Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile
Participants 18 years of age and older

The safety of Prevenar 20 was evaluated in 4,552 participants 18 years of age and older in six clinical trials (two Phase 1, one Phase 2, and three Phase 3), and 2,496 participants in the control groups.

In the Phase 3 trials, 4,263 participants received Prevenar 20. This, included 1,798 participants 18 through 49 years of age, 334 participants 50 through 59 years of age, and 2,131 participants 60 years of age and older (1,138 were 65 years of age and older). Of the participants who received Prevenar 20 in the Phase 3 trials, 3,639 were naïve to pneumococcal vaccines, 253 had previously received Pneumovax 23 (pneumococcal polysaccharide vaccine [23-valent]; PPSV23) (≥ 1 to ≤ 5 years prior to enrollment), 246 had previously received Prevenar 13 only (≥ 6 months prior to enrollment), and 125 had previously received Prevenar 13 followed by PPSV23 (the dose of PPSV23 ≥ 1-year prior to enrollment).

Participants in the Phase 3 trial B7471007 (Pivotal Study 1007) were evaluated for adverse events for 1 month after vaccination, and serious adverse events through 6 months after vaccination. This study included 447 participants 18 to 49 years of age, 445 participants 50 to 59 years of age, 1,985 participants 60 to 64 years of age, 624 participants 65 to 69 years of age, 319 participants 70 to 79 years of age, and 69 participants ≥ 80 years of age.

In participants 18 to 49 years of age in Studies 1007 and a Phase 3 trial B7471008 (Lot Consistency Study 1008), 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 in Study 1007, 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 in Study 1007, 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%). These were usually mild or moderate in intensity and resolved within a few days after vaccination.

Phase 3 Study B7471006 (Study 1006) evaluated Prevenar 20 in participants ≥ 65 years of age with varying prior pneumococcal status (prior PPSV23, prior Prevenar 13 or prior Prevenar 13 followed by PPSV23). In this study, the most frequently reported adverse reactions for participants were similar in frequency to those described for participants ≥ 60 years of age in Study 1007, with slightly higher injection site pain (61.2%) in participants with prior Prevenar 13, and joint pain (16.8%) in participants with prior Prevenar 13 followed by PPSV23.

Tabulated list of adverse reactions

Tabulated lists of adverse reactions from the Phase 3 clinical trials and postmarketing experience are presented below.

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Adverse reactions from clinical trials

As Prevenar 20 contains the same 13 serotype-specific capsular polysaccharide conjugates and the same vaccine excipients as Prevenar 13, the adverse reactions already identified for Prevenar 13 have been adopted for Prevenar 20. Table 1 presents adverse reactions reported in Phase 3 trials of Prevenar 20, based on the highest frequency among adverse reactions, local reactions, or systemic events after vaccination in any Prevenar 20 group. In clinical trials, the safety profile of Prevenar 20 was similar to that of Prevenar 13. No new adverse reactions were identified as compared to Prevenar 13.

Adverse reactions are listed by system organ class in decreasing order of frequency and seriousness.
The frequency is defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from available data).

Table 1. Adverse Drug Reactions From Prevenar 20 Clinical Trials
System Organ Class    Very Common             Common                                         Uncommon                 Frequency Not Known
Immune system                                                                           Hypersensitivity disorders                                                                               reaction, including face oedema,
dyspnoea,
bronchospasm
Metabolism and                                                                                                      Decreased nutrition disorders                                                                                                 appetitea 
Nervous system               Headache disorders
Gastrointestinal                                                                        Diarrhoeaa disorders                                                                               Nausea Vomitinga
Skin and                                                                                Rasha subcutaneous tissue                                                                     Angioedema disorders
Musculoskeletal and          Joint pain connective tissue            Muscle pain disorders
General disorders            Vaccination-site                  Vaccination-site         Vaccination-site            Limitation of and administration           pain/tenderness                   induration/swellinga     pruritus                    arm site conditions              Fatigue                           Vaccination-site         Lymphadenopathy             movementa erythemaa                Vaccination-site
Pyrexia                  urticaria
Chillsa a. Event reported in clinical trials with Prevenar 13 with very common frequency (≥ 1/10). Decreased appetite and limitation of arm movement were not reported in the adult Phase 3 trials of Prevenar 20; therefore, the frequency is not known.


Safety with concomitant vaccine administration in adults
When Prevenar 20 was administered to adults aged ≥ 65 years together with the third (booster) dose of a COVID-19 mRNA vaccine (nucleoside modified), the tolerability profile generally resembled that of the COVID-19 mRNA vaccine (nucleoside modified) administered alone. There were a few differences in the safety profile when compared to administration of Prevenar 20 alone. In the phase 3 trial B7471026 (Study 1026), pyrexia (13.0%) and chills (26.5%) were reported as “very common” with co-administration. There was also one report of dizziness (0.5%) in the co-administration group.


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Adverse reactions from postmarketing experience

Table 2 includes adverse experiences that have been spontaneously reported during the postmarketing use of Prevenar 13, which may also occur with Prevenar 20. The postmarketing safety experience with Prevenar 13 is relevant to Prevenar 20, as Prevenar 20 contains all components (polysaccharide conjugates and excipients) of Prevenar 13. These events were reported voluntarily from a population of uncertain size. Therefore, it is not possible to reliably estimate their frequency or to establish, for all events, a causal relationship to vaccine exposure.

Table 2. Adverse Reactions From Prevenar 13 Postmarketing 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                 Vaccination-site dermatitis conditions
Events reported spontaneously in Prevenar 13 postmarketing experience; therefore, the frequencies could not be estimated from the available data and are considered as not known.

Additional information in special populations in studies with Prevenar 13 
Participants ≥ 18 years of age with HIV infection have similar frequencies of adverse reactions in Table 1, except for pyrexia (5% to 18%) and vomiting (8% to 12%) which were very common and nausea (< 1% to 3%) which was common.

Participants ≥ 18 years of age with an HSCT have similar frequencies of adverse reactions in Table 1, except for pyrexia (4% to 15%), vomiting (6% to 21%), and diarrhoea (25% to 36%) which were very common.

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.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il/