Medication Guide
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Prescribing Information
Adverse Reactions
An overview of clinical studies contributing to the safety assessment of COMIRNATY is provided in Table 1. Participants in these clinical studies received a 2-dose series, 3 weeks apart (referred to as a primary series) and subsequent doses referred to as booster doses.
| Abbreviation: SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2. | ||||
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Study | Age Group | Vaccine Strain Composition | Dosing | Number of Participants |
Primary Series | ||||
Study 1 (NCT04380701) | 18 through 55 years | Original* | Primary series | 60 |
Study 2 (NCT04368728) | 12 through 15 years of age | Original* | Primary series | 1131† |
≥16 years of age | Original* | Primary series | 22026† | |
Booster Dose | ||||
Study 2 (NCT04368728) | 12 through 15 years of age | Original* | 1st booster | 825 |
18 through 55 years of age | Original* | 1st booster | 306 | |
Study 4 (NCT04955626) | 12 through 17 years of age | Original* | 1st booster | 65 |
≥16 years of age | Original* | 1st booster | 5081† | |
Study 5 (NCT05472038) | ≥12 years of age | Original and Omicron BA.4/BA.5‡ | 2nd booster | 726 |
Concomitant Administration | ||||
Study 8 (NCT05310084) | 18 through 64 years of age | Original* | 2nd booster administered alone or concomitantly with Influenza Vaccine§ | 1128 |
Primary Series with COMIRNATY
Participants 12 through 15 years of age in Study 2: the most commonly reported adverse reactions (≥8%) following any dose were pain at the injection site (90.5%), fatigue (77.5%), headache (75.5%), chills (49.2%), muscle pain (42.2%), fever (24.3%), joint pain (20.2%), injection site swelling (9.2%), and injection site redness (8.6%).
Participants 16 through 55 years of age in Study 2: the most commonly reported adverse reactions (≥10%) following any dose were pain at the injection site (88.6%), fatigue (70.1%), headache (64.9%), muscle pain (45.5%), chills (41.5%), joint pain (27.5%), fever (17.8%), and injection site swelling (10.6%).
Participants 56 years of age and older in Study 2: the most commonly reported adverse reactions (≥10%) following any dose were pain at the injection site (78.2%), fatigue (56.9%), headache, (45.9%), muscle pain (32.5%), chills (24.8%), joint pain (21.5%), injection site swelling (11.8%), fever (11.5%), and injection site redness (10.4%).
Booster Dose with COMIRNATY
Participants 12 years of age and older in Studies 2 and 4: the most commonly reported adverse reactions (≥5%) following administration of a first booster dose with COMIRNATY were similar to those reported by participants who received COMIRNATY in the primary series.
Booster Dose With Pfizer-BioNTech COVID-19 Vaccine, Bivalent
Participants 12 years of age and older in Study 5: the most commonly reported adverse reactions (≥5%) following administration of a second booster dose with Pfizer-BioNTech COVID-19 Vaccine, Bivalent were pain at the injection site (67.3%), fatigue (52.6%), headache (40.5%), muscle pain (24.6%), chills (18.0%), joint pain (13.3%), fever (5.3%), injection site swelling (5.3%), and injection site redness (5.3%).
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared to rates in the clinical trials of another vaccine and may not reflect the rates observed in practice.
Primary Series With COMIRNATY
The safety of a 2-dose primary series of COMIRNATY was evaluated in participants 12 years of age and older in 2 clinical studies conducted in Germany (Study 1), United States, Argentina, Brazil, Turkey, South Africa, and Germany (Study 2). Study BNT162-01 (Study 1) was a Phase 1/2, 2-part, dose-escalation trial that enrolled 60 participants, 18 through 55 years of age and 36 participants, 56 through 85 years of age. Study 2 was a Phase 1/2/3 multicenter, randomized, saline placebo-controlled, double-blinded (Phase 2/3), dose finding-, vaccine candidate-selection and efficacy study that enrolled approximately 46,000 participants 12 years of age or older. Of these, approximately 2,260 participants were 12 through 15 years of age (1,131 COMIRNATY; 1,129 placebo) and 754 were 16 through 17 years of age (378 COMIRNATY; 376 placebo). In all, 44,047 participants in Phase 2/3 were 16 years of age or older (22,026 COMIRNATY; 22,021 placebo).
Study 2 included 200 participants with confirmed stable human immunodeficiency virus (HIV) infection. Confirmed stable HIV infection was defined as documented viral load <50 copies/mL and CD4 count >200 cells/mm3 within 6 months before enrollment, and on stable antiretroviral therapy for at least 6 months. HIV-positive participants are included in the safety population but are summarized separately in the safety analyses.
In Study 2, participants 12 years and older in the reactogenicity subset were monitored using an electronic diary for solicited local and systemic reactions and use of antipyretic medication after each vaccination. Participants were also monitored for unsolicited adverse events throughout the study (from Dose 1 through 1 month [all unsolicited adverse events] or through 6 months [serious adverse events] after the last vaccination). Tables 2 and 3 present the frequency and severity of solicited local and systemic reactions, respectively, within 7 days following any dose of COMIRNATY.
Adolescents 12 Through 15 Years of Age
In Study 2, 2,260 adolescents (1,131 COMIRNATY; 1,129 placebo) were 12 through 15 years of age. At the time of the analysis of the ongoing Study 2 with a data cutoff of September 2, 2021, there were 1,559 (69.0%) adolescents (786 COMIRNATY and 773 placebo) 12 through 15 years of age followed for ≥4 months after the second dose.
Demographic characteristics in Study 2 were generally similar with regard to age, gender, race, and ethnicity among adolescents who received COMIRNATY and those who received placebo. Overall, among the adolescents who received COMIRNATY, 50.1% were male and 49.9% were female, 85.8% were White, 4.6% were Black or African American, 11.7% were Hispanic/Latino, 6.4% were Asian, and 0.4% were American Indian/Alaska Native.
Local and Systemic Adverse Reactions Solicited in Study 2
In adolescents 12 through 15 years of age after receiving Dose 2, the mean duration of pain at the injection site was 2.5 days (range 1 to 11 days), for redness 1.8 days (range 1 to 5 days), and for swelling 1.6 days (range 1 to 5 days) in the COMIRNATY group.
| Note: Reactions were collected in the electronic diary (e-diary) from Day 1 to Day 7 after vaccination. | |||||
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COMIRNATY† Dose 1 N‡=1127 n§ (%) | Placebo Dose 1 N‡=1127 n§ (%) | COMIRNATY† Dose 2 N‡=1097 n§ (%) | Placebo Dose 2 N‡=1078 n§ (%) | ||
Redness¶ | |||||
Any (>2 cm) | 65 (5.8) | 12 (1.1) | 55 (5.0) | 10 (0.9) | |
Mild | 44 (3.9) | 11 (1.0) | 29 (2.6) | 8 (0.7) | |
Moderate | 20 (1.8) | 1 (0.1) | 26 (2.4) | 2 (0.2) | |
Severe | 1 (0.1) | 0 (0.0) | 0 (0.0) | 0 (0.0) | |
Swelling¶ | |||||
Any (>2 cm) | 78 (6.9) | 11 (1.0) | 54 (4.9) | 6 (0.6) | |
Mild | 55 (4.9) | 9 (0.8) | 36 (3.3) | 4 (0.4) | |
Moderate | 23 (2.0) | 2 (0.2) | 18 (1.6) | 2 (0.2) | |
Severe | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | |
Pain at the injection site# | |||||
Any | 971 (86.2) | 263 (23.3) | 866 (78.9) | 193 (17.9) | |
Mild | 467 (41.4) | 227 (20.1) | 466 (42.5) | 164 (15.2) | |
Moderate | 493 (43.7) | 36 (3.2) | 393 (35.8) | 29 (2.7) | |
Severe | 11 (1.0) | 0 (0.0) | 7 (0.6) | 0 (0.0) | |
| Note: Events and use of antipyretic or pain medication were collected in the electronic diary (e-diary) from Day 1 to Day 7 after each dose. | |||||
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COMIRNATY† Dose 1 N‡=1127 n§ (%) | Placebo Dose 1 N‡=1127 n§ (%) | COMIRNATY† Dose 2 N‡=1097 n§ (%) | Placebo Dose 2 N‡=1078 n§ (%) | ||
Fever | |||||
≥38.0℃ | 114 (10.1) | 12 (1.1) | 215 (19.6) | 7 (0.6) | |
≥38.0℃ to 38.4℃ | 74 (6.6) | 8 (0.7) | 107 (9.8) | 5 (0.5) | |
>38.4℃ to 38.9℃ | 29 (2.6) | 2 (0.2) | 83 (7.6) | 1 (0.1) | |
>38.9℃ to 40.0℃ | 10 (0.9) | 2 (0.2) | 25 (2.3) | 1 (0.1) | |
>40.0℃ | 1 (0.1) | 0 (0.0) | 0 (0.0) | 0 (0.0) | |
Fatigue¶ | |||||
Any | 677 (60.1) | 457 (40.6) | 726 (66.2) | 264 (24.5) | |
Mild | 278 (24.7) | 250 (22.2) | 232 (21.1) | 133 (12.3) | |
Moderate | 384 (34.1) | 199 (17.7) | 468 (42.7) | 127 (11.8) | |
Severe | 15 (1.3) | 8 (0.7) | 26 (2.4) | 4 (0.4) | |
Headache¶ | |||||
Any | 623 (55.3) | 396 (35.1) | 708 (64.5) | 264 (24.5) | |
Mild | 361 (32.0) | 256 (22.7) | 302 (27.5) | 170 (15.8) | |
Moderate | 251 (22.3) | 131 (11.6) | 384 (35.0) | 93 (8.6) | |
Severe | 11 (1.0) | 9 (0.8) | 22 (2.0) | 1 (0.1) | |
Chills¶ | |||||
Any | 311 (27.6) | 109 (9.7) | 455 (41.5) | 74 (6.9) | |
Mild | 195 (17.3) | 82 (7.3) | 221 (20.1) | 53 (4.9) | |
Moderate | 111 (9.8) | 25 (2.2) | 214 (19.5) | 21 (1.9) | |
Severe | 5 (0.4) | 2 (0.2) | 20 (1.8) | 0 (0.0) | |
Vomiting# | |||||
Any | 31 (2.8) | 10 (0.9) | 29 (2.6) | 12 (1.1) | |
Mild | 30 (2.7) | 8 (0.7) | 25 (2.3) | 11 (1.0) | |
Moderate | 0 (0.0) | 2 (0.2) | 4 (0.4) | 1 (0.1) | |
Severe | 1 (0.1) | 0 (0.0) | 0 (0.0) | 0 (0.0) | |
DiarrheaÞ | |||||
Any | 90 (8.0) | 82 (7.3) | 65 (5.9) | 44 (4.1) | |
Mild | 77 (6.8) | 72 (6.4) | 59 (5.4) | 39 (3.6) | |
Moderate | 13 (1.2) | 10 (0.9) | 6 (0.5) | 5 (0.5) | |
Severe | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | |
New or worsened muscle pain¶ | |||||
Any | 272 (24.1) | 148 (13.1) | 355 (32.4) | 90 (8.3) | |
Mild | 125 (11.1) | 88 (7.8) | 152 (13.9) | 51 (4.7) | |
Moderate | 145 (12.9) | 60 (5.3) | 197 (18.0) | 37 (3.4) | |
Severe | 2 (0.2) | 0 (0.0) | 6 (0.5) | 2 (0.2) | |
New or worsened joint pain¶ | |||||
Any | 109 (9.7) | 77 (6.8) | 173 (15.8) | 51 (4.7) | |
Mild | 66 (5.9) | 50 (4.4) | 91 (8.3) | 30 (2.8) | |
Moderate | 42 (3.7) | 27 (2.4) | 78 (7.1) | 21 (1.9) | |
Severe | 1 (0.1) | 0 (0.0) | 4 (0.4) | 0 (0.0) | |
Use of antipyretic or pain medicationß | 413 (36.6) | 111 (9.8) | 557 (50.8) | 95 (8.8) | |
Unsolicited Adverse Events in Study 2
In Study 2, 2,260 adolescents (1,131 COMIRNATY; 1,129 placebo) were 12 through 15 years of age. Of these, 634 (56.1%) participants in the COMIRNATY group and 629 (55.7%) participants in the placebo group had follow-up time between ≥4 months to <6 months after Dose 2 in the blinded placebo-controlled follow-up period with an additional 152 (13.4%) and 144 (12.8%) with ≥6 months of blinded follow-up time in the COMIRNATY and placebo groups, respectively.
A total of 1,113 (98.4%) participants 12 through 15 years of age originally randomized to COMIRNATY had ≥6 months total (blinded and unblinded) follow-up after Dose 2. An analysis of all unsolicited adverse events in Study 2 from Dose 1 up to the participant unblinding date was conducted. Among participants 12 through 15 years of age who received at least 1 dose of study vaccine, unsolicited adverse events were reported by 95 (8.4%) participants in the COMIRNATY group and 113 (10.0%) participants in the placebo group.
In an analysis of all unsolicited adverse events reported during blinded follow-up from Dose 1 through 1 month after Dose 2, in adolescents 12 to 15 years of age, those assessed as adverse reactions not already captured by solicited local and systemic reactions were lymphadenopathy (9 vs. 2), and nausea (5 vs. 2).
In the analysis of blinded, placebo-controlled follow-up, there were no other notable patterns or numerical imbalances between treatment groups for specific categories of unsolicited adverse events (including other neurologic or neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to COMIRNATY. In the analysis of unblinded follow-up, there were no notable patterns of specific categories of non-serious adverse events that would suggest a causal relationship to COMIRNATY.
Serious Adverse Events
In Study 2, among participants 12 through 15 years of age who had received at least 1 dose of vaccine or placebo (COMIRNATY = 1,131; placebo = 1,129), serious adverse events from Dose 1 up to the participant unblinding date in ongoing follow-up were reported by 10 (0.9%) COMIRNATY recipients and 2 (0.2%) placebo recipients. In these analyses, 69.0% of study participants had at least 4 months of follow-up after Dose 2. In the analysis of blinded, placebo-controlled follow-up, there were no notable patterns between treatment groups for specific categories of serious adverse events (including neurologic, neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to COMIRNATY. In the analysis of unblinded follow-up, there were no notable patterns of specific categories of serious adverse events that would suggest a causal relationship to COMIRNATY.
Participants 16 Years of Age and Older
At the time of the analysis of Study 2 with a data cutoff of March 13, 2021, there were 25,651 (58.2%) participants (13,031 COMIRNATY; 12,620 placebo) 16 years of age and older followed for ≥4 months after the second dose.
Demographic characteristics in Study 2 were generally similar with regard to age, gender, race, and ethnicity among participants who received COMIRNATY and those who received placebo. Overall, among the total participants who received either COMIRNATY or placebo, 50.9% were male, 49.1% were female, 79.3% were 16 through 64 years of age, 20.7% were 65 years of age and older, 82.0% were White, 9.6% were Black or African American, 25.9% were Hispanic/Latino, 4.3% were Asian, and 1.0% were American Indian or Alaska Native.
Local and Systemic Adverse Reactions Solicited in the Study 2
In participants 16 through 55 years of age after receiving Dose 2, the mean duration of pain at the injection site was 2.5 days (range 1 to 70 days), for redness 2.2 days (range 1 to 9 days), and for swelling 2.1 days (range 1 to 8 days) for participants in the COMIRNATY group.
In participants 56 years of age and older after receiving Dose 2, the mean duration of pain at the injection site was 2.4 days (range 1 to 36 days), for redness 3.0 days (range 1 to 34 days), and for swelling 2.6 days (range 1 to 34 days) for participants in the COMIRNATY group.
| Notes: Reactions were collected in the electronic diary (e-diary) from Day 1 to Day 7 after vaccination. No Grade 4 solicited local reactions were reported in participants 16 through 55 years of age. | ||||
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COMIRNATY† Dose 1 N‡=2899 n§ (%) | Placebo Dose 1 N‡=2908 n§ (%) | COMIRNATY† Dose 2 N‡=2682 n§ (%) | Placebo Dose 2 N‡=2684 n§ (%) | |
Redness¶ | ||||
Any (>2.0 cm) | 156 (5.4) | 28 (1.0) | 151 (5.6) | 18 (0.7) |
Mild | 113 (3.9) | 19 (0.7) | 90 (3.4) | 12 (0.4) |
Moderate | 36 (1.2) | 6 (0.2) | 50 (1.9) | 6 (0.2) |
Severe | 7 (0.2) | 3 (0.1) | 11 (0.4) | 0 |
Swelling¶ | ||||
Any (>2.0 cm) | 184 (6.3) | 16 (0.6) | 183 (6.8) | 5 (0.2) |
Mild | 124 (4.3) | 6 (0.2) | 110 (4.1) | 3 (0.1) |
Moderate | 54 (1.9) | 8 (0.3) | 66 (2.5) | 2 (0.1) |
Severe | 6 (0.2) | 2 (0.1) | 7 (0.3) | 0 |
Pain at the injection site# | ||||
Any | 2426 (83.7) | 414 (14.2) | 2101 (78.3) | 312 (11.6) |
Mild | 1464 (50.5) | 391 (13.4) | 1274 (47.5) | 284 (10.6) |
Moderate | 923 (31.8) | 20 (0.7) | 788 (29.4) | 28 (1.0) |
Severe | 39 (1.3) | 3 (0.1) | 39 (1.5) | 0 |
| Notes: Reactions and use of antipyretic or pain medication were collected in the electronic diary (e-diary) from Day 1 to Day 7 after each dose. No Grade 4 solicited systemic reactions were reported in participants 16 through 55 years of age. | |||||
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COMIRNATY† Dose 1 N‡=2899 n§ (%) | Placebo Dose 1 N‡=2908 n§ (%) | COMIRNATY† Dose 2 N‡=2682 n§ (%) | Placebo Dose 2 N‡=2684 n§ (%) | ||
Fever | |||||
≥38.0℃ | 119 (4.1) | 25 (0.9) | 440 (16.4) | 11 (0.4) | |
≥38.0℃ to 38.4℃ | 86 (3.0) | 16 (0.6) | 254 (9.5) | 5 (0.2) | |
>38.4℃ to 38.9℃ | 25 (0.9) | 5 (0.2) | 146 (5.4) | 4 (0.1) | |
>38.9℃ to 40.0℃ | 8 (0.3) | 4 (0.1) | 39 (1.5) | 2 (0.1) | |
>40.0℃ | 0 | 0 | 1 (0.0) | 0 | |
Fatigue¶ | |||||
Any | 1431 (49.4) | 960 (33.0) | 1649 (61.5) | 614 (22.9) | |
Mild | 760 (26.2) | 570 (19.6) | 558 (20.8) | 317 (11.8) | |
Moderate | 630 (21.7) | 372 (12.8) | 949 (35.4) | 283 (10.5) | |
Severe | 41 (1.4) | 18 (0.6) | 142 (5.3) | 14 (0.5) | |
Headache¶ | |||||
Any | 1262 (43.5) | 975 (33.5) | 1448 (54.0) | 652 (24.3) | |
Mild | 785 (27.1) | 633 (21.8) | 699 (26.1) | 404 (15.1) | |
Moderate | 444 (15.3) | 318 (10.9) | 658 (24.5) | 230 (8.6) | |
Severe | 33 (1.1) | 24 (0.8) | 91 (3.4) | 18 (0.7) | |
Chills¶ | |||||
Any | 479 (16.5) | 199 (6.8) | 1015 (37.8) | 114 (4.2) | |
Mild | 338 (11.7) | 148 (5.1) | 477 (17.8) | 89 (3.3) | |
Moderate | 126 (4.3) | 49 (1.7) | 469 (17.5) | 23 (0.9) | |
Severe | 15 (0.5) | 2 (0.1) | 69 (2.6) | 2 (0.1) | |
Vomiting# | |||||
Any | 34 (1.2) | 36 (1.2) | 58 (2.2) | 30 (1.1) | |
Mild | 29 (1.0) | 30 (1.0) | 42 (1.6) | 20 (0.7) | |
Moderate | 5 (0.2) | 5 (0.2) | 12 (0.4) | 10 (0.4) | |
Severe | 0 | 1 (0.0) | 4 (0.1) | 0 | |
DiarrheaÞ | |||||
Any | 309 (10.7) | 323 (11.1) | 269 (10.0) | 205 (7.6) | |
Mild | 251 (8.7) | 264 (9.1) | 219 (8.2) | 169 (6.3) | |
Moderate | 55 (1.9) | 58 (2.0) | 44 (1.6) | 35 (1.3) | |
Severe | 3 (0.1) | 1 (0.0) | 6 (0.2) | 1 (0.0) | |
New or worsened muscle pain¶ | |||||
Any | 664 (22.9) | 329 (11.3) | 1055 (39.3) | 237 (8.8) | |
Mild | 353 (12.2) | 231 (7.9) | 441 (16.4) | 150 (5.6) | |
Moderate | 296 (10.2) | 96 (3.3) | 552 (20.6) | 84 (3.1) | |
Severe | 15 (0.5) | 2 (0.1) | 62 (2.3) | 3 (0.1) | |
New or worsened joint pain¶ | |||||
Any | 342 (11.8) | 168 (5.8) | 638 (23.8) | 147 (5.5) | |
Mild | 200 (6.9) | 112 (3.9) | 291 (10.9) | 82 (3.1) | |
Moderate | 137 (4.7) | 55 (1.9) | 320 (11.9) | 61 (2.3) | |
Severe | 5 (0.2) | 1 (0.0) | 27 (1.0) | 4 (0.1) | |
Use of antipyretic or pain medicationß | 805 (27.8) | 398 (13.7) | 1213 (45.2) | 320 (11.9) | |
| Notes: Reactions were collected in the electronic diary (e-diary) from Day 1 to Day 7 after vaccination. No Grade 4 solicited local reactions were reported in participants 56 years of age and older. | |||||
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COMIRNATY† Dose 1 N‡=2008 n§ (%) | Placebo Dose 1 N‡=1989 n§ (%) | COMIRNATY† Dose 2 N‡=1860 n§ (%) | Placebo Dose 2 N‡=1833 n§ (%) | ||
Redness¶ | |||||
Any (>2.0 cm) | 106 (5.3) | 20 (1.0) | 133 (7.2) | 14 (0.8) | |
Mild | 71 (3.5) | 13 (0.7) | 65 (3.5) | 10 (0.5) | |
Moderate | 30 (1.5) | 5 (0.3) | 58 (3.1) | 3 (0.2) | |
Severe | 5 (0.2) | 2 (0.1) | 10 (0.5) | 1 (0.1) | |
Swelling¶ | |||||
Any (>2.0 cm) | 141 (7.0) | 23 (1.2) | 145 (7.8) | 13 (0.7) | |
Mild | 87 (4.3) | 11 (0.6) | 80 (4.3) | 5 (0.3) | |
Moderate | 52 (2.6) | 12 (0.6) | 61 (3.3) | 7 (0.4) | |
Severe | 2 (0.1) | 0 | 4 (0.2) | 1 (0.1) | |
Pain at the injection site# | |||||
Any (>2.0 cm) | 1408 (70.1) | 185 (9.3) | 1230 (66.1) | 143 (7.8) | |
Mild | 1108 (55.2) | 177 (8.9) | 873 (46.9) | 138 (7.5) | |
Moderate | 296 (14.7) | 8 (0.4) | 347 (18.7) | 5 (0.3) | |
Severe | 4 (0.2) | 0 | 10 (0.5) | 0 | |
| Notes: Reactions and use of antipyretic or pain medication were collected in the electronic diary (e-diary) from Day 1 to Day 7 after each dose. The only Grade 4 solicited systemic reaction reported in participants 56 years of age and older was fatigue. | |||||
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COMIRNATY† Dose 1 N‡=2008 n§ (%) | Placebo Dose 1 N‡=1989 n§ (%) | COMIRNATY† Dose 2 N‡=1860 n§ (%) | Placebo Dose 2 N‡=1833 n§ (%) | ||
Fever | |||||
≥38.0℃ | 26 (1.3) | 8 (0.4) | 219 (11.8) | 4 (0.2) | |
≥38.0℃ to 38.4℃ | 23 (1.1) | 3 (0.2) | 158 (8.5) | 2 (0.1) | |
>38.4℃ to 38.9℃ | 2 (0.1) | 3 (0.2) | 54 (2.9) | 1 (0.1) | |
>38.9℃ to 40.0℃ | 1 (0.0) | 2 (0.1) | 7 (0.4) | 1 (0.1) | |
>40.0℃ | 0 | 0 | 0 | 0 | |
Fatigue¶ | |||||
Any | 677 (33.7) | 447 (22.5) | 949 (51.0) | 306 (16.7) | |
Mild | 415 (20.7) | 281 (14.1) | 391 (21.0) | 183 (10.0) | |
Moderate | 259 (12.9) | 163 (8.2) | 497 (26.7) | 121 (6.6) | |
Severe | 3 (0.1) | 3 (0.2) | 60 (3.2) | 2 (0.1) | |
Grade 4 | 0 | 0 | 1 (0.1) | 0 | |
Headache¶ | |||||
Any | 503 (25.0) | 363 (18.3) | 733 (39.4) | 259 (14.1) | |
Mild | 381 (19.0) | 267 (13.4) | 464 (24.9) | 189 (10.3) | |
Moderate | 120 (6.0) | 93 (4.7) | 256 (13.8) | 65 (3.5) | |
Severe | 2 (0.1) | 3 (0.2) | 13 (0.7) | 5 (0.3) | |
Chills¶ | |||||
Any | 130 (6.5) | 69 (3.5) | 435 (23.4) | 57 (3.1) | |
Mild | 102 (5.1) | 49 (2.5) | 229 (12.3) | 45 (2.5) | |
Moderate | 28 (1.4) | 19 (1.0) | 185 (9.9) | 12 (0.7) | |
Severe | 0 | 1 (0.1) | 21 (1.1) | 0 | |
Vomiting# | |||||
Any | 10 (0.5) | 9 (0.5) | 13 (0.7) | 5 (0.3) | |
Mild | 9 (0.4) | 9 (0.5) | 10 (0.5) | 5 (0.3) | |
Moderate | 1 (0.0) | 0 | 1 (0.1) | 0 | |
Severe | 0 | 0 | 2 (0.1) | 0 | |
DiarrheaÞ | |||||
Any | 168 (8.4) | 130 (6.5) | 152 (8.2) | 102 (5.6) | |
Mild | 137 (6.8) | 109 (5.5) | 125 (6.7) | 76 (4.1) | |
Moderate | 27 (1.3) | 20 (1.0) | 25 (1.3) | 22 (1.2) | |
Severe | 4 (0.2) | 1 (0.1) | 2 (0.1) | 4 (0.2) | |
New or worsened muscle pain¶ | |||||
Any | 274 (13.6) | 165 (8.3) | 537 (28.9) | 99 (5.4) | |
Mild | 183 (9.1) | 111 (5.6) | 229 (12.3) | 65 (3.5) | |
Moderate | 90 (4.5) | 51 (2.6) | 288 (15.5) | 33 (1.8) | |
Severe | 1 (0.0) | 3 (0.2) | 20 (1.1) | 1 (0.1) | |
New or worsened joint pain¶ | |||||
Any | 175 (8.7) | 124 (6.2) | 353 (19.0) | 72 (3.9) | |
Mild | 119 (5.9) | 78 (3.9) | 183 (9.8) | 44 (2.4) | |
Moderate | 53 (2.6) | 45 (2.3) | 161 (8.7) | 27 (1.5) | |
Severe | 3 (0.1) | 1 (0.1) | 9 (0.5) | 1 (0.1) | |
Use of antipyretic or pain medicationß | 382 (19.0) | 224 (11.3) | 688 (37.0) | 170 (9.3) | |
In participants with chronic, stable HIV infection the frequencies of solicited local and systemic adverse reactions were similar to or lower than those observed for all participants 16 years of age and older.
Unsolicited Adverse Events
Overall, 11,253 (51.1%) participants 16 years of age and older in the COMIRNATY group and 11,316 (51.4%) participants in the placebo group had follow-up time between ≥4 months to <6 months after Dose 2 in the blinded placebo-controlled follow-up period with an additional 1,778 (8.1%) and 1,304 (5.9%) with ≥6 months of blinded follow-up time in the COMIRNATY and placebo groups, respectively.
A total of 12,006 (54.5%) participants originally randomized to COMIRNATY had ≥6 months total (blinded and unblinded) follow-up after Dose 2.
In an analysis of all unsolicited adverse events reported following any dose, through 1 month after Dose 2, in participants 16 years of age and older (N = 43,847; 21,926 COMIRNATY group vs. 21,921 placebo group), those assessed as adverse reactions not already captured by solicited local and systemic reactions were nausea (274 vs. 87), malaise (130 vs. 22), lymphadenopathy (83 vs. 7), asthenia (76 vs. 25), decreased appetite (39 vs. 9), hyperhidrosis (31 vs. 9), lethargy (25 vs. 6), and night sweats (17 vs. 3).
In analyses of all unsolicited adverse events in Study 2 from Dose 1 up to the participant unblinding date, 58.2% of study participants had at least 4 months of follow-up after Dose 2. Among participants 16 through 55 years of age who received at least 1 dose of study vaccine, 12,995 of whom received COMIRNATY and 13,026 of whom received placebo, unsolicited adverse events were reported by 4,396 (33.8%) participants in the COMIRNATY group and 2,136 (16.4%) participants in the placebo group. In a similar analysis in participants 56 years of age and older that included 8,931 COMIRNATY recipients and 8,895 placebo recipients, unsolicited adverse events were reported by 2,551 (28.6%) participants in the COMIRNATY group and 1,432 (16.1%) participants in the placebo group. Among participants with confirmed stable HIV infection that included 100 COMIRNATY recipients and 100 placebo recipients, unsolicited adverse events were reported by 29 (29%) participants in the COMIRNATY group and 15 (15%) participants in the placebo group. The higher frequency of reported unsolicited adverse events among COMIRNATY recipients compared to placebo recipients was primarily attributed to events that are consistent with adverse reactions solicited among participants in the reactogenicity subset (Table 6 and Table 7).
Throughout the placebo-controlled safety follow-up period, Bell's palsy (facial paralysis) was reported by 4 participants in the COMIRNATY group and 2 participants in the placebo group. Onset of facial paralysis was Day 37 after Dose 1 (participant did not receive Dose 2) and Days 3, 9, and 48 after Dose 2. In the placebo group the onset of facial paralysis was Day 32 and Day 102. Currently available information is insufficient to determine a causal relationship with the vaccine. In the analysis of blinded, placebo-controlled follow-up, there were no other notable patterns or numerical imbalances between treatment groups for specific categories of non-serious adverse events (including other neurologic or neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to COMIRNATY. In the analysis of unblinded follow-up, there were no notable patterns of specific categories of non-serious adverse events that would suggest a causal relationship to COMIRNATY.
Serious Adverse Events
Participants 16 through 55 years of age in Study 2 who had received at least 1 dose of vaccine or placebo (COMIRNATY = 12,995; placebo = 13,026), reported serious adverse events from Dose 1 up to the participant unblinding date in ongoing follow-up as follows: 103 (0.8%) COMIRNATY recipients and 117 (0.9%) placebo recipients. In a similar analysis, in participants 56 years of age and older (8,931 COMIRNATY group and 8,895 placebo group), serious adverse events were reported by 165 (1.8%) COMIRNATY recipients and 151 (1.7%) placebo recipients who received at least 1 dose of COMIRNATY or placebo, respectively. In these analyses, 58.2% of study participants had at least 4 months of follow-up after Dose 2. Among participants with confirmed stable HIV infection serious adverse events from Dose 1 up to the participant unblinding date in ongoing follow-up were reported by 2 (2%) COMIRNATY recipients and 2 (2%) placebo recipients.
In the analysis of blinded, placebo-controlled follow-up, there were no notable patterns between treatment groups for specific categories of serious adverse events (including neurologic, neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to COMIRNATY. In the analysis of unblinded follow-up, there were no notable patterns of specific categories of serious adverse events that would suggest a causal relationship to COMIRNATY.
First Booster Dose With COMIRNATY Following the Primary Series
12 Through 15 Years of Age
A subset of 825 Study 2 Phase 2/3 participants 12 through 15 years of age received a booster dose of COMIRNATY 11.2 months (median time, range 6.3 to 20.1 months) after completing the primary series and had a median follow-up time of 9.5 months up to a data cutoff date of November 3, 2022. The median age of participants was 14.0 years (range 13 through 15 years of age), 49.3% were male and 50.7% were female, 83.5% were White, 10.8% were Hispanic/Latino, 4.6% were Black or African American, 7.5% were Asian, and 0.4% were American Indian/Alaska Native.
Adverse reactions reported in participants receiving a booster dose of COMIRNATY were similar to those previously observed in participants receiving COMIRNATY as part of the primary series. Lymphadenopathy occurred in 8 (1.0%) participants who received a booster dose of COMIRNATY and in 9 (0.8%) participants who received COMIRNATY as a primary series.
12 Through 17 Years of Age
A subset of 65 Study 4 participants 12 through 17 years of age received a booster dose of COMIRNATY 13.3 months (median time, range 6.5 to 16.9 months) after completing the primary series and had a median follow-up time of 5.6 months up to a data cutoff date of July 14, 2022. The median age of participants was 14 years (range 12 through 17 years of age), 49.2% were male and 50.8% were female, 76.9% were White, 16.9% were Hispanic/Latino, 13.8% were Black or African American, 7.7% were Asian, and 1.5% were American Indian/Alaska Native.
Adverse reactions reported in participants receiving a booster dose of COMIRNATY were similar to those previously observed in participants receiving COMIRNATY as part of the primary series. There were no cases of lymphadenopathy reported in participants who received a booster dose of COMIRNATY.
16 Years of Age and Older
In Study 4, a double-blind placebo-controlled booster study, 5,081 participants 16 years of age and older recruited from Study 2 received a booster dose of COMIRNATY 10.8 months (median time, range of 5.0 to 12.6 months) after completing the primary series of COMIRNATY series and had a median follow-up time of 2.9 months based on data up to the cutoff date of February 8, 2022. The median age of participants who received COMIRNATY or placebo was 53.0 years (range 16 through 87 years of age), 49.1% were male and 50.9% were female, 79.0% were White, 14.9% were Hispanic/Latino, 9.2% were Black or African American, 5.5% were Asian, and 1.7% were American Indian/Alaska Native.
Adverse reactions reported in participants receiving a booster dose of COMIRNATY were similar to those previously observed in participants receiving COMIRNATY as part of the primary series. Lymphadenopathy occurred in 141 (2.8%) participants who received a booster dose of COMIRNATY and in 83 (0.4%) participants who received COMIRNATY as a primary series.
18 Through 55 Years of Age
A subset of 306 Study 2 Phase 2/3 participants 18 through 55 years of age received a booster dose of COMIRNATY 6.8 months (median time, range 4.8 to 8.0 months) after completing the primary series. These participants had a median follow-up time of 8.3 months up to a data cutoff date of November 22, 2021. Among the 306 participants, the median age was 42 years (range 19 through 55 years of age), 45.8% were male and 54.2% were female, 81.4% were White, 27.8% were Hispanic/Latino, 9.2% were Black or African American, 5.2% were Asian, and 0.7% were American Indian/Alaska Native.
Adverse reactions reported in participants receiving a booster dose of COMIRNATY were similar to those previously observed in participants receiving COMIRNATY as part of the primary series. Lymphadenopathy occurred in 16 (5.2%) of participants who received a booster dose of COMIRNATY and 83 (0.4%) in participants who received COMIRNATY as a primary series.
Second Booster With Pfizer-BioNTech COVID-19 Vaccine, Bivalent
12 Years of Age and Older
A subset of 107 Study 5 Phase 2/3 participants 12 through 17 years of age, 313 participants 18 through 55 years of age and 306 participants 56 years of age and older previously vaccinated with a 2-dose primary series and 1 booster dose of COMIRNATY, went on to receive a second booster dose with Pfizer-BioNTech COVID-19 Vaccine, Bivalent.
Participants received a second booster dose 11.1 months (median time; range 5.4 to 16.9 months) after receiving the first booster dose and had a median follow-up time of 1.5 months up to a data cutoff date of October 31, 2022. The median age was 48.0 years, 42.7% were male, 57.3% were female, 80.6% were White, 11.4% were Hispanic/Latino, 5.9% were Asian, and 11.4% were Black or African American.
Local and Systemic Adverse Reactions Solicited in Study 5
Table 8 and Table 9 present the frequency and severity of reported solicited local reactions and systemic reactions, respectively, within 7 days of a second booster dose of Pfizer-BioNTech COVID-19 Vaccine, Bivalent.
In participants 12 years of age and older who received a second booster dose, the mean duration of injection site pain was 2.1 to 2.4 days (range 1 to 11 days), injection site redness was 1.5 to 2.5 days (range 1 to 4 days), and injection site swelling was 1.3 to 1.9 days (range 1 to 4 days), respectively.
| Note: Adverse Reactions were collected in the electronic diary (e-diary) from day of vaccination (Day 1) through Day 7 after the study vaccination. | |||
| |||
Pfizer-BioNTech COVID-19 Vaccine, Bivalent* | |||
12 Through 17 Years of Age N†=107 n‡ (%) | 18 Through 55 Years of Age n‡ (%) | 56 Years of Age and Older n‡ (%) | |
Redness¶ | |||
Any (>2 cm) | 6 (5.6) | 21 (6.8%) | 11 (3.7%) |
Mild | 4 (3.7) | 16 (5.2%) | 7 (2.3) |
Moderate | 2 (1.9) | 5 (1.6) | 4 (1.3%) |
Severe | 0 | 0 | 0 |
Swelling¶ | |||
Any (>2 cm) | 8 (7.5) | 23 (7.4%) | 8 (2.7) |
Mild | 6 (5.6) | 19 (6.1%) | 5 (1.7) |
Moderate | 2 (1.9) | 4 (1.3) | 3 (1.0) |
Severe | 0 | 0 | 0 |
Pain at the injection site# | |||
Any | 75 (70.1) | 236 (76.1) | 172 (57.1) |
Mild | 45 (42.1) | 178 (57.4) | 147 (48.8) |
Moderate | 29 (27.1) | 58 (18.7) | 24 (8.0) |
Severe | 1 (0.9) | 0 | 1 (0.3) |
| Note: Adverse reactions and use of antipyretic or pain medication were collected in the electronic diary (e-diary) from day of vaccination (Day 1) through Day 7 after the study vaccination. | |||
| |||
Pfizer-BioNTech COVID-19 Vaccine, Bivalent* | |||
12 Through 17 Years of Age N†=107 n‡ (%) | 18 Through 55 Years of Age N†=309 n‡ (%) | 56 Years of Age and Older n‡ (%) | |
Fever | |||
≥38.0℃ | 10 (9.3) | 15 (4.9) | 14 (4.7) |
≥38.0℃ to 38.4℃ | 7 (6.5) | 9 (2.9) | 10 (3.3) |
>38.4℃ to 38.9℃ | 2 (1.9) | 6 (1.9) | 3 (1.0) |
>38.9℃ to 40.0℃ | 1 (0.9) | 0 | 0 |
>40.0℃ | 0 | 0 | 0 |
Fatigue¶ | |||
Any | 72 (67.3) | 189 (61.2) | 116 (38.5) |
Mild | 27 (25.2) | 83 (26.9) | 56 (18.6) |
Moderate | 45 (42.1) | 100 (32.4) | 56 (18.6) |
Severe | 0 | 6 (1.9) | 4 (1.3) |
Headache¶ | |||
Any | 54 (50.5) | 144 (46.6) | 92 (30.7) |
Mild | 28 (26.2) | 87 (28.2) | 62 (20.7) |
Moderate | 26 (24.3) | 55 (17.8) | 30 (10.0) |
Severe | 0 | 2 (0.6) | 0 |
Chills¶ | |||
Any | 25 (23.4) | 68 (22.0) | 36 (12.0) |
Mild | 19 (17.8) | 38 (12.3) | 21 (7.0) |
Moderate | 6 (5.6) | 28 (9.1) | 14 (4.7) |
Severe | 0 | 2 (0.6) | 1 (0.3) |
Vomiting# | |||
Any | 3 (2.8) | 6 (1.9) | 2 (0.7) |
Mild | 3 (2.8) | 5 (1.6) | 2 (0.7) |
Moderate | 0 | 1 (0.3) | 0 |
Severe | 0 | 0 | 0 |
DiarrheaÞ | |||
Any | 7 (6.5) | 33 (10.7) | 29 (9.6) |
Mild | 7 (6.5) | 27 (8.7) | 23 (7.6) |
Moderate | 0 | 5 (1.6) | 6 (2.0) |
Severe | 0 | 1 (0.3) | 0 |
New or worsened muscle pain¶ | |||
Any | 28 (26.2) | 94 (30.4) | 54 (18.0) |
Mild | 12 (11.2) | 47 (15.2) | 30 (10.0) |
Moderate | 16 (15.0) | 47 (15.2) | 24 (8.0) |
Severe | 0 | 0 | 0 |
New or worsened joint pain¶ | |||
Any | 13 (12.1) | 46 (14.9) | 36 (12.0) |
Mild | 9 (8.4) | 21 (6.8) | 20 (6.7) |
Moderate | 4 (3.7) | 25 (8.1) | 16 (5.3) |
Severe | 0 | 0 | 0 |
Use of antipyretic or pain medicationß | 36 (33.6) | 105 (34.0) | 74 (24.7) |
Unsolicited Adverse Events
Among participants 12 years of age and older, unsolicited adverse events were reported by 48 (6.6%) participants who received a second booster dose through 1 month after the booster dose. Lymphadenopathy occurred in 7 (1.0%) participants.
Concomitant Administration of COMIRNATY With Influenza Vaccine in Individuals 18 Through 64 Years of Age
In Study 8 (NCT05310084), a Phase 3 study, participants 18 through 64 years of age who received COMIRNATY concomitantly administered with Influenza Vaccine (Afluria Quadrivalent) followed 1 month later by saline placebo (n = 564) were compared to participants who received influenza vaccine with saline placebo followed 1 month later by COMIRNATY (n = 564).
Demographic characteristics in Study 8 among the participants in the concomitant administration and separate administration groups were similar with regard to age, sex, race, and ethnicity. Among the 564 participants in the concomitant administration group, the median age was 39.0 years (range 18 through 64 years of age), 36.9% were male and 63.1% were female, 79.1% were White, 12.9% were Asian, and 0.9% were Hispanic/Latino.
Solicited local and systemic adverse reactions were reported more frequently by participants who received COMIRNATY concomitantly with influenza vaccine, compared to participants who received COMIRNATY alone. The most common adverse reactions reported in the concomitant administration group and after COMIRNATY alone were injection site pain (COMIRNATY injection site) (86.2% and 84.4%, respectively), fatigue (64.0% and 50.8%, respectively), and headache (47.2% and 37.8%, respectively).
The following adverse reactions have been identified during postmarketing use of COMIRNATY, Pfizer-BioNTech COVID-19 Vaccine and Pfizer-BioNTech COVID-19 Vaccine, Bivalent. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccine exposure.
Cardiac Disorders: myocarditis, pericarditis
Gastrointestinal Disorders: diarrhea, vomiting
Immune System Disorders: severe allergic reactions, including anaphylaxis, and other hypersensitivity reactions (e.g., rash, pruritus, urticaria, angioedema)
Musculoskeletal and Connective Tissue Disorders: pain in extremity (arm)
Nervous System Disorders: syncope, dizziness
Cardiovascular Outcomes in Patients Diagnosed With mRNA COVID-19 Vaccine-associated Myocarditis
In a longitudinal retrospective observational cohort study across 38 hospitals in the U.S., information on cardiovascular outcomes was collected on 333 patients 5 through 29 years of age who had been diagnosed with COVID-19 vaccine-associated myocarditis. Among these patients, 322 were confirmed to have received an mRNA COVID-19 vaccine encoding the S glycoprotein of the Original SARS-CoV-2. Of 331 patients, 278 had onset of symptoms following the second dose of a primary series, 33 following the first dose of a primary series, and 20 following a first booster dose1.
Among 307 patients who had been diagnosed with COVID-19 vaccine-associated myocarditis for whom follow-up information was available, 89 reported cardiac symptoms at a median follow-up of 91 days (interquartile range 25-186 days) post-vaccination1.
Initial gadolinium-enhanced cardiac magnetic resonance imaging (CMR) was performed on 216 patients, of whom 177 had late gadolinium enhancement (LGE), a marker of myocardial injury. Among 161 patients who had LGE on initial CMR and who had a follow-up gadolinium-enhanced CMR at a median follow-up of 159 days (interquartile range 78-253 days), 98 had persistence of LGE. Overall, the severity of LGE decreased during follow-up. The clinical and prognostic significance of these CMR findings is not known1.
Limitations of this study include potential selection bias towards patients with more severe myocarditis who are more likely to be hospitalized and have CMR, variability in diagnostic testing, and variability in follow-up1.
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