
|
1.2
|
1.3
|
0.0
|
3.3
|
6.2
|
8.5
|
13.0
|
20.8
|
39.4
|
|
* For 118-9, 2 of 60 subjects were ³24
months of age.
|
|
For 118-12, dose 3 was administered at 15
- 18 mos. of age. For 118-16, dose 3 was administered at 12 - 15 mos.
of age.
|
|
For 118-16 and 118-18, ³2
cm.
|
|
§ Tenderness interfering with limb movement.
|
Tables 11 and 12 present the rates of systemic events observed
in the efficacy study when Prevnar®was administered concomitantly
with DTP or DTaP.
|
TABLE 11 Percentage of Subjects* Reporting Systemic
Events Within 2 Days Following Immunization With Prevnar®
or Control Vaccine Concurrently With DTP-HbOC Vaccine at 2,
4, 6, and 12-15 Months of Age24,25
|
| |
Reaction
|
Dose 1
|
Dose 2
|
Dose 3
|
Dose 4
|
| |
|
Prevnar®
|
Control
|
Prevnar®
|
Control
|
Prevnar®
|
Control
|
Prevnar®
|
Control
|
| |
|
N=2998
|
N=2982
|
N=2788
|
N=2761
|
N=2596
|
N=2591
|
N=709
|
N=733
|
|
Fever
|
|
|
|
|
|
|
|
|
| |
³38.0°C
|
33.4
|
28.7
|
34.7
|
27.4
|
40.6
|
32.4
|
41.9
|
36.9
|
| |
>39.0°C
|
1.3
|
1.3
|
3.0
|
1.6
|
5.3
|
3.4
|
4.5
|
4.5
|
|
Irritability
|
71.3
|
67.9
|
69.4
|
63.8
|
68.9
|
61.6
|
72.8
|
65.8
|
|
Drowsiness
|
49.2
|
50.6
|
32.5
|
33.6
|
25.9
|
23.4
|
21.3
|
22.7
|
|
Restless Sleep
|
18.1
|
17.9
|
27.3
|
24.3
|
33.3
|
30.1
|
29.9
|
28.0
|
|
DecreasedAppetite
|
24.7
|
23.6
|
22.8
|
20.3
|
27.7
|
25.6
|
33.0
|
27.4
|
|
Vomiting
|
17.9
|
14.9
|
16.2
|
14.4
|
15.5
|
12.7
|
9.6
|
6.8
|
|
Diarrhea
|
12.0
|
10.7
|
10.9
|
9.9
|
11.5
|
10.4
|
12.1
|
11.2
|
|
Urticaria-like Rash
|
0.7
|
0.6
|
0.8
|
0.8
|
1.4
|
1.1
|
1.4
|
0.8
|
|
* Approximately 90% of subjects received prophylactic
or therapeutic antipyretics within 48 hours of each dose.
|
|
Investigational meningococcal group C conjugate
vaccine (MnCC).
|
|
p<0.05 when
Prevnar® compared to control group using a Chi-Square test.
|
|
TABLE 12 Percentage of Subjects* Reporting Systemic
Events Within 2 Days Following Immunization With Prevnar®or
Control Vaccine Concurrently With DTaP Vaccine at 2, 4, 6,
and 12-15 Months of Age 24,25
|
|
Reaction
|
Dose 1
|
Dose 2
|
Dose 3
|
Dose 4
|
| |
|
Prevnar®
|
Control
|
Prevnar®
|
Control
|
Prevnar®
|
Control
|
Prevnar®
|
Control
|
| |
|
N=710
|
N=711
|
N=559
|
N=508
|
N=461
|
N=414
|
N=224
|
N=230
|
|
Fever
|
|
|
|
|
|
|
|
|
| |
³38.0°C
|
15.1
|
9.4§
|
23.9
|
10.8§
|
19.1
|
11.8§
|
21.0
|
17.0
|
| |
>39.0°C
|
0.9
|
0.3
|
2.5
|
0.8§
|
1.7
|
0.7
|
1.3
|
1.7
|
|
Irritability
|
48.0
|
48.2
|
58.7
|
45.3§
|
51.2
|
44.8
|
44.2
|
42.6
|
|
Drowsiness
|
40.7
|
42.0
|
25.6
|
22.8
|
19.5
|
21.9
|
17.0
|
16.5
|
|
Restless Sleep
|
15.3
|
15.1
|
20.2
|
19.3
|
25.2
|
19.0§
|
20.2
|
19.1
|
|
Decreased Appetite
|
17.0
|
13.5
|
17.4
|
13.4
|
20.7
|
13.8§
|
20.5
|
23.1
|
|
Vomiting
|
14.6
|
14.5
|
16.8
|
14.4
|
10.4
|
11.6
|
4.9
|
4.8
|
|
Diarrhea
|
11.9
|
8.4§
|
10.2
|
9.3
|
8.3
|
9.4
|
11.6
|
9.2
|
|
Urticaria-like Rash
|
1.4
|
0.3§
|
1.3
|
1.4
|
0.4
|
0.5
|
0.5
|
1.7
|
|
* Approximately 75% of subjects received prophylactic
or therapeutic antipyretics within 48 hours of each dose.
|
|
Investigational meningococcal group C conjugate
vaccine (MnCC).
|
|
Most of these children had received DTP
for the primary series. Thus, this is a 4th dose of a pertussis
vaccine, but not of DTaP.
|
|
§ p0.05 when Prevnar® compared
to control group using a Chi-Square test.
|
Table 13 presents results from a second study (Manufacturing
Bridging Study) conducted at Northern California and Denver Kaiser sites, in
which children were randomized to receive one of three lots of Pneumococcal
7-valent Conjugate Vaccine (Diphtheria CRM197 Protein),
Prevnar®, with concomitant vaccines including
DTaP, or the same concomitant vaccines alone. Information was ascertained by
scripted telephone interview, as described above.
|
TABLE 13 Percentage of Subjects* Reporting Systemic
Reactions Within 3 Days Following Immunization With Prevnar®
, DTaP, HbOC, Hep B, and IPV vs. Control In Manufacturing
Bridging Study 29
|
|
Reaction
|
Dose 1
|
Dose 2
|
Dose 3
|
| |
Prevnar®
|
Control
|
Prevnar®
|
Control
|
Prevnar®
|
Control
|
|
N=498
|
N=108
|
N=452
|
N=99
|
N=445
|
N=89
|
|
Fever
|
| |
³38.0°C
|
21.9
|
10.2
|
33.6
|
17.2
|
28.1
|
23.6
|
| |
>39.0°C
|
0.8
|
0.9
|
3.8
|
0.0
|
2.2
|
0.0
|
|
Irritability
|
59.7
|
60.2
|
65.3
|
52.5
|
54.2
|
50.6
|
|
Drowsiness
|
50.8
|
38.9
|
30.3
|
31.3
|
21.2
|
20.2
|
|
Decreased Appetite
|
19.1
|
15.7
|
20.6
|
11.1
|
20.4
|
9.0
|
|
* Approximately 72% of subjects received prophylactic
or therapeutic antipyretics within 48 hours of each dose.
|
|
Control group received concomitant vaccines
only in the same schedule as the Prevnar®group (DTaP, HbOC
at dose 1, 2, 3; IPV at doses 1 and 2; Hep B at doses 1 and 3).
|
|
p<0.05 when
Prevnar®compared to control group using Fishers Exact
test.
|
Fever (³38.0°C) within 48 hours
of a vaccine dose was reported by a greater proportion of subjects who received
Prevnar®, compared to control (investigational meningococcal
group C conjugate vaccine [MnCC]), after each dose when administered concurrently
with DTP-HbOC or DTaP in the efficacy study. In the Manufacturing Bridging Study,
fever within 48-72 hours was also reported more commonly after each dose compared
to infants in the control group who received only recommended vaccines. When
administered concurrently with DTaP in either study, fever rates among Prevnar®recipients
ranged from 15% to 34%, and were greatest after the 2nd dose.
Table 14 presents the frequencies of systemic reactions in
previously unvaccinated older infants and children.
|
TABLE 14 Percentage of Subjects Reporting Systemic
Reactions Within 3 Days of Immunization With Prevnar®in
Infants and Children from 7 Months Through 9 Years of Age35
|
|
Age at 1st Vaccination
|
7 - 11 Mos.
|
12 - 23 Mos
|
24 - 35 Mos.
|
36 - 59 Mos.
|
5 - 9 Yrs.
|
|
Study No.
|
118-12
|
118-16
|
118-9*
|
118-18
|
118-18
|
118-18
|
118-18
|
|
Dose Number
|
1
|
2
|
3
|
1
|
2
|
3
|
1
|
1
|
2
|
1
|
1
|
1
|
|
Number of Subjects
|
54
|
51
|
24
|
85
|
80
|
50
|
60
|
120
|
117
|
47
|
52
|
100
|
|
Reaction
|
|
Fever
|
|
³38.0°C
|
20.8
|
21.6
|
25.0
|
17.6
|
18.8
|
22.0
|
36.7
|
11.7
|
6.8
|
14.9
|
11.5
|
7.0
|
|
>39.0°C
|
1.9
|
5.9
|
0.0
|
1.6
|
3.9
|
2.6
|
0.0
|
4.4
|
0.0
|
4.2
|
2.3
|
1.2
|
|
Fussiness
|
29.6
|
39.2
|
16.7
|
54.1
|
41.3
|
38.0
|
40.0
|
37.5
|
36.8
|
46.8
|
34.6
|
29.3
|
|
Drowsiness
|
11.1
|
17.6
|
16.7
|
24.7
|
16.3
|
14.0
|
13.3
|
18.3
|
11.1
|
12.8
|
17.3
|
11.0
|
|
Decreased Appetite
|
9.3
|
15.7
|
0.0
|
15.3
|
15.0
|
30.0
|
25.0
|
20.8
|
16.2
|
23.4
|
11.5
|
9.0
|
|
* For 118-9, 2 of 60 subjects were ³24
months of age.
|
|
For 118-12, dose 3 was administered at 15
- 18 mos. of age. For 118-16, dose 3 was administered at 12 - 15 mos.
of age.
|
Of the 17,066 subjects who received at least one dose of Prevnar®in
the efficacy trial, there were 24 hospitalizations (for 29 diagnoses) within
3 days of a dose from October 1995 through April 1998. Diagnoses were as follows:
bronchiolitis (5); congenital anomaly (4); elective procedure, UTI (3 each);
acute gastroenteritis, asthma, pneumonia (2 each); aspiration, breath holding,
influenza, inguinal hernia repair, otitis media, febrile seizure, viral syndrome,
well child/reassurance (1 each). There were 162 visits to the emergency room
(for 182 diagnoses) within 3 days of a dose from October 1995 through April
1998. Diagnoses were as follows: febrile illness (20); acute gastroenteritis
(19); trauma, URI (16 each); otitis media (15); well child (13); irritable child,
viral syndrome (10 each); rash (8); croup, pneumonia (6 each); poisoning/ingestion
(5); asthma, bronchiolitis (4 each); febrile seizure, UTI (3 each); thrush,
wheezing, breath holding, choking, conjunctivitis, inguinal hernia repair, pharyngitis
(2 each); colic, colitis, congestive heart failure, elective procedure, hives,
influenza, ingrown toenail, local swelling, roseola, sepsis (1 each).24,25
In the large-scale efficacy study, urticaria-like rash was
reported in 0.4%-1.4% of children within 48 hours following immunization with
Prevnar®administered concurrently with other routine childhood
vaccines. Urticaria-like rash was reported in 1.3%-6% of children in the period
from 3 to 14 days following immunization, and was most often reported following
the fourth dose when it was administered concurrently with MMR vaccine. Based
on limited data, it appears that children with urticaria-like rash after a dose
of Prevnar®may be more likely to report urticaria-like rash following
a subsequent dose of Prevnar®.
One case of a hypotonic-hyporesponsive episode (HHE) was reported
in the efficacy study following Prevnar®and concurrent DTP vaccines
in the study period from October 1995 through April 1998. Two additional cases
of HHE were reported in four other studies and these also occurred in children
who received Prevnar®concurrently with DTP vaccine. 31,34
In the Kaiser efficacy study in which 17,066 children received
a total of 55,352 doses of Prevnar®and 17,080 children received
a total of 55,387 doses of the control vaccine
(investigational meningococcal group C conjugate vaccine [MnCC]),
seizures were reported in 8 Prevnar®recipients and 4 control
vaccine recipients within 3 days of immunization from October 1995 through April
1998. Of the 8 Prevnar®recipients, 7 received concomitant DTP-containing
vaccines and one received DTaP. Of the 4 control vaccine recipients, 3 received
concomitant DTP-containing vaccines and one received DTaP.24,25 In
the other 4 studies combined, in which 1,102 children were immunized with 3,347
doses of Prevnar®and 408 children were immunized with 1,310 doses
of control vaccine (either investigational meningococcal group C conjugate vaccine
[MnCC] or concurrent vaccines), there was one seizure event reported within
3 days of immunization.32 This subject received Prevnar®concurrent
with DTaP vaccine.
Twelve deaths (5 SIDS and 7 with clear alternative cause) occurred
among subjects receiving Prevnar®, of which 11 (4 SIDS and 7
with clear alternative cause) occurred in the Kaiser efficacy study from October
1995 until April 20, 1999. In comparison, 21 deaths (8 SIDS, 12 with clear alternative
cause and one SIDS-like death in an older child), occurred in the control vaccine
group during the same time period in the efficacy study.24,25,29 The
number of SIDS deaths in the efficacy study from October 1995 until April 20,
1999 was similar to or lower than the age and season-adjusted expected rate
from the California State data from 1995-1997 and are presented in Table 15.
|
TABLE 15 Age and Season-Adjusted Comparison of SIDS Rates
in the NCKP Efficacy Trial With the Expected Rate from the California
State Data for 1995-1997 24,25
|
|
Vaccine
|
<One Week After
Immunization
|
£Two Weeks After Immunization
|
£One Month After Immunization
|
£One Year After Immunization
|
| |
Exp
|
Obs
|
Exp
|
Obs
|
Exp
|
Obs
|
Exp
|
Obs
|
|
Prevnar®
|
1.06
|
1
|
2.09
|
2
|
4.28
|
2
|
8.08
|
4
|
|
Control*
|
1.06
|
2
|
2.09
|
3
|
4.28
|
3
|
8.08
|
8
|
|
* Investigational meningococcal group C conjugate vaccine
(MnCC).
|
|
Does not include one additional case of
SIDS-like death in a child older than the usual SIDS age (448 days).
|
In a review of all hospitalizations that occurred between October
1995 and August 1999 in the efficacy study for the specific diagnoses of aplastic
anemia, autoimmune disease, autoimmune hemolytic anemia, diabetes mellitus,
neutropenia, and thrombocytopenia, the numbers of such cases were equal to or
less than the expected numbers based on the 1995 Kaiser Vaccine Safety Data
Link (VSD) data set.
Overall, the safety of Prevnar®was evaluated
in a total of five clinical studies in the US in which 18,168 infants and children
received a total of 58,699 doses of vaccine at 2, 4, 6, and 12-15 months of
age. In addition, the safety of Prevnar®was evaluated in 831
Finnish infants using the same schedule, and the overall safety profile was
similar to that in US infants. The safety of Prevnar®was also
evaluated in 560 children from 4 ancillary studies in the US who started immunization
at 7 months to 9 years of age. Tables 16 and 17 summarize systemic reactogenicity
data within 2 or 3 days across 4,748 subjects in US studies (13,039 infant doses
and 1,706 toddler doses) for whom these data were collected and according to
the pertussis vaccine administered concurrently.
|
TABLE 16 Overall Percentage of Doses Associated With
Systemic Events Within 2 or 3 Days For The US Efficacy Study and All US
Ancillary Studies When Prevnar®Administered To Infants
As a Primary Series at 2, 4, and 6 Months of Age24,25, 29,31,32,33
|
|
Systemic Event
|
Prevnar® Concurrently With DTP-HbOC(9,191
Doses)*
|
Prevnar® Concurrently With DTaP and HbOC(3,848
Doses)
|
DTaP and HbOC Control(538 Doses)
|
|
Fever
|
| |
³38.0°C
|
35.6
|
21.1
|
14.2
|
| |
>39.0°C
|
3.1
|
1.8
|
0.4
|
|
Irritability
|
69.1
|
52.5
|
45.2
|
|
Drowsiness
|
36.9
|
32.9
|
27.7
|
|
Restless Sleep
|
25.8
|
20.6
|
22.3
|
|
Decreased Appetite
|
24.7
|
18.1
|
13.6
|
|
Vomiting
|
16.2
|
13.4
|
9.8
|
|
Diarrhea
|
11.4
|
9.8
|
4.4
|
|
Urticaria-like Rash
|
0.9
|
0.6
|
0.3
|
|
* Total from which reaction data are available varies
between reactions from 8,874-9,191 doses. Data from studies 118-3, 118-7,
118-8.
|
|
Total from which reaction data are available
varies between reactions from 3,121-3,848 doses. Data from studies 118-8,
118-12, 118-16.
|
|
Total from which reaction data are available
varies between reactions from 295-538 doses. Data from studies 118-12
and 118-16.
|
|
TABLE 17 Overall Percentage of Doses Associated With
Systemic Events Within 2 or 3 Days For The US Efficacy Study and All US
Ancillary Studies When Prevnar® Administered To
Toddlers as a Fourth Dose At 12 to 15 Months of Age 24,25,31
|
|
Systemic Event
|
Prevnar®Concurrently With DTP-HbOC (709
Doses)*
|
Prevnar®Concurrently With DTaP and HbOC
(270 Doses)
|
Prevnar®Only No Concurrent Vaccines
(727 Doses)
|
|
Fever
|
| |
³38.0°C
|
41.9
|
19.6
|
13.4
|
| |
>39.0°C
|
4.5
|
1.5
|
1.2
|
|
Irritability
|
72.8
|
45.9
|
45.8
|
|
Drowsiness
|
21.3
|
17.5
|
15.9
|
|
Restless Sleep
|
29.9
|
21.2
|
21.2
|
|
Decreased Appetite
|
33.0
|
21.1
|
18.3
|
|
Vomiting
|
9.6
|
5.6
|
6.3
|
|
Diarrhea
|
12.1
|
13.7
|
12.8
|
|
Urticaria-like Rash
|
1.4
|
0.7
|
1.2
|
|
* Total from which reaction data are available varies
between reactions from 706-709 doses. Data from study 118-8.
|
|
Total from which reaction data are available
varies between reactions from 269-270 doses. Data from studies 118-7 and
118-8.
|
|
Total from which reaction data are available
varies between reactions from 725-727 doses. Data from studies 118-7 and
118-8.
|
With vaccines in general, including Pneumococcal 7-valent Conjugate
Vaccine (Diphtheria CRM197 Protein), PrevnarÒ,
it is not uncommon for patients to note within 48 to 72 hours at or around the
injection site the following minor reactions: edema; pain or tenderness; redness,
inflammation or skin discoloration; mass; or local hypersensitivity reaction.
Such local reactions are usually self-limited and require no therapy.
As with other aluminum-containing vaccines, a nodule may occasionally
be palpable at the injection site for several weeks.42
Postmarketing Experience
Additional adverse reactions identified from postmarketing
experience are listed below:
Administration site conditions: injection site dermatitis,
injection site urticaria, injection site pruritus
Blood and lymphatic system disorders: lymphadenopathy
localized to the region of the injection site
Immune system disorders: hypersensitivity reaction including
face edema, dyspnea, bronchospasm; anaphylactic/anaphylactoid reaction including
shock
Skin and subcutaneous tissue disorders: angioneurotic
edema, erythema multiforme
There have been spontaneous reports of apnea in temporal association
with the administration of Prevnar. In most cases Prevnar was administered concomitantly
with other vaccines including diphtheria tetanus pertussis vaccine (DTP), diphtheria
tetanus acellular pertussis vaccine (DTaP), hepatitis B vaccines, inactivated
polio vaccine (IPV), Haemophilus influenzae type b vaccine (Hib), measles-mumps-rubella
vaccine (MMR), and/or varicella vaccine. In addition, in most of the reports
existing medical conditions such as history of apnea, infection, prematurity,
and/or seizure were present.
ADVERSE EVENT REPORTING
Any suspected adverse events following immunization should
be reported by the healthcare professional to the US Department of Health and
Human Services (DHHS). The National Vaccine Injury Compensation Program requires
that the manufacturer and lot number of the vaccine administered be recorded
by the healthcare professional in the vaccine recipients permanent medical
record (or in a permanent office log or file), along with the date of administration
of the vaccine and the name, address, and title of the person administering
the vaccine.
The US DHHS has established the Vaccine Adverse Event Reporting
System (VAERS) to accept all reports of suspected adverse events after the administration
of any vaccine including, but not limited to, the reporting of events required
by the National Childhood Vaccine Injury Act of 1986. The FDA web site is: http://www.fda.gov/cber/vaers/vaers.htm.
The VAERS toll-free number for VAERS forms and information
is 800-822-7967.43
DRUG INTERACTIONS
Children receiving therapy with immunosuppressive agents (large
amounts of corticosteroids, antimetabolites, alkylating agents, cytotoxic agents)
may not respond optimally to active immunization.37,38,40,41 (See
PRECAUTIONS, General.)
As with other intramuscular injections, Prevnar®
should be given with caution to children on anticoagulant therapy.
Simultaneous Administration with Other Vaccines
During clinical studies, Prevnar®was administered
simultaneously with DTP-HbOC or DTaP and HbOC, OPV or IPV, Hep B vaccines, MMR,
and Varicella vaccine. Thus, the safety experience with Prevnar® reflects
the use of this product as part of the routine immunization schedule.24,25,29,31,32,34
The immune response to routine vaccines when administered with
Prevnar®(at separate sites) was assessed in 3 clinical studies
in which there was a control group for comparison. Results for the concurrent
immunizations in infants are shown in Table 6 and for toddlers in Table 7. Enhancement
of antibody response to HbOC in the infant series was observed. Some suppression
of Haemophilus influenzae type b (Hib) response was seen at the 4th
dose, but over 97% of children achieved titers ³1
mg/mL. Although some inconsistent differences in
response to pertussis antigens were observed, the clinical relevance is unknown.
The response to 2 doses of IPV given concomitantly with Prevnar®,
assessed 3 months after the second dose, was equivalent to controls for poliovirus
Types 2 and 3, but lower for Type 1. MMR and Varicella immunogenicity data from
controlled clinical trials with concurrent administration of Prevnar®are
not available.
|
TABLE 6 Concurrent Administration of Prevnar®With
Other Vaccines to Infants in Non-Efficacy Studies 29,32
|
|
Antigen*
|
GMC*
|
% Responders
|
Study
|
Vaccine Schedule
|
N
|
|
| |
Prevnar®
|
Control§
|
Prevnar®
|
Control§
|
|
(mo.)
|
Prevnar®
|
Control§
|
|
Hib
|
6.2
|
4.4
|
99.5, 88.3
|
97.0, 88.1
|
118-12
|
2, 4, 6
|
214
|
67
|
|
Diphtheria
|
0.9
|
0.8
|
100
|
97.0
|
|
|
|
|
|
Tetanus
|
3.5
|
4.1II
|
100
|
100
|
|
|
|
|
|
PT
|
19.1
|
17.8
|
74.0
|
69.7
|
|
|
|
|
|
FHA
|
43.8
|
46.7
|
66.4
|
69.7
|
|
|
|
|
|
Pertactin
|
40.1
|
50.9
|
65.6
|
77.3
|
|
|
|
|
|
Fimbriae 2
|
3.3
|
4.2
|
44.7
|
62.5ll
|
|
|
|
|
|
Hib
|
11.9
|
7.8 ll
|
100, 96.9
|
98.8, 92.8
|
118-16
|
2, 4, 6
|
159
|
83
|
|
Hep B
|
--
|
--
|
99.4
|
96.2
|
118-16
|
0, 2, 6
|
156
|
80
|
|
IPV Type 1
|
--
|
--
|
89.0
|
93.6Ά
|
118-16
|
2, 4
|
156
|
80
|
| |
Type 2
|
--
|
--
|
94.2
|
93.6
|
|
|
|
|
| |
Type 3
|
--
|
--
|
83.8
|
80.8
|
|
|
|
|
|
* Hib vaccine was HibTITER®, DTaP vaccine
was Acel-Imune®. Hib (mg/mL);
Dip, Tet (IU/mL); Pertussis Antigens (PT, FHA, Ptn, Fim) (units/mL).
|
|
Responders Hib (³
0.15 mg/mL, ³1.0
mg/mL); Dip, Tet (³0.1
IU/mL); Pertussis Antigens (PT, FHA, Ptn, Fim) [4-fold rise]; IPV (³1:10);
Hep B (³ 10 mIU/mL).
|
|
Schedule for concurrently administered vaccines;
Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM197 Protein),
Prevnar®administered at 2, 4, 6 mos.; blood for antibody assessment
attained 1 month after third dose, except for IPV (3 months post-immunization).
|
|
§ Concurrent vaccines only.
|
|
ll p<0.05 when
Prevnar®compared to control group using the following tests:
ANCOVA for GMCs in 118-12; ANOVA for GMCs in 118-16; and Fishers Exact
test for % Responders in 118-12.
|
|
Ά Lower bound of 90% CI of difference >10%.
|
|
TABLE 7 Concurrent Administration of Prevnar®With
Other Vaccines to Toddlers in a Non-Efficacy Study 31
|
|
Antigen*
|
GMC*
|
% Responders
|
Study
|
Vaccine Schedule§
|
N
|
| |
Prevnar®
|
Controlll
|
Prevnar®
|
Controlll
|
|
(mo.)
|
Prevnar®
|
Controlll
|
|
Hib
|
22.7
|
47.9Ά
|
100, 97.9
|
100, 100
|
118-7
|
12-15
|
47
|
26
|
|
Diphtheria
|
2.0
|
3.2Ά
|
100
|
100
|
|
|
|
|
|
Tetanus
|
14.4
|
18.8
|
100
|
100
|
|
|
|
|
|
PT
|
68.6
|
121.2Ά
|
68.1
|
73.1
|
|
|
|
|
|
FHA
|
29.0
|
48.2Ά
|
68.1
|
84.6
|
|
|
|
|
|
Pertactin
|
84.4
|
83.0
|
83.0
|
96.2
|
|
|
|
|
|
Fimbriae 2
|
5.2
|
3.8
|
63.8
|
50.0
|
|
|
|
|
|
* Hib vaccine was HibTITER®, DTaP vaccine
was Acel-Imune®. Hib (mg/mL);
Dip, Tet (IU/mL); Pertussis Antigens (PT, FHA, Ptn, Fim) (units/mL).
|
|
Responders = Hib
(³0.15 mg/mL, ³1.0
mg/mL); Dip, Tet (³0.1
IU/mL); Pertussis Antigens (PT, FHA, Ptn, Fim) [4-fold rise].
|
|
Children received a primary series of DTP-HbOC
(Tetramune®).
|
|
§ Blood for antibody assessment obtained 1
month after dose.
|
|
ll Concurrent vaccines only.
|
|
Ά p<0.05 when
Prevnar®compared to control group using a two-sample t-test.
|
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