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COMIRNATY® (COVID-19 Vaccine, mRNA) is indicated for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 6 months of age and older. COMIRNATY must be injected intramuscularly only.
Health Canada has authorized the sale of COMIRNATY Original & Omicron BA.4/BA.5 bivalent vaccine with terms and conditions.
COMIRNATY® Original & Omicron BA.4/BA.5 [COVID-19 mRNA Vaccine, Bivalent (Original and Omicron BA.4/BA.5)] is indicated for active immunization against coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) in individuals 5 years of age and older. COMIRNATY Original & Omicron BA.4/BA.5 bivalent vaccine must be injected intramuscularly only.
- Marketing authorization has been issued with Terms and Conditions that need to be met by the Market Authorization Holder to ascertain the continued quality, safety and effectiveness of the vaccine.
- The safety and effectiveness of a primary vaccination course or booster dose of COMIRNATY Original & Omicron BA.4/BA.5 for individuals 5 years of age and older is inferred from studies which evaluated the primary series and booster vaccination with COMIRNATY and supported by studies of a booster dose of COMIRNATY Original & Omicron BA.4/BA.5 in individuals >5 years of age.
Please review the label carefully to ensure that you select the appropriate vaccine for immunization. Please review the COMIRNATY or the COMIRNATY Original & Omicron BA.4/BA.5, Bivalent Product Monograph for more complete information. Each Product Monograph is available below, at www.pfizer.ca/en/our-products, or www.cvdvaccine.ca.
Comirnaty (COVID-19 Vaccine, mRNA) and Comirnaty Original & Omicron BA.4/BA.5 [bivalent]
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Comirnaty and Comirnaty Original & Omicron BA.4/BA.5 Quick Finder
1 Health Professional Information
1 INDICATIONS
COMIRNATY (COVID-19 Vaccine, mRNA) is indicated for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) in individuals 6 months of age and older.
1.1 Pediatrics
The safety and efficacy of COMIRNATY in children under 6 months of age have not yet been established (see 8 ADVERSE REACTIONS and 14 CLINICAL TRIALS).
1.2 Geriatrics
Clinical studies of COMIRNATY include participants 65 years of age and older and their data contributes to the overall assessment of safety and efficacy (see 8 ADVERSE REACTIONS and 14 CLINICAL TRIALS).
2 Contraindications
COMIRNATY is contraindicated in individuals who are hypersensitive to the active substance or to any ingredient in the formulation. For a complete listing see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.
3 Serious Warnings And Precautions
At the time of authorization, there are no known serious warnings or precautions associated with this product.
4 Dosage And Administration
4.1 Dosing Considerations
The storage, preparation and administration information differ depending on which presentation of the vaccine is considered. Careful attention should be paid to the vial cap and label border colour and the appropriate corresponding instructions must be followed under the subsections below.
For 12 Years of Age and Older
COMIRNATY is a suspension for intramuscular injection. There are two formulations of COMIRNATY authorized for use in individuals 12 years of age and older.
- DILUTE BEFORE USE (Vials with Purple Cap and Purple Label Border)
- DO NOT DILUTE (Vials with Gray Cap and Gray Label Border)
After preparation, a single dose is 0.3 mL.
For Age 5 Years to <12 Years
COMIRNATY is a suspension for intramuscular injection which must be diluted prior to administration.
- DILUTE PRIOR TO USE (Vials with Orange Cap and Orange Label Border)
After preparation, a single dose is 0.2 mL.
For Age 6 Months to <5 Years
COMIRNATY is a suspension for intramuscular injection which must be diluted prior to administration.
- DILUTE PRIOR TO USE (Vials with Maroon Cap and Maroon Label Border)
After preparation, a single dose is 0.2 mL.
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Dosage Form | Vial Cap and Label Border Colour | Age Range | Dilution Information | Doses Per Vial | Dose Volume |
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COMIRNATY* Multiple Dose Vial (for 12 years of age and older: DILUTE BEFORE USE) | Purple | 12 years and older | Dilute with 1.8 mL sterile 0.9% Sodium Chloride Injection, USP prior to use | 6 | 0.3 mL |
COMIRNATY* Multiple Dose Vial (for 12 years of age and older: DO NOT DILUTE) | Gray | 12 years and older | DO NOT DILUTE prior to use | 6 | 0.3 mL |
COMIRNATY* Multiple Dose Vial (for age 5 years to <12 years: DILUTE PRIOR TO USE) | Orange | 5 to <12 years | Dilute with 1.3 mL sterile 0.9% Sodium Chloride Injection, USP prior to use | 10 | 0.2 mL |
COMIRNATY* Multiple Dose Vial (for age 6 months to <5 years: DILUTE PRIOR TO USE) | Maroon | 6 months to <5 years | Dilute with 2.2 mL sterile 0.9% Sodium Chloride Injection, USP prior to use | 10 | 0.2 mL |
4.2 Recommended Dose and Dosage Adjustment
4.2.1 Vaccination Schedule for Individuals 12 Years of Age and Older
- COMIRNATY is administered intramuscularly as a primary series of two doses (0.3 mL each) 3 weeks apart in individuals 12 years of age and older.
- A booster dose of COMIRNATY (0.3 mL) may be administered intramuscularly at least 6 months after completion of the primary series in individuals 16 years of age or older.
There are currently no data available from Pfizer and BioNTech clinical trials on the interchangeability of COMIRNATY with other COVID-19 vaccines to complete the primary vaccination series or for a booster dose.
When prepared according to their respective instructions, COMIRNATY for 12 years of age and older (DILUTE BEFORE USE: purple cap and purple label border) and COMIRNATY for 12 years of age and older (DO NOT DILUTE: gray cap and gray label border) can be used interchangeably to provide the COVID-19 vaccination series.
COMIRNATY and the Interim Order authorized Pfizer-BioNTech COVID-19 Vaccine, for use in individuals 12 years of age and older, have the same formulation and can be used interchangeably to provide the COVID-19 vaccination series.
Vials of COMIRNATY intended for individuals 12 years of age and older (purple cap/purple label border or gray cap/gray label border) cannot be used to prepare doses for individuals aged 6 months to <12 years.
4.2.2 Vaccination Schedule for Individuals Aged 5 Years to <12 Years
- COMIRNATY is administered intramuscularly as a primary series of two doses (0.2 mL each) 3 weeks apart.
- A booster dose of COMIRNATY (0.2 mL) may be administered intramuscularly at least 6 months after completion of the primary series in individuals 5 years through ˂12 years of age.
There are no data available on the interchangeability of COMIRNATY with other COVID-19 vaccines to complete the primary vaccination series or for a booster dose. Individuals who have received one dose of COMIRNATY should receive a second dose of COMIRNATY to complete the primary vaccination series and for any additional doses.
Vials of COMIRNATY intended for individuals aged 5 years to <12 years (orange cap/orange label border) cannot be used to prepare doses for individuals 6 months to <5 years or 12 years of age and older.
4.2.3 Vaccination Schedule for Individuals Aged 6 Months to <5 Years
COMIRNATY is administered intramuscularly as a primary series of three doses (0.2 mL each). The initial 2 doses are administered 3 weeks apart followed by a third dose administered at least 8 weeks after the second dose.
Children who will turn from 4 to 5 years of age between their doses in the vaccination series should receive their age-appropriate dose at the time of the vaccination and the interval between doses is determined by the child’s age at the start of the vaccination series.
There are no data available on the interchangeability of COMIRNATY with other COVID-19 vaccines to complete the vaccination series. Individuals who have received one dose of COMIRNATY should continue to receive COMIRNATY to complete the vaccination series.
Vials of COMIRNATY intended for individuals aged 6 months to <5 years (maroon cap/maroon label border) cannot be used to prepare doses for individuals 5 years of age and older.
4.3 Reconstitution
4.3.1 For 12 Years of Age and Older
Two formulations of COMIRNATY are available for individuals 12 years of age and older.
4.3.1.1 For 12 Years of Age and Older: DILUTE BEFORE USE (Vials with Purple Cap and Purple Label Border)
Preparation for Administration
Prior to Dilution:
- The COMIRNATY multiple dose vial with a purple cap and purple label border contains a volume of 0.45 mL. It is supplied as a frozen suspension that does not contain preservative. Each vial must be thawed and diluted prior to administration.
- Vials may be thawed in the refrigerator (2°C to 8°C [35°F to 46°F])or at room temperature (up to 25°C [77°F]) (see 11 STORAGE, STABILITY AND DISPOSAL).
- Prior to dilution, the thawed suspension may contain white to off-white opaque amorphous particles.
- Refer to thawing instructions in the panels below.
Dilution:
- Dilute the vial contents using 1.8 mL of sterile 0.9% Sodium Chloride Injection, USP to form COMIRNATY. Do not add more than 1.8 mL of diluent.
- ONLY use 0.9% Sodium Chloride Injection, USP as the diluent. This diluent is not packaged with the vaccine and must be sourced separately. Do not use bacteriostatic 0.9% Sodium Chloride Injection or any other diluent.
- After dilution, one vial contains 6† doses of 0.3 mL.
- After dilution, the vaccine will be an off-white suspension. Inspect vials to confirm there are no particulates and no discolouration is observed.
- Strict adherence to aseptic techniques must be followed.
- Refer to dilution and dose preparation instructions in the panels below.
- †
- Low dead-volume syringes and/or needles can be used to extract 6 doses from a single vial. If standard syringes and needles are used, there may not be sufficient volume to extract a 6th dose from a single vial.
For 12 Years of Age and Older: DILUTE BEFORE USE (Vials with Purple Cap and Purple Label Border) VIAL AND DOSE VERIFICATION | |
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For 12 Years of Age and Older: DILUTE BEFORE USE (Vials with Purple Cap and Purple Label Border) THAWING PRIOR TO DILUTION | |
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For 12 Years of Age and Older: DILUTE BEFORE USE (Vials with Purple Cap and Purple Label Border) DILUTION | |
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For 12 Years of Age and Older: DILUTE BEFORE USE (Vials with Purple Cap and Purple Label Border) PREPARATION OF INDIVIDUAL 0.3 mL DOSES | |
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4.3.1.2 For 12 Years of Age and Older: DO NOT DILUTE (Vials with Gray Cap and Gray Label Border)
The COMIRNATY multiple dose vial with a gray cap and gray label border MUST NOT BE DILUTED prior to administration. Instructions on the handling and dose preparation of the vaccine prior to administration are provided below.
Preparation for Administration
DO NOT DILUTE
- The COMIRNATY multiple dose vial with a gray cap and a gray label border contains a volume of 2.25 mL, and is supplied as a frozen suspension that does not contain preservative. Each vial must be thawed prior to administration. DO NOT DILUTE prior to use.
- Vials may be thawed in the refrigerator (2°C to 8°C [35°F to 46°F]) or at room temperature (up to 25°C [77°F]) (see 11 STORAGE, STABILITY AND DISPOSAL).
- The thawed suspension may contain white to off-white opaque amorphous particles.
- One vial contains 6† doses of 0.3 mL.
- Refer to thawing and dose preparation instructions in the panels below.
- †
- Low dead-volume syringes and/or needles can be used to extract 6 doses from a single vial. If standard syringes and needles are used, there may not be sufficient volume to extract a 6th dose from a single vial.
For 12 Years of Age and Older: DO NOT DILUTE (Vials with Gray Cap and Gray Label Border) VIAL AND DOSE VERIFICATION | |
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For 12 Years of Age and Older: DO NOT DILUTE (Vials with Gray Cap and Gray Label Border) THAWING PRIOR TO USE | |
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For 12 Years of Age and Older: DO NOT DILUTE (Vials with Gray Cap and Gray Label Border) PREPARATION OF INDIVIDUAL 0.3 mL DOSES | |
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- Vial labels and cartons may state that a vial should be discarded 6 hours after first use. The information in this Product Monograph supersedes the number of hours printed on vial labels and cartons.
4.3.2 For Age 5 Years to <12 Years: DILUTE PRIOR TO USE (Vials with Orange Cap and Orange Label Border)
Preparation for Administration
Prior to Dilution:
- The COMIRNATY multiple dose vial (for ages 5 years to <12 years) has an orange cap and an orange label border and contains a volume of 1.3 mL. It is supplied as a frozen suspension that does not contain preservative. Each vial must be thawed and diluted prior to administration.
- Vials of COMIRNATY intended for 12 years of age or older with a purple cap/purple label border or gray cap/gray label border and vials of COMIRNATY intended for individuals aged 6 months to <5 years with a maroon cap/maroon label border cannot be used to prepare doses for individuals aged 5 years to <12 years.
- Vials may be thawed in the refrigerator at 2°C to 8°C [35°F to 46°F] or at room temperature (up to 25°C [77°F]) (see 11 STORAGE, STABILITY AND DISPOSAL).
- Prior to dilution, the thawed suspension may contain opaque amorphous particles.
- Refer to thawing instructions in the panels below.
Dilution:
- Dilute the vial contents using 1.3 mL of sterile 0.9% Sodium Chloride Injection, USP to form COMIRNATY. Do not add more than 1.3 mL of diluent.
- ONLY use 0.9% Sodium Chloride Injection, USP as the diluent. This diluent is not packaged with the vaccine and must be sourced separately. Do not use bacteriostatic 0.9% Sodium Chloride Injection or any other diluent.
- After dilution, one vial contains 10* doses of 0.2 mL.
- After dilution, the vaccine will be a white to off-white suspension. Inspect vials to confirm there are no particulates and no discolouration is observed.
- Strict adherence to aseptic techniques must be followed.
- Refer to dilution and dose preparation instructions in the panels below.
- *
- Low dead-volume syringes and/or needles can be used to extract 10 doses from a single vial. If standard syringes and needles are used, there may not be sufficient volume to extract 10 doses from a single vial.
For Age 5 Years to <12 Years: DILUTE PRIOR TO USE (Vials with Orange Cap and Orange Label Border) VIAL AND DOSE VERIFICATION | |
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THAWING PRIOR TO DILUTION | |
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DILUTION | |
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PREPARATION OF INDIVIDUAL 0.2 mL DOSES | |
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4.3.3 For Age 6 Months to <5 Years: DILUTE PRIOR TO USE (Vials with Maroon Cap and Maroon Label Border)
Preparation for Administration
Prior to Dilution:
- The COMIRNATY multiple dose vial (for age 6 months to <5 years) has a maroon cap and a maroon label border and contains a volume of 0.4 mL. It is supplied as a frozen suspension that does not contain preservative. Each vial must be thawed and diluted prior to administration.
- Vials of COMIRNATY intended for individuals 12 years of age or older with a purple cap/purple label border or gray cap/gray label border and vials of COMIRNATY intended for individuals aged 5 years to <12 years with an orange cap/orange label border cannot be used to prepare doses for individuals aged 6 months to <5 years.
- Vials may be thawed in the refrigerator at 2°C to 8°C [35°F to 46°F] or at room temperature (up to 25°C [77°F]) (see 11 STORAGE, STABILITY AND DISPOSAL).
- Prior to dilution, the thawed suspension may contain opaque amorphous particles.
- Refer to thawing instructions in the panels below.
Dilution:
- Dilute the vial contents using 2.2 mL of sterile 0.9% Sodium Chloride Injection, USP to form COMIRNATY. Do not add more than 2.2 mL of diluent.
- ONLY use 0.9% Sodium Chloride Injection, USP as the diluent. This diluent is not packaged with the vaccine and must be sourced separately. Do not use bacteriostatic 0.9% Sodium Chloride Injection or any other diluent.
- After dilution, one vial contains 10* doses of 0.2 mL.
- After dilution, the vaccine will be a white to off-white suspension. Inspect vials to confirm there are no particulates and no discolouration is observed.
- Strict adherence to aseptic techniques must be followed.
- Refer to dilution and dose preparation instructions in the panels below.
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- Vial labels and cartons may state that a vial should be discarded 6 hours after dilution. The information in this Product Monograph supersedes the number of hours printed on vial labels and cartons.
- *
- Low dead-volume syringes and/or needles can be used to extract 10 doses from a single vial. If standard syringes and needles are used, there may not be sufficient volume to extract 10 doses from a single vial.
For Age 6 Months to <5 Years: DILUTE PRIOR TO USE (Vials with Maroon Cap and Maroon Label Border) VIAL AND DOSE VERIFICATION | |
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For Age 6 Months to <5 Years: DILUTE PRIOR TO USE (Vials with Maroon Cap and Maroon Label Border) THAWING PRIOR TO DILUTION | |
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For Age 6 Months to <5 Years: DILUTE PRIOR TO USE (Vials with Maroon Cap and Maroon Label Border) DILUTION | |
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For Age 6 Months to <5 Years: DILUTE PRIOR TO USE (Vials with Maroon Cap and Maroon Label Border) PREPARATION OF INDIVIDUAL 0.2 mL DOSES | |
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- Vial labels and cartons may state that a vial should be discarded 6 hours after dilution. The information in this Product Monograph supersedes the number of hours printed on vial labels and cartons.
4.4 Administration
4.4.1 For 12 Years of Age and Older
Administer a single 0.3 mL dose of COMIRNATY intramuscularly, preferably in the deltoid muscle.
Do not inject the vaccine intravascularly, subcutaneously or intradermally.
Two formulations of COMIRNATY are available for individuals 12 years of age and older.
- DILUTE BEFORE USE (Vials with Purple Cap and Purple Label Border)
After dilution, vials of COMIRNATY (with purple cap and purple label border) contain 6 doses of 0.3 mL of vaccine. - DO NOT DILUTE (Vials with Gray Cap and Gray Label Border)
Vials of COMIRNATY with gray caps and gray label borders contain 6 doses of 0.3 mL of vaccine.
Visually inspect each dose in the dosing syringe prior to administration. The vaccine will be an off white suspension. During the visual inspection:
- Verify the final dosing volume of 0.3 mL.
- Confirm there are no particulates and that no discolouration is observed.
- Do not administer if vaccine is discoloured or contains particulate matter.
Low dead-volume syringes and/or needles can be used to extract 6 doses from a single vial. In order to ensure consistent withdrawal of 6 doses of 0.3 mL, it is important to adhere to minimizing volume loss during dose extraction. If standard syringes and needles are used, there may not be sufficient volume to extract a 6th dose from a single vial. Irrespective of the type of syringe and needle:
- Each dose must contain 0.3 mL of vaccine.
- If the amount of vaccine remaining in the vial cannot provide a full dose of 0.3 mL, discard the vial and any excess volume.
- Do not pool excess vaccine from multiple vials.
4.4.2 For Age 5 Years to <12 Years
Administer a single 0.2 mL dose of COMIRNATY intramuscularly, preferably in the deltoid muscle.
Do not inject the vaccine intravascularly, subcutaneously or intradermally.
DILUTE PRIOR TO USE (Vial with Orange Cap and Orange Label Border).
Visually inspect each dose in the dosing syringe prior to administration. The diluted vaccine will be a white to off white suspension. During the visual inspection:
- Verify the final dosing volume of 0.2 mL.
- Confirm there are no particulates and that no discolouration is observed.
- Do not administer if vaccine is discoloured or contains particulate matter.
After dilution, vials of COMIRNATY (for age 5 years to <12 years) contain 10 doses of 0.2 mL of vaccine. Low dead-volume syringes and/or needles can be used to extract 10 doses from a single vial. In order to ensure consistent withdrawal of 10 doses of 0.2 mL, it is important to adhere to minimizing volume loss during dose extraction. If standard syringes and needles are used, there may not be sufficient volume to extract 10 doses from a single vial. Irrespective of the type of syringe and needle:
- Each dose must contain 0.2 mL of vaccine.
- If the amount of vaccine remaining in the vial cannot provide a full dose of 0.2 mL, discard the vial and any excess volume.
- Do not pool excess vaccine from multiple vials.
4.4.3 For Age 6 Months to <5 Years
Administer a single 0.2 mL dose of COMIRNATY intramuscularly. In individuals from 6 to less than 12 months of age, the recommended injection site is the anterolateral aspect of the thigh. In individuals 1 year of age and older, the recommended injection site is the anterolateral aspect of the thigh or the deltoid muscle.
Do not inject the vaccine intravascularly, subcutaneously or intradermally.
DILUTE PRIOR TO USE (Vial with Maroon Cap and Maroon Label Border).
Visually inspect each dose in the dosing syringe prior to administration. The diluted vaccine will be a white to off white suspension. During the visual inspection:
- Verify the final dosing volume of 0.2 mL.
- Confirm there are no particulates and that no discolouration is observed.
- Do not administer if vaccine is discoloured or contains particulate matter.
After dilution, vials of COMIRNATY (for age 6 months to <5 years) contain 10 doses of 0.2 mL of vaccine. Low dead-volume syringes and/or needles can be used to extract 10 doses from a single vial. In order to ensure consistent withdrawal of 10 doses of 0.2 mL, it is important to adhere to minimizing volume loss during dose extraction. If standard syringes and needles are used, there may not be sufficient volume to extract 10 doses from a single vial. Irrespective of the type of syringe and needle:
- Each dose must contain 0.2 mL of vaccine.
- If the amount of vaccine remaining in the vial cannot provide a full dose of 0.2 mL, discard the vial and any excess volume.
- Do not pool excess vaccine from multiple vials.
5 Overdosage
In the event of suspected overdose, monitoring of vital functions and symptomatic treatment is recommended. Contact your regional poison control centre.
6 Dosage Forms, Strengths, Composition And Packaging
To help ensure the traceability of vaccines for patient immunization record-keeping as well as safety monitoring, health professionals should record the time and date of administration, quantity of administered dose (if applicable), anatomical site and route of administration, brand name and generic name of the vaccine, the product lot number and expiry date (or manufacture date).
For 12 Years of Age and Older: DILUTE BEFORE USE (Vials with Purple Cap and Purple Label Border)
COMIRNATY is supplied as a frozen suspension in multiple dose vials. Each vial must be diluted with 1.8 mL of sterile 0.9% Sodium Chloride Injection, USP prior to use to form the vaccine, and contains 6† doses of 0.3 mL after dilution. Each 0.3 mL dose of COMIRNATY contains 30 mcg of a nucleoside modified messenger RNA (modRNA) encoding the viral spike (S) glycoprotein of SARS-CoV-2 (original strain) and the non-medicinal ingredients listed in Table 1.
COMIRNATY does not contain preservative. The vial stoppers are not made with natural rubber latex.
COMIRNATY multiple dose vials (with purple cap and purple label border) are supplied in a carton containing 25 multiple dose vials or 195 multiple dose vials. Not all pack sizes may be available.
For 12 Years of Age and Older: DO NOT DILUTE (Vials with Gray Cap and Gray Label Border)
COMIRNATY is supplied as a frozen suspension in multiple dose vials. Do not dilute. Each vial contains 6† doses of 0.3 mL. Each 0.3 mL dose of COMIRNATY contains 30 mcg of a nucleoside modified messenger RNA (modRNA) encoding the viral spike (S) glycoprotein of SARS-CoV-2 (original strain) and the non-medicinal ingredients listed in Table 1.
COMIRNATY does not contain preservative. The vial stoppers are not made with natural rubber latex.
COMIRNATY multiple dose vials (with gray cap and gray label border) are supplied in a carton containing 10 multiple dose vials or 195 multiple dose vials. Not all pack sizes may be available.
- †
- Low dead-volume syringes and/or needles can be used to extract 6 doses from a single vial. If standard syringes and needles are used, there may not be sufficient volume to extract a 6th dose from a single vial.
Route of Administration | Dosage Form / Strength/Composition | Non-medicinal Ingredients |
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Intramuscular injection | DILUTE BEFORE USE (Vials with Purple Cap and Purple Label Border) Suspension
Multiple dose vial |
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Intramuscular injection | DO NOT DILUTE (Vials with Gray Cap and Gray Label Border) Suspension
Multiple dose vial |
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For Age 5 Years to < 12 Years: DILUTE PRIOR TO USE (Vials with Orange Cap and Orange Label Border)
COMIRNATY is supplied as a frozen suspension in multiple dose vials with an orange cap and an orange label border. Each vial must be diluted with 1.3 mL of sterile 0.9% Sodium Chloride Injection, USP prior to use to form the vaccine, and contains 10* doses of 0.2 mL after dilution. Each 0.2 mL dose of COMIRNATY contains 10 mcg of a nucleoside modified messenger RNA (modRNA) encoding the viral spike (S) glycoprotein of SARS-CoV-2 (original strain) and the non-medicinal ingredients listed in Table 2. COMIRNATY does not contain preservative. The vial stoppers are not made with natural rubber latex.
COMIRNATY multiple dose vials (with orange cap and orange label border) are supplied in a carton containing 10 multiple dose vials or 195 multiple dose vials. Not all pack sizes may be available.
- *
- Low dead-volume syringes and/or needles can be used to extract 10 doses from a single vial. If standard syringes and needles are used, there may not be sufficient volume to extract 10 doses from a single vial.
Route of Administration | Dosage Form / Strength/Composition | Non-medicinal Ingredients |
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Intramuscular injection | Suspension (to be diluted before use)
Multiple dose vial (after dilution, each vial contains 10* doses of 0.2 mL) |
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For Age 6 Months to <5 Years: DILUTE PRIOR TO USE (Vials with Maroon Cap and Maroon Label Border)
COMIRNATY is supplied as a frozen suspension in multiple dose vials with a maroon cap and a maroon label border. Each vial must be diluted with 2.2 mL of sterile 0.9% Sodium Chloride Injection, USP prior to use to form the vaccine, and contains 10* doses of 0.2 mL after dilution. Each 0.2 mL dose of COMIRNATY contains 3 mcg of a nucleoside modified messenger RNA (modRNA) encoding the viral spike (S) glycoprotein of SARS-CoV-2 (original strain) and the non-medicinal ingredients listed in Table 2. COMIRNATY does not contain preservative. The vial stoppers are not made with natural rubber latex.
COMIRNATY multiple dose vials (with maroon cap and maroon label border) are supplied in a carton containing 10 multiple dose vials.
7 Warnings And Precautions
General
The administration of COMIRNATY should be postponed in individuals suffering from acute severe febrile illness.
Fainting may occur in association with administration of injectable vaccines. Individuals should be advised to bring symptoms (e.g., dizziness, increases in heart rate, feeling short of breath, tingling sensations or sweating) to the attention of the vaccination provider for evaluation. Procedures should be in place to avoid injury from fainting.
As with any vaccine, vaccination with COMIRNATY may not protect all recipients.
Individuals may not be optimally protected until at least 7 days after their second dose of vaccine (see 14 CLINICAL TRIALS).
Acute Allergic Reactions
Anaphylaxis has been reported. As with all vaccines, training for immunizers, appropriate medical treatment and supervision after immunization should always be readily available in case of a rare anaphylactic event following the administration of this vaccine.
Vaccine recipients should be kept under observation for at least 15 minutes after immunization; 30 minutes is a preferred interval when there is a specific concern about a possible vaccine reaction.
Subsequent doses of the vaccine should not be given to those who have experienced anaphylaxis to a prior dose of COMIRNATY, COMIRNATY Original/Omicron BA.1, COMIRNATY Original & Omicron BA.4/BA.5.
Cardiovascular
Myocarditis and Pericarditis
Very rare cases of myocarditis and/or pericarditis following vaccination with COMIRNATY have been reported during post-authorization use. These cases occurred more commonly after the second dose and in adolescents and young adults. Typically, the onset of symptoms has been within a few days following receipt of COMIRNATY. Based on accumulating data, the reporting rates of myocarditis and pericarditis after COMIRNATY primary series in children ages 5 through <12 years are lower than in ages 12 through 17 years. Available short-term follow-up data suggest that the symptoms resolve in most individuals, but information on long-term sequelae is lacking. The decision to administer COMIRNATY to an individual with a history of myocarditis or pericarditis should take into account the individual’s clinical circumstances.
Healthcare professionals are advised to consider the possibility of myocarditis and/or pericarditis in their differential diagnosis if individuals present with chest pain, shortness of breath, palpitations or other signs and symptoms of myocarditis and/or pericarditis following immunization with a COVID-19 vaccine. This could allow for early diagnosis and treatment. Cardiology consultation for management and follow up should be considered.
Driving and Operating Machinery
COMIRNATY has no or negligible influence on the ability to drive and use machines. However, some of the effects mentioned under 8 ADVERSE REACTIONS may temporarily affect the ability to drive or use machines.
Fertility
It is unknown whether COMIRNATY has an impact on fertility. Animal studies do not indicate direct or indirect harmful effects with respect to female fertility or reproductive toxicity (see 16 NON-CLINICAL TOXICOLOGY).
Hematologic
Individuals receiving anticoagulant therapy or those with a bleeding disorder that would contraindicate intramuscular injection should not be given the vaccine unless the potential benefit clearly outweighs the risk of administration.
Immune
Immunocompromised persons, including individuals receiving immunosuppressant therapy, may have a diminished immune response to the vaccine. In these individuals, a third dose may be considered as part of the primary series.
7.1 Special Populations
7.1.1 Pregnant Women
The safety and efficacy of COMIRNATY in pregnant women have not yet been established.
Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryo/ fetal development, parturition, or post-natal development (see 16 NON-CLINICAL TOXICOLOGY).
7.1.2 Breast-feeding
It is unknown whether COMIRNATY is excreted in human milk. A risk to the newborns/infants cannot be excluded.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for immunization against COVID-19.
7.1.3 Pediatrics
The safety and efficacy of COMIRNATY in children under 6 months of age have not yet been established.
7.1.4 Geriatrics
Clinical studies of COMIRNATY include participants 65 years of age and older, who received the primary series and a booster dose of COMIRNATY, and their data contributes to the overall assessment of safety and efficacy (See 8 ADVERSE REACTIONS and 14 CLINICAL TRIALS).
8 Adverse Reactions
8.1 Adverse Reaction Overview
The safety of the primary series of COMIRNATY was evaluated in participants 6 months of age and older in three clinical studies conducted in the United States, Europe, Turkey, South Africa, and South America.
Study BNT162‑01 (Study 1) was a Phase 1/2, two-part dose-escalation trial that enrolled 60 participants 18 through 55 years of age and 36 participants 56 through 85 years of age.
Study C4591001 (Study 2) is a Phase 1/2/3, multicenter, multinational, randomized, saline placebo-controlled, observer-blind, dose-finding, vaccine candidate-selection (Phase 1) and efficacy (Phase 2/3) study that has enrolled approximately 46,000 participants, 12 years of age or older. Of these, approximately 44,047 participants (22,026 COMIRNATY; 22,021 placebo) in Phase 2/3 are 16 years of age or older (including 378 and 376 adolescents 16 and 17 years of age in the vaccine and placebo groups, respectively) and 2,260 adolescents are 12 to 15 years of age (1,131 and 1,129 in the vaccine and placebo groups, respectively). Of the total number of COMIRNATY recipients in the study, 20.7 % were 65 years of age and older. Study 2 also included 200 participants with confirmed stable human immunodeficiency virus (HIV) infection. HIV-positive participants are included in safety population disposition but are summarized separately in safety analyses.
Study C4591007 (Study 3) is a Phase 1/2/3 study comprised of an open-label vaccine dose finding portion (Phase 1) and a multicenter, multinational, randomized, saline placebo-controlled, observer-blind immunogenicity and efficacy portion (Phase 2/3) that has enrolled approximately 4,600 participants 5 years through <12 years of age. Of these, approximately 3,100 participants received COMIRNATY 10 mcg and approximately 1,500 participants received placebo in the Phase 2/3 part of the study. Study 3 also enrolled 1,776 participants 6 months through <2 years of age (1,178 COMIRNATY 3 mcg; 598 placebo), and 2,750 participants 2 through <5 years of age (1,835 COMIRNATY 3 mcg; 915 placebo) in Phase 2/3.
Additionally, 306 existing Phase 3 participants 18 through 55 years of age received a booster dose of COMIRNATY approximately 6 months (range of 4.8 to 8.0 months) after completing 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 a subset of Study 3 Phase 2/3 participants, 401 participants 5 years through <12 years of age received a booster dose of COMIRNATY at least 5 months (range 5 to 9 months) after completing the primary series. The overall safety profile for the booster dose was similar to that seen after the primary series. The analysis of the Study 3 Phase 2/3 subset is based on data up to the cut-off date of March 22, 2022 (median follow-up time of 1.3 months).
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 at least 6 months after the second dose. The overall safety profile for the booster dose was similar to that seen after 2 doses.
The safety evaluation of participants in Study 2, Study 3 and Study 4 is ongoing. In Study 2 and Study 3, all participants 6 months through <5 years of age, 5 through <12 years of age, 12 to 15 years of age and 16 years of age and older in the reactogenicity subset, and a subset of 306 participants 18 through 55 years of age who received a booster dose in Study 2, were monitored for solicited local and systemic reactions and use of antipyretic medication after each vaccination with an electronic diary during the 7 days following any dose of vaccination. Participants, including those who received a booster in Study 4, continue to be monitored for unsolicited adverse events, including serious adverse events, throughout the study [from Dose 1 to 1 month after the last dose (all unsolicited adverse events) and 6 months (serious adverse events) after the last vaccination].
Participants 12 Years of Age and Older
At the time of the analysis of Study 2 (data accrued through March 13, 2021), a total of 25,651 (58.2%) participants (13,031 in vaccine group and 12,620 in placebo group) 16 years of age and older had been followed up for at least 4 months, with 3,082 (7.0%) participants (1,778 in vaccine group and 1,304 in placebo group) followed up for at least 6 months after the second dose during the blinded placebo-controlled follow-up period. A total of 12,006 (54.5%) participants originally randomized to the vaccine group in Study 2 had been followed up for at least 6 months after the second dose including the blinded and open-label periods.
In an analysis of Study 2, based on data up to the cut-off date of March 13, 2021, a total of 2,260 adolescents (1,131 COMIRNATY; 1,129 placebo) were 12 to 15 years of age. Of these, 1,559 (786 COMIRNATY and 773 placebo) adolescents have been followed for ≥4 months after the second dose of COMIRNATY.
In clinical studies with a data cut-off of March 13, 2021, and where 2 doses were administered 3 weeks apart, the most common adverse reactions in the reactogenicity subset (n=4,924) of participants 16 years of age and older after any dose included injection site pain (84.3%), fatigue (64.7%), headache (57.1%), muscle pain (40.2%), chills (34.7%), joint pain (25.0%), fever (15.2%), injection site swelling (11.1%), and injection site redness (9.9%). Additional adverse events reported in the safety population (n=21,926) of participants 16 years of age and older from dose 1 to 1 month after dose 2 included nausea (1.2%), malaise (0.6%), lymphadenopathy (0.4%), asthenia (0.3%), decreased appetite (0.2%), hyperhidrosis (0.1%), lethargy (0.1%), and night sweats (0.1%). Adverse reactions were usually mild or moderate in intensity and resolved within a few days after vaccination.
The safety profile in 545 participants receiving COMIRNATY that were seropositive for SARS-CoV-2 at baseline was similar to that seen in the general population.
In a clinical study with a data cut-off date of 02 September 2021, the most commonly reported (≥8%) adverse reactions in adolescents 12 through 15 years of age 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%).
In a clinical study of participants 18 through 55 years of age (N=306), 289 participants (94%) completed the e-diary recording adverse reactions. The most commonly reported adverse reactions (≥10%) following administration of a booster dose were pain at the injection site (83.0%), fatigue (63.7%), headache (48.4%), muscle pain (39.1%), chills (29.1%), and joint pain (25.3%).
In a clinical study of approximately 10,000 participants 16 years of age and older, unsolicited adverse reactions following administration of a booster dose included headache (5%), fever (4.8%), lymphadenopathy (2.8%), pain in extremity (1.1%), nausea (0.9%), malaise (0.7%), and decreased appetite (0.2%).
Participants 5 Years Through ˂12 Years of Age
In an analysis of Study 3 Phase 2/3, based on data up to the cut-off date of October 8, 2021, 2,268 participants (initial enrolment group: 1,518 COMIRNATY 10 mcg and 750 placebo) were 5 years through ˂12 years of age. Of these, 2,171 (95.7%) (1,456 COMIRNATY 10 mcg and 715 placebo) participants have been followed for at least 3 months after Dose 2. An analysis of Study 3 Phase 2/3 adverse event data also included another 2,379 participants (safety expansion group: 1,591 COMIRNATY 10 mcg and 788 placebo), of whom 71.2% had a follow-up period for at least 2 weeks after Dose 2. The safety evaluation in Study 3 is ongoing.
Adverse reactions following administration of any dose in the initial enrolment safety population (n = 1,518) of children 5 years through ˂12 years of age included pain at the injection site (84.3%), fatigue (51.7%), headache (38.2%), injection site redness (26.4%), injection site swelling (20.4%), muscle pain (17.5%), chills (12.4%), fever (8.3%), joint pain (7.6%), lymphadenopathy (0.9%), rash (0.5%), nausea (0.4%), malaise (0.1%), and decreased appetite (0.1%).
The most frequent adverse reactions in participants 5 years through <12 years of age following the booster dose (data cut-off date of March 22, 2022; median follow-up time of 1.3 months) were injection site pain (73.9%), fatigue (45.6%), headache (34.0%), myalgia (18.3%), chills (10.5%), injection site redness (15.6%), and swelling (16.4%). The most frequently reported unsolicited adverse event was lymphadenopathy (2.5%).
Participants 2 Through <5 Years of Age
Study 3 (Phase 2/3) enrolled 2,750 participants 2 through <5 years of age (1,835 COMIRNATY 3 mcg; 915 placebo). Of these, 2,726 participants (1,819 COMIRNATY 3 mcg; 907 placebo) received 2 doses and 1,369 (50.2%; 910 COMIRNATY 3 mcg and 459 placebo) participants have been followed for at least 4 months after the second dose; 886 participants received a 3-dose primary series (606 COMIRNATY 3 mcg; 280 placebo) and have been followed for a median of 1.4 months after the third dose, based on data in the blinded, placebo-controlled follow-up period up to the cut-off date of April 29, 2022. Adverse reactions following administration of any dose included pain at the injection site (47.0%), fatigue (44.8%), injection site redness (18.9%), fever (10.5%), headache (8.7%), injection site swelling (8.4%), chills (5.7%), muscle pain (5.0%), joint pain (2.4%), and lymphadenopathy (0.1%).
Participants 6 Months Through <2 Years of Age
Study 3 (Phase 2/3) also enrolled 1,776 participants 6 months through <2 years of age (1,178 COMIRNATY 3 mcg; 598 placebo). Of these, 1,762 participants (1,166 COMIRNATY 3 mcg; 596 placebo) received 2 doses and 1,207 (68.5%; 801 COMIRNATY 3 mcg and 406 placebo) participants have been followed for at least 4 months after the second dose; 570 participants received a 3-dose primary series (386 COMIRNATY 3 mcg; 184 placebo) and have been followed for a median of 1.3 months after the third dose, based on data in the blinded, placebo-controlled follow-up period up to the cut-off date of April 29, 2022. Adverse reactions following administration of any dose included irritability (68.4%), decreased appetite (38.6%), tenderness at the injection site (26.4%), injection site redness (17.8%), fever (14.4%), injection site swelling (7.3%), and lymphadenopathy (0.2%).
8.2 Clinical Trial Adverse Reactions
Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials, therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use.
Participants 16 Years of Age and Older – Primary Series (Two Doses)
Solicited Adverse Reactions
Tables 3 through 6 present the frequency and severity of solicited local and systemic reactions, respectively, within 7 days following each dose of COMIRNATY and placebo in the subset of participants 16 years of age and older (n=9,839) in the safety population who were monitored for reactogenicity with an electronic diary.
| ||||
Solicited Local Reaction | Dose 1 | Dose 2 | ||
---|---|---|---|---|
COMIRNATY Na=2,899 | Placebo Na=2,908 | COMIRNATY Na=2,682 | Placebo Na=2,684 | |
Redness | ||||
Anyc | 156 (5.4) | 28 (1.0) | 151 (5.6) | 18 (0.7) |
Severed | 7 (0.2) | 3 (0.1) | 11 (0.4) | 0 (0.0) |
Swelling | ||||
Anyc | 184 (6.3) | 16 (0.6) | 183 (6.8) | 5 (0.2) |
Severed | 6 (0.2) | 2 (0.1) | 7 (0.3) | 0 (0.0) |
Pain at the Injection Site | ||||
Anyc | 2,426 (83.7) | 414 (14.2) | 2,101 (78.3) | 312 (11.6) |
Severee | 39 (1.3) | 3 (0.1) | 39 (1.5) | 0 (0.0) |
Any local reactionc | 2,444 (84.3) | 432 (14.9) | 2,108 (78.6) | 325 (12.1) |
| ||||
Solicited Systemic Reaction | Dose 1 | Dose 2 | ||
---|---|---|---|---|
COMIRNATY Na=2,899 | Placebo Na=2,908 | COMIRNATY Na=2,682 | Placebo Na=2,684 | |
Fever | ||||
≥38.0°C | 119 (4.1) | 25 (0.9) | 440 (16.4) | 11 (0.4) |
>38.9°C | 8 (0.3) | 4 (0.1) | 40 (1.5) | 2 (0.1) |
Fatigue | ||||
Any | 1,431 (49.4) | 960 (33.0) | 1,649 (61.5) | 614 (22.9) |
Severed | 41 (1.4) | 18 (0.6) | 142 (5.3) | 14 (0.5) |
Headache | ||||
Any | 1,262 (43.5) | 975 (33.5) | 1,448 (54.0) | 652 (24.3) |
Severed | 33 (1.1) | 24 (0.8) | 91 (3.4) | 18 (0.7) |
Chills | ||||
Any | 479 (16.5) | 199 (6.8) | 1,015 (37.8) | 114 (4.2) |
Severed | 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) |
Severee | 0 (0.0) | 1 (0.0) | 4 (0.1) | 0 (0.0) |
Diarrhea | ||||
Any | 309 (10.7) | 323 (11.1) | 269 (10.0) | 205 (7.6) |
Severef | 3 (0.1) | 1 (0.0) | 6 (0.2) | 1 (0.0) |
New or worsened muscle pain | ||||
Any | 664 (22.9) | 329 (11.3) | 1,055 (39.3) | 237 (8.8) |
Severed | 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) |
Severed | 5 (0.2) | 1 (0.0) | 27 (1.0) | 4 (0.1) |
Any systemic reactionc | 1,979 (68.3) | 1,559 (53.6) | 2,034 (75.8) | 1,026 (38.2) |
Use of antipyretic or pain medication | 805 (27.8) | 398 (13.7) | 1213 (45.2) | 320 (11.9) |
| ||||
Solicited Local Reaction | Dose 1 | Dose 2 | ||
---|---|---|---|---|
COMIRNATY Na=2,008 | Placebo Na=1,989 | COMIRNATY Na=1,860 | Placebo Na=1,833 | |
Redness | ||||
Anyc | 106 (5.3) | 20 (1.0) | 133 (7.2) | 14 (0.8) |
Severed | 5 (0.2) | 2 (0.1) | 10 (0.5) | 1 (0.1) |
Swelling | ||||
Anyc | 141 (7.0) | 23 (1.2) | 145 (7.8) | 13 (0.7) |
Severed | 2 (0.1) | 0 (0.0) | 4 (0.2) | 1 (0.1) |
Pain at the Injection Site | ||||
Anyc | 1,408 (70.1) | 185 (9.3) | 1,230 (66.1) | 143 (7.8) |
Severee | 4 (0.2) | 0 (0.0) | 10 (0.5) | 0 (0.0) |
Any local reactionc | 1,433 (71.4) | 207 (10.4) | 1,243 (66.8) | 158 (8.6) |
| ||||
Solicited Systemic Reaction | Dose 1 | Dose 2 | ||
---|---|---|---|---|
COMIRNATY Na=2,008 | Placebo
Na=1,989 | COMIRNATY Na=1,860 | Placebo
Na=1,833 | |
Fever | ||||
≥38.0°C | 26 (1.3) | 8 (0.4) | 219 (11.8) | 4 (0.2) |
>38.9°C | 1 (0.0) | 2 (0.1) | 7 (0.4) | 1 (0.1) |
Fatigue | ||||
Any | 677 (33.7) | 447 (22.5) | 949 (51.0) | 306 (16.7) |
Severed | 3 (0.1) | 3 (0.2) | 60 (3.2) | 2 (0.1) |
Grade 4g | 0 (0.0) | 0 (0.0) | 1 (0.1) | 0 (0.0) |
Headache | ||||
Any | 503 (25.0) | 363 (18.3) | 733 (39.4) | 259 (14.1) |
Severed | 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) |
Severed | 0 (0.0) | 1 (0.1) | 21 (1.1) | 0 (0.0) |
Vomiting | ||||
Any | 10 (0.5) | 9 (0.5) | 13 (0.7) | 5 (0.3) |
Severee | 0 (0.0) | 0 (0.0) | 2 (0.1) | 0 (0.0) |
Diarrhea | ||||
Any | 168 (8.4) | 130 (6.5) | 152 (8.2) | 102 (5.6) |
Severef | 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) |
Severed | 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) |
Severed | 3 (0.1) | 1 (0.1) | 9 (0.5) | 1 (0.1) |
Any systemic reactionc | 984 (49.0) | 749 (37.7) | 1,203 (64.7) | 516 (28.2) |
Use of antipyretic or pain medication | 382 (19.0) | 224 (11.3) | 688 (37.0) | 170 (9.3) |
Study 2 also included 200 participants with confirmed stable human immunodeficiency virus
(HIV) infection. The safety profile of the participants with stable HIV infection receiving COMIRNATY (n = 100) was similar to that seen in the general population.
Unsolicited Adverse Events
The participants were unblinded to offer placebo participants COMIRNATY when they became locally eligible under regulatory approval in December 2020. A total of 25,651 (58.2%) participants (13,031 in vaccine group and 12,620 in placebo group) 16 years of age and older had been followed up for at least 4 months, with 3,082 (7.0%) participants (1,778 in vaccine group and 1,304 in placebo group) followed up for at least 6 months after the second dose during the blinded placebo-controlled follow-up period in Study 2. Adverse events detailed below for participants 16 years of age and older are for the placebo-controlled blinded follow-up period up to the participants’ unblinding dates.
No deaths related to the vaccine were reported in the study.
Among participants 16 through 55 years of age who received at least one 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.
Lymphadenopathy was reported in 87 (0.4%) participants in the vaccine group compared to 8 (<0.1%) participants in the placebo group, which is plausibly related to vaccination. Bell’s palsy (facial paralysis and facial paresis) was reported by four participants in the vaccine group and two in the placebo group. In the four vaccinated participants, events began from 3 to 48 days after their last dose, were mild to moderate in severity, and duration ranged from 3 to 68 days. Currently available information is insufficient to determine a causal relationship with the vaccine. 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. Cumulative safety follow-up to at least 6 months after Dose 2 for approximately 12,000 participants who received COMIRNATY showed no other safety signals arising from longer-term follow-up of the study.
Serious Adverse Events
In Study 2, among participants 16 through 55 years of age who had received at least 1 dose of vaccine or placebo (COMIRNATY =12,995; placebo = 13,026), serious adverse events from Dose 1 up to the participant unblinding date in ongoing follow-up were reported by 103 (0.8%) COMIRNATY recipients and 117 (0.9%) placebo recipients. In a similar analysis, in participants 56 years of age and older (COMIRNATY = 8,931; placebo = 8,895), 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. 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.
Pericarditis was reported for one participant in the vaccine group, and no case was reported in the placebo group. Appendicitis was reported as a serious adverse event for 27 participants, 15 vaccine participants and 12 placebo participants. Currently available information is insufficient to determine a causal relationship with the vaccine. There were no other notable patterns or numerical imbalances between treatment groups for specific categories of serious adverse events (including neurologic, neuro-inflammatory, thrombotic events, myocarditis or anaphylactic reaction to the vaccine) reported during the blinded placebo-controlled follow-up period of the study.
Participants 16 Years of Age and Older – After Booster Dose
A subset from Study C4591001 (Study 2) Phase 2/3 participants, of 306 adults 18 through 55 years of age who completed the original COMIRNATY 2-dose series, received a booster dose of COMIRNATY approximately 6 months (range of 4.8 to 8.0 months) after receiving Dose 2.
In Study C4591031 (Study 4), a placebo-controlled booster study, participants 16 years of age and older recruited from Study C4591001 (Study 2) received a booster dose of COMIRNATY (5,081 participants), or placebo (5,044 participants) at least 6 months after the second dose of COMIRNATY. Overall, participants who received a booster dose, had a median follow-up time of 2.5 months after the booster dose to the cut-off date (5 October 2021). Among the participants, the median age was 53.0 years (range 16 through 87 years of age), including 1,175 booster dose recipients (23.1%) who were ≥65 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.
Solicited Local and Systemic Adverse Reactions
Overall, among participants who received a booster dose in a subset from Study C4591001 (Study 2), 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.
Solicited Local Reaction | COMIRNATY Booster Dose Na = 289 nb (%) |
---|---|
Rednessc | |
Any (>2 cm) | 17 (5.9) |
Severe | 0 |
Swellingc | |
Any (>2 cm) | 23 (8.0) |
Severe | 1 (0.3) |
Pain at the injection sited | |
Any | 240 (83.0) |
Severe | 1 (0.3) |
|
In participants who received a booster dose the mean duration of pain at the injection site after the booster dose was 2.6 days (range 1 to 8 days), for redness 2.2 days (range 1 to 15 days), and for swelling 2.2 days (range 1 to 8 days).
Solicited Systemic Reaction | COMIRNATY Booster Dose Na = 289 nb (%) |
---|---|
Fever |
|
≥38.0℃ | 25 (8.7) |
≥38.0℃ to 38.4℃ | 12 (4.2) |
>38.4℃ to 38.9℃ | 12 (4.2) |
>38.9℃ to 40.0℃ | 1 (0.3) |
>40.0℃ | 0 |
Fatiguec |
|
Any | 184 (63.7) |
Severe | 13 (4.5) |
Headachec |
|
Any | 140 (48.4) |
Severe | 3 (1.0) |
Chillsc |
|
Any | 84 (29.1) |
Severe | 3 (1.0) |
Vomitingd |
|
Any | 5 (1.7) |
Severe | 0 |
Diarrheae |
|
Any | 25 (8.7) |
Severe | 0 |
New or worsened muscle painc |
|
Any | 113 (39.1) |
Severe | 4 (1.4) |
New or worsened joint painc |
|
Any | 73 (25.3) |
Severe | 1 (0.3) |
Use of antipyretic or pain medicationf | 135 (46.7) |
|
Unsolicited Adverse Events
Overall, participants who received a booster dose in Study C4591031 (Study 4), had a median follow-up time of 2.5 months after the booster dose to the cut-off date (October 5, 2021).
In an analysis of all unsolicited adverse events reported following the booster dose of COMIRNATY, through 1 month after the booster dose, in participants 16 through 87 years of age (N = 5,055), adverse reactions included headache (5%), fever (4.8%), lymphadenopathy (2.8%), decreased appetite (0.2%), malaise (0.7%), nausea (0.9%), and pain in extremity (1.1%).
Serious Adverse Events
Of the participants who received a booster dose of COMIRNATY or placebo (COMIRNATY = 5,055; placebo = 5,020) to the cut-off date (October 5, 2021), serious adverse events were reported by 0.3% of COMIRNATY recipients and 0.5% by placebo recipients. There were no notable patterns or numerical imbalances between treatment groups for specific categories of serious adverse events that would suggest a causal relationship to COMIRNATY. A 17-year-old male in Study 2 was diagnosed with myocarditis three days after receiving the booster dose (Dose 3). The participant was treated and recovered.
Adolescents 12 to 15 Years of Age– Primary Series (Two Doses)
Solicited Adverse Reactions
Table 9 and Table 10 present the frequency and severity of solicited local and systemic reactions, respectively, within 7 days following each dose of COMIRNATY and placebo in adolescents 12 to 15 years of age included in the safety population who were monitored for reactogenicity with an electronic diary.
| ||||
Solicited Local Reaction | COMIRNATY | Placebo | COMIRNATY | Placebo |
---|---|---|---|---|
Redness |
|
|
|
|
Any (>2 cm) | 65 (5.8) | 12 (1.1) | 55 (5.0) | 10 (0.9) |
Severec | 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) |
Severec | 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) |
Severed | 11 (1.0) | 0 (0.0) | 7 (0.6) | 0 (0.0) |
Any local reactione | 976 (86.6) | 271 (24.0) | 872 (79.5) | 198 (18.4) |
| ||||
Solicited Systemic Reaction | COMIRNATY | Placebo | COMIRNATY | Placebo |
---|---|---|---|---|
Fever |
|
|
|
|
≥38.0°C | 114 (10.1) | 12 (1.1) | 215 (19.6) | 7 (0.6) |
>38.9°C | 11 (1.0) | 2 (0.2) | 25 (2.3) | 1 (0.1) |
Fatigue |
|
|
|
|
Any | 677 (60.1) | 457 (40.6) | 726 (66.2) | 264 (24.5) |
Severec | 15 (1.3) | 8 (0.7) | 26 (2.4) | 4 (0.4) |
Headache |
|
|
|
|
Any | 623 (55.3) | 396 (35.1) | 708 (64.5) | 263 (24.4) |
Severec | 11 (1.0) | 9 (0.8) | 22 (2.0) | 1 (0.1) |
Chills |
|
|
|
|
Any | 311 (27.6) | 109 (9.7) | 455 (41.5) | 73 (6.8) |
Severec | 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) |
Severed | 1 (0.1) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
Diarrhea |
|
|
|
|
Any | 90 (8.0) | 82 (7.3) | 65 (5.9) | 43 (4.0) |
Severee | 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) |
Severec | 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) |
Severec | 1 (0.1) | 0 (0.0) | 4 (0.4) | 0 (0.0) |
Any systemic reactionsf | 877 (77.8) | 636 (56.4) | 904 (82.4) | 439 (40.7) |
Use of antipyretic or pain medication | 413 (36.6) | 111 (9.8) | 557 (50.8) | 95 (8.8) |
Unsolicited Adverse Events
In the analysis of Study 2 of all unsolicited adverse events reported following any dose, through 1 month after Dose 2, in adolescents 12 to 15 years of age (N=2260; 1,131 COMIRNATY group vs. 1,129 placebo group), those assessed as adverse reactions not already captured by solicited local and systemic reactions were lymphadenopathy (9 (0.8%) vs. 2 (0.2%)), and nausea (5 (0.4%) vs. 1 (0.1%)).
In analyses of all unsolicited adverse events in Study 2 from Dose 1 up to the participant unblinding date, 69.0% of study participants 12 through 15 years of age had at least 4 months of follow-up after Dose 2. Among participants 12 through 15 years of age who received at least one dose of study vaccine, 1,131 of whom received COMIRNATY and 1,129 of whom received placebo, unsolicited adverse events were reported by 95 (8.4%) participants in the COMIRNATY group and 113 (10.0%) participants in the placebo group.
Non-serious adverse events from Dose 1 through up to 30 days after Dose 2 in ongoing follow up were reported by 5.8% of COMIRNATY recipients and by 5.8% of placebo recipients. From Dose 1 through 30 days after Dose 2, reports of lymphadenopathy plausibly related to the study intervention were imbalanced, with notably more cases in the COMIRNATY group (7) vs. the placebo group (1). 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
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% (786 COMIRNATY and 773 placebo) 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. In study 2, a 16-year-old male was diagnosed with myopericarditis 3 days after his 2nd dose. The participant was treated and recovered.
Children 5 Years Through ˂12 Years of Age – Primary Series (Two Doses)
Solicited Adverse Reactions
Table 11 and Table 12 present the frequency and severity of solicited local and systemic reactions, respectively, within 7 days following each dose of COMIRNATY and placebo in children 5 years through ˂12 years of age included in the initial enrolment safety population who were monitored for reactogenicity with an electronic diary.
| ||||
Solicited Local Reaction | COMIRNATY Dose 1 Na=1,511 nc (%) | Placebo Dose 1 Na,b=748 nc (%) | COMIRNATY Dose 2 Na=1,501 nc (%) | Placebo Dose 2 Na,b=740 nc (%) |
Rednessd |
|
|
|
|
Any (≥0.5 cm) | 222 (14.7) | 43 (5.7) | 278 (18.5) | 40 (5.4) |
Severe | 0 (0.0) | 0 (0.0) | 3 (0.2) | 0 (0.0) |
Swellingd |
|
|
|
|
Any (≥0.5 cm) | 158 (10.5) | 20 (2.7) | 229 (15.3) | 20 (2.7) |
Severe | 1 (0.1) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
Pain at the injection sitee |
|
|
| |
Any | 1,119 (74.1) | 234 (31.3) | 1,065 (71.0) | 218 (29.5) |
Severe | 4 (0.3) | 0 (0.0) | 5 (0.3) | 0 (0.0) |
| ||||
Solicited Systemic Reaction | COMIRNATY Dose 1 Na=1,511 nc (%) | Placebo Dose 1 Na,b=748 nc (%) | COMIRNATY Dose 2 Na=1,501 nc (%) | Placebo Dose 2 Na,b=740 nc (%) |
Fever |
|
|
|
|
≥38.0℃ | 38 (2.5) | 10 (1.3) | 98 (6.5) | 9 (1.2) |
>38.9℃ | 3 (0.2) | 1 (0.1) | 9 (0.6) | 1 (0.1) |
Fatigued |
|
|
|
|
Any | 508 (33.6) | 234 (31.3) | 592 (39.4) | 180 (24.3) |
Severe | 4 (0.3) | 1 (0.1) | 11 (0.7) | 1 (0.1) |
Headached |
|
|
|
|
Any | 339 (22.4) | 180 (24.1) | 420 (28.0) | 138 (18.6) |
Severe | 2 (0.1) | 4 (0.5) | 3 (0.2) | 0 (0.0) |
Chillsd |
|
|
|
|
Any | 70 (4.6) | 35 (4.7) | 147 (9.8) | 32 (4.3) |
Severe | 0 (0.0) | 0 (0.0) | 2 (0.1) | 1 (0.1) |
Vomitinge |
|
|
|
|
Any | 33 (2.2) | 11 (1.5) | 28 (1.9) | 6 (0.8) |
Severe | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
Diarrheaf |
|
|
|
|
Any | 89 (5.9) | 31 (4.1) | 79 (5.3) | 35 (4.7) |
Severe | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
New or worsened muscle paind |
|
|
| |
Any | 137 (9.1) | 51 (6.8) | 175 (11.7) | 55 (7.4) |
Severe | 1 (0.1) | 0 (0.0) | 1 (0.1) | 0 (0.0) |
New or worsened joint paind |
|
|
| |
Any | 50 (3.3) | 41 (5.5) | 78 (5.2) | 27 (3.6) |
Severe | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
Use of antipyretic or pain medicationg | 217 (14.4) | 62 (8.3) | 296 (19.7) | 60 (8.1) |
Unsolicited Adverse Events
In the analyses of Study 3 in children 5 years through ˂12 years of age (initial enrolment group: 1,518 COMIRNATY 10 mcg and 750 placebo), 99.5% of participants had at least 30 days and 95.7% of participants had at least 3 months follow-up after Dose 2.
Serious adverse events from Dose 1 through up to 30 days after Dose 2 in ongoing follow‑up in the initial enrolment group were reported by 1 participant (0.1%) in each group after receiving the vaccine or placebo through the data cut-off date. No serious adverse events were reported that were considered related to vaccination.
Non-serious adverse events from Dose 1 through up to 30 days after Dose 2 in ongoing follow‑up in the initial enrolment group were reported by 10.9% of COMIRNATY 10 mcg recipients and by 9.1% of placebo recipients. Lymphadenopathy was reported in 13 (0.9%) participants in the COMIRNATY 10 mcg group vs. 1 (0.1%) in the placebo group. All cases were considered to be mild, with a median onset of 3 days after Dose 1, and 2 days after Dose 2 in the vaccine group. The median duration was 3.5 days (ranged from 1 to 14 days) in the vaccine group. Skin and subcutaneous tissue disorders (including skin rash, dermatitis, eczema and urticaria) were reported in 17 (1.1%) participants in the vaccine group and 5 (0.7%) participants in the placebo group. Most of the events began from 3-11 days after the second dose and were characterized as mild and self-limited. There were no other notable patterns between treatment groups for specific categories of non-serious adverse events that would suggest a causal relationship to COMIRNATY. There were no reports of myocarditis/pericarditis or anaphylaxis by the study cut-off date.
Children 5 Years Through ˂12 Years of Age – After Booster Dose
A subset of Phase 2/3 participants 5 years through ˂12 years of age received a booster dose of COMIRNATY at least 5 months after completing the primary series (range 5 to 9 months, 86.8% of participants received the booster dose at least 8 months after Dose 2). Those participants vaccinated prior to February 22, 2022 provided the safety database (n=401), and had a median safety follow-up of 1.3 months from vaccination through the data cut-off date of March 22, 2022.
The median age of these 401 participants was 8.0 years (range 5 years through ˂12 years of age), 52.4% were male and 47.6% were female, 70.1% were White, 7.2% were Black or African American, 22.9% were Hispanic/Latino, 7.7% were Asian, and 2.0% were American Indian/Alaska Native.
Solicited Local and Systemic Adverse Reactions
Table 13 and Table 14 present the frequency and severity of reported solicited local and systemic reactions, respectively, within 7 days of a booster dose of COMIRNATY for Phase 2/3 participants 5 years through ˂12 years of age.
In participants who received a booster dose, the mean duration of pain at the injection site after the booster dose was 2.4 days (range 1 to 35 days), for redness 2.3 days (range 1 to 12 days), and for swelling 2.3 days (range 1 to 9 days).
| |
| COMIRNATY Booster Na=371 nb (%) |
Rednessc |
|
Any (≥0.5 cm) | 58 (15.6) |
Severe | 1 (0.3) |
Swellingc |
|
Any (≥0.5 cm) | 61 (16.4) |
Severe | 0 |
Pain at the injection sited |
|
Any | 274 (73.9) |
Severe | 2 (0.5) |
| |
Solicited Systemic Reaction | COMIRNATY Booster Na=371 nb (%) |
Fever |
|
≥38.0℃ | 25 (6.7) |
>38.9℃ | 3 (0.8) |
Fatiguec |
|
Any | 169 (45.6) |
Severe | 7 (1.9) |
Headachec |
|
Any | 126 (34.0) |
Severe | 0 |
Chillsc |
|
Any | 39 (10.5) |
Severe | 1 (0.3) |
Vomitingd |
|
Any | 9 (2.4) |
Severe | 0 |
Diarrheae |
|
Any | 18 (4.9) |
Severe | 1 (0.3) |
New or worsened muscle painc |
|
Any | 68 (18.3) |
Severe | 0 |
New or worsened joint painc |
|
Any | 25 (6.7) |
Severe | 0 |
Use of antipyretic or pain medicationf | 114 (30.7) |
Unsolicited Adverse Events
Overall, the 401 participants who received a booster dose of COMIRNATY had a median follow-up time of 1.3 months after the booster dose through the cut-off date.
In an analysis of all unsolicited adverse events reported in participants 5 years through ˂12 years of age (N = 401) through up to 1 month after the booster dose, lymphadenopathy (n = 10, 2.5%) was an adverse reaction not already captured by solicited local and systemic reactions.
Serious Adverse Events
No serious adverse events were reported after the booster dose through the cut-off date.
Children 2 Through <5 Years of Age – Primary Series (Three Doses)
Solicited Adverse Reactions
Table 15 and Table 16 present the frequency of solicited local and systemic reactions, respectively, within 7 days following each dose of COMIRNATY and placebo in children 2 through <5 years of age who were monitored for reactogenicity with an electronic diary.
Table 15: Study 3 – Frequency of Solicited Local Reactions Within 7 Days After Each Dose – Children 2 Through <5 Years of Age – Safety Population* | ||||||
Solicited Local Reaction | COMIRNATY† Dose 1 Na=1,814 to 1,825 nb (%) | Placebo Dose 1 Na=905 to 909 nb (%) | COMIRNATY† Dose 2 Na=1,772 to 1,779 nb (%) | Placebo Dose 2 Na=877 to 878 nb (%) | COMIRNATY† Dose 3 Na=547 to 552
nb (%) | Placebo Dose 3 Na=262
nb (%) |
Redness |
|
|
|
|
|
|
Any (≥0.5cm) | 160 (8.8) | 77 (8.5) | 202 (11.4) | 50 (5.7) | 60 (10.9) | 9 (3.4) |
Severec | 1 (0.1) | 1 (0.1) | 1 (0.1) | 0 | 0 | 0 |
Swelling |
|
|
|
|
|
|
Any (≥0.5cm) | 67 (3.7) | 26 (2.9) | 102 (5.7) | 18 (2.1) | 17 (3.1) | 3 (1.1) |
Severec | 0 | 0 | 0 | 0 | 0 | 0 |
Pain at the injection site |
|
|
|
|
| |
Any | 559 (30.8) | 186 (20.6) | 550 (31.0) | 178 (20.3) | 146 (26.7) | 35 (13.4) |
Severed | 0 | 1 (0.1) | 0 | 1 (0.1) | 0 | 0 |
* Randomized participants who received at least 1 dose of the study intervention. † COMIRNATY 3mcg. Note: Reactions were collected in an electronic diary (e-diary) from Day 1 to Day 7 after vaccination. a. N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. b. n = Number of participants with the specified reaction. c. Severe: >7.0 cm. d. Severe: prevents daily activity. |
Table 16: Study 3 – Frequency of Solicited Systemic Reactions Within 7 Days After Each Dose – Children 2 Through <5 Years of Age – Safety Population* | ||||||
Solicited Systemic Reaction | COMIRNATY† Dose 1 Na=1,813 to 1,824 nb (%) | Placebo Dose 1 Na=905 to 909 nb (%) | COMIRNATY† Dose 2 Na=1,772 to 1,779 nb (%) | Placebo Dose 2 Na=877 to 878 nb (%) | COMIRNATY† Dose 3 Na=547 to 552
nb (%) | Placebo Dose 3 Na=262
nb (%) |
Fever |
|
|
|
|
|
|
≥38.0℃ | 95 (5.2) | 48 (5.3) | 88 (4.9) | 46 (5.2) | 28 (5.1) | 11 (4.2) |
>38.9℃ | 14 (0.8) | 8 (0.9) | 21 (1.2) | 8 (0.9) | 4 (0.7) | 3 (1.1) |
Fatigue |
|
|
|
|
|
|
Any | 539 (29.7) | 277 (30.6) | 456 (25.7) | 201 (22.9) | 134 (24.5) | 57 (21.8) |
Severec | 6 (0.3) | 5 (0.6) | 8 (0.5) | 3 (0.3) | 2 (0.4) | 0 |
Headache |
|
|
|
|
|
|
Any | 81 (4.5) | 44 (4.9) | 81 (4.6) | 36 (4.1) | 27 (4.9) | 11 (4.2) |
Severec | 0 | 1 (0.1) | 0 | 1 (0.1) | 0 | 0 |
Chills |
|
|
|
|
|
|
Any | 41 (2.3) | 22 (2.4) | 53 (3.0) | 23 (2.6) | 18 (3.3) | 7 (2.7) |
Severec | 3 (0.2) | 0 | 0 | 0 | 1 (0.2) | 0 |
Vomiting |
|
|
|
|
|
|
Any | 54 (3.0) | 24 (2.7) | 61 (3.4) | 29 (3.3) | 9 (1.6) | 10 (3.8) |
Severed | 0 | 0 | 0 | 0 | 0 | 0 |
Diarrhea |
|
|
|
|
|
|
Any | 139 (7.7) | 72 (8.0) | 118 (6.7) | 64 (7.3) | 28 (5.1) | 13 (5.0) |
Severee | 0 | 0 | 1 (0.1) | 0 | 0 | 0 |
New or worsened muscle pain | ||||||
Any | 43 (2.4) | 15 (1.7) | 46 (2.6) | 21 (2.4) | 11 (2.0) | 4 (1.5) |
Severec | 1 (0.1) | 0 | 0 | 0 | 0 | 0 |
New or worsened joint pain |
|
|
|
|
| |
Any | 14 (0.8) | 18 (2.0) | 24 (1.4) | 9 (1.0) | 7 (1.3) | 2 (0.8) |
Severec | 0 | 0 | 0 | 0 | 1 (0.2) | 0 |
Use of antipyretic or pain medicationf | 197 (10.8) | 83 (9.1) | 177 (9.9) | 74 (8.4) | 47 (8.5) | 18 (6.9) |
* Randomized participants who received at least 1 dose of the study intervention. † COMIRNATY 3mcg. Note: Events and use of antipyretic or pain medication were collected in an electronic diary (e-diary) from Day 1 to Day 7 after each dose. a. N = Number of participants reporting at least 1 yes or no response for the specified event after the specified dose. b. n = Number of participants with the specified reaction. c. Severe: prevents daily activity. d. Severe: requires intravenous hydration. e. Severe: 6 or more loose stools in 24 hours. f. Severity was not collected for use of antipyretic or pain medication. |
Unsolicited Adverse Events
In the analyses of Study 3 in participants 2 through <5 years of age (606 COMIRNATY; 280 placebo), 76.6% of participants had at least 30 days of follow-up after Dose 3.
Serious adverse events from Dose 1 through 1 month after Dose 3, with an overall median of 1.4 months follow-up after Dose 3, were reported by 0.7% of COMIRNATY recipients and by 0.9% of placebo recipients. One serious adverse event of fever (maximum temperature 40.3°C) on Day 3 after Dose 2 in a 4-year-old was considered possibly related to vaccination.
Non-serious adverse events from Dose 1 through up to 30 days after Dose 3, in ongoing follow up were reported by 18.5% of COMIRNATY recipients and by 18.5% of placebo recipients.
From Dose 1 through 30 days after Dose 3, lymphadenopathy was reported in 1 (0.1%) of COMIRNATY recipients vs. 0 (0.0%) of placebo recipients. There were no other notable patterns between treatment groups for specific categories of non-serious adverse events that would suggest a causal relationship to COMIRNATY.
Children 6 Months Through <2 Years of Age – Primary Series (Three Doses)
Solicited Adverse Reactions
Table 17 and Table 18 present the frequency of solicited local and systemic reactions, respectively, within 7 days following each dose of COMIRNATY and placebo in children 6 months through <2 years of age who were monitored for reactogenicity with an electronic diary.
Table 17: Study 3 – Frequency of Solicited Local Reactions Within 7 Days After Each Dose – Children 6 Months Through <2 Years of Age – Safety Population* | ||||||
Solicited Local Reaction | COMIRNATY† Dose 1 Na=1,159 to 1,173 nb (%) | Placebo Dose 1 Na=591 to 595 nb (%) | COMIRNATY† Dose 2 Na=1,137 to 1,147 nb (%) | Placebo Dose 2 Na=590 to 591 nb (%) | COMIRNATY† Dose 3 Na=362 to 365
nb (%) | Placebo Dose 3 Na=170
nb (%) |
Redness | ||||||
Any (≥0.5 cm) | 124 (10.6) | 44 (7.4) | 107 (9.3) | 39 (6.6) | 26 (7.1) | 9 (5.3) |
Severec | 0 | 0 | 0 | 0 | 1 (0.3) | 0 |
Swelling | ||||||
Any (≥0.5 cm) | 46 (3.9) | 15 (2.5) | 45 (3.9) | 9 (1.5) | 10 (2.7) | 3 (1.8) |
Severec | 0 | 0 | 0 | 0 | 0 | 0 |
Tenderness at the injection site | ||||||
Any | 192 (16.6) | 66 (11.2) | 171 (15.0) | 50 (8.5) | 58 (16.0) | 20 (11.8) |
Severed | 0 | 0 | 1 (0.1) | 0 | 0 | 0 |
* Randomized participants who received at least 1 dose of the study intervention. † COMIRNATY 3 mcg. Note: Reactions were collected in an electronic diary (e-diary) from Day 1 to Day 7 after vaccination. a. N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. b. n = Number of participants with the specified reaction. c. Severe: >7.0 cm. d. Severe: causes limitation of limb movement. |
Table 18: Study 3 – Frequency of Solicited Systemic Reactions Within 7 Days After Each Dose – Children 6 Months Through <2 Years of Age – Safety Population* | ||||||
Solicited Systemic Reaction | COMIRNATY† Dose 1 Na=1,159 to 1,173 nb (%) | Placebo Dose 1 Na=591 to 595 nb (%) | COMIRNATY† Dose 2 Na=1,137 to 1,147 nb (%) | Placebo Dose 2 Na=590 to 591 nb (%) | COMIRNATY† Dose 3 Na=362 to 365
nb (%) | Placebo Dose 3 Na=170
nb (%) |
Fever | ||||||
≥38.0℃ | 85 (7.2) | 43 (7.2) | 85 (7.4) | 36 (6.1) | 25 (6.8) | 10 (5.9) |
>38.9℃ to 40.0℃ | 20 (1.7) | 7 (1.2) | 24 (2.1) | 7 (1.2) | 6 (1.6) | 1 (0.6) |
Decreased appetite | ||||||
Any | 257 (22.2) | 125 (21.2) | 252 (22.2) | 106 (18.0) | 73 (20.2) | 23 (13.5) |
Severec | 3 (0.3) | 1 (0.2) | 4 (0.4) | 1 (0.2) | 4 (1.1) | 0 |
Drowsiness | ||||||
Any | 313 (27.0) | 173 (29.3) | 271 (23.8) | 125 (21.2) | 72 (19.9) | 22 (12.9) |
Severed | 2 (0.2) | 2 (0.3) | 4 (0.4) | 1 (0.2) | 1 (0.3) | 1 (0.6) |
Irritability | ||||||
Any | 593 (51.2) | 279 (47.2) | 539 (47.4) | 240 (40.7) | 158 (43.6) | 64 (37.6) |
Severee | 7 (0.6) | 0 | 7 (0.6) | 5 (0.8) | 1 (0.3) | 0 |
Use of antipyretic or pain medicationf | 281 (24.0) | 117 (19.7) | 243 (21.2) | 111 (18.8) | 70 (19.2) | 28 (16.5) |
* Randomized participants who received at least 1 dose of the study intervention. † COMIRNATY 3 mcg. Note: Events and use of antipyretic or pain medication were collected in an electronic diary (e-diary) from Day 1 to Day 7 after each dose. a. N = Number of participants reporting at least 1 yes or no response for the specified event after the specified dose. b. n = Number of participants with the specified reaction. c. Severe: refusal to feed. d. Severe: disabling; not interested in usual daily activity. e. Severe: inconsolable; crying cannot be comforted. f. Severity was not collected for use of antipyretic or pain medication. |
Unsolicited Adverse Events
In the analyses of Study 3 in participants 6 months through 2 years of age (386 COMIRNATY; 184 placebo), 83.7% of participants had at least 30 days of follow-up after Dose 3.
Serious adverse events from Dose 1 through 1 month after Dose 3, with an overall median of 1.3 months follow up after Dose 3, were reported by 1.4% of COMIRNATY recipients and by 2.3% of placebo recipients. No serious adverse events were reported that were considered related to vaccination.
Non-serious adverse events from Dose 1 through up to 1 month after Dose 3, in ongoing follow up were reported by 29.1% of COMIRNATY recipients and by 26.3% of placebo recipients.
From Dose 1 through 30 days after Dose 3, lymphadenopathy was reported in 2 (0.2%) of COMIRNATY recipients vs. 0 (0%) of placebo recipients. There were no other notable patterns between treatment groups for specific categories of non-serious adverse events that would suggest a causal relationship to COMIRNATY.
8.5 Post-Market Adverse Reactions
The following adverse reactions have been identified during post authorization use of COMIRNATY.
Cardiac disorders: myocarditis and/or pericarditis (see WARNING AND PRECAUTIONS section)
Immune System Disorders: severe allergic reactions, including anaphylaxis
Musculoskeletal and Connective Tissue Disorders: pain in extremity (arm)
Nervous System Disorders: Facial paralysis / Bell’s Palsy, hypoesthesia, paresthesia, dizziness
Skin and subcutaneous tissue disorders and other hypersensitivity reactions: skin rash, pruritus, urticaria, angioedema, erythema multiforme
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 product exposure. They are included because: a) they represent reactions that are known to occur following immunizations generally; b) they are potentially serious; or c) on the basis of their frequency of reporting.
9 Drug Interactions
No interaction studies have been performed. There is no information on the co-administration of COMIRNATY with other vaccines.
Do not mix COMIRNATY with other vaccines/products in the same syringe.
10 Clinical Pharmacology
10.1 Mechanism of Action
The nucleoside-modified messenger RNA in COMIRNATY is formulated in lipid nanoparticles, which enable delivery of the RNA into host cells to allow expression of the SARS-CoV-2 S antigen. The vaccine elicits both neutralizing antibody and cellular immune responses to the spike (S) antigen, which may contribute to protection against COVID-19 disease.
11 Storage, Stability And Disposal
During storage, minimize exposure to room light, and avoid exposure to direct sunlight and ultraviolet light.
Do not refreeze thawed vials.
For 12 Years and Older: DILUTE BEFORE USE (Vials with Purple Cap and Purple Label Border)
Frozen Vials Prior to Use
Cartons of COMIRNATY multiple dose vials (for 12 years and older: DILUTE BEFORE USE) arrive in thermal containers with dry ice. To ensure all appropriate safeguards are in place, refer to the Dry Ice Safety Data Sheet and the COMIRNATY Shipping and Handling Guidelines available at COMIRNATY.ca. Once received, remove the vial cartons immediately from the thermal container and preferably store in an ultra-low temperature freezer between ‑90°C to -60°C (-130°F to -76°F) until the expiry date printed on the label. Vials may also be stored at -25°C to -15°C (‑13°F to 5°F) for up to 2 weeks. Vials must be kept frozen and protected from light, in the original cartons, until ready to use. Vials stored at -25°C to ‑15°C (-13°F to 5°F) for up to 2 weeks may be returned one time to the recommended storage condition of -90°C to -60°C (-130°F to -76°F). Total cumulative time the vials are stored at -25°C to -15°C (-13°F to 5°F) should be tracked and should not exceed 2 weeks.
If an ultra-low temperature freezer is not available, the thermal container in which COMIRNATY arrives may be used as temporary storage when consistently re-filled to the top of the container with dry ice. Refer to the re-icing guidelines packed in the original thermal container for instructions regarding the use of the thermal container for temporary storage. The thermal container maintains a temperature range of -90°C to -60°C (‑130°F to -76°F). Storage of the vials between -96°C to -60°C (-141°F to -76°F) is not considered an excursion from the recommended storage condition.
Transportation of Frozen Vials
If local redistribution is needed and full cartons containing vials cannot be transported at ‑90°C to ‑60°C (‑130°F to ‑76°F), vials may be transported at -25°C to ‑15°C (-13°F to 5°F). Any hours used for transport at -25°C to -15°C (-13°F to 5°F) count against the 2‑week limit for storage at -25°C to -15°C (-13°F to 5°F). Frozen vials transported at -25°C to -15°C (‑13°F to 5°F) may be returned one time to the recommended storage condition of -90°C to -60°C (-130°F to -76°F).
Thawed Vials Prior to Dilution
Thawed Under Refrigeration: Thaw and then store undiluted vials in the refrigerator (2°C to 8°C [35°F to 46°F]) for up to 1 month. A carton of 25 vials or 195 vials may take up to 2 or 3 hours, respectively, to thaw in the refrigerator, whereas a fewer number of vials will thaw in less time.
Thawed at Room Temperature: For immediate use, thaw undiluted vials at room temperature (up to 25°C (77°F)] for 30 minutes.
Thawed vials can be handled in room light conditions.
Vials must reach room temperature before dilution.
Undiluted vials may be stored at room temperature for no more than 2 hours.
Transportation of Thawed Vials
Available data support transportation of one or more thawed, undiluted vials at 2°C to 8°C (35°F to 46°F) for up to 12 hours. Any hours used for transport at 2°C to 8°C (35°F to 46°F) count against the 1-month limit for storage at 2°C to 8°C (35°F to 46°F).
Vials After Dilution
After dilution, store vials between 2°C to 25°C (35°F to 77°F) and use within 6 hours from the time of dilution. Any vaccine remaining in vials must be discarded after 6 hours. After dilution, the vaccine vials can be handled in room light conditions. During storage, minimize exposure to room light, and avoid exposure to direct sunlight and ultraviolet light. Do not freeze. If the vaccine is frozen, it must be discarded.
For 12 Years and Older: DO NOT DILUTE (Vials with Gray Cap and Gray Label Border)
Vial Storage Prior to Use
Cartons of COMIRNATY multiple dose vials (for 12 years and older: DO NOT DILUTE) may arrive frozen at ultra cold conditions in thermal containers with dry ice.
Once received, frozen vials may be immediately transferred to the refrigerator [2°C to 8°C (35°F to 46°F)], thawed and stored for a single period of up to 10 weeks within the 18-month shelf-life. The 10 week refrigerated expiry date should be recorded on the carton at the time of transfer. A carton of 10 vials may take up to 6 hours to thaw at this temperature.
Alternatively, frozen vials may be stored in an ultra-low temperature freezer at 90°C to 60°C ( 130°F to 76°F). Do not store vials at 25°C to 15°C (-13°F to 5°F). Once vials are thawed they should not be refrozen.
Cartons of COMIRNATY multiple dose vials (for 12 years and older: DO NOT DILUTE) may also arrive at 2°C to 8°C. If received at 2°C to 8°C, they should be stored at 2°C to 8°C. Check that the carton has been updated to reflect the 10-week refrigerated expiry date.
Regardless of storage condition, vaccine should not be used after 18 months from the date of manufacture printed on the vial and cartons.
Vial Storage During Use
If not previously thawed at 2°C to 8°C (35°F to 46°F), allow vials to thaw at room temperature [up to 25°C (77°F)] for 30 minutes.
COMIRNATY multiple dose vials (for 12 years and older: DO NOT DILUTE) may be stored at room temperature up to 25°C (77°F) for a total of 12 hours prior to the first puncture.
DO NOT DILUTE PRIOR TO USE.
After first puncture, the vial should be stored at 2°C to 25°C (35°F to 77°F). Vials should be discarded 12 hours after first puncture. Vial labels and cartons may state that a vial should be discarded 6 hours after the first puncture. The information in this Product Monograph supersedes the number of hours printed on vial labels and cartons.
Thawed vials can be handled in room light conditions.
Transportation of Vials
If local redistribution is needed, full cartons containing unpunctured vials may be transported at -90°C to -60°C (-130°F to -76°F); full cartons or individual unpunctured vials may also be transported at 2°C to 8°C (35°F to 46°F).
For Age 5 Years to <12 Years: DILUTE PRIOR TO USE (Vials with Orange Cap and Orange Label Border)
And
For Age 6 Months to <5 Years: DILUTE PRIOR TO USE (Vials with Maroon Cap and Maroon Label Border)
Vial Storage Prior to Use
Cartons of COMIRNATY multiple dose vials (for age 5 years to <12 years) and COMIRNATY multiple dose vials (for age 6 months to <5 years) may arrive frozen at ultra-cold conditions in thermal containers with dry ice.
Once received, frozen vials may be immediately transferred to the refrigerator [2°C to 8°C (35°F to 46°F)], thawed and stored for a single period of up to 10 weeks within the 18-month shelf-life. The 10 week refrigerated expiry date should be recorded on the carton at the time of transfer.
- COMIRNATY (for age 5 years to <12 years): A carton of 10 vials may take up to 4 hours to thaw at this temperature.
- COMIRNATY (for age 6 months to <5 years): A carton of 10 vials may take up to 2 hours to thaw at this temperature.
Alternatively, frozen vials may be stored in an ultra-low temperature freezer at 90°C to 60°C ( 130°F to 76°F) for up to 18 months from the date of manufacture. Do not store vials at 25°C to 15°C (-13°F to 5°F). Once vials are thawed they should not be refrozen.
Cartons of COMIRNATY (for age 5 years to <12 years) and COMIRNATY (for age 6 months to <5 years) may also arrive at 2°C to 8°C (35°F to 46°F). If vials are received at 2°C to 8°C, they should be stored at 2°C to 8°C. Check that the carton has been updated to reflect the 10-week refrigerated expiry date.
Regardless of storage condition, vaccines should not be used after 18 months from the date of manufacture printed on the vial and cartons.
Vial Storage During Use
If not previously thawed at 2°C to 8°C (35°F to 46°F), allow vials to thaw at room temperature [up to 25°C (77°F)] for 30 minutes.
Vials of COMIRNATY (for age 5 years to <12 years) and COMIRNATY (for age 6 months to <5 years) may be stored at temperatures up to 25°C (77°F) for a total of 12 hours prior to dilution.
After dilution the vials should be stored at 2°C to 25°C (35°F to 77°F). Vials should be discarded 12 hours after dilution (i.e., the first puncture). Vial labels and cartons may state that a vial should be discarded 6 hours after dilution. The information in this Product Monograph supersedes the number of hours printed on vial labels and cartons.
Thawed vials can be handled in room light conditions.
Transportation of Vials
If local redistribution is needed, full cartons containing undiluted vials may be transported at ‑90°C to ‑60°C (‑130°F to ‑76°F); full cartons or individual undiluted vials may also be transported at 2°C to 8°C (35°F to 46°F).
12 Special Handling Instructions
COMIRNATY multiple dose vial contain a frozen suspension that does not contain preservative and must be thawed and may require dilution prior to administration.
Careful attention should be paid to the vial cap colour and label border and the appropriate corresponding instructions must be followed. For important information on handling and preparation for administration, please refer to 11 STORAGE, STABILITY AND DISPOSAL and 4 DOSAGE AND ADMINISTRATION.
Control #: 270734
March 21, 2023
1 Health Professional Information
1 INDICATIONS
COMIRNATY Original & Omicron BA.4/BA.5 (COVID-19 mRNA Vaccine, Bivalent (Original and Omicron BA.4/BA.5)) is indicated for active immunization against coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) in individuals 5 years of age and older (see 4.2 Recommended Dose and Dosage Adjustment).
The safety and effectiveness of a primary vaccination course or booster dose of COMIRNATY Original & Omicron BA.4/BA.5 for individuals 5 years of age and older is inferred from studies which evaluated the primary series and booster vaccination with COMIRNATY and supported by studies of a booster dose of COMIRNATY Original & Omicron BA.4/BA.5 in individuals > 5 years of age.
1.1 Pediatrics
The safety and efficacy of COMIRNATY Original & Omicron BA.4/BA.5 in children under 5 years of age have not yet been established (see 8 ADVERSE REACTIONS and 14 CLINICAL TRIALS).
1.2 Geriatrics
Clinical studies of COMIRNATY and COMIRNATY Original & Omicron BA.4/BA.5 include participants 65 years of age and older and their data contributes to the overall assessment of safety and efficacy (see 8 ADVERSE REACTIONS and 14 CLINICAL TRIALS).
2 Contraindications
COMIRNATY Original & Omicron BA.4/BA.5 is contraindicated in individuals who are hypersensitive to the active substance or to any ingredient in the formulation. For a complete listing see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.
3 Serious Warnings And Precautions
At the time of authorization, there are no known serious warnings or precautions associated with this product.
4 Dosage And Administration
4.1 Dosing Considerations
The storage, preparation and administration information differ depending on which presentation of the vaccine is considered. Careful attention should be paid to the vial cap and label border colour and information on the label, and the appropriate corresponding instructions must be followed under the subsections below.
For 12 Years of Age and Older
COMIRNATY Original & Omicron BA.4/BA.5 is a suspension for intramuscular injection. DO NOT DILUTE (Single Dose or Multiple dose Vials with Gray Cap and Gray Label Border).
A single dose is 0.3 mL.
For Age 5 Years to <12 Years
COMIRNATY Original & Omicron BA.4/BA.5 is a suspension for intramuscular injection which must be diluted prior to administration. DILUTE PRIOR TO USE (Multiple Dose Vials with Orange Cap and Orange Label Border).
After preparation, a single dose is 0.2 mL.
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Dosage Form | Vial Cap and Label Border Colour | Age Range | Dilution Information | Dose(s) Per Vial | Dose Volume |
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COMIRNATY* Original & Omicron BA.4/BA.5 Single Dose Vial (for 12 years of age and older: DO NOT DILUTE) | Gray | 12 years and older | DO NOT DILUTE prior to use | 1 | 0.3 mL |
COMIRNATY* Original & Omicron BA.4/BA.5 Multiple Dose Vial (for 12 years of age and older: DO NOT DILUTE) | Gray | 12 years and older | DO NOT DILUTE prior to use | 6 | 0.3 mL |
COMIRNATY* Original & Omicron BA.4/BA.5 Multiple Dose Vial (for age 5 years to <12 years: DILUTE PRIOR TO USE) | Orange | 5 to <12 years | Dilute with 1.3 mL sterile 0.9% Sodium Chloride Injection, USP prior to use | 10 | 0.2 mL |
4.2 Recommended Dose and Dosage Adjustment
4.2.1 Vaccination Schedule for Individuals 12 Years of Age and Older
Primary Vaccination Course
COMIRNATY Original & Omicron BA.4/BA.5 is administered intramuscularly as a primary course of two doses (0.3 mL each) 3 weeks apart.
If an individual starts a primary vaccination course of COMIRNATY, they may complete the primary vaccination course with COMIRNATY Original & Omicron BA.4/BA.5.
The interchangeability of COMIRNATY Original & Omicron BA.4/BA.5 with COVID-19 vaccines from other manufacturers to complete the primary course has not been established. Individuals who have received a dose of COMIRNATY Original & Omicron BA.4/BA.5 should receive COMIRNATY Original & Omicron BA.4/BA.5 to complete the primary course.
Booster Dose
A booster dose (0.3 mL) of COMIRNATY Original & Omicron BA.4/BA.5 may be administered intramuscularly at least 3 to 6 months after completing the primary course of COMIRNATY and/or a previous booster dose of COMIRNATY in individuals 12 years of age or older.
Vials of COMIRNATY Original & Omicron BA.4/BA.5 intended for individuals 12 years of age and older (gray cap/gray label border) cannot be used to prepare doses for individuals aged 5 to <12 years of age.
4.2.2 Vaccination Schedule for Individuals Aged 5 Years to <12 Years
Primary Vaccination Course
COMIRNATY Original & Omicron BA.4/BA.5 is administered intramuscularly as a primary series of two doses (0.2 mL each) 3 weeks apart.
If an individual starts a primary vaccination course of COMIRNATY, they may complete the primary vaccination course with COMIRNATY Original & Omicron BA.4/BA.5.
The interchangeability of COMIRNATY Original & Omicron BA.4/BA.5 with COVID-19 vaccines from other manufacturers to complete the primary course has not been established. Individuals who have received a dose of COMIRNATY Original & Omicron BA.4/BA.5 should receive COMIRNATY Original & Omicron BA.4/BA.5 to complete the primary course.
Booster Dose
A booster dose (0.2 mL) of COMIRNATY Original & Omicron BA.4/BA.5 may be administered intramuscularly at least 6 months after completing the primary course of COMIRNATY and/or a previous booster dose of COMIRNATY in children 5 years through <12 years of age.
Vials of COMIRNATY Original & Omicron BA.4/BA.5 intended for individuals aged 5 years to <12 years (orange cap/orange label border) cannot be used to prepare doses for individuals 12 years of age and older.
4.3 Reconstitution
4.3.1 For 12 Years of Age and Older: DO NOT DILUTE (Single Dose or Multiple Dose Vials with Gray Cap and Gray Label Border)
The COMIRNATY Original & Omicron BA.4/BA.5 single dose or multiple dose vial with a gray cap and gray label border MUST NOT BE DILUTED prior to administration. Instructions on the handling and dose preparation of the vaccine prior to administration are provided below.
Preparation for Administration
Single Dose Vials
DO NOT DILUTE
- The COMIRNATY Original & Omicron BA.4/BA.5 single dose vial with a gray cap and a gray label border is supplied as a frozen suspension that does not contain preservative. Each vial must be thawed prior to administration. DO NOT DILUTE prior to use.
- Single dose vials of COMIRNATY Original & Omicron BA.4/BA.5 intended for 12 years of age or older with a gray cap/gray label border cannot be used to prepare doses for individuals aged 5 years to <12 years.
- Single dose vials may be thawed in the refrigerator (2°C to 8°C [35°F to 46°F]) or at room temperature (up to 25°C [77°F]) (see 11 STORAGE, STABILITY AND DISPOSAL).
- The thawed suspension may contain white to off-white opaque amorphous particles.
- One single dose vial contains 1 dose of 0.3 mL.
- Refer to thawing and dose preparation instructions in the panels below.
Multiple Dose Vials
DO NOT DILUTE
- The COMIRNATY Original & Omicron BA.4/BA.5 multiple dose vial with a gray cap and a gray label border contains a volume of 2.25 mL, and is supplied as a frozen suspension that does not contain preservative. Each vial must be thawed prior to administration. DO NOT DILUTE prior to use.
- Multiple dose vials of COMIRNATY Original & Omicron BA.4/BA.5 intended for 12 years of age or older with a gray cap/gray label border cannot be used to prepare doses for individuals aged 5 years to <12 years.
- Multiple dose vials may be thawed in the refrigerator (2°C to 8°C [35°F to 46°F]) or at room temperature (up to 25°C [77°F]) (see 11 STORAGE, STABILITY AND DISPOSAL).
- The thawed suspension may contain white to off-white opaque amorphous particles.
- One multiple dose vial contains 6† doses of 0.3 mL.
- Refer to thawing and dose preparation instructions in the panels below.
† Low dead-volume syringes and/or needles can be used to extract 6 doses from a single vial. If standard syringes and needles are used, there may not be sufficient volume to extract a 6th dose from a single vial.
COMIRNATY Original & Omicron BA.4/BA.5 For 12 Years of Age and Older: DO NOT DILUTE (Single Dose & Multiple Dose Vials with Gray Cap and Gray Label Border) | |
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VIAL AND DOSE VERIFICATION | |
✓ Gray plastic cap and label with gray border |
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THAWING PRIOR TO USE | |
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Gently × 10 |
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PREPARATION OF INDIVIDUAL 0.3 mL DOSES | |
Withdraw 0.3 mL dose of vaccine | Single dose vials
Multiple dose vials
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Record the date and time of first multiple dose vial puncture | Multiple Dose Vial Only:
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4.3.2 For Age 5 Years to <12 Years: DILUTE PRIOR TO USE (Multiple Dose Vials with Orange Cap and Orange Label Border)
Preparation for Administration
Prior to Dilution:
- The COMIRNATY Original & Omicron BA.4/BA.5 multiple dose vial (for ages 5 years to <12 years) has an orange cap and an orange label border and contains a volume of 1.3 mL. It is supplied as a frozen suspension that does not contain preservative. Each vial must be thawed and diluted prior to administration.
- Single dose and multiple dose vials of COMIRNATY Original & Omicron BA.4/BA.5 intended for 12 years of age or older with a gray cap/gray label border cannot be used to prepare doses for individuals aged 5 years to <12 years.
- Multiple dose vials may be thawed in the refrigerator at 2°C to 8°C [35°F to 46°F] or at room temperature (up to 25°C [77°F]) (see 11 STORAGE, STABILITY AND DISPOSAL).
- Prior to dilution, the thawed suspension may contain opaque amorphous particles.
- Refer to thawing instructions in the panels below.
Dilution:
- Dilute the multiple dose vial contents using 1.3 mL of sterile 0.9% Sodium Chloride Injection, USP to form COMIRNATY Original & Omicron BA.4/BA.5. Do not add more than 1.3 mL of diluent.
- ONLY use 0.9% Sodium Chloride Injection, USP as the diluent. This diluent is not packaged with the vaccine and must be sourced separately. Do not use bacteriostatic 0.9% Sodium Chloride Injection or any other diluent.
- After dilution, one multiple dose vial contains 10* doses of 0.2 mL.
- After dilution, the vaccine will be a white to off-white suspension. Inspect vials to confirm there are no particulates and no discolouration is observed.
- Strict adherence to aseptic techniques must be followed.
- Refer to dilution and dose preparation instructions in the panels below.
*Low dead-volume syringes and/or needles can be used to extract 10 doses from a single vial. If standard syringes and needles are used, there may not be sufficient volume to extract 10 doses from a single vial.
COMIRNATY Original & Omicron BA.4/BA.5 For Age 5 Years to <12 Years: DILUTE PRIOR TO USE (Multiple Dose Vials with Orange Cap and Orange Label Border) | |
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VIAL AND DOSE VERIFICATION | |
✓ Orange plastic cap and label with orange border |
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THAWING PRIOR TO DILUTION | |
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DILUTION | |
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PREPARATION OF INDIVIDUAL 0.2 mL DOSES | |
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4.4 Administration
4.4.1 For 12 Years of Age and Older
DO NOT DILUTE (Single Dose or Multiple Dose Vials with Gray Cap and Gray Label Border)
Administer a single 0.3 mL dose of COMIRNATY Original & Omicron BA.4/BA.5 intramuscularly, preferably in the deltoid muscle.
Do not inject the vaccine intravascularly, subcutaneously or intradermally.
Visually inspect each dose in the dosing syringe prior to administration. The vaccine will be an off white suspension. During the visual inspection:
- Verify the final dosing volume of 0.3 mL.
- Confirm there are no particulates and that no discolouration is observed.
- Do not administer if vaccine is discoloured or contains particulate matter.
Single Dose Vials
Single dose vials of COMIRNATY Original & Omicron BA.4/BA.5 with gray caps and gray label borders contain 1 dose of 0.3 mL of vaccine.
- Withdraw a single 0.3 mL dose of vaccine.
- Discard the vial and any excess volume.
- Do not pool excess vaccine from multiple vials.
Multiple Dose Vials
Multiple dose vials of COMIRNATY Original & Omicron BA.4/BA.5 with gray caps and gray label borders contain 6 doses of 0.3 mL of vaccine.
Low dead-volume syringes and/or needles can be used to extract 6 doses from a single vial. In order to ensure consistent withdrawal of 6 doses of 0.3 mL, it is important to adhere to minimizing volume loss during dose extraction. If standard syringes and needles are used, there may not be sufficient volume to extract a 6th dose from a single vial. Irrespective of the type of syringe and needle:
- Each dose must contain 0.3 mL of vaccine.
- If the amount of vaccine remaining in the vial cannot provide a full dose of 0.3 mL, discard the vial and any excess volume.
- Do not pool excess vaccine from multiple vials.
4.4.2 For Age 5 Years to <12 Years
Administer a single 0.2 mL dose of COMIRNATY Original & Omicron BA.4/BA.5 intramuscularly, preferably in the deltoid muscle.
Do not inject the vaccine intravascularly, subcutaneously or intradermally. DO NOT administer COMIRNATY Original & Omicron BA.4/BA.5 with Gray Cap and Gray Label Border to children 5 years to <12 years.
DILUTE PRIOR TO USE (Multiple Dose Vial with Orange Cap and Orange Label Border).
Visually inspect each dose in the dosing syringe prior to administration. The diluted vaccine will be a white to off white suspension. During the visual inspection:
- Verify the final dosing volume of 0.2 mL.
- Confirm there are no particulates and that no discolouration is observed.
- Do not administer if vaccine is discoloured or contains particulate matter.
After dilution, multiple dose vials of COMIRNATY Original & Omicron BA.4/BA.5 (for age 5 years to <12 years) contain 10 doses of 0.2 mL of vaccine. Low dead-volume syringes and/or needles can be used to extract 10 doses from a single vial. In order to ensure consistent withdrawal of 10 doses of 0.2 mL, it is important to adhere to minimizing volume loss during dose extraction. If standard syringes and needles are used, there may not be sufficient volume to extract 10 doses from a single vial. Irrespective of the type of syringe and needle:
- Each dose must contain 0.2 mL of vaccine.
- If the amount of vaccine remaining in the vial cannot provide a full dose of 0.2 mL, discard the vial and any excess volume.
- Do not pool excess vaccine from multiple vials.
5 Overdosage
In the event of suspected overdose, monitoring of vital functions and symptomatic treatment is recommended. Contact your regional poison control centre.
6 Dosage Forms, Strengths, Composition And Packaging
To help ensure the traceability of vaccines for patient immunization record-keeping as well as safety monitoring, health professionals should record the time and date of administration, quantity of administered dose (if applicable), anatomical site and route of administration, brand name and generic name of the vaccine, the product lot number and expiry date (or manufacture date).
For 12 Years of Age and Older: DO NOT DILUTE (Single Dose or Multiple Dose Vials with Gray Cap and Gray Label Border)
COMIRNATY Original & Omicron BA.4/BA.5 is supplied as a frozen suspension in single dose or multiple dose vials with gray caps and labels with gray borders. Do not dilute. Each single dose vial contains 1 dose of 0.3 mL and each multiple dose vial contains 6† doses of 0.3 mL. Each 0.3 mL dose of COMIRNATY Original & Omicron BA.4/BA.5 contains 15 mcg of a nucleoside modified messenger RNA (modRNA) encoding the viral spike (S) glycoprotein of SARS-CoV-2 original strain and 15 mcg of modRNA encoding the S glycoprotein of SARS-CoV-2 Omicron variant lineages BA.4 and BA.5 (Omicron BA.4/BA.5). Each dose contains 30 mcg modRNA in total and also includes the non-medicinal ingredients listed in Table 1.
COMIRNATY Original & Omicron BA.4/BA.5 does not contain preservative. The vial stoppers are not made with natural rubber latex.
COMIRNATY Original & Omicron BA.4/BA.5 single dose or multiple dose vials (with gray cap and gray label border) are supplied in a carton containing 10 single dose or multiple dose vials.
Route of Administration | Dosage Form / Strength/Composition | Non-medicinal Ingredients |
---|---|---|
Intramuscular injection | DO NOT DILUTE (Vials with Gray Cap and Gray Label Border) Suspension Tozinameran (mRNA) encodes for the viral spike (S) protein of SARS-CoV-2 Single dose vial: (each vial contains 1 dose of 0.3 mL) Multiple dose vial: (each vial contains 6† doses of 0.3 mL) |
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For Age 5 Years to <12 Years: DILUTE PRIOR TO USE (Vials with Orange Cap and Orange Label Border)
COMIRNATY Original & Omicron BA.4/BA.5 is supplied as a frozen suspension in multiple dose vials with an orange cap and an orange label border. Each multiple dose vial must be diluted with 1.3 mL of sterile 0.9% Sodium Chloride Injection, USP prior to use to form the vaccine, and contains 10* doses of 0.2 mL after dilution. Each 0.2 mL dose of COMIRNATY Original & Omicron BA.4/BA.5 contains 5 mcg of a nucleoside modified messenger RNA (modRNA) encoding the viral spike (S) glycoprotein of SARS-CoV-2 original strain and 5 mcg of modRNA encoding the S glycoprotein of SARS-CoV-2 Omicron variant lineages BA.4 and BA.5 (Omicron BA.4/BA.5) and the non-medicinal ingredients listed in Table 2. COMIRNATY Original & Omicron BA.4/BA.5 does not contain preservative. The vial stoppers are not made with natural rubber latex.
COMIRNATY Original & Omicron BA.4/BA.5 multiple dose vials (with orange cap and orange label border) are supplied in a carton containing 10 multiple dose vials.
* Low dead-volume syringes and/or needles can be used to extract 10 doses from a single vial. If standard syringes and needles are used, there may not be sufficient volume to extract 10 doses from a single vial.
Route of Administration | Dosage Form / Strength/Composition | Non-medicinal Ingredients |
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Intramuscular injection | Suspension
Tozinameran (mRNA) encodes for the viral spike (S) protein of SARS-CoV-2 Original strain and famtozinameran (mRNA) encodes for the viral spike (S) protein of SARS-CoV-2 Omicron BA.4/BA.5 strain
Multiple dose vial |
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7 Warnings And Precautions
General
The administration of COMIRNATY Original & Omicron BA.4/BA.5 should be postponed in individuals suffering from acute severe febrile illness.
Fainting may occur in association with administration of injectable vaccines. Individuals should be advised to bring symptoms (e.g., dizziness, increases in heart rate, feeling short of breath, tingling sensations or sweating) to the attention of the vaccination provider for evaluation. Procedures should be in place to avoid injury from fainting.
As with any vaccine, vaccination with COMIRNATY Original & Omicron BA.4/BA.5 may not protect all recipients.
Acute Allergic Reactions
Anaphylaxis has been reported. As with all vaccines, training for immunizers, appropriate medical treatment and supervision after immunization should always be readily available in case of a rare anaphylactic event following the administration of this vaccine.
Vaccine recipients should be kept under observation for at least 15 minutes after immunization; 30 minutes is a preferred interval when there is a specific concern about a possible vaccine reaction.
COMIRNATY Original & Omicron BA.4/BA.5 should not be given to those who have experienced anaphylaxis after a prior dose of COMIRNATY, COMIRNATY Original/Omicron BA.1, or COMIRNATY Original & Omicron BA.4/BA.5.
Cardiovascular
Myocarditis and Pericarditis
Very rare cases of myocarditis and/or pericarditis following vaccination with COMIRNATY have been reported during post-authorization use. These cases occurred more commonly after the second dose and in adolescents and young adults. Typically, the onset of symptoms has been within a few days following receipt of COMIRNATY. Based on accumulating data, the reporting rates of myocarditis and pericarditis after COMIRNATY primary series in children ages 5 through <12 years are lower than in ages 12 through 17 years. Available short-term follow-up data suggest that the symptoms resolve in most individuals, but information on long-term sequelae is lacking. The decision to administer COMIRNATY Original & Omicron BA.4/BA.5 to an individual with a history of myocarditis or pericarditis should take into account the individual’s clinical circumstances.
Healthcare professionals are advised to consider the possibility of myocarditis and/or pericarditis in their differential diagnosis if individuals present with chest pain, shortness of breath, palpitations or other signs and symptoms of myocarditis and/or pericarditis following immunization with a COVID-19 vaccine. This could allow for early diagnosis and treatment. Cardiology consultation for management and follow up should be considered.
Driving and Operating Machinery
COMIRNATY Original & Omicron BA.4/BA.5 has no or negligible influence on the ability to drive and use machines. However, some of the effects mentioned under 8 ADVERSE REACTIONS may temporarily affect the ability to drive or use machines.
Fertility
It is unknown whether this vaccine has an impact on fertility. Animal studies do not indicate direct or indirect harmful effects with respect to female fertility or reproductive toxicity (see 16 NON-CLINICAL TOXICOLOGY).
Hematologic
Individuals receiving anticoagulant therapy or those with a bleeding disorder that would contraindicate intramuscular injection should not be given the vaccine unless the potential benefit clearly outweighs the risk of administration.
Immune
The efficacy and safety of the vaccine has not been assessed in immunocompromised individuals, including those receiving immunosuppressant therapy. Immunocompromised persons, including individuals receiving immunosuppressant therapy, may have a diminished immune response to the vaccine.
7.1 Special Populations
7.1.1 Pregnant Women
No data are available yet regarding the use of COMIRNATY Original & Omicron BA.4/BA.5 during pregnancy.
Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryo/ fetal development, parturition, or post-natal development (see 16 NON-CLINICAL TOXICOLOGY).
7.1.2 Breast-feeding
No data are available yet regarding the use of COMIRNATY Original & Omicron BA.4/BA.5 during breast- feeding.
It is unknown whether COMIRNATY Original & Omicron BA.4/BA.5 is excreted in human milk. A risk to the newborns/infants cannot be excluded.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for immunization against COVID-19.
7.1.3 Pediatrics
The safety and efficacy of COMIRNATY Original & Omicron BA.4/BA.5 in children under 5 years of age have not yet been established.
7.1.4 Geriatrics
Clinical studies of COMIRNATY Original & Omicron BA.4/BA.5 include participants 65 years of age and older, who received the primary series and a booster dose of COMIRNATY, and their data contributes to the overall assessment of safety and efficacy (See 8 ADVERSE REACTIONS and 14 CLINICAL TRIALS).
8 Adverse Reactions
8.1 Adverse Reaction Overview
8.1.1 COMIRNATY Original & Omicron BA.4/BA.5
The safety of a primary vaccination course or booster dose of COMIRNATY Original & Omicron BA.4/BA.5 for individuals 5 years of age and older is inferred from:
- safety data from clinical trials which evaluated primary and booster vaccination with COMIRNATY (see 8.2 Clinical Trial Adverse Reactions);
- safety data for a booster dose of COMIRNATY Original & Omicron BA.4/BA.5; and
- post marketing safety data with COMIRNATY.
Safety data accrued with the COMIRNATY formulations are relevant to the COMIRNATY Original & Omicron BA.4/BA.5 vaccine because these vaccines are manufactured using the same process.
Participants ≥12 Years of Age – After a Dose of COMIRNATY Original & Omicron BA.4/BA.5 as a Second Booster (4th Dose)
Study C4591044 (Study 5) is an ongoing Phase 2/3 study to evaluate the safety, tolerability, and immunogenicity of new bivalent vaccines including COMIRNATY Original & Omicron BA.4/BA.5. In Cohorts 2 and 3 of the study 317 participants 12 years and older and 410 participants 18 years and older, respectively, received COMIRNATY Original & Omicron BA.4/BA.5 30 mcg (15/15 mcg) as a second booster dose following a previous primary series and one booster dose of COMIRNATY. The safety evaluation of participants in the study is ongoing. All participants were monitored for solicited local and systemic reactions and use of antipyretic medication after vaccination with an electronic diary during the 7 days following the dose of vaccination. Participants continue to be monitored for unsolicited adverse events (AEs), including serious adverse events (SAEs), throughout the study [from Dose 1 to 1 month after the last dose (all AEs) and 6 months (SAEs) after the last vaccination].
In a substudy from Study 5, 108 participants 12 to 17 years of age, 313 participants 18 to 55 years of age and 306 participants ≥56 years of age who had completed 3 doses of COMIRNATY, received a booster (fourth dose) of COMIRNATY Original & Omicron BA.4/BA.5 (15/15 mcg) 5.4 to 16.9 months after receiving Dose 3. Participants who received a booster (fourth dose) of COMIRNATY Original & Omicron BA.4/BA.5 had a median follow-up time of at least 1.5 months.
The overall safety profile for the COMIRNATY Original & Omicron BA.4/BA.5 booster (fourth dose) was similar to that seen after 3 doses of COMIRNATY. The most frequent adverse reactions in participants 12 years of age and older were injection site pain (>60%), fatigue (>50%), headache (>40%), muscle pain (>20%), chills (>10%), and joint pain (>10%).
Participants 5 to <12 Years of Age – After a Dose of COMIRNATY Original & Omicron BA.4/BA.5 as a Second Booster (4th Dose)
Study C4591048 (Study 6) is an ongoing study to evaluate the safety, tolerability, and immunogenicity of new bivalent vaccines including COMIRNATY Original & Omicron BA.4/BA.5.
In a subset from Study 6 (Phase 3), 113 participants 5 to <12 years of age who had completed 3 doses of COMIRNATY, received a booster (fourth dose) of COMIRNATY Original & Omicron BA.4/BA.5 (5/5 mcg) 2.6 to 8.5 months after receiving Dose 3. Participants who received a booster (fourth dose) of COMIRNATY Original & Omicron BA.4/BA.5 had a median follow-up time of at least 1.6 months.
The overall safety profile for the COMIRNATY Original & Omicron BA.4/BA.5 booster (fourth dose) was similar to that seen after 3 doses of COMIRNATY. The most frequent adverse reactions in participants 5 to <12 years were injection site pain (>60%), fatigue (>40%), headache (>20%), and muscle pain (>10%).
8.1.2 COMIRNATY (30 mcg)
Study BNT162‑01 (Study 1) was a Phase 1/2, two-part dose-escalation trial that enrolled 60 participants 18 through 55 years of age and 36 participants 56 through 85 years of age.
Study C4591001 (Study 2) is a Phase 1/2/3, multicenter, multinational, randomized, saline placebo-controlled, observer-blind, dose-finding, vaccine candidate-selection (Phase 1) and efficacy (Phase 2/3) study that has enrolled approximately 46,000 participants, 12 years of age or older. Of these, approximately 44,047 participants (22,026 COMIRNATY; 22,021 placebo) in Phase 2/3 are 16 years of age or older (including 378 and 376 adolescents 16 and 17 years of age in the vaccine and placebo groups, respectively) and 2,260 adolescents are 12 to 15 years of age (1,131 and 1,129 in the vaccine and placebo groups, respectively). Of the total number of COMIRNATY recipients in the study, 20.7% were 65 years of age and older. Study 2 also included 200 participants with confirmed stable human immunodeficiency virus (HIV) infection. HIV-positive participants are included in safety population disposition but are summarized separately in safety analyses.
Additionally, 306 existing Phase 3 participants 18 through 55 years of age received a booster dose of COMIRNATY approximately 6 months (range of 4.8 to 8.0 months) after completing 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 at least 6 months after the second dose. The overall safety profile for the booster dose was similar to that seen after 2 doses.
The safety evaluation of participants in Study 2 and Study 4 is ongoing. In Study 2, all participants 12 to 15 years of age and 16 years of age and older in the reactogenicity subset, and a subset of 306 participants 18 through 55 years of age who received a booster dose in Study 2, were monitored for solicited local and systemic reactions and use of antipyretic medication after each vaccination with an electronic diary during the 7 days following any dose of vaccination. Participants, including those who received a booster in Study 4, continue to be monitored for unsolicited adverse events (AEs), including serious adverse events (SAEs), throughout the study [from Dose 1 to 1 month after the last dose (all AEs) and 6 months (SAEs) after the last vaccination].
Participants 12 Years of Age and Older
At the time of the analysis of Study 2 (data accrued through March 13, 2021), a total of 25,651 (58.2%) participants (13,031 in vaccine group and 12,620 in placebo group) 16 years of age and older had been followed up for at least 4 months, with 3,082 (7.0%) participants (1,778 in vaccine group and 1,304 in placebo group) followed up for at least 6 months after the second dose during the blinded placebo-controlled follow-up period. A total of 12,006 (54.5%) participants originally randomized to the vaccine group in Study 2 had been followed up for at least 6 months after the second dose including the blinded and open-label periods.
In an analysis of Study 2, based on data up to the cut-off date of March 13, 2021, a total of 2,260 adolescents (1,131 COMIRNATY; 1,129 placebo) were 12 to 15 years of age. Of these,1,559 (786 COMIRNATY and 773 placebo) adolescents have been followed for ≥4 months after the second dose of COMIRNATY.
In clinical studies with a data cut-off of March 13, 2021, and where 2 doses were administered 3 weeks apart, the most common adverse reactions in the reactogenicity subset (n=4,924) of participants 16 years of age and older after any dose included injection site pain (84.3%), fatigue (64.7%), headache (57.1%), muscle pain (40.2%), chills (34.7%), joint pain (25.0%), fever (15.2%), injection site swelling (11.1%), and injection site redness (9.9%). Additional AEs reported in the safety population (n=21,926) of participants 16 years of age and older from dose 1 to 1 month after dose 2 included nausea (1.2%), malaise (0.6%), lymphadenopathy (0.4%), asthenia (0.3%), decreased appetite (0.2%), hyperhidrosis (0.1%), lethargy (0.1%), and night sweats (0.1%). Adverse reactions were usually mild or moderate in intensity and resolved within a few days after vaccination.
The safety profile in 545 participants receiving COMIRNATY that were seropositive for SARS-CoV-2 at baseline was similar to that seen in the general population.
In a clinical study with a data cut-off date of 02 September 2021, the most commonly reported (≥8%) adverse reactions in adolescents 12 through 15 years of age 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%).
In a clinical study of participants 18 through 55 years of age (N=306), 289 participants (94%) completed the e-diary recording adverse reactions. The most commonly reported adverse reactions (≥10%) following administration of a booster dose were pain at the injection site (83.0%), fatigue (63.7%), headache (48.4%), muscle pain (39.1%), chills (29.1%), and joint pain (25.3%).
In a clinical study of approximately 10,000 participants 16 years of age and older, unsolicited adverse reactions following administration of a booster dose included headache (5%), fever (4.8%), lymphadenopathy (2.8%), pain in extremity (1.1%), nausea (0.9%), malaise (0.7%), and decreased appetite (0.2%).
8.1.3 COMIRNATY (10 mcg)
Study C4591007 (Study 3) is a Phase 1/2/3 study comprised of an open-label vaccine dose finding portion (Phase 1) and a multicenter, multinational, randomized, saline placebo-controlled, observer-blind immunogenicity and efficacy portion (Phase 2/3) that has enrolled approximately 4,600 participants 5 years through <12 years of age. Of these, approximately 3,100 participants received COMIRNATY 10 mcg and approximately 1,500 participants received placebo in the Phase 2/3 part of the study. Study 3 also enrolled 1,776 participants 6 months through <2 years of age (1,178 COMIRNATY 3 mcg; 598 placebo), and 2,750 participants 2 through <5 years of age (1,835 COMIRNATY 3 mcg; 915 placebo) in Phase 2/3.
In a subset of Study 3 Phase 2/3 participants, 401 participants 5 years through <12 years of age received a booster dose of COMIRNATY at least 5 months (range 5 to 9 months) after completing the primary series. The overall safety profile for the booster dose was similar to that seen after the primary series. The analysis of the Study 3 Phase 2/3 subset is based on data up to the cut-off date of March 22, 2022 (median follow-up time of 1.3 months).
Participants 5 Years Through <12 Years of Age
In an analysis of Study 3 Phase 2/3, based on data up to the cut-off date of October 8, 2021, 2,268 participants (initial enrolment group: 1,518 COMIRNATY 10 mcg and 750 placebo) were 5 years through <12 years of age. Of these, 2,171 (95.7%) (1,456 COMIRNATY 10 mcg and 715 placebo) participants have been followed for at least 3 months after Dose 2. An analysis of Study 3 Phase 2/3 adverse event data also included another 2,379 participants (safety expansion group: 1,591 COMIRNATY 10 mcg and 788 placebo), of whom 71.2% had a follow-up period for at least 2 weeks after Dose 2. The safety evaluation in Study 3 is ongoing.
Adverse reactions following administration of any dose in the initial enrolment safety population (n = 1,518) of children 5 years through <12 years of age included pain at the injection site (84.3%), fatigue (51.7%), headache (38.2%), injection site redness (26.4%), injection site swelling (20.4%), muscle pain (17.5%), chills (12.4%), fever (8.3%), joint pain (7.6%), lymphadenopathy (0.9%), rash (0.5%), nausea (0.4%), malaise (0.1%), and decreased appetite (0.1%).
The most frequent adverse reactions in participants 5 years through <12 years of age following the booster dose (data cut-off date of March 22, 2022; median follow-up time of 1.3 months) were injection site pain (73.9%), fatigue (45.6%), headache (34.0%), myalgia (18.3%), chills (10.5%), injection site redness (15.6%), and swelling (16.4%). The most frequently reported unsolicited adverse event was lymphadenopathy (2.5%).
8.2 Clinical Trial Adverse Reactions
Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials, therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use.
8.2.1 COMIRNATY Original & Omicron BA.4/BA.5
Participants 12 Years of Age and Older
Solicited Local Adverse Reactions
Table 3 presents the frequency of reported solicited local reactions within 7 days of a second booster dose with COMIRNATY Original & Omicron BA.4/BA.5.
Most local reactions were mild or moderate in severity and no Grade 4 local reactions were reported in any group. The median onset for all local reactions was 1 to 3 days, and all events resolved within a median duration of 1 to 3 days after onset.
Local Reaction |
COMIRNATY Original & Omicron BA.4/BA.5 (15 mcg/15 mcg) |
||
---|---|---|---|
12– 17 years (N=107) |
18 – 55 years (N=309) |
>55 years (N=300) |
|
Pain at injection site |
70.1% |
76.1% |
57.1% |
Redness at injection site |
5.6% |
6.5% |
4.0% |
Swelling at injection site |
7.5% |
7.1% |
2.7% |
Solicited Systemic Adverse Reactions
Table 4 presents the frequency of reported systemic reactions within 7 days of a second booster dose of COMIRNATY Original & Omicron BA.4/BA.5. Most systemic reactions were mild or moderate in severity and no Grade 4 systemic reactions were reported in any group. The median onset for all systemic reactions was 2 to 4 days, and all events resolved within a median duration of 1 to 2 days after onset.
Systemic Reaction |
COMIRNATY Original & Omicron BA.4/BA.5 (15 mcg/15 mcg) |
||
---|---|---|---|
12 – 17 years (N=107) |
18 – 55 years (N=309) |
>55 years (N=300) |
|
Fatigue |
67.3% |
61.2% |
38.5% |
Headache |
50.5% |
46.6% |
30.7% |
New or worsened muscle pain |
26.2% |
30.4% |
18.0% |
Chills |
23.4% |
22.0% |
12.0% |
New or worsened joint pain |
12.1% |
14.9% |
12.0% |
Fever |
9.3% |
4.9% |
4.3% |
Diarrhea |
6.5% |
10.7% |
9.6% |
Vomiting |
2.8% |
1.9% |
0.7% |
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.
Participants 5 to <12 Years of Age
Solicited Local Adverse Reactions
Table 5 presents the frequency of reported solicited local reactions within 7 days of a second booster dose with COMIRNATY Original & Omicron BA.4/BA.5.
All local reactions were mild or moderate in severity. The median onset for all local reactions was 1 to 2 days, and all events resolved within a median duration of 2 days after onset.
Local Reaction |
COMIRNATY Original & Omicron BA.4/BA.5 (5 mcg/5 mcg) |
---|---|
5 – <12 years (N=111) |
|
Pain at injection site |
64.0% |
Redness at injection site |
7.2% |
Swelling at injection site |
4.5% |
Solicited Systemic Adverse Reactions
Table 6 presents the frequency of reported solicited systemic reactions within 7 days of a second booster dose with COMIRNATY Original & Omicron BA.4/BA.5.
Most systemic events were mild or moderate in severity, and no Grade 4 systemic events were reported. The median onset for all systemic events was 2 to 4 days, and all events resolved within a median duration of 1 to 2 days after onset.
Systemic Reaction |
COMIRNATY Original & Omicron BA.4/BA.5 (5 mcg/5 mcg) |
---|---|
5 – <12 years (N=111) |
|
Fatigue |
40.5% |
Headache |
25.2% |
New or worsened muscle pain |
13.5% |
Chills |
9.0% |
New or worsened joint pain |
9.0% |
Fever |
4.5% |
Diarrhea |
3.6% |
Vomiting |
3.6% |
Unsolicited Adverse Events
Among participants 5 to <12 years of age, unsolicited adverse events were reported by 4 (3.5%) participants who received a second booster dose through 1 month after the booster dose. Lymphadenopathy occurred in 1 (0.9%) participant.
8.2.2 COMIRNATY (30 mcg)
Participants 16 Years of Age and Older – Primary Series (Two Doses)
Solicited Adverse Reactions
Tables 7 through 10 present the frequency and severity of solicited local and systemic reactions, respectively, within 7 days following each dose of COMIRNATY and placebo in the subset of participants 16 years of age and older (n=9,839) in the safety population who were monitored for reactogenicity with an electronic diary.
Local Reaction |
Dose 1 |
Dose 2 |
||
---|---|---|---|---|
COMIRNATY Na=2,899 nb (%) |
Placebo Na=2,908 nb (%) |
COMIRNATY Na=2,682 nb (%) |
Placebo Na=2,684 nb (%) |
|
Redness |
||||
Anyc |
156 (5.4) |
28 (1.0) |
151 (5.6) |
18 (0.7) |
Severed |
7 (0.2) |
3 (0.1) |
11 (0.4) |
0 (0.0) |
Swelling |
||||
Anyc |
184 (6.3) |
16 (0.6) |
183 (6.8) |
5 (0.2) |
Severed |
6 (0.2) |
2 (0.1) |
7 (0.3) |
0 (0.0) |
Pain at the injection site |
||||
Anyc |
2,426 (83.7) |
414 (14.2) |
2,101 (78.3) |
312 (11.6) |
Severee |
39 (1.3) |
3 (0.1) |
39 (1.5) |
0 (0.0) |
Any local reactionc |
2,444 (84.3) |
432 (14.9) |
2,108 (78.6) |
325 (12.1) |
*Randomized participants in the safety analysis population who received at least 1 dose of the study intervention.
- N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. No Grade 4 solicited local reactions were reported in participants 16-55 years of age.
- n = Number of participants with the specified reaction.
- Any local reaction: any redness >2.0 cm, any swelling >2.0 cm, or any pain at the injection site.
- Severe: >10.0 cm.
- Severe: prevents daily activity.
Systemic Reaction |
Dose 1 |
Dose 2 |
||
---|---|---|---|---|
COMIRNATY Na=2,899 nb (%) |
Placebo Na=2,908 nb (%) |
COMIRNATY Na=2,682 nb (%) |
Placebo Na=2,684 nb (%) |
|
Fever |
||||
≥38.0°C |
119 (4.1) |
25 (0.9) |
440 (16.4) |
11 (0.4) |
>38.9°C |
8 (0.3) |
4 (0.1) |
40 (1.5) |
2 (0.1) |
Fatigue |
||||
Any |
1,431 (49.4) |
960 (33.0) |
1,649 (61.5) |
614 (22.9) |
Severed |
41 (1.4) |
18 (0.6) |
142 (5.3) |
14 (0.5) |
Headache |
||||
Any |
1,262 (43.5) |
975 (33.5) |
1,448 (54.0) |
652 (24.3) |
Severed |
33 (1.1) |
24 (0.8) |
91 (3.4) |
18 (0.7) |
Chills |
||||
Any |
479 (16.5) |
199 (6.8) |
1,015 (37.8) |
114 (4.2) |
Severed |
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) |
Severee |
0 (0.0) |
1 (0.0) |
4 (0.1) |
0 (0.0) |
Diarrhea |
||||
Any |
309 (10.7) |
323 (11.1) |
269 (10.0) |
205 (7.6) |
Severef |
3 (0.1) |
1 (0.0) |
6 (0.2) |
1 (0.0) |
New or worsened muscle pain |
||||
Any |
664 (22.9) |
329 (11.3) |
1,055 (39.3) |
237 (8.8) |
Severed |
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) |
Severed |
5 (0.2) |
1 (0.0) |
27 (1.0) |
4 (0.1) |
Any systemic reactionc |
1,979 (68.3) |
1,559 (53.6) |
2,034 (75.8) |
1,026 (38.2) |
Use of antipyretic or pain medication |
805 (27.8) |
398 (13.7) |
1,213 (45.2) |
320 (11.9) |
*Randomized participants in the safety analysis population who received at least 1 dose of the study intervention.
- N =Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. No Grade 4 solicited systemic reactions were reported in participants 16-55 years of age.
- n = Number of participants with the specified reaction.
- Any systemic reaction: any fever ≥38.0°C, any fatigue, any vomiting, any chills, any diarrhea, any headache, any new or worsened muscle pain, or any new or worsened joint pain.
- Severe: prevents daily activity.
- Severe: requires intravenous hydration.
- Severe: 6 or more loose stools in 24 hours.
Local Reaction |
Dose 1 |
Dose 2 |
||
---|---|---|---|---|
COMIRNATY Na=2,008 nb (%) |
Placebo Na=1,989 nb (%) |
COMIRNATY Na=1,860 nb (%) |
Placebo Na=1,833 nb (%) |
|
Redness |
||||
Anyc |
106 (5.3) |
20 (1.0) |
133 (7.2) |
14 (0.8) |
Severed |
5 (0.2) |
2 (0.1) |
10 (0.5) |
1 (0.1) |
Swelling |
||||
Anyc |
141 (7.0) |
23 (1.2) |
145 (7.8) |
13 (0.7) |
Severed |
2 (0.1) |
0 (0.0) |
4 (0.2) |
1 (0.1) |
Pain at the injection site |
||||
Anyc |
1,408 (70.1) |
185 (9.3) |
1,230 (66.1) |
143 (7.8) |
Severee |
4 (0.2) |
0 (0.0) |
10 (0.5) |
0 (0.0) |
Any local reactionc |
1,433 (71.4) |
207 (10.4) |
1,243 (66.8) |
158 (8.6) |
*Randomized participants in the safety analysis population who received at least 1 dose of the study intervention.
- N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. No Grade 4 solicited local reactions were reported in participants 56 years of age and older.
- n = Number of participants with the specified reaction.
- Any local reaction: any redness >2.0 cm, any swelling >2.0 cm, or any pain at the injection site.
- Severe: >10.0 cm.
- Severe: prevents daily activity.
Systemic Reaction |
Dose 1 |
Dose 2 |
||
---|---|---|---|---|
COMIRNATY Na=2,008 nb (%) |
Placebo Na=1,989 nb (%) |
COMIRNATY Na=1,860 nb (%) |
Placebo Na=1,833 nb (%) |
|
Fever |
||||
≥38.0°C |
26 (1.3) |
8 (0.4) |
219 (11.8) |
4 (0.2) |
>38.9°C |
1 (0.0) |
2 (0.1) |
7 (0.4) |
1 (0.1) |
Fatigue |
||||
Any |
677 (33.7) |
447 (22.5) |
949 (51.0) |
306 (16.7) |
Severed |
3 (0.1) |
3 (0.2) |
60 (3.2) |
2 (0.1) |
Grade 4g |
0 (0.0) |
0 (0.0) |
1 (0.1) |
0 (0.0) |
Headache |
||||
Any |
503 (25.0) |
363 (18.3) |
733 (39.4) |
259 (14.1) |
Severed |
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) |
Severed |
0 (0.0) |
1 (0.1) |
21 (1.1) |
0 (0.0) |
Vomiting |
||||
Any |
10 (0.5) |
9 (0.5) |
13 (0.7) |
5 (0.3) |
Severee |
0 (0.0) |
0 (0.0) |
2 (0.1) |
0 (0.0) |
Diarrhea |
||||
Any |
168 (8.4) |
130 (6.5) |
152 (8.2) |
102 (5.6) |
Severef |
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) |
Severed |
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) |
Severed |
3 (0.1) |
1 (0.1) |
9 (0.5) |
1 (0.1) |
Any systemic reactionc |
984 (49.0) |
749 (37.7) |
1,203 (64.7) |
516 (28.2) |
Use of antipyretic or pain medication |
382 (19.0) |
224 (11.3) |
688 (37.0) |
170 (9.3) |
*Randomized participants in the safety analysis population who received at least 1 dose of the study intervention.
- N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. The only Grade 4 solicited systemic reaction reported in participants 56 years of age and older was fatigue.
- n = Number of participants with the specified reaction.
- Any systemic reaction: any fever ≥38.0°C, any fatigue, any vomiting, any chills, any diarrhea, any headache, any new or worsened muscle pain, or any new or worsened joint pain.
- Severe: prevents daily activity.
- Severe: requires intravenous hydration.
- Severe: 6 or more loose stools in 24 hours.
- Grade 4: emergency room visit or hospitalization.
Study 2 also included 200 participants with confirmed stable human immunodeficiency virus
(HIV) infection. The safety profile of the participants with stable HIV infection receiving COMIRNATY (n = 100) was similar to that seen in the general population.
Unsolicited Adverse Events
The participants were unblinded to offer placebo participants COMIRNATY when they became locally eligible under regulatory approval in December 2020. A total of 25,651 (58.2%) participants (13,031 in vaccine group and 12,620 in placebo group) 16 years of age and older had been followed up for at least 4 months, with 3,082 (7.0%) participants (1,778 in vaccine group and 1,304 in placebo group) followed up for at least 6 months after the second dose during the blinded placebo-controlled follow-up period in Study 2. Adverse events detailed below for participants 16 years of age and older are for the placebo-controlled blinded follow-up period up to the participants’ unblinding dates.
Among participants 16 through 55 years of age who received at least one 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.
Lymphadenopathy was reported in 87 (0.4%) participants in the vaccine group compared to 8 (<0.1%) participants in the placebo group. Bell’s palsy (facial paralysis and facial paresis) was reported by four participants in the vaccine group and two in the placebo group. In the four vaccinated participants, events began from 3 to 48 days after their last dose, were mild to moderate in severity, and duration ranged from 3 to 68 days. Currently available information is insufficient to determine a causal relationship with the vaccine. 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. Cumulative safety follow-up to at least 6 months after Dose 2 for approximately 12,000 participants who received COMIRNATY showed no other safety signals arising from longer-term follow-up of the study.
Serious Adverse Events
In Study 2, among participants 16 through 55 years of age who had received at least 1 dose of vaccine or placebo (COMIRNATY = 12,995; placebo = 13,026), serious adverse events from Dose 1 up to the participant unblinding date in ongoing follow-up were reported by 103 (0.8%) COMIRNATY recipients and 117 (0.9%) placebo recipients. In a similar analysis, in participants 56 years of age and older (COMIRNATY = 8,931; placebo = 8,895), 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. 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.
Pericarditis was reported for one participant in the vaccine group, and no case was reported in the placebo group. Appendicitis was reported as a serious adverse event for 27 participants, 15 vaccine participants and 12 placebo participants. Currently available information is insufficient to determine a causal relationship with the vaccine. There were no other notable patterns or numerical imbalances between treatment groups for specific categories of serious adverse events (including neurologic, neuro-inflammatory, thrombotic events, myocarditis or anaphylactic reaction to the vaccine) reported during the blinded placebo-controlled follow-up period of the study.
Participants 16 Years of Age and Older – After Booster Dose
A subset from Study C4591001 (Study 2) Phase 2/3 participants, of 306 adults 18 through 55 years of age who completed the original COMIRNATY 2-dose series, received a booster dose of COMIRNATY approximately 6 months (range of 4.8 to 8.0 months) after receiving Dose 2.
In Study C4591031 (Study 4), a placebo-controlled booster study, participants 16 years of age and older recruited from Study C4591001 (Study 2) received a booster dose of COMIRNATY (5,081 participants), or placebo (5,044 participants) at least 6 months after the second dose of COMIRNATY. Overall, participants who received a booster dose, had a median follow-up time of 2.5 months after the booster dose to the cut-off date (5 October 2021). Among the participants, the median age was 53.0 years (range 16 through 87 years of age), including 1,175 booster dose recipients (23.1%) who were ≥65 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.
Solicited Local and Systemic Adverse Reactions
Overall, among participants who received a booster dose in a subset from Study C4591001 (Study 2), 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.
Solicited Local Reaction |
COMIRNATY Booster Dose Na = 289 nb (%) |
---|---|
Rednessc |
|
Any (>2 cm) |
17 (5.9) |
Severe |
0 |
Swellingc |
|
Any (>2 cm) |
23 (8.0) |
Severe |
1 (0.3) |
Pain at the injection sited |
|
Any |
240 (83.0) |
Severe |
1 (0.3) |
Note: Reactions were collected in the electronic diary (e-diary) from Day 1 to Day 7 after the booster dose. Note: No Grade 4 solicited local reactions were reported. *Participants in the safety analysis population who received the booster dose of COMIRNATY. a. N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. b. n = Number of participants with the specified reaction. c. Mild: >2.0 to 5.0 cm; Moderate: >5.0 to 10.0 cm; Severe: >10.0 cm. d. Mild: does not interfere with activity; Moderate: interferes with activity; Severe: prevents daily activity. |
In participants who received a booster dose the mean duration of pain at the injection site after the booster dose was 2.6 days (range 1 to 8 days), for redness 2.2 days (range 1 to 15 days), and for swelling 2.2 days (range 1 to 8 days).
Solicited Systemic Reaction |
COMIRNATY Booster Dose Na = 289 nb (%) |
---|---|
Fever |
|
≥38.0℃ |
25 (8.7) |
≥38.0℃ to 38.4℃ |
12 (4.2) |
>38.4℃ to 38.9℃ |
12 (4.2) |
>38.9℃ to 40.0℃ |
1 (0.3) |
>40.0℃ |
0 |
Fatiguec |
|
Any |
184 (63.7) |
Severe |
13 (4.5) |
Headachec |
|
Any |
140 (48.4) |
Severe |
3 (1.0) |
Chillsc |
|
Any |
84 (29.1) |
Severe |
3 (1.0) |
Vomitingd |
|
Any |
5 (1.7) |
Severe |
0 |
Diarrheae |
|
Any |
25 (8.7) |
Severe |
0 |
New or worsened muscle painc |
|
Any |
113 (39.1) |
Severe |
4 (1.4) |
New or worsened joint painc |
|
Any |
73 (25.3) |
Severe |
1 (0.3) |
Use of antipyretic or pain medicationf |
135 (46.7) |
Note: Events and use of antipyretic or pain medication were collected in the electronic diary (e-diary) from Day 1 to Day 7 after the booster dose. Note: No Grade 4 solicited systemic reactions were reported. *Randomized participants in the safety analysis population who received the booster dose of COMIRNATY. a. N = Number of participants reporting at least 1 yes or no response for the specified event after the specified dose. b. n = Number of participants with the specified reaction. c. Mild: does not interfere with activity; Moderate: some interference with activity; Severe: prevents daily activity. d. Mild: 1 to 2 times in 24 hours; Moderate: >2 times in 24 hours; Severe: requires intravenous hydration. e. Mild: 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. f. Severity was not collected for use of antipyretic or pain medication. |
Unsolicited Adverse Events
Overall, participants who received a booster dose in Study C4591031 (Study 4), had a median follow-up time of 2.5 months after the booster dose to the cut-off date (October 5, 2021).
In an analysis of all unsolicited adverse events reported following the booster dose of COMIRNATY, through 1 month after the booster dose, in participants 16 through 87 years of age (N = 5,055), adverse reactions included headache (5%), fever (4.8%), lymphadenopathy (2.8%), decreased appetite (0.2%), malaise (0.7%), nausea (0.9%), and pain in extremity (1.1%).
Serious Adverse Events
Of the participants who received a booster dose of COMIRNATY or placebo (COMIRNATY = 5,055; placebo = 5,020) to the cut-off date (October 5, 2021), serious adverse events were reported by 0.3% of COMIRNATY recipients and 0.5% by placebo recipients. There were no notable patterns or numerical imbalances between treatment groups for specific categories of serious adverse events that would suggest a causal relationship to COMIRNATY. A 17-year-old male in Study 2 was diagnosed with myocarditis three days after receiving the booster dose (Dose 3). The participant was treated and recovered.
Adolescents 12 to 15 Years of Age – Primary Series (Two Doses)
Solicited Adverse Reactions
Table 13 and Table 14 present the frequency and severity of solicited local and systemic reactions, respectively, within 7 days following each dose of COMIRNATY and placebo in adolescents 12 to 15 years of age included in the safety population who were monitored for reactogenicity with an electronic diary.
Local Reaction |
COMIRNATY Dose 1 Na=1,127 nb (%) |
Placebo Dose 1 Na=1,127 nb (%) |
COMIRNATY Dose 2 Na=1,097 nb (%) |
Placebo Dose 2 Na=1,078 nb (%) |
---|---|---|---|---|
Redness |
|
|
|
|
Any (>2 cm) |
65 (5.8) |
12 (1.1) |
55 (5.0) |
10 (0.9) |
Severec |
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) |
Severec |
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) |
Severed |
11 (1.0) |
0 (0.0) |
7 (0.6) |
0 (0.0) |
Any local reactione |
976 (86.6) |
271 (24.0) |
872 (79.5) |
198 (18.4) |
Note: Reactions were collected in the electronic diary (e-diary) from Day 1 to Day 7 after vaccination. a. N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. b. n = Number of participants with the specified reaction. c. Severe: >10.0 cm. d. Severe: prevents daily activity. e. Any local reaction: any redness >2.0 cm, any swelling >2.0 cm, or any pain at the injection site * Randomized participants in the safety analysis population who received at least 1 dose of the study intervention. |
Systemic Reaction |
COMIRNATY Dose 1 Na=1,127 nb (%) |
Placebo Dose 1 Na=1,127 nb (%) |
COMIRNATY Dose 2 Na=1,097 nb (%) |
Placebo Dose 2 Na=1,078 nb (%) |
---|---|---|---|---|
Fever |
|
|
|
|
≥38.0°C |
114 (10.1) |
12 (1.1) |
215 (19.6) |
7 (0.6) |
>38.9°C |
11 (1.0) |
2 (0.2) |
25 (2.3) |
1 (0.1) |
Fatigue |
|
|
|
|
Any |
677 (60.1) |
457 (40.6) |
726 (66.2) |
264 (24.5) |
Severec |
15 (1.3) |
8 (0.7) |
26 (2.4) |
4 (0.4) |
Headache |
|
|
|
|
Any |
623 (55.3) |
396 (35.1) |
708 (64.5) |
263 (24.4) |
Severec |
11 (1.0) |
9 (0.8) |
22 (2.0) |
1 (0.1) |
Chills |
|
|
|
|
Any |
311 (27.6) |
109 (9.7) |
455 (41.5) |
73 (6.8) |
Severec |
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) |
Severed |
1 (0.1) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
Diarrhea |
|
|
|
|
Any |
90 (8.0) |
82 (7.3) |
65 (5.9) |
43 (4.0) |
Severee |
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) |
Severec |
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) |
Severec |
1 (0.1) |
0 (0.0) |
4 (0.4) |
0 (0.0) |
Any systemic reactionsf |
877 (77.8) |
636 (56.4) |
904 (82.4) |
439 (40.7) |
Use of antipyretic or pain medication |
413 (36.6) |
111 (9.8) |
557 (50.8) |
95 (8.8) |
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. a. N = Number of participants reporting at least 1 yes or no response for the specified event after the specified dose. b. n = Number of participants with the specified reaction. c. Severe: prevents daily activity. d. Severe: requires intravenous hydration. e. Severe: 6 or more loose stools in 24 hours. f. Any systemic reaction: any fever ≥38.0°C, any fatigue, any vomiting, any chills, any diarrhea, any headache, any new or worsened muscle pain, or any new or worsened joint pain * Randomized participants in the safety analysis population who received at least 1 dose of the study intervention.
|
Unsolicited Adverse Events
In the analysis of Study 2 of all unsolicited adverse events reported following any dose, through 1 month after Dose 2, in adolescents 12 to 15 years of age (N=2260; 1,131 COMIRNATY group vs. 1,129 placebo group), those assessed as adverse reactions not already captured by solicited local and systemic reactions were lymphadenopathy (9 (0.8%) vs. 2 (0.2%)), and nausea (5 (0.4%) vs. 1 (0.1%)).
In analyses of all unsolicited adverse events in Study 2 from Dose 1 up to the participant unblinding date, 69.0% of study participants 12 through 15 years of age had at least 4 months of follow-up after Dose 2. Among participants 12 through 15 years of age who received at least one dose of study vaccine, 1,131 of whom received COMIRNATY and 1,129 of whom received placebo, unsolicited adverse events were reported by 95 (8.4%) participants in the COMIRNATY group and 113 (10.0%) participants in the placebo group.
Non-serious adverse events from Dose 1 through up to 30 days after Dose 2 in ongoing follow‑up were reported by 5.8% of COMIRNATY recipients and by 5.8% of placebo recipients. From Dose 1 through 30 days after Dose 2, reports of lymphadenopathy plausibly related to the study intervention were imbalanced, with notably more cases in the COMIRNATY group (7) vs. the placebo group (1). 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
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% (786 COMIRNATY and 773 placebo) 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. In study 2, a 16-year-old male was diagnosed with myopericarditis 3 days after his 2nd dose. The participant was treated and recovered.
8.2.3 COMIRNATY (10 mcg)
Children 5 Years Through <12 Years of Age – Primary Series (Two Doses)
Solicited Adverse Reactions
Table 15 and Table 16 present the frequency and severity of solicited local and systemic reactions, respectively, within 7 days following each dose of COMIRNATY and placebo in children 5 years through <12 years of age included in the initial enrolment safety population who were monitored for reactogenicity with an electronic diary.
Local Reaction |
|
COMIRNATY Dose 1 Na=1,511 nc (%) |
Placebo Dose 1 Na,b=748 nc (%) |
COMIRNATY Dose 2 Na=1,501 nc (%) |
Placebo Dose 2 Na,b=740 nc (%) |
---|---|---|---|---|---|
Rednessd |
|
|
|
|
|
Any (≥0.5 cm) |
|
222 (14.7) |
43 (5.7) |
278 (18.5) |
40 (5.4) |
Severe |
|
0 (0.0) |
0 (0.0) |
3 (0.2) |
0 (0.0) |
Swellingd |
|
|
|
|
|
Any (≥0.5 cm) |
|
158 (10.5) |
20 (2.7) |
229 (15.3) |
20 (2.7) |
Severe |
|
1 (0.1) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
Pain at the injection sitee |
|
|
|
|
|
Any |
|
1,119 (74.1) |
234 (31.3) |
1,065 (71.0) |
218 (29.5) |
Severe |
|
4 (0.3) |
0 (0.0) |
5 (0.3) |
0 (0.0) |
Note: Reactions were collected in the electronic diary (e-diary) from Day 1 to Day 7 after vaccination.
- N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose.
- The denominators (N) used in the percentage calculations for redness and swelling were 749 after Dose 1 and 741 after Dose 2 in the placebo group, due to an e-diary error.
- n = Number of participants with the specified reaction.
- Severe: >7.0 cm.
- Severe: prevents daily activity.
* Randomized participants who received at least 1 dose of the study intervention.
Systemic Reaction |
COMIRNATY Dose 1 Na=1,511 nc (%) |
Placebo Dose 1 Na,b=748 nc (%) |
COMIRNATY Dose 2 Na=1,501 nc (%) |
Placebo Dose 2 Na,b=740 nc (%) |
---|---|---|---|---|
Fever |
|
|
|
|
≥38.0 |
38 (2.5) |
10 (1.3) |
98 (6.5) |
9 (1.2) |
>38.9℃ |
3 (0.2) |
1 (0.1) |
9 (0.6) |
1 (0.1) |
Fatigued |
|
|
|
|
Any |
508 (33.6) |
234 (31.3) |
592 (39.4) |
180 (24.3) |
Severe |
4 (0.3) |
1 (0.1) |
11 (0.7) |
1 (0.1) |
Headached |
|
|
|
|
Any |
339 (22.4) |
180 (24.1) |
420 (28.0) |
138 (18.6) |
Severe |
2 (0.1) |
4 (0.5) |
3 (0.2) |
0 (0.0) |
Chillsd |
|
|
|
|
Any |
70 (4.6) |
35 (4.7) |
147 (9.8) |
32 (4.3) |
Severe |
0 (0.0) |
0 (0.0) |
2 (0.1) |
1 (0.1) |
Vomitinge |
|
|
|
|
Any |
33 (2.2) |
11 (1.5) |
28 (1.9) |
6 (0.8) |
Severe |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
Diarrheaf |
|
|
|
|
Any |
89 (5.9) |
31 (4.1) |
79 (5.3) |
35 (4.7) |
Severe |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
New or worsened muscle paind |
|
|
|
|
Any |
137 (9.1) |
51 (6.8) |
175 (11.7) |
55 (7.4) |
Severe |
1 (0.1) |
0 (0.0) |
1 (0.1) |
0 (0.0) |
New or worsened joint paind |
|
|
|
|
Any |
50 (3.3) |
41 (5.5) |
78 (5.2) |
27 (3.6) |
Severe |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
Use of antipyretic or pain medicationg |
217 (14.4) |
62 (8.3) |
296 (19.7) |
60 (8.1) |
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.
- N = Number of participants reporting at least 1 yes or no response for the specified event after the specified dose.
- The denominators (N) used in the percentage calculations for fever and use of antipyretic or pain medication were 749 after Dose 1 and 741 after Dose 2 in the placebo group, due to an e-diary error.
- n = Number of participants with the specified reaction.
- Severe: prevents daily activity.
- Severe: requires intravenous hydration.
- Severe: 6 or more loose stools in 24 hours.
- Severity was not collected for use of antipyretic or pain medication.
* Randomized participants who received at least 1 dose of the study intervention.
Unsolicited Adverse Events
In the analyses of Study 3 in children 5 years through <12 years of age (initial enrolment group: 1,518 COMIRNATY 10 mcg and 750 placebo), 99.5% of participants had at least 30 days and 95.7% of participants had at least 3 months follow-up after Dose 2.
Serious adverse events from Dose 1 through up to 30 days after Dose 2 in ongoing follow-up in the initial enrolment group were reported by 1 participant (0.1%) in each group after receiving the vaccine or placebo through the data cut-off date. No serious adverse events were reported that were considered related to vaccination.
Non-serious adverse events from Dose 1 through up to 30 days after Dose 2 in ongoing follow-up in the initial enrolment group were reported by 10.9% of COMIRNATY 10 mcg recipients and by 9.1% of placebo recipients. Lymphadenopathy was reported in 13 (0.9%) participants in the COMIRNATY 10 mcg group vs. 1 (0.1%) in the placebo group. All cases were considered to be mild, with a median onset of 3 days after Dose 1, and 2 days after Dose 2 in the vaccine group. The median duration was 3.5 days (ranged from 1 to 14 days) in the vaccine group. Skin and subcutaneous tissue disorders (including skin rash, dermatitis, eczema and urticaria) were reported in 17 (1.1%) participants in the vaccine group and 5 (0.7%) participants in the placebo group. Most of the events began from 3-11 days after the second dose and were characterized as mild and self-limited. There were no other notable patterns between treatment groups for specific categories of non-serious adverse events that would suggest a causal relationship to COMIRNATY. There were no reports of myocarditis/pericarditis or anaphylaxis by the study cut-off date.
Children 5 Years Through ˂12 Years of Age – After Booster Dose
A subset of Phase 2/3 participants 5 years through ˂12 years of age received a booster dose of COMIRNATY at least 5 months after completing the primary series (range 5 to 9 months, 86.8% of participants received the booster dose at least 8 months after Dose 2). Those participants vaccinated prior to February 22, 2022 provided the safety database (n=401), and had a median safety follow-up of 1.3 months from vaccination through the data cut-off date of March 22, 2022.
The median age of these 401 participants was 8.0 years (range 5 years through ˂12 years of age), 52.4% were male and 47.6% were female, 70.1% were White, 7.2% were Black or African American, 22.9% were Hispanic/Latino, 7.7% were Asian, and 2.0% were American Indian/Alaska Native.
Solicited Local and Systemic Adverse Reactions
Table 17 and Table 18 present the frequency and severity of reported solicited local and systemic reactions, respectively, within 7 days of a booster dose of COMIRNATY for Phase 2/3 participants 5 years through ˂12 years of age.
In participants who received a booster dose, the mean duration of pain at the injection site after the booster dose was 2.4 days (range 1 to 35 days), for redness 2.3 days (range 1 to 12 days), and for swelling 2.3 days (range 1 to 9 days).
Local Reaction |
COMIRNATY Booster Na=371 nb (%) |
---|---|
Rednessc |
|
Any (≥0.5 cm) |
58 (15.6) |
Severe |
1 (0.3) |
Swellingc |
|
Any (≥0.5 cm) |
61 (16.4) |
Severe |
0 |
Pain at the injection sited |
|
Any |
274 (73.9) |
Severe |
2 (0.5) |
* Randomized participants who received at least 1 dose of the study intervention.
Note: Reactions were collected in the e-diary and unscheduled clinical assessments from Day 1 through Day 7 after vaccination.
- N = number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose.
- n = Number of participants with the specified characteristic.
- Mild: ≥0.5 to 2.0 cm; moderate: >2.0 to 7.0 cm; severe: >7.0 cm.
- Mild: does not interfere with activity; moderate: interferes with activity; severe: prevents daily activity.
Systemic Reaction |
COMIRNATY Booster Na=371 nb (%) |
---|---|
Fever |
|
≥38.0℃ | 25 (6.7) |
>38.9℃ | 3 (0.8) |
Fatiguec |
|
Any |
169 (45.6) |
Severe |
7 (1.9) |
Headachec |
|
Any |
126 (34.0) |
Severe |
0 |
Chillsc |
|
Any |
39 (10.5) |
Severe |
1 (0.3) |
Vomitingd |
|
Any |
9 (2.4) |
Severe |
0 |
Diarrheae |
|
Any |
18 (4.9) |
Severe |
1 (0.3) |
New or worsened muscle painc |
|
Any |
68 (18.3) |
Severe |
0 |
New or worsened joint painc |
|
Any |
25 (6.7) |
Severe |
0 |
Use of antipyretic or pain medicationf |
114 (30.7) |
* Randomized participants who received at least 1 dose of the study intervention.
Note: Events and use of antipyretic or pain medication were collected in the e-diary and unscheduled clinical assessments from Day 1 through Day 7 after vaccination.
- N = number of participants reporting at least 1 yes or no response for the specified event after the specified dose.
- n = Number of participants with the specified characteristic.
- Mild: does not interfere with activity; moderate: some interference with activity; severe: prevents daily activity.
- Mild: 1 to 2 times in 24 hours; moderate: >2 times in 24 hours; severe: requires intravenous hydration.
- Mild: 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.
- Severity was not collected for use of antipyretic or pain medication.
Unsolicited Adverse Events
Overall, the 401 participants who received a booster dose of COMIRNATY had a median follow-up time of 1.3 months after the booster dose through the cut-off date.
In an analysis of all unsolicited adverse events reported in participants 5 years through ˂12 years of age (N = 401) through up to 1 month after the booster dose, lymphadenopathy (n = 10, 2.5%) was an adverse reaction not already captured by solicited local and systemic reactions.
Serious Adverse Events
No serious adverse events were reported after the booster dose of COMIRNATY through the cut-off date.
8.5 Post-Market Adverse Reactions
The following adverse reactions have been identified during post authorization use of COMIRNATY.
Cardiac Disorders: myocarditis and/or pericarditis (see 7 WARNING AND PRECAUTIONS)
Immune System Disorders: severe allergic reactions, including anaphylaxis
Musculoskeletal and Connective Tissue Disorders: pain in extremity (arm)
Nervous System Disorders: Facial paralysis / Bell’s Palsy, hypoesthesia, paresthesia, dizziness
Skin and subcutaneous tissue disorders and other hypersensitivity reactions: skin rash, pruritus, urticaria, angioedema, erythema multiforme
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 product exposure. They are included because: a) they represent reactions that are known to occur following immunizations generally; b) they are potentially serious; or c) on the basis of their frequency of reporting.
9 Drug Interactions
No interaction studies have been performed. There is no information on the co-administration of COMIRNATY Original & Omicron BA.4/BA.5 with other vaccines.
Do not mix COMIRNATY Original & Omicron BA.4/BA.5 with other vaccines/products in the same syringe.
10 Clinical Pharmacology
10.1 Mechanism of Action
The nucleoside-modified messenger RNA in tozinameran encodes for the viral spike (S) protein of SARS-CoV-2 Original strain and famtozinameran (mRNA) encodes the viral spike of SARS-CoV-2 Omicron variant lineages BA.4 and BA.5 (Omicron BA.4/BA.5). The mRNAs are formulated in lipid nanoparticles, which enable delivery of the RNA into host cells to allow expression of the SARS-CoV-2 S antigen. The vaccine elicits both neutralizing antibody and cellular immune responses to the spike (S) antigen, which may contribute to protection against COVID-19 disease.
11 Storage, Stability And Disposal
During storage, minimize exposure to room light, and avoid exposure to direct sunlight and ultraviolet light.
Do not refreeze thawed vials.
For 12 Years and Older: DO NOT DILUTE (Single Dose or Multiple Dose Vials with Gray Cap and Gray Label Border)
Single Dose or Multiple Dose Vial Storage Prior to Use
Cartons of COMIRNATY Original & Omicron BA.4/BA.5 single dose or multiple dose vials (for 12 years and older: DO NOT DILUTE) may arrive frozen at ultra cold conditions in thermal containers with dry ice.
Once received, frozen single dose or multiple dose vials may be immediately transferred to the refrigerator [2°C to 8°C (35°F to 46°F)], thawed and stored for a single period of up to 10 weeks within the 18-month shelf-life. The 10 week refrigerated expiry date should be recorded on the carton at the time of transfer.
A carton of 10 single dose vials may take up to 2 hours to thaw at this temperature.
A carton of 10 multiple dose vials may take up to 6 hours to thaw at this temperature.
Alternatively, frozen single dose or multiple dose vials may be stored in an ultra-low temperature freezer at ‑90°C to ‑60°C (‑130°F to ‑76°F) for up to 18 months from the date of manufacture. Do not store single dose or multiple dose vials at ‑25°C to ‑15°C (-13°F to 5°F). Once single dose or multiple dose vials are thawed they should not be refrozen.
Cartons of COMIRNATY Original & Omicron BA.4/BA.5 single dose or multiple dose vials (for 12 years and older: DO NOT DILUTE) may also arrive at 2°C to 8°C (35°F to 46°F). If received at 2°C to 8°C, they should be stored at 2°C to 8°C. Check that the carton has been updated to reflect the 10-week refrigerated expiry date.
Regardless of storage condition, vaccine should not be used after 18 months from the date of manufacture printed on the single dose or multiple dose vials and cartons.
Single Dose or Multiple Dose Vial Storage During Use
If not previously thawed at 2°C to 8°C (35°F to 46°F), allow single dose or multiple dose vials to thaw at room temperature [up to 25°C (77°F)] for 30 minutes.
COMIRNATY Original & Omicron BA.4/BA.5 single dose or multiple dose vials (for 12 years and older: DO NOT DILUTE) may be stored at room temperature up to 25°C (77°F) for a total of 12 hours prior to the first puncture.
DO NOT DILUTE PRIOR TO USE.
After first puncture, the single dose or multiple dose vial should be stored at 2°C to 25°C (35°F to 77°F). Vials should be discarded 12 hours after first puncture.
Thawed single dose or multiple dose vials can be handled in room light conditions.
Transportation of Single Dose or Multiple Dose Vials
If local redistribution is needed, full cartons containing unpunctured single dose or multiple dose vials may be transported at -90°C to -60°C (-130°F to -76°F); full cartons or individual unpunctured single dose or multiple dose vials may also be transported at 2°C to 8°C (35°F to 46°F).
For Age 5 Years to <12 Years: DILUTE PRIOR TO USE (Multiple Dose Vials with Orange Cap and Orange Label Border)
Multiple Dose Vial Storage Prior to Use
Cartons of COMIRNATY Original & Omicron BA.4/BA.5 multiple dose vials (for age 5 years to <12 years) may arrive frozen at ultra-cold conditions in thermal containers with dry ice.
Once received, frozen multiple dose vials may be immediately transferred to the refrigerator [2°C to 8°C (35°F to 46°F)], thawed and stored for a single period of up to 10 weeks within the 18-month shelf-life. The 10 week refrigerated expiry date should be recorded on the carton at the time of transfer. A carton of 10 multiple dose vials may take up to 4 hours to thaw at this temperature.
Alternatively, frozen multiple dose vials may be stored in an ultra-low temperature freezer at -90°C to -60°C (-130°F to -76°F) for up to 18 months from the date of manufacture. Do not store multiple dose vials at -25°C to -15°C (-13°F to 5°F). Once multiple dose vials are thawed they should not be refrozen.
Cartons of COMIRNATY Original & Omicron BA.4/BA.5 (for age 5 years to <12 years) may also arrive at 2°C to 8°C (35°F to 46°F). If multiple dose vials are received at 2°C to 8°C, they should be stored at 2°C to 8°C. Check that the carton has been updated to reflect the 10-week refrigerated expiry date.
Regardless of storage condition, vaccines should not be used after 18 months from the date of manufacture printed on the vial and cartons.
Multiple Dose Vial Storage During Use
If not previously thawed at 2°C to 8°C (35°F to 46°F), allow multiple dose vials to thaw at room temperature [up to 25°C (77°F)] for 30 minutes.
Multiple dose vials of COMIRNATY Original & Omicron BA.4/BA.5 (for age 5 years to <12 years) may be stored at temperatures up to 25°C (77°F) for a total of 12 hours prior to dilution.
After dilution the multiple dose vials should be stored at 2°C to 25°C (35°F to 77°F). Vials should be discarded 12 hours after dilution (i.e., the first puncture).
Thawed vials can be handled in room light conditions.
Transportation of Multiple Dose Vials
If local redistribution is needed, full cartons containing undiluted multiple dose vials may be transported at -90°C to -60°C (-130°F to -76°F); full cartons or individual undiluted multiple dose vials may also be transported at 2°C to 8°C (35°F to 46°F).
12 Special Handling Instructions
COMIRNATY Original & Omicron BA.4/BA.5 single dose and multiple dose vials contain a frozen suspension that does not contain preservative and must be thawed and may require dilution prior to administration.
Careful attention should be paid to the vial cap colour and label border and information on the label, and the appropriate corresponding instructions must be followed. For important information on handling and preparation for administration, please refer to 11 STORAGE, STABILITY AND DISPOSAL and 4 DOSAGE AND ADMINISTRATION.
Control #: 274152
JUL 06, 2023
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