Comirnaty Adverse Reactions

Summary of safety profile: The safety of Comirnaty JN.1 is inferred from safety data of the prior Comirnaty vaccine.
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.
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%).
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 the initially approved Comirnaty vaccine 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.
Participants 12 years of age and older - after booster dose: A subset from Study 2 Phase 2/3 participants of 306 adults 18 to 55 years of age who completed the original Comirnaty 2-dose course, received a booster dose of Comirnaty approximately 6 months (range of 4.8 to 8.0 months) after receiving Dose 2. Overall, participants who received a booster dose, had a median follow-up time of 8.3 months (range 1.1 to 8.5 months) and 301 participants had been followed for ≥6 months after the booster dose to the cut-off date (22 November 2021).
The overall safety profile for the booster dose was similar to that seen after 2 doses. The most frequent adverse reactions in participants 18 to 55 years of age were injection site pain (>80%), fatigue (>60%), headache (>40%), myalgia (>30%), chills and arthralgia (>20%).
In Study 4, a placebo-controlled booster study, participants 16 years of age and older recruited from Study 2 received a booster dose of Comirnaty (5,081 participants), or placebo (5,044 participants) at least 6 months after the second dose of Comirnaty. Overall, participants who received a booster dose, had a median follow-up time of 2.8 months (range 0.3 to 7.5 months) after the booster dose in the blinded placebo-controlled follow up period to the cut-off date (8 February 2022). Of these, 1,281 participants (895 Comirnaty and 386 placebo) have been followed for ≥4 months after the booster dose of Comirnaty. No new adverse reactions of Comirnaty were identified.
A subset from Study 2 Phase 2/3 participants of 825 adolescents 12 to 15 years of age who completed the original Comirnaty 2-dose course, received a booster dose of Comirnaty approximately 11.2 months (range of 6.3 to 20.1 months) after receiving Dose 2. Overall, participants who received a booster dose, had a median follow-up time of 9.5 months (range 1.5 to 10.7 months) based on data up to the cut-off date (3 November 2022). No new adverse reactions of Comirnaty were identified.
Booster dose following primary vaccination with another authorised COVID-19 vaccine: In 5 independent studies on the use of a Comirnaty booster dose in individuals who had completed primary vaccination with another authorised COVID-19 vaccine (heterologous booster dose), no new safety issues were identified (see Pharmacology: Pharmacodynamics under Actions).
Omicron-adapted Comirnaty: Participants 12 years of age and older - after a booster dose of Comirnaty Original/Omicron BA.4-5 (fourth dose): In a subset from Study 5 (Phase 2/3), 107 participants 12 to 17 years of age, 313 participants 18 to 55 years of age and 306 participants 56 years of age and older who had completed 3 doses of Comirnaty, received a booster (fourth dose) of Comirnaty Original/Omicron BA.4-5 (15/15 mcg) 5.4 to 16.9 months after receiving Dose 3. Participants who received a booster (fourth dose) of Comirnaty Original/Omicron BA.4-5 had a median follow-up time of at least 1.5 months.
The overall safety profile for the Comirnaty Original/Omicron BA.4-5 booster (fourth dose) was similar to that seen after 3 doses. The most frequent adverse reactions in participants 12 years of age and older were injection site pain (>60%), fatigue (>50%), headache (>40%), muscle pain (>20%), chills (>10%), and joint pain (>10%).
Comirnaty 3 mcg: Infants 6 to 23 months of age - after 3 doses: In an analysis of Study 3 (Phase 2/3), 2176 infants (1458 initially approved Comirnaty 3 mcg and 718 placebo) were 6 to 23 months of age. Based on data in the blinded placebo-controlled follow-up period up to the cut-off date of 28 February 2023, 720 infants 6 to 23 months of age who received a 3-dose primary course (483 Comirnaty 3 mcg and 237 placebo) have been followed for a median of 1.7 months after the third dose.
The most frequent adverse reactions in infants 6 to 23 months of age that received any primary course dose included irritability (>60%), drowsiness (>40%), decreased appetite (>30%), tenderness at the injection site (>20%), injection site redness and fever (>10%).
Children 2 to 4 years of age - after 3 doses: In an analysis of Study 3 (Phase 2/3), 3541 children (2368 Comirnaty 3 mcg and 1173 placebo) were 2 to 4 years of age. Based on data in the blinded placebo-controlled follow-up period up to the cut-off date of 28 February 2023, 1268 children 2 to 4 years of age who received a 3-dose primary course (863 Comirnaty 3 mcg and 405 placebo) have been followed a median of 2.2 months after the third dose.
The most frequent adverse reactions in children 2 to 4 years of age that received any primary course dose included pain at injection site and fatigue (>40%), injection site redness and fever (>10%).
Omicron-adapted Comirnaty: Infants 6 to 23 months of age - after the booster (fourth dose): In a subset from Study 6 (Phase 3), 39 participants 6 to 23 months of age who had completed 3 doses of Comirnaty, received a booster (fourth dose) of Comirnaty Original/Omicron BA.4-5 (1.5/1.5 mcg) 2.1 to 8.6 months after receiving Dose 3. Participants who received a booster (fourth dose) of Comirnaty Original/Omicron BA.4-5 had a median follow-up time of at least 1.7 months.
The overall safety profile for the Comirnaty Original/Omicron BA.4-5 booster (fourth dose) was similar to that seen after 3 doses. The most frequent adverse reaction in participants 6 to 23 months of age was irritability (>20%), decreased appetite (>10%), and drowsiness (>10%).
Children 2 to 4 years of age - after the booster (fourth dose): In a subset from Study 6 (Phase 3), 124 participants 2 to 4 years of age who had completed 3 doses of Comirnaty, received a booster (fourth dose) of Comirnaty Original/Omicron BA.4-5 (1.5/1.5 mcg) 2.2 to 8.6 months after receiving Dose 3. Participants who received a booster (fourth dose) of Comirnaty Original/Omicron BA.4-5 had a median follow-up time of at least 1.8 months.
The overall safety profile for the Comirnaty Original/Omicron BA.4-5 booster (fourth dose) was similar to that seen after 3 doses. The most frequent adverse reactions in participants 2 to 4 years of age were injection site pain (>30%) and fatigue (>20%).
Comirnaty 3 mcg/10 mcg: Children 5 to 11 years of age (i.e., 5 to less than 12 years of age) - after 2 doses: In Study 3, a total of 3,109 children 5 to 11 years of age received at least 1 dose of the initially approved Comirnaty vaccine 10 mcg and a total of 1,538 children 5 to 11 years of age received placebo. At the time of the analysis of Study 3 Phase 2/3 with data up to the cut-off date of 20 May 2022, 2,206 (1,481 Comirnaty 10 mcg and 725 placebo) children have been followed for ≥4 months after the second dose in the placebo-controlled blinded follow-up period. The safety evaluation in Study 3 is ongoing.
The overall safety profile of Comirnaty in participants 5 to 11 years of age was similar to that seen in participants 16 years of age and older. The most frequent adverse reactions in children 5 to 11 years of age that received 2 doses were injection site pain (>80%), fatigue (>50%), headache (>30%), injection site redness and swelling (≥20%), myalgia, chills, and diarrhoea (>10%).
Children 5 to 11 years of age (i.e., 5 to less than 12 years of age) - after booster dose: In a subset from Study 3, a total of 2408 children 5 to 11 years of age received a booster dose of Comirnaty 10 mcg at least 5 months (range of 5.3 to 19.4 months) after completing the primary series. The analysis of the Study 3 Phase 2/3 subset is based on data up to the cut-off date of 28 February 2023 (median follow-up time of 6.4 months).
The overall safety profile for the booster dose was similar to that seen after the primary course. The most frequent adverse reactions in children 5 to 11 years of age after the booster dose were injection site pain (>60%), fatigue (>30%), headache (>20%), myalgia, chills, injection site redness and swelling (>10%).
Omicron-adapted Comirnaty: Children 5 to 11 years of age (i.e., 5 to less than 12 years of age) - after the booster (fourth dose): In a subset from Study 6 (Phase 3), 113 participants 5 to 11 years of age who had completed 3 doses of Comirnaty, received a booster (fourth dose) of Comirnaty Original/Omicron BA.4-5 (5/5 mcg) 2.6 to 8.5 months after receiving Dose 3. Participants who received a booster (fourth dose) of Comirnaty Original/Omicron BA.4-5 had a median follow-up time of at least 1.6 months.
The overall safety profile for the Comirnaty Original/Omicron BA.4-5 booster (fourth dose) was similar to that seen after 3 doses. The most frequent adverse reactions in participants 5 to 11 years of age were injection site pain (>60%), fatigue (>40%), headache (>20%), and muscle pain (>10%).
Comirnaty 30 mcg: Participants 12 years of age and older - after subsequent booster doses: The safety of a booster dose of Comirnaty in participants 12 years of age and older is inferred from safety data from studies of a booster dose of Comirnaty in participants 18 years of age and older.
A subset of 325 adults 18 to ≤55 years of age who had completed 3 doses of Comirnaty, received a booster (fourth dose) of Comirnaty 90 to 180 days after receiving Dose 3. Participants who received a booster (fourth dose) of Comirnaty had a median follow-up time of 1.4 months up to a data cut-off date of 11 March 2022. The most frequent adverse reactions in these participants were injection site pain (>70%), fatigue (>60%), headache (>40%), myalgia and chills (>20%), and arthralgia (>10%).
In a subset from Study 4 (Phase 3), 305 adults >55 years of age who had completed 3 doses of Comirnaty, received a booster (fourth dose) of Comirnaty 5 to 12 months after receiving Dose 3. Participants who received a booster (fourth dose) of Comirnaty had a median follow-up time of at least 1.7 months up to a data cut-off date of 16 May 2022. The overall safety profile for the Comirnaty booster (fourth dose) was similar to that seen after the Comirnaty booster (third dose). The most frequent adverse reactions in participants >55 years of age were injection site pain (>60%), fatigue (>40%), headache (>20%), myalgia and chills (>10%).
Tabulated list of adverse reactions from clinical studies of Comirnaty and Comirnaty Original/Omicron BA.4-5 and post-authorisation experience of Comirnaty in individuals 6 months of age and older (3 mcg), 5 years of age and older (10 mcg) and 12 years of age and older (30 mcg): Adverse reactions observed during clinical studies are listed as follows 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).
3 mcg: See Table 19.

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10 mcg: See Table 20.

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30 mcg: See Table 21.

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Safety with concomitant vaccine administration: In Study 8, a Phase 3 study, participants 18 through 64 years of age who received Comirnaty co-administered with seasonal inactivated influenza vaccine (SIIV), quadrivalent followed 1 month later by placebo, were compared to participants who received an inactivated influenza vaccine with placebo followed 1 month later by Comirnaty alone (n=553 to 564 participants in each group). Reactogenicity events were reported more frequently by participants who received Comirnaty co-administered with SIIV, quadrivalent, compared to participants who received Comirnaty alone, but overall the reactogenicity events were mostly mild to moderate in severity. The most common adverse reactions reported in the co-administration group and after Comirnaty alone were injection site pain (86.2% and 84.4%, respectively), fatigue (64.0% and 50.8%, respectively) and headache (47.2% and 37.8%, respectively).
Description of selected adverse reactions: Myocarditis and pericarditis: The increased risk of myocarditis after vaccination with Comirnaty is highest in younger males (see Precautions).
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.