Comirnaty Adverse Reactions

Summary of safety profile: The safety of COMIRNATY (Original) was evaluated in participants 5 years of age and older in 3 clinical studies conducted in the United States, Europe, Turkey, South Africa, and South America. Study BNT162-01 (Study 1) enrolled 60 participants, 18 through 55 years of age and 36 participants, 56 through 85 years of age. Study C4591001 (Study 2) enrolled approximately 46,000 participants, 12 years of age or older. Study C4591007 (Study 3) enrolled approximately 4,600 participants 5 through <12 years of age. Study 3 also enrolled approximately 3,600 participants 2 through 4 years of age and 2,200 participants 6 months through 23 months of age.
Additionally, 306 existing Phase 3 participants at least 18 through 55 years of age received a booster dose of COMIRNATY (Original) approximately 6 months after the second dose in the non-placebo-controlled booster dose portion of Study 2. The overall safety profile for the booster dose was similar to that seen after 2 doses.
In Study C4591031 (Study 4), a placebo-controlled booster study, 5,081 participants 16 years of age and older were recruited from Study 2 to receive a booster dose of COMIRNATY (Original) at least 6 months after the second dose. The overall safety profile for the booster dose was similar to that seen after 2 doses.
In a subset of Study 3 (Phase 2/3), 2,408 participants 5 through <12 years of age received a booster dose of COMIRNATY (Original) at least 5 months after completing the primary series. The overall safety profile of COMIRNATY (Original) for the booster dose was similar to that seen after the primary series.
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 (Original) 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.
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 (Original), that were seropositive for SARS-CoV-2 at baseline, was similar to that seen in the general population.
Study 2 also included 200 participants with confirmed stable human immunodeficiency virus (HIV) infection. The safety profile of the participants receiving COMIRNATY (Original) (n = 100) in the individuals with stable HIV infection was similar to that seen in the general population.
Adolescents 12 through 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 (Original); 1,129 placebo] were 12 through 15 years of age. Of these, 1,559 adolescents [786 COMIRNATY (Original) and 773 placebo] were followed for ≥4 months after the second dose.
The most frequent adverse reactions in adolescents 12 through 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%).
In adolescents 12 through 15 years of age, psychiatric-related serious adverse events were numerically higher in the vaccine group, 4 recipients (3 [0.3%] with depression and 1 [0.1%] with suicidal ideation) and none in the placebo group. The events in the vaccine group were confounded by prior medical history as all 4 participants had concurrent psychiatric illness including depression prior to vaccination. Currently available information is insufficient to determine a causal relationship with the vaccine.
Children 5 through <12 years of age - after 2 doses: In an analysis of Study 3 (Phase 2/3), 4,647 participants [3,109 COMIRNATY (Original) 10 micrograms; 1,538 placebo] were 5 through <12 years of age. Of these, 2,206 [1,481 COMIRNATY (Original) 10 micrograms; 725 placebo] participants 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 most frequent adverse reactions in children 5 through <12 years of age that received 2 doses included injection site pain (>80%), fatigue (>50%), headache (>30%), injection site redness and swelling (≥20%), myalgia, chills and diarrhoea (>10%).
Children 2 through 4 years of age - after 3 doses: In an analysis of Study 3 (Phase 2/3), 3,541 individuals [2,368 COMIRNATY (Original) 3 micrograms and 1,173 placebo] were 2 through 4 years age. Based on data in the blinded placebo-controlled follow-up period up to the cut-off date of 28 February 2023, 1,268 individuals 2 through 4 years of age who received a 3-dose primary course [863 COMIRNATY (Original) 3 micrograms; 405 placebo] have been followed a median of 2.2 months after the third dose.
The most frequent adverse reactions in children 2 through 4 years of age that received any primary series dose included pain at injection site and fatigue (>40%), injection site redness and fever (>10%).
Children 6 through 23 months of age - after 3 doses: In an analysis of Study 3 (Phase 2/3), 2,176 individuals [1,458 COMIRNATY (Original) 3 micrograms and 718 placebo] were 6 through 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 individuals 6 through 23 months of age who received a 3-dose primary course [483 COMIRNATY (Original) 3 micrograms; 237 placebo] have been followed for a median of 1.7 months after the third dose.
The most frequent adverse reactions in children 6 through 23 months of age that received any primary series dose included irritability (>60%), decrease appetite (>30%), tenderness at the injection site (>20%), injection site redness and fever (>10%).
Participants 12 years of age and older - after booster dose: A subset from Study 2 (Phase 2/3) participants of 306 adults at least 18 through 55 years of age who completed the primary COMIRNATY (Original) 2-dose course, received a booster dose of COMIRNATY (Original) approximately 6 months (range 4.8 to 8.0 months) after receiving Dose 2. Of these, 301 participants have been followed for ≥4 months after the booster dose of COMIRNATY (Original).
The most frequent adverse reactions in participants 18 through 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 (Original) (5,081 participants), or placebo (5,044 participants) at least 6 months after the second dose of COMIRNATY (Original). 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 (08 February 2022). Of these, 1,281 participants [895 COMIRNATY (Original); 386 placebo] were followed for ≥4 months after the booster dose of COMIRNATY (Original). The overall safety profile for the booster dose was similar to that seen after 2 doses.
In another subset from Study 2, 825 adolescents 12 to 15 years of age who completed the COMIRNATY (Original) 2-dose course, received a booster dose of COMIRNATY (Original) approximately 11.2 months (range 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 (Original) were identified.
Children 5 through <12 years of age - after booster dose: In a subset from Study 3, a total of 2,408 children 5 through <12 years of age received a booster dose of COMIRNATY (Original) 10 micrograms at least 5 months (range 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 most frequent adverse reactions in participants 5 through <12 years of age were injection site pain (>60%), fatigue (>30%), headache (>20%), myalgia, chills, injection site redness, and swelling (>10%).
Tabulated list of adverse reactions from clinical studies and post-authorisation experience: 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). (See Tables 35, 36, 37 and 38.)

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Safety with concomitant vaccine administration - COMIRNATY 30 micrograms: Concomitant administration with seasonal influenza vaccine: In Study 8 (C4591030), a Phase 3 study, participants 18 through 64 years of age who received COMIRNATY (Original) co-administered with seasonal inactivated influenza vaccine (SIIV), quadrivalent followed 1 month later by placebo (n=564), were compared to participants who received an inactivated influenza vaccine with placebo followed 1 month later by COMIRNATY (Original) alone (n=564). Reactogenicity events were reported more frequently by participants who received COMIRNATY (Original) co-administered with SIIV, quadrivalent, compared to participants who received COMIRNATY (Original) alone, but overall the reactogenicity events were mostly mild to moderate in severity. The most common adverse reactions reported in the co-administration group versus COMIRNATY (Original) alone were injection site pain (86.2% versus 84.4%, respectively), fatigue (64.0% versus 50.8%, respectively) and headache (47.2% versus 37.8%, respectively).
Concomitant administration with pneumococcal conjugate vaccine: In Study 11 (B7471026), a Phase 3 study, participants 65 years of age and older who received a booster dose of COMIRNATY (Original) co-administered with 20-valent pneumococcal conjugate vaccine (20vPnC [Prevenar 20]) (n=187), the overall safety profile was similar with COMIRNATY (Original) given alone (n=185). Overall, reactogenicity events were mostly mild to moderate in severity. The most common adverse reactions reported in the co-administration group versus COMIRNATY (Original) alone were injection site pain (72.4% versus 67.6%, respectively), fatigue (54.1% versus 54.6%, respectively), and myalgia (32.4% versus 31.9%, respectively).
Concomitant administration with an RSV vaccine or with an RSV vaccine and a high dose influenza vaccine: In Study 12 (C5481001), a Phase 1/2 study, participants 65 years of age and older who received COMIRNATY (Bivalent BA.4/BA.5) and RSV (bivalent, recombinant [ABRYSVO]) vaccine co-administered in one arm plus high dose quadrivalent influenza vaccine (QIV [Fluzone HD]) (n=158) or placebo (n=157) in the opposite arm were compared to participants who received the individual vaccines given with placebo. The overall safety profile was similar with COMIRNATY (Bivalent BA.4/BA.5) given alone (n=150).
Overall, reactogenicity events reported for the concomitantly administered vaccines were mostly mild to moderate in severity. The most common reported adverse reactions in the COMIRNATY (Bivalent BA.4/BA.5) administered concomitantly with RSV vaccine group, COMIRNATY (Bivalent BA.4/BA.5) administered concomitantly with both RSV vaccine and high dose quadrivalent influenza vaccine group, and COMIRNATY (Bivalent BA.4/BA.5) alone were injection site pain (56.7%, 53.8%, and 62.7%, respectively) and fatigue (38.9%, 46.8%, and 35.3%, respectively).
Other reporting instructions: Vaccination providers may report all other adverse events, to the extent feasible, to Pfizer Singapore using the contact information as follows.
Email: SGP.AEReporting@pfizer.com.
Fax number: 8001012817 (local toll free).
Telephone number: +65 6403 8888.
Adverse event reporting to HSA: Healthcare professionals are required to report any suspected serious adverse events observed with the use of COMIRNATY to HSA as soon as possible. All fatal and life-threatening events are to be reported as soon as possible, within 24 hours. Report the adverse events to the Vigilance and Compliance Branch at Tel: 6866 1111, or report online at https://www.hsa.gov.sg/adverse-events.