8.1 Adverse Reaction Overview
The safety profile is based on the analysis of three Phase 3 clinical trials (see 14 CLINICAL TRIALS). There were 4,263 adult participants who received PREVNAR 20, which included 3,639 adults that were naïve to pneumococcal vaccines, 253 that had previously received the 23-valent pneumococcal polysaccharide vaccine, (Pneumovax® 23 [PPSV23]) only, 246 that had previously received PREVNAR 13 only, and 125 that had previously received both PPSV23 and PREVNAR 13. The most commonly reported solicited adverse reactions (>10%) were vaccination-site pain/tenderness, muscle pain, fatigue, headache and joint pain. Overall, the serious adverse events (SAEs) reported were consistent with diseases and conditions observed in adults of different age groups, and none were considered to be related to the study vaccine. In all three Phase 3 trials, PREVNAR 20 demonstrated a tolerability and safety profile similar to that of PREVNAR 13.
8.2 Clinical Trial Adverse Reactions
Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials, therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use.
Solicited Adverse Reactions
The frequency of solicited adverse reactions in adults <65 years of age naïve to pneumococcal vaccination and in adults ≥65 years of age by prior pneumococcal vaccination status are shown in Table 2 and Table 3, respectively. Local adverse reactions (redness, swelling, and pain at the injection site) were prompted daily for 10 consecutive days after vaccination. Systemic adverse events (fever, fatigue, headache, muscle pain, and joint pain) were prompted daily for 7 days after vaccination.
In general, the median onset day for local reactions was between Day 1 (day of vaccination) to Day 2.5, and they resolved with a median duration of 1 to 2 days. The median onset day for most systemic events was generally between Day 1 to Day 3.5, and they resolved with a median duration of 1 to 2 days.
Table 2. Solicited Local Adverse Reactions and Systemic Events After Vaccination in Pneumococcal Vaccine Naïve Adults <65 Years of Age from Studies 1007 and 1008
Adverse Reactionb
|
Study 1007
60-64 Years of Age
|
Study 1007
50-59 Years of Age
|
Study 1007 and Study 1008
18-49 Years of Age
|
PREVNAR 20
(Na=991)
%
|
PREVNAR 13
(Na=990)
%
|
PREVNAR 20
(Na=331)
%
|
PREVNAR 13
(Na=111)
%
|
PREVNAR 20
(Na=1791)
%
|
PREVNAR 13
(Na=355)
%
|
Local Reaction
|
Redness
|
7.1
|
6.3
|
8.2
|
5.4
|
7.4
|
7.3
|
Swelling
|
8.0
|
8.3
|
8.8
|
10.8
|
9.1
|
9.9
|
Pain at injection site
|
61.6
|
59.2
|
72.5
|
69.4
|
79.2
|
77.7
|
Systemic Event
|
Fever ≥38.0℃
|
0.8
|
0.4
|
1.5
|
0.9
|
1.2
|
1.1
|
Fever >40.0℃
|
0.2
|
0
|
0.3
|
0
|
0
|
0
|
Fatigue
|
32.7
|
32.4
|
39.3
|
36.0
|
46.7
|
43.7
|
Headache
|
24.5
|
25.3
|
32.3
|
36.0
|
36.7
|
36.6
|
Muscle pain
|
42.8
|
39.8
|
49.8
|
49.5
|
62.9
|
64.8
|
Joint pain
|
12.2
|
14.5
|
15.4
|
20.7
|
16.2
|
15.2
|
- a.
- N = number of participants with any e-diary data reported after vaccination.
- b.
- Local reactions solicited within 10 days after vaccination; systemic events solicited within 7 days after vaccination.
|
Table 3. Solicited Local Adverse Reactions and Systemic Events After Vaccination in Adults ≥65 Years of Age by Prior Pneumococcal Vaccination Status from Studies 1006 and 1007
Adverse Reactionb.
|
Study 1007
|
Study 1006
|
Prior Pneumococcal Vaccination Statusc
|
Naïve
|
PPSV23
|
PREVNAR 13
|
PREVNAR 13 & PPSV23
|
PREVNAR 20 (Na=514)
%
|
PREVNAR 13 (Na=493)
%
|
PREVNAR 20
(Na=253)
%
|
PREVNAR 13
(Na=121)
%
|
PREVNAR 20
(Na=245)
%
|
PPSV23 (Na=126)
%
|
PREVNAR 20 (Na=125)
%
|
Local Reaction
|
Redness
|
7.8
|
6.1
|
7.9
|
2.5
|
8.6
|
12.7
|
4.8
|
Swelling
|
6.6
|
7.3
|
9.9
|
6.6
|
9.4
|
14.3
|
4.0
|
Pain at injection site
|
43.6
|
44.0
|
50.2
|
43.0
|
61.2
|
56.3
|
52.8
|
Systemic Event
|
Fever ≥38.0℃
|
1.2
|
1.6
|
0.8
|
0
|
0
|
1.6
|
0
|
Fever >40.0℃
|
0.6
|
0.6
|
0
|
0
|
0
|
0
|
0
|
Fatigue
|
25.3
|
27.2
|
28.9
|
22.3
|
31.0
|
33.3
|
32.8
|
Headache
|
15.8
|
19.3
|
17.8
|
18.2
|
13.5
|
21.4
|
19.2
|
Muscle pain
|
31.9
|
32.3
|
32.0
|
31.4
|
33.9
|
46.0
|
37.6
|
Joint pain
|
13.4
|
12.0
|
6.7
|
10.7
|
11.8
|
15.9
|
16.8
|
- a.
- N = number of participants with any e-diary data reported after vaccination.
- b.
- Local reactions solicited within 10 days after vaccination; systemic events solicited within 7 days after vaccination.
- c.
- Includes participants who previously received either PPSV23 ≥1 to ≤5 years before enrollment (PPSV23), PREVNAR 13 ≥6 months before enrollment (PREVNAR 13), or PREVNAR 13 followed by PPSV23 ≥1 year before enrollment (PREVNAR 13 and PPSV23) in the study.
|
Additional Information in Immunocompromised Patients in Studies with PREVNAR 13
Adults 18 years and older with HIV infection who received PREVNAR 13 had similar frequencies of adverse reactions as adults 50 years of age and older who received PREVNAR 13, except that fever and vomiting had a frequency category of Very Common (≥1/10) and nausea had a frequency category of Common (≥1/100 to <1/10).
Adults 18 years and older with a hematopoietic stem cell transplant who received PREVNAR 13 had similar frequencies of adverse reactions as adults 18 years and older who received PREVNAR 13, except that fever and vomiting had a frequency category of Very Common (≥1/10).
8.3 Less Common Clinical Trial Adverse Reactions
Listed below are the less common adverse reactions reported in clinical trials with PREVNAR 20 (Uncommon frequency ≥1/1,000 to < 1/100).
Immune system disorders: Hypersensitivity reaction, including face edema, dyspnea, bronchospasm
Gastrointestinal disorders: Diarrhea, nausea, vomiting
Skin and subcutaneous tissue disorders: Rash, angioedema
General disorders and administration site conditions: Vaccination-site pruritus, lymphadenopathy, vaccination-site urticaria, chills
8.5 Post-Market Adverse Reactions
Post-marketing Experience with PREVNAR 13
The following adverse reactions have been reported since market introduction of PREVNAR 13, and are included based on one or more of the following factors: severity, frequency of reporting, or strength of evidence for a causal relationship to PREVNAR 13. Although these adverse reactions reported in the post-marketing experience of PREVNAR 13 were not observed in the PREVNAR 20 clinical trials, they are considered possible adverse reactions for PREVNAR 20 as the components of PREVNAR 13 are also contained in PREVNAR 20.
Table 4. Adverse Reactions From PREVNAR 13 Post-marketing Experience
System Organ Class
|
Frequency Not Known
|
Immune system disorders
|
Anaphylactic/anaphylactoid reaction including shock
|
Skin and subcutaneous tissue disorders
|
Erythema multiforme
|
General disorders and administration site conditions
|
Vaccination-site dermatitis
|
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