Comirnaty (COVID-19 Vaccine, mRNA) injection, suspension
Pfizer Laboratories Div Pfizer Inc

Pfizer Laboratories Div Pfizer Inc
Pfizer Inc
Pfizer Manufacturing Belgium NV
Wyeth BioPharma Division of Wyeth Pharmaceuticals LLC
Pfizer Ireland Pharmaceuticals
BioNTech Innovative Manufacturing Services GmbH
BioNTech Manufacturing GmbH
BioNTech Manufacturing Marburg GmbH
Pharmacia & Upjohn Company LLC
Exela Pharma Sciences, LLC.
Comirnaty
COVID-19 Vaccine, mRNA
RAXTOZINAMERAN
RAXTOZINAMERAN
((4-HYDROXYBUTYL)AZANEDIYL)BIS(HEXANE-6,1-DIYL)BIS(2-HEXYLDECANOATE)
2-(MPEG 2000)-N,N-DITETRADECYLACETAMIDE
1,2-DISTEAROYL-SN-GLYCERO-3-PHOSPHOCHOLINE
CHOLESTEROL
SUCROSE
TROMETHAMINE
TROMETHAMINE HYDROCHLORIDE
WATER
Comirnaty
COVID-19 Vaccine, mRNA
RAXTOZINAMERAN
RAXTOZINAMERAN
((4-HYDROXYBUTYL)AZANEDIYL)BIS(HEXANE-6,1-DIYL)BIS(2-HEXYLDECANOATE)
2-(MPEG 2000)-N,N-DITETRADECYLACETAMIDE
1,2-DISTEAROYL-SN-GLYCERO-3-PHOSPHOCHOLINE
CHOLESTEROL
SUCROSE
TROMETHAMINE
TROMETHAMINE HYDROCHLORIDE
WATER
Comirnaty
COVID-19 Vaccine, mRNA
RAXTOZINAMERAN
RAXTOZINAMERAN
((4-HYDROXYBUTYL)AZANEDIYL)BIS(HEXANE-6,1-DIYL)BIS(2-HEXYLDECANOATE)
2-(MPEG 2000)-N,N-DITETRADECYLACETAMIDE
1,2-DISTEAROYL-SN-GLYCERO-3-PHOSPHOCHOLINE
CHOLESTEROL
SUCROSE
TROMETHAMINE
TROMETHAMINE HYDROCHLORIDE
WATER

Dosage and Administration, Preparation for Administration (2.1)

10/2023

Dosage and Administration, Administration Information (2.2)

9/2023

Dosage and Administration, Vaccination Schedule (2.3)

9/2023

Warnings and Precautions, Myocarditis and Pericarditis (5.2)

9/2023

1 INDICATIONS AND USAGE

COMIRNATY is a vaccine indicated for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 12 years of age and older.

COMIRNATY is a vaccine indicated for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 12 years of age and older. (1)

2 DOSAGE AND ADMINISTRATION

For intramuscular injection only.

  •   For intramuscular injection only. (2)
  • COMIRNATY is administered as a single 0.3 mL dose. (2.2)
  • For individuals previously vaccinated with any COVID-19 vaccine, administer the dose of COMIRNATY at least 2 months after the last dose of COVID-19 vaccine. (2.3)

2.1 Preparation for Administration

COMIRNATY Single Dose Glass Prefilled Syringes

  • If glass prefilled syringe has been frozen, discard.
  • Do not shake.
  • Remove tip cap by slowly turning the cap counterclockwise while holding the Luer lock and attach a sterile needle.

COMIRNATY Single Dose Plastic Prefilled Syringes

  • If syringes are frozen, thaw syringe in the carton in the refrigerator [2ºC to 8ºC (35ºF to 46ºF)] or at room temperature [up to 25ºC (77ºF)]. Do not remove syringe from carton to thaw.
  • Do not shake.
  • Remove tip cap and attach a sterile needle.

COMIRNATY Single Dose Vials

  • Verify that the vial states 2023-2024 Formula.
  • If vials are frozen, thaw vial in the refrigerator [2ºC to 8ºC (35ºF to 46ºF)] or at room temperature [up to 25ºC (77ºF)].
  • Prior to use, mix by inverting vial gently 10 times. Do not shake.
  • Withdraw a single 0.3 mL dose using a sterile needle and syringe.
  • Discard vial and any excess volume.

2.2 Administration Information

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The vaccine will be a white to off-white suspension. Do not administer if vaccine is discolored or contains particulate matter.

Administer the 0.3 mL dose intramuscularly immediately after preparation. For the prefilled syringe, administer the entire volume to deliver a single 0.3 mL dose.

2.3 Vaccination Schedule

COMIRNATY is administered as a single dose for individuals 12 years of age and older.

For individuals previously vaccinated with any COVID-19 vaccine, administer the dose of COMIRNATY at least 2 months after the last dose of COVID-19 vaccine.

3 DOSAGE FORMS AND STRENGTHS

COMIRNATY is a suspension for injection. A single dose is 0.3 mL.

Suspension for injection. A single dose is 0.3 mL. (3)

4 CONTRAINDICATIONS

Do not administer COMIRNATY to individuals with known history of a severe allergic reaction (e.g., anaphylaxis) to any component of COMIRNATY [see Description (11)] or to individuals who had a severe allergic reaction (e.g., anaphylaxis) following a previous dose of a Pfizer-BioNTech COVID-19 vaccine.

Known history of a severe allergic reaction (e.g., anaphylaxis) to any component of COMIRNATY. (4)

5 WARNINGS AND PRECAUTIONS

  • Postmarketing data with authorized or approved mRNA COVID-19 vaccines demonstrate increased risks of myocarditis and pericarditis, particularly within the first week following vaccination. For COMIRNATY, the observed risk is highest in males 12 through 17 years of age. (5.2)
  • Syncope (fainting) may occur in association with administration of injectable vaccines, including COMIRNATY. Procedures should be in place to avoid injury from fainting. (5.3)

5.1 Management of Acute Allergic Reactions

Appropriate medical treatment used to manage immediate allergic reactions must be immediately available in the event an acute anaphylactic reaction occurs following administration of COMIRNATY.

5.2 Myocarditis and Pericarditis

Postmarketing data with authorized or approved mRNA COVID-19 vaccines demonstrate increased risks of myocarditis and pericarditis, particularly within the first week following vaccination. For COMIRNATY, the observed risk is highest in males 12 through 17 years of age. Although some cases required intensive care support, available data from short-term follow-up suggest that most individuals have had resolution of symptoms with conservative management. Information is not yet available about potential long-term sequelae.

The Centers for Disease Control and Prevention (CDC) has published considerations related to myocarditis and pericarditis after vaccination, including for vaccination of individuals with a history of myocarditis or pericarditis (https://www.cdc.gov/vaccines/covid-19/clinical-considerations/myocarditis.html).

5.3 Syncope

Syncope (fainting) may occur in association with administration of injectable vaccines, including COMIRNATY. Procedures should be in place to avoid injury from fainting.

5.4 Altered Immunocompetence

Immunocompromised persons, including individuals receiving immunosuppressant therapy, may have a diminished immune response to COMIRNATY [see Use in Specific Populations (8.6)].

5.5 Limitation of Effectiveness

COMIRNATY may not protect all vaccine recipients.

6 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.

Table 1: Clinical Studies
Abbreviation: SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.

Study

Age Group

Vaccine Strain Composition

Dosing

Number of Participants

Primary Series

Study 1

(NCT04380701)

18 through 55 years

OriginalCOMIRNATY encoding the viral spike (S) glycoprotein of SARS-CoV-2 Wuhan-Hu-1 strain (Original).

Primary series

60

Study 2

(NCT04368728)

12 through 15 years of age

Original

Primary series

1131Received COMIRNATY during placebo-control period.

≥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.5Vaccine encoding the viral spike (S) glycoprotein of SARS-CoV-2 Wuhan-Hu-1 strain (Original) and Omicron variant lineages BA.4 and BA.5 (Omicron BA.4/BA.5), authorized as Pfizer-BioNTech COVID-19 Vaccine, Bivalent.

2nd booster

726

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%).

  • The most commonly reported adverse reactions (≥10%) after a dose of COMIRNATY were pain at the injection site (up to 90.5%), fatigue (up to 77.5%), headache (up to 75.5%), chills (up to 49.2%), muscle pain (up to 45.5%), joint pain (up to 27.5%), fever (up to 24.3%), injection site swelling (up to 11.8%), and injection site redness (up to 10.4%). (6.1)

    To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or VAERS at 1-800-822-7967 or http://vaers.hhs.gov.

6.1 Clinical Trials Experience

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.

Table 2: Study 2 – Frequency and Percentages of Adolescents With Solicited Local Reactions, by Maximum Severity, Within 7 Days After Each Dose – Adolescents 12 Through 15 Years of Age – Safety PopulationRandomized participants in the safety analysis population who received at least 1 dose of the study intervention.
Note: Reactions were collected in the electronic diary (e-diary) from Day 1 to Day 7 after vaccination.

COMIRNATY Vaccine encoding the viral spike (S) glycoprotein of SARS-CoV-2 Wuhan-Hu-1 strain (Original).

Dose 1

N N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. =1127

n n = Number of participants with the specified reaction. (%)

Placebo

Dose 1

N

=1127

n

(%)

COMIRNATY

Dose 2

N

=1097

n

(%)

Placebo

Dose 2

N

=1078

n

(%)

RednessMild: >2.0 to ≤5.0 cm; Moderate: >5.0 to ≤10.0 cm; Severe: >10.0 cm.

  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 siteMild: does not interfere with activity; Moderate: interferes with activity; Severe: prevents daily activity.

  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)

Table 3: Study 2 – Frequency and Percentages of Adolescents With Solicited Systemic Reactions, by Maximum Severity, Within 7 Days After Each Dose – Adolescents 12 Through 15 Years of Age – Safety PopulationRandomized participants in the safety analysis population who received at least 1 dose of the study intervention.
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.

COMIRNATY Vaccine encoding the viral spike (S) glycoprotein of SARS-CoV-2 Wuhan-Hu-1 strain (Original).

Dose 1

N N = Number of participants reporting at least 1 yes or no response for the specified event after the specified dose. =1127

n n = Number of participants with the specified reaction. (%)

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)

FatigueMild: does not interfere with activity; Moderate: some interference with activity; Severe: prevents daily activity.

  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)

VomitingMild: 1 to 2 times in 24 hours; Moderate: >2 times in 24 hours; Severe: requires intravenous hydration.

  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)

DiarrheaMild: 2 to 3 loose stools in 24 hours; Moderate: 4 to 5 loose stools in 24 hours; Severe: 6 or more loose stools in 24 hours.

  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 medicationSeverity was not collected for use of antipyretic or pain medication.

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.

Table 4: Study 2 – Frequency and Percentages of Participants With Solicited Local Reactions, by Maximum Severity, Within 7 Days After Each Dose – Participants 16 Through 55 Years of Age – Reactogenicity Subset of the Safety PopulationRandomized participants in the safety analysis population who received at least 1 dose of the study intervention. Participants with chronic, stable HIV infection were excluded.
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.

COMIRNATY Vaccine encoding the viral spike (S) glycoprotein of SARS-CoV-2 Wuhan-Hu-1 strain (Original).

Dose 1

N N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. The N for each reaction was the same, therefore, this information was included in the column header. =2899

n n = Number of participants with the specified reaction. (%)

Placebo

Dose 1

N

=2908

n

(%)

COMIRNATY

Dose 2

N

=2682

n

(%)

Placebo

Dose 2

N

=2684

n

(%)

RednessMild: >2.0 to ≤5.0 cm; Moderate: >5.0 to ≤10.0 cm; Severe: >10.0 cm.

  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 siteMild: does not interfere with activity; Moderate: interferes with activity; Severe: prevents daily activity.

  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

Table 5: Study 2 – Frequency and Percentages of Participants With Solicited Systemic Reactions, by Maximum Severity, Within 7 Days After Each Dose – Participants 16 Through 55 Years of Age – Reactogenicity Subset of the Safety PopulationRandomized participants in the safety analysis population who received at least 1 dose of the study intervention. Participants with chronic, stable HIV infection were excluded.
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.

COMIRNATY Vaccine encoding the viral spike (S) glycoprotein of SARS-CoV-2 Wuhan-Hu-1 strain (Original).

Dose 1

N N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. The N for each reaction or use of antipyretic or pain medication was the same, therefore, this information was included in the column header. =2899

n n = Number of participants with the specified reaction. (%)

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

FatigueMild: does not interfere with activity; Moderate: some interference with activity; Severe: prevents daily activity.

  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)

VomitingMild: 1 to 2 times in 24 hours; Moderate: >2 times in 24 hours; Severe: requires intravenous hydration.

  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

DiarrheaMild: 2 to 3 loose stools in 24 hours; Moderate: 4 to 5 loose stools in 24 hours; Severe: 6 or more loose stools in 24 hours.

  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 medicationSeverity was not collected for use of antipyretic or pain medication.

805 (27.8)

398 (13.7)

1213 (45.2)

320 (11.9)

Table 6: Study 2 – Frequency and Percentages of Participants With Solicited Local Reactions, by Maximum Severity, Within 7 Days After Each Dose – Participants 56 Years of Age and Older – Reactogenicity Subset of the Safety PopulationRandomized participants in the safety analysis population who received at least 1 dose of the study intervention. Participants with chronic, stable HIV infection were excluded.
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.

COMIRNATY Vaccine encoding the viral spike (S) glycoprotein of SARS-CoV-2 Wuhan-Hu-1 strain (Original).

Dose 1

N N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. The N for each reaction was the same, therefore, the information was included in the column header. =2008

n n = Number of participants with the specified reaction. (%)

Placebo

Dose 1

N

=1989

n

(%)

COMIRNATY

Dose 2

N

=1860

n

(%)

Placebo

Dose 2

N

=1833

n

(%)

RednessMild: >2.0 to ≤5.0 cm; Moderate: >5.0 to ≤10.0 cm; Severe: >10.0 cm.

  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 siteMild: does not interfere with activity; Moderate: interferes with activity; Severe: prevents daily activity.

  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

Table 7: Study 2 – Frequency and Percentages of Participants With Solicited Systemic Reactions, by Maximum Severity, Within 7 Days After Each Dose – Participants 56 Years of Age and Older – Reactogenicity Subset of the Safety PopulationRandomized participants in the safety analysis population who received at least 1 dose of the study intervention. Participants with chronic, stable HIV infection were excluded.
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.

COMIRNATY Vaccine encoding the viral spike (S) glycoprotein of SARS-CoV-2 Wuhan-Hu-1 strain (Original).

Dose 1

N N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. N for each reaction or use of antipyretic or pain medication was the same, therefore was included in the column header. =2008

n n = Number of participants with the specified reaction. (%)

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

FatigueMild: does not interfere with activity; Moderate: some interference with activity; Severe: prevents daily activity; Grade 4 reactions were defined in the clinical study protocol as emergency room visit or hospitalization for severe fatigue, severe headache, severe chills, severe muscle pain, or severe joint pain.

  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

VomitingMild: 1 to 2 times in 24 hours; Moderate: >2 times in 24 hours; Severe: requires intravenous hydration; Grade 4 emergency visit or hospitalization for severe 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

DiarrheaMild: 2 to 3 loose stools in 24 hours; Moderate: 4 to 5 loose stools in 24 hours; Severe: 6 or more loose stools in 24 hours; Grade 4: emergency room or hospitalization for severe diarrhea.

  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 medicationSeverity was not collected for use of antipyretic or pain medication.

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.

Table 8: Study 5 – Frequency and Percentages of Participants With Solicited Local Reactions, by Maximum Severity, Within 7 Days After a Second Booster Dose – Participants 12 Years of Age and Older – Safety Population
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 Vaccine encoding the viral spike (S) glycoprotein of SARS-CoV-2 Wuhan-Hu-1 strain (Original) and Omicron variant lineages BA.4 and BA.5 (Omicron BA.4/BA.5).

12 Through 17 Years of Age

N N = Number of participants reporting at least 1 yes or no response for the specified reaction after the study vaccination. =107

n n = Number of participants with the specified adverse reaction. (%)

18 Through 55 Years of Age

N

=309 N = 310 for redness and pain at injection site in participants 18 through 55 years of age; N=301 for pain at injection site in participants 56 years of age and older.

n

(%)

56 Years of Age and Older

N

=300

n

(%)

RednessMild: >2.0 to 5.0 cm; Moderate: >5.0 to 10.0 cm; Severe: >10.0 cm.

    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 siteMild: does not interfere with activity; Moderate: interferes with activity; Severe: prevents daily activity.

    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)

Table 9: Study 5 – Frequency and Percentages of Participants With Solicited Systemic Adverse Reactions, by Maximum Severity, Within 7 Days After a Second Booster Dose – Participants 12 Years of Age and Older – Safety Population
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 Vaccine encoding the viral spike (S) glycoprotein of SARS-CoV-2 Wuhan-Hu-1 strain (Original) and Omicron variant lineages BA.4 and BA.5 (Omicron BA.4/BA.5).

12 Through 17 Years of Age

N N = Number of participants reporting at least 1 yes or no response for the specified adverse reaction after the study vaccination. =107

n n = Number of participants with the specified adverse reaction. (%)

18 Through 55 Years of Age

N

=309

n

(%)

56 Years of Age and Older

N

=300 N=301 for fever, fatigue and diarrhea in participants 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

FatigueMild: does not interfere with activity; Moderate: some interference with activity; Severe: prevents daily activity.

    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)

VomitingMild: 1 to 2 times in 24 hours; Moderate: >2 times in 24 hours; Severe: requires intravenous hydration.

    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

DiarrheaMild: 2 to 3 loose stools in 24 hours; Moderate: 4 to 5 loose stools in 24 hours; Severe: 6 or more loose stools in 24 hours.

    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 medicationSeverity was not collected for use of antipyretic or pain medication.

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.

6.2 Postmarketing Experience

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

8 USE IN SPECIFIC POPULATIONS

     

8.1 Pregnancy

Risk Summary

All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Available data on COMIRNATY administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy.

A developmental toxicity study has been performed in female rats administered the equivalent of a single human dose of COMIRNATY [encoding the viral spike (S) glycoprotein of SARS-CoV-2 Wuhan-Hu-1 strain (Original)] on 4 occasions, twice prior to mating and twice during gestation. These studies revealed no evidence of harm to the fetus due to the vaccine (see Animal Data).

Clinical Considerations

Disease-Associated Maternal and/or Embryo/Fetal Risk

Pregnant individuals infected with SARS-CoV-2 are at increased risk of severe COVID-19 compared with non-pregnant individuals.

Data

Animal Data

In a developmental toxicity study, 0.06 mL of a vaccine formulation containing the same quantity of nucleoside-modified messenger ribonucleic acid (mRNA) (30 mcg) and other ingredients included in a single human dose of COMIRNATY [encoding the viral spike (S) glycoprotein of SARS-CoV-2 Wuhan-Hu-1 strain (Original)] was administered to female rats by the intramuscular route on 4 occasions: 21 and 14 days prior to mating, and on gestation days 9 and 20. No vaccine-related adverse effects on female fertility, fetal development, or postnatal development were reported in the study.

8.2 Lactation

Risk Summary

It is not known whether COMIRNATY is excreted in human milk. Data are not available to assess the effects of COMIRNATY on the breastfed infant or on milk production/excretion. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for COMIRNATY and any potential adverse effects on the breastfed child from COMIRNATY or from the underlying maternal condition. For preventive vaccines, the underlying maternal condition is susceptibility to disease prevented by the vaccine.