Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Summary of safety profile
Participants 16 years of age and older – after 2 doses

In Study 2, a total of 22 026 participants 16 years of age or older received at least 1 dose of Comirnaty and a total of 22 021 participants 16 years of age or older received placebo (including 138 and 145 adolescents 16 and 17 years of age in the vaccine and placebo groups, respectively). A total of 20 519 participants 16 years of age or older received 2 doses of Comirnaty.

At the time of the analysis of Study 2 with a data cut-off of 13 March 2021 for the placebo-controlled blinded follow-up period up to the participants’ unblinding dates, a total of 25 651 (58.2%) participants (13 031 Comirnaty and 12 620 placebo) 16 years of age and older were followed up for ≥ 4 months after the second dose. This included a total of 15 111 (7 704 Comirnaty and 7 407 placebo) participants 16 to 55 years of age and a total of 10 540 (5 327 Comirnaty and 5 213 placebo) participants 56 years of age and older.

The most frequent adverse reactions in participants 16 years of age and older that received 2 doses were injection site pain (> 80%), fatigue (> 60%), headache (> 50%), myalgia (> 40%), chills (> 30%), arthralgia (> 20%), pyrexia and injection site swelling (> 10%) and 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.

The safety profile in 545 participants 16 years of age and older receiving Comirnaty, that were seropositive for SARS-CoV-2 at baseline, was similar to that seen in the general population.

Adolescents 12 to 15 years of age – after 2 doses

In an analysis of long-term safety follow-up in Study 2, 2 260 adolescents (1 131 Comirnaty and 1 129 placebo) were 12 to 15 years of age. Of these, 1 559 adolescents (786 Comirnaty and 773 placebo) have been followed for ≥ 4 months after the second dose of Comirnaty. The safety evaluation in Study 2 is ongoing.

The overall safety profile of Comirnaty in adolescents 12 to 15 years of age was similar to that seen in participants 16 years of age and older. The most frequent adverse reactions in adolescents 12 to 15 years of age that received 2 doses were injection site pain (> 90%), fatigue and headache (> 70%), myalgia and chills (> 40%), arthralgia and pyrexia (> 20%).


Tabulated list of adverse reactions from clinical studies and post-authorisation experience in individuals 12 years of age and older

Adverse reactions observed during clinical studies are listed below according to the following frequency categories:

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).

Table 1.    Adverse reactions from Comirnaty clinical trials and post-authorisation experience in individuals 12 years of age and older
Not known
Rare
Very                           Uncommon                                       (cannot be System Organ                     Common                                (≥ 1/10 00 Very rare common                           (≥ 1/1 000 to                                estimated from Class                       (≥ 1/100 to < 1/10)                           0 to    (< 1/10 000) (≥ 1/10)                            < 1/100)                                   the available < 1/1 000) data)
Blood and                   Lymphadenopathy lymphatic system disorders
Immune system                                   Hypersensitivity                               Anaphylaxis disorders                                       reactions (e.g. rash, pruritus, urticariaa,
angioedemaa)
Metabolism and                                  Decreased appetite nutrition disorders
Psychiatric                                     Insomnia disorders
Nervous system Headache                         Dizzinessc;           Acute                    Paraesthesiac; disorders                                       Lethargy              peripheral               Hypoaesthesiac facial paralysisb
Cardiac                                                                                  Myocarditisc; disorders                                                                                Pericarditisc Gastrointestinal Diarrhoeac Nausea; Vomitingc disorders
Skin and                                             Hyperhidrosis;                                      Erythema subcutaneous                                         Night sweats                                        multiformec tissue disorder
Musculoskeletal Arthralgia;                          Pain in extremityd and connective Myalgia tissue disorders
Reproductive                                                                                             Heavy menstrual system and                                                                                               bleedingg breast disorders
General          Injection Injection site            Asthenia;                                           Extensive disorders and site pain; redness                     Malaise;                                            swelling of administration Fatigue;                              Injection site                                      vaccinated limb;c site conditions Chills;                              pruritus                                            Facial swellingf Pyrexia;e
Injection site swelling a. The frequency category for urticaria and angioedema was rare.
b. Through the clinical trial safety follow-up period to 14 November 2020, acute peripheral facial paralysis (or palsy) was reported by four participants in the COVID-19 mRNA Vaccine group. Onset was Day 37 after Dose 1 (participant did not receive Dose 2) and Days 3, 9, and 48 after Dose 2. No cases of acute peripheral facial paralysis (or palsy) were reported in the placebo group.
c. Adverse reaction determined post-authorisation.
d. Refers to vaccinated arm.
e. A higher frequency of pyrexia was observed after the second dose compared to the first dose.
f. Facial swelling in vaccine recipients with a history of injection of dermatological fillers has been reported in the post-marketing phase.
g. Most cases appeared to be non-serious and temporary in nature.

Description of selected adverse reactions

Myocarditis and pericarditis
The increased risk of myocarditis after vaccination with Comirnaty 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 Comirnaty. One study showed that in a period of 7 days after the second dose there were about 0.265 (95% CI 0.255 - 0.275) extra cases of myocarditis in 12-29 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 0.56 (95% CI 0.37 - 0.74) extra cases of myocarditis in 16-24 year old males per 10 000 compared to unexposed persons.

Limited data indicate that the risk of myocarditis and pericarditis after vaccination with Comirnaty in children aged 5 to 11 years seems lower than in ages 12 to 17 years.

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