Adverse reactions : תופעות לוואי

4.8. Undesirable effects

Summary of the safety profile
Adults
The safety of Spikevax was evaluated in an ongoing Phase 3 randomised, placebo- controlled, observer-blind clinical study conducted in the United States involving 30,351 participants 18 years of age and older who received at least one dose of Spikevax (n=15,185) or placebo (n=15,166) (NCT04470427). At the time of vaccination, the mean age of the population was 52 years (range 18- 95); 22,831 (75.2%) of participants were 18 to 64 years of age and 7,520 (24.8%) of participants were 65 years of age and older.

The most frequently reported adverse reactions were pain at the injection site (92%), fatigue (70%), headache (64.7%), myalgia (61.5%), arthralgia (46.4%), chills (45.4%), nausea/vomiting (23%), axillary swelling/tenderness (19.8%), fever (15.5%), injection site swelling (14.7%) and redness (10%). Adverse reactions were usually mild or moderate in intensity and resolved within a few days after vaccination. A slightly lower frequency of reactogenicity events was associated with greater age.

Overall, there was a higher incidence of some adverse reactions in younger age groups: the incidence of axillary swelling/tenderness, fatigue, headache, myalgia, arthralgia, chills, nausea/vomiting and fever was higher in adults aged 18 to < 65 years than in those aged 65 years and above.
Local and systemic adverse reactions were more frequently reported after Dose 2 than after Dose 1.

Tabulated list of adverse reactions

The safety profile presented below is based on data generated in several placebo- controlled clinical studies: 30,351 adults ≥ 18 years of age and post-marketing experience.

Adverse reactions reported are listed according to the following frequency  convention:

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 the available data)
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness (Table 3).

Table 3: Adverse reactions from Spikevax clinical studies and post authorisation experience in individuals 18 years of age and older

MedDRA system organ class             Frequency              Adverse reactions Blood and lymphatic system            Very common            Lymphadenopathy* disorders
Immune system disorders               Not known              Anaphylaxis Hypersensitivity
Nervous system disorders              Very common            Headache Uncommon               Dizziness
Rare                   Acute peripheral facial paralysis‡
Hypoaesthesia
Paraesthesia
Cardiac disorders                     Very rare              Myocarditis Pericarditis
Gastrointestinal disorders            Very common            Nausea/vomiting Common                 Diarrhoea
Skin and subcutaneous tissue          Common                 Rash disorders                             Uncommon               Urticaria¶ Not known              Erythema multiforme
Mechanical urticaria
Musculoskeletal and connective Very common                   Myalgia tissue disorders                                             Arthralgia Reproductive system and breast Not known                     Heavy menstrual bleeding# disorders
General disorders              Very common                     Injection site pain and administration site                                        Fatigue conditions                                                     Chills Pyrexia
Injection site swelling
Injection site erythema
Common                  Injection site urticaria
Injection site rash
Delayed injection site reaction♠
Uncommon                Injection site pruritus
Rare                    Facial swelling♥
Not known               Extensive swelling of vaccinated limb
*Lymphadenopathy was captured as axillary lymphadenopathy on the same side as the injection site. Other lymph nodes (e.g., cervical, supraclavicular) were affected in some cases.
‡ Throughout the safety follow-up period, acute peripheral facial paralysis (or palsy) was reported by three participants in the Spikevax group and one participant in the placebo group. Onset in the vaccine group participants was 22 days, 28 days,
and 32 days after Dose 2.
¶ Urticaria has been observed with either acute onset (within a few days after vaccination) or delayed onset (up to approximately two weeks after vaccination).
# Most cases appeared to be non-serious and temporary in nature.
♠ Median time to onset was 9 days after the first injection, and 11 days after the second injection. Median duration was 4 days after the first injection, and 4 days after the second injection.
♥There were two serious adverse events of facial swelling in vaccine recipients with a history of injection of dermatological fillers. The onset of swelling was reported on Day 1 and Day 3, respectively, relative to day of vaccination.

The reactogenicity and safety profile in 343 subjects receiving Spikevax, that were seropositive for SARS-CoV-2 at baseline, was comparable to that in subjects seronegative for SARS-CoV-2 at baseline.

Adults (booster dose)

The safety, reactogenicity, and immunogenicity of a booster dose of Spikevax are evaluated in an ongoing Phase 2, randomised, observer-blind, placebo-controlled, dose-confirmation study in participants 18 years of age and older (NCT04405076). In this study, 198 participants received two doses (0.5 mL, 100 micrograms 1 month apart) of the Spikevax vaccine primary series. In an open- label phase of this study, 167 of those participants received a single booster dose (0.25 mL, 50 micrograms) at least 6 months after receiving the second dose of the primary series. The solicited adverse reaction profile for the booster dose (0.25 mL, 50 micrograms) was similar to that after the second dose in the primary series.


Spikevax (original) in solid organ transplant recipients
The safety, reactogenicity, and immunogenicity of Spikevax (original) were evaluated in a two-part Phase 3b open-label study in adult solid organ transplant (SOT) recipients, including kidney and liver transplants (mRNA-1273-P304). A 100 microgram (0.5 mL) dose was administered, which was the dose authorised at the time of study conduct.

In Part A, 128 SOT recipients received a third dose of Spikevax (original). In Part B, 159 SOT recipients received a booster dose at least 4 months after the last dose (fourth dose for mRNA vaccines and third dose for non-mRNA vaccines).

Reactogenicity was consistent with the known profile of Spikevax (original). There were no unexpected safety findings.


Description of selected adverse reactions

Myocarditis
The increased risk of myocarditis after vaccination with Spikevax is highest in younger males (see section 4.4).

Two large European pharmacoepidemiological studies have estimated the excess risk in younger males following the second dose of Spikevax. One study showed that in a period of 7 days after the second dose, there were about 1.316 (95% CI: 1.299, 1.333) extra cases of myocarditis in 12 to 29 year-old males per 10,000 compared to unexposed persons. In another study, in a period of 28 days after the second dose, there were 1.88 (95% CI: 0.956, 2.804) extra cases of myocarditis in 16 to 24 year-old males per 10,000 compared to unexposed persons.

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