Prevenar 20 Adverse Reactions

Summary of the safety profile: Infants and children 6 weeks to less than 15 months of age: Clinical trials were conducted in healthy infants and children 6 weeks to less than 15 months of age using a 3-dose series (Phase 3 trial B7471012 [Study 1012]) or a 4-dose series (Phase 3 trials B7471011 and B7471013 [Studies 1011 and 1013] and the Phase 2 trial B7471003 [Study 1003]). In these 4 infant trials 5,156 participants received at least 1 dose of vaccine: 2,833 received PREVENAR 20 and 2,323 received 13vPnC. Overall, approximately 90% of participants in each group received all doses through the study-specified toddler dose. In all studies, local reactions and systemic events were collected after each dose, and adverse events were collected from the first dose through 1 month after the last infant vaccination and from the toddler dose through 1 month after vaccination in all studies. Serious adverse events were evaluated through 1 month after the last dose in Studies 1012 and 6 months after the last dose in Studies 1011, 1013, and 1003.
PREVENAR 20 was well tolerated when administered on a 3-dose and a 4-dose series, in the infant study populations with low rates of severe local reactions and systemic events, and most reactions resolving within 1 to 3 days. The percentages of participants with reactogenicity events after PREVENAR 20 were generally similar to those after 13vPnC. Based on the infant data, the most frequently reported local reactions and systemic events after any dose of PREVENAR 20 were irritability, drowsiness, and pain at injection site.
In these studies, PREVENAR 20 was co-administered or permitted to be administered with certain routine pediatric vaccines (see Interactions).
Study 1012 was a pivotal double-blind, active-controlled Phase 3 trial, in which 601 healthy infants, 2 months (≥42 to ≤112 days) of age and born at >36 weeks of gestation received PREVENAR 20 in a 3-dose series. The most frequently reported adverse reactions (>10%) after any dose of PREVENAR 20 were irritability (71.0% to 71.9%), drowsiness/increased sleep (50.9% to 61.2%), pain at injection site (22.8% to 42.4%), decreased appetite (24.7% to 39.3%), redness at the injection site (25.3% to 36.9%), swelling at the injection site (21.4% to 29.8%) and fever of ≥38.0℃ (8.9% to 24.3%). Most adverse reactions occurred within 1 to 2 days following vaccination and were mild to moderate in severity and of short duration (1 to 2 days).
Study 1011 was a pivotal double-blind, active-controlled Phase 3 trial, in which 1,001 healthy infants, 2 months (≥42 to ≤98 days) of age and born at >36 weeks of gestation received PREVENAR 20 in a 4-dose series. The most frequently reported adverse reactions (>10%) after any dose of PREVENAR 20 were irritability (61.0% to 71.6%), drowsiness/increased sleep (39.5% to 67.2%), pain at injection site (35.7% to 49.1%), decreased appetite (20.6% to 26.4%), redness (23.2% to 25.5%), swelling (14.9% to 17.1%) and fever of ≥38.0℃ (10.3% to 17.3%). Most adverse reactions were mild or moderate following vaccination and severe reactions were reported infrequently.
Study 1013 was a double-blind, active-controlled Phase 3 safety trial, in which 1,000 healthy infants, 2 months (≥42 to ≤98 days) of age and born at ≥34 weeks of gestation received PREVENAR 20 in a 4-dose series. The most frequently reported adverse reactions (>10%) after any dose of PREVENAR 20 were irritability (54.8% to 68.2%), drowsiness/increased sleep (35.3% to 64.8%), pain at injection site (24.7% to 40.5%), decreased appetite (23.6% to 28.4%), redness (21.2% to 23.5%), swelling (14.8% to 20.0%) and fever of ≥38.0℃ (9.3% to 18.0%). In Study 1013, the local reactions and systemic events in the preterm subgroup (111 infants born at 34 to less than 37 weeks of gestation) were similar to or lower than the term infants in the study. In the preterm subgroup the frequency of any reported local reaction (31.7% to 55.3% in the PREVENAR 20 group and 37.9% to 47.1% in the 13vPnC group) and systemic event (65.0% to 85.5% in the PREVENAR 20 group and 59.4% to 77.4% in the 13vPnC group).
Study 1003 was a double-blind, active-controlled Phase 2 trial, in which 231 infants, 2 months (≥42 to ≤98 days) of age and born at >36 weeks of gestation received PREVENAR 20 in a 4-dose series. The most frequently reported adverse reactions (>10%) after any dose of PREVENAR 20 were irritability (62.4% to 79.5%), drowsiness/increased sleep (32.8% to 68.1%), pain at injection site (35.5% to 51.1%), decreased appetite (23.3% to 30.8%), redness (24.7% to 26.9%), and swelling (12.7% to 17.9%).
The frequency and severity of the adverse reactions in all infant clinical trials were generally similar in the PREVENAR 20 and 13vPnC groups.
Adults 18 years of age and older: The safety profile presented is based on analysis of over 7,000 individuals 18 years of age and older, of which 4,552 were vaccinated with PREVENAR 20 in three Phase 1 and Phase 2 clinical trials and three Phase 3 clinical trials. In the Phase 3 trials, 4,263 participants received PREVENAR 20, which included 1,798 adults 18 through 49 years of age, 334 adults 50 through 59 years of age, and 2,132 adults 60 years of age and older (1,138 were 65 years of age and older). Of the Phase 3 PREVENAR 20 recipients, 3,639 adults were naïve to pneumococcal vaccines, 253 had previously received Pneumovax 23 (pneumococcal polysaccharide vaccine [23-valent]; PPSV23) only, 246 had previously received 13vPnC only, and 125 had previously received both PPSV23 and 13vPnC.
In participants 18 to 49 years of age, the most frequently reported adverse reactions were pain at injection site (79.2%), muscle pain (62.9%), fatigue (46.7%), headache (36.7%), and joint pain (16.2%). In participants 50 to 59 years of age, the most frequently reported adverse reactions were pain at injection site (72.5%), muscle pain (49.8%), fatigue (39.3%), headache (32.3%), and joint pain (15.4%). In participants ≥60 years of age, the most frequently reported adverse reactions were pain at injection site (55.4%), muscle pain (39.1%), fatigue (30.2%), headache (21.5%), and joint pain (12.6%).
Adverse reactions from clinical trials with PREVENAR 20: As PREVENAR 20 contains the same 13 serotype-specific capsular polysaccharide conjugates and the same vaccine excipients as 13vPnC, the adverse reactions already identified for 13vPnC have been adopted for PREVENAR 20.
Tabulated list of adverse reactions: Table 14 present adverse reactions reported in the Phase 2 infant trial, and Phase 3 trials in pediatric and adult populations, based on the highest frequency among adverse events, local reactions, or systemic events, after vaccination in a PREVENAR 20 group in a study or integrated dataset. The data from clinical trials in infants reflect PREVENAR 20 administered simultaneously with other routine childhood vaccines. In the case of adverse reactions reported in clinical trials of 13vPnC, but not reported in PREVENAR 20 trials, the frequency is not known. In clinical trials, the safety profile of PREVENAR 20 was similar to that of 13vPnC. (See Table 14.)


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Not all ARs reported in 13vPnC Phase 3 trials in adults were reported in the PREVENAR 20 trials. The following ARs were not reported in the PREVENAR 20 Phase 3 trials in adults: General disorders and administration site conditions: Limitation of arm movement (reported in 13vPnC clinical trials with Very Common frequency [≥1/10]).
Metabolism and nutrition disorders: Decreased appetite (reported in 13vPnC clinical trials with Very Common frequency [≥1/10]).
Safety with concomitant vaccine administration: Infants and children: The safety profile of PREVENAR 20 was acceptable, and similar to 13vPnC when administered concomitantly with routine pediatric vaccines containing diphtheria, tetanus, acellular pertussis, hepatitis B virus, poliovirus, and Haemophilus influenzae type b antigens (Infanrix hexa); measles, mumps, and rubella antigens (MMRVaxPro); and varicella antigens (Varilrix).
Adults: The safety profile was similar when PREVENAR 20 was administered with or without influenza vaccine, adjuvanted (Fluad Quadrivalent [QIV]).
PREVENAR 20 administered together with COVID-19 mRNA vaccine (nucleoside modified) was observed to have a tolerability profile similar to COVID-19 mRNA vaccine (nucleoside modified) administered alone, and an overall safety profile consistent with PREVENAR 20 or COVID-19 mRNA vaccine (nucleoside modified) given alone.
Adverse reactions from post marketing experience: The following adverse events have been reported through passive surveillance since market introduction of 13vPnC. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to the vaccine. The following adverse events were included based on one or more of the following factors: severity, frequency of reporting, or strength of evidence for a causal relationship to 13vPnC and are, therefore, considered adverse reactions. Although these adverse reactions reported in the postmarketing experience of 13vPnC in pediatric and adult populations were not observed in the PREVENAR 20 clinical trials, they are considered adverse reactions for PREVENAR 20 as the components of 13vPnC are also contained in PREVENAR 20. (See Table 15.)


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Three events (angioedema, vaccination-site pruritus, vaccination-site urticaria) that had been reported as adverse reactions from the 13vPnC postmarketing experience were reported in the PREVENAR 20 Phase 3 adult clinical trials, so they are listed in Table 14 for the adult populations. Lymphadenopathy localized to the region of the vaccination site had been reported in both 13vPnC clinical trials and in the postmarketing period. Since the term lymphadenopathy was reported in Phase 3 adult clinical trials of PREVENAR 20, it is noted in Table 14 for the adult population.
Additional information in special populations in studies with 13vPnC: Adults with HIV infection had similar frequencies of adverse reactions as adults 18 years of age and older, except that fever and vomiting had a frequency category of very common (≥1/10) and nausea had a frequency category of common (≥1/1000 to <1/10).
Adults with HSCT have similar frequencies of adverse reactions as adults 18 years and older, except that fever, diarrhea and vomiting had a frequency category of very common (≥1/10).
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via: https://e-meso.pom.go.id/ADR.