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COVID-19 mRNA vaccines: Pediatric drug information

COVID-19 mRNA vaccines: Pediatric drug information
(For additional information see "COVID-19 mRNA vaccines: Drug information" and see "COVID-19 mRNA vaccines: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Special Alerts
COVID-19 Vaccine (mRNA): Health Canada Extends Shelf Life for Spikevax Updated January 2022 ​

Health Canada has authorized a 2-month shelf life extension (from 7 months to 9 months) for 5 mL vials of Spikevax (previously known as the COVID-19 Moderna vaccine). The 2-month extension may be retroactively applied to vials that are currently on the market with printed expiry dates between February 2022 and August 2022, as long as the approved storage conditions have been maintained.

Further information is available at https://recalls-rappels.canada.ca/en/alert-recall/shelf-life-extension-spikevax-elasomeran-covid-19-vaccine-printed-expiry-dates-vial.

In October 2021, Health Canada authorized a 2-month shelf life extension (from 7 months to 9 months) for certain lots of US-labeled vaccine supplies with English-only vial and carton labels of Spikevax.

Further information, including the lots with their extended expiration dates, is available at https://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2021/75807a-eng.php.

Brand Names: US
  • Comirnaty;
  • Moderna COVID-19 Bival Booster;
  • Moderna COVID-19 Vac (Booster);
  • Moderna COVID-19 Vacc 6m-5y;
  • Moderna COVID-19 Vaccine;
  • Pfizer COVID-19 Vac Bival 5-11;
  • Pfizer COVID-19 Vac Bivalent;
  • Pfizer COVID-19 Vac-TriS 5-11y;
  • Pfizer COVID-19 Vac-TriS 6m-4y;
  • Pfizer-BioNT COVID-19 Vac-TriS;
  • Pfizer-BioNTech COVID-19 Vacc;
  • Spikevax COVID-19 Vaccine
Brand Names: Canada
  • Comirnaty;
  • Comirnaty (Gray Cap);
  • Comirnaty (Purple Cap);
  • Comirnaty Original & Omicron;
  • Spikevax;
  • Spikevax Bivalent
Therapeutic Category
  • Vaccine;
  • Vaccine, Inactivated (Viral)
Dosing: Pediatric
COVID-19 prevention

COVID-19 prevention:

Note: Due to complexity of product formulations and variations in recommendations, dosing is provided for patients <18 years of age only; for dosing in adolescents 18 years of age, refer to "Dosing: Adult." In general, patients who will change dosing age groups between doses should receive the vaccine dosage and formulation based on their age on the day of vaccination for each dose. However, children who turn from 4 years of age to 5 years of age during a Pfizer-BioNTech primary series must complete the primary series with the same product and schedule they started with (CDC 2022c).

Infants ≥6 months and Children <5 years (CDC 2022c):

Moderna product: IM: Vaccination consists of primary series (2 doses of monovalent product [3 doses for moderately to severely immunocompromised patients]) and a booster dose (Moderna bivalent product only); see dosing table below for doses and timing.

Pfizer-BioNTech product: IM: Vaccination consists of 3 primary series doses; the monovalent product should be used for the first 2 doses and the bivalent product should be used for the third dose; see dosing table below for doses and timing. No booster dose in this age group is authorized at this time; if 3 doses of monovalent product were already administered, no bivalent vaccine dose is indicated.

Mixed series: Mixed primary series are not recommended; however, patients who receive different mRNA products for the first 2 doses should follow a 3-dose schedule, with either the monovalent Moderna vaccine or bivalent Pfizer-BioNTech vaccine used for the third dose. Do not administer a booster dose after the 3 doses.

Pediatric COVID-19 Vaccine (mRNA) Dose Recommendations for Patients 6 Months to <5 Years of Agea

Manufacturer

Composition

Vial description

Total amount of mRNA per dose

Primary series (administer IM)

Booster doses (administer IM)

Initial 2 primary series dosesb,d

Third primary series dose

Additional dose for immunocompromised personsc

a CDC 2022c.

b For the primary series, a shorter interval between the first and second dose (Moderna: 4 weeks, Pfizer-BioNTech: 3 weeks) is recommended for persons who are moderately to severely immunocompromised, and others who need rapid protection. A longer interval (8 weeks) with an age-appropriate product may be optimal for some persons 6 months to <65 years of age (especially males 12 to 39 years of age) to potentially reduce the small risk for myocarditis and pericarditis while also possibly increasing peak antibody responses and vaccine effectiveness.

c Examples of moderately to severely immunocompromised persons include solid organ transplant or hematopoietic cell transplant recipients, persons receiving immunosuppressing therapies (eg, high-dose corticosteroids, chemotherapeutic agents), persons with HIV infection (advanced or untreated), and persons with moderate or severe primary immunodeficiency. See CDC recommendations for more details.

d Patients who receive different mRNA products for the first 2 doses should follow a 3-dose schedule, with the third dose administered ≥8 weeks after the second. Either the age-appropriate monovalent Moderna vaccine or bivalent Pfizer-BioNTech vaccine may be used for the third dose; do not administer a booster dose after the 3 doses.

Moderna products

Moderna

Monovalent

Magenta label border with dark blue cap

25 mcg per 0.25 mL

2 doses of 0.25 mL separated by 4 to 8 weeksb,d

N/A (2 dose primary series)

0.25 mL given ≥4 weeks after second dose

N/A (use bivalent product for booster dose)

Moderna

Bivalent

Yellow label border with dark pink cap

10 mcg per 0.2 mL

N/A (for booster dose only; use monovalent product for primary series)

0.2 mL given ≥2 months after last primary series dose

Pfizer-BioNTech products

Pfizer-BioNTech

Monovalent

Maroon cap (dilution required)

3 mcg per 0.2 mL

2 doses of 0.2 mL separated by 3 to 8 weeksb,d

Use bivalent product for third dose

N/A

No booster authorized in patients who receive Pfizer-BioNTech primary series in this age group

Pfizer-BioNTech

Bivalent

Maroon cap (dilution required)

3 mcg per 0.2 mL

Use monovalent product for first 2 doses

0.2 mL given ≥8 weeks after second dose

N/A

Not authorized for use as booster dose

Children 5 to <6 years (CDC 2022c):

Moderna product: IM: Vaccination consists of primary series (2 or 3 doses of monovalent product, depending on immune status) and a bivalent booster dose. Either Moderna or Pfizer-BioNTech bivalent product may be used for booster dose; see table below for doses and timing.

Pfizer-BioNTech product: IM: Vaccination consists of primary series (2 or 3 doses of monovalent product, depending on immune status) and a bivalent Pfizer-BioNTech booster dose; see table below for doses and timing.

Children ≥6 years and Adolescents (CDC 2022c): IM: Vaccination consists of a primary series (2 or 3 doses, depending on immune status, of monovalent product from the same manufacturer) and a bivalent booster dose (either age-appropriate product may be used for booster dose, regardless of initial series manufacturer); see table below for doses and timing.

Summary of Pediatric COVID-19 Vaccine (mRNA) Dose Recommendations f or Patients 5 to <18 Years of Agea

Manufacturer

Patient age

Composition

Vial description

Total amount of mRNA per dose

Primary series (administer IM)

Booster doses (administer IM)

Primary series dosesb

Additional dose for immunocompromised personsc

a CDC 2022c. See "Dosing: Adult" for dosing in patients ≥18 years.

b For the primary series, a shorter interval between the first and second dose (Moderna: 4 weeks, Pfizer-BioNTech: 3 weeks) is recommended for persons who are moderately to severely immunocompromised, and others who need rapid protection. A longer interval (8 weeks) with an age-appropriate product may be optimal for some persons 6 months to <65 years of age (especially males 12 to 39 years of age) to potentially reduce the small risk for myocarditis and pericarditis while also possibly increasing peak antibody responses and vaccine effectiveness.

c Examples of moderately to severely immunocompromised persons include solid organ transplant or hematopoietic cell transplant recipients, persons receiving immunosuppressing therapies (eg, high-dose corticosteroids, chemotherapeutic agents), persons with HIV infection (advanced or untreated), and persons with moderate or severe primary immunodeficiency. See CDC recommendations for more details.

d Last dose is defined as the last dose of the most recent monovalent mRNA COVID-19 vaccine, including primary series doses or monovalent booster doses received prior to availability of bivalent booster product.

Moderna Products

Moderna

5 to <6 years

Monovalent

Magenta label border with dark blue cap

25 mcg per 0.25 mL

2 doses of 0.25 mL separated by 4 to 8 weeksb,d

0.25 mL given ≥4 weeks after second dose

N/A (use bivalent product for booster dose)

Moderna

5 to <6 years

Bivalent

Yellow label border with dark pink cap

10 mcg per 0.2 mL

N/A (use monovalent product for primary series)

0.2 mL given ≥2 months after last dosed

Moderna

6 to <12 years

Monovalent

Purple label border with dark blue cap

50 mcg per 0.5 mL

2 doses of 0.5 mL separated by 4 to 8 weeksb

0.5 mL given ≥4 weeks after second dose

N/A (use bivalent product for booster dose)

Moderna

6 to <12 years

Bivalent

Gray label border with dark blue cap

25 mcg per 0.25 mL

N/A (use monovalent product for primary series)

0.25 mL given ≥2 months after last dosed

Moderna

≥12 years

Monovalent

Light blue label border with red cap

100 mcg per 0.5 mL

2 doses of 0.5 mL separated by 4 to 8 weeksb

0.5 mL given ≥4 weeks after second dose

N/A (use bivalent product for booster dose)

Moderna

≥12 years

Bivalent

Gray label border with dark blue cap

50 mcg per 0.5 mL

N/A (use monovalent product for primary series)

0.5 mL given ≥2 months after last dosed

Pfizer-BioNTech Products

Pfizer-BioNTech

5 to <12 years

Monovalent

Orange cap (dilution required)

10 mcg per 0.2 mL

2 doses of 0.2 mL separated by 3 to 8 weeksb

0.2 mL given ≥4 weeks after second dose

N/A (for primary series only)

Pfizer-BioNTech

5 to <12 years

Bivalent

Orange cap (dilution required)

10 mcg per 0.2 mL

N/A (use monovalent product for primary series)

0.2 mL given ≥2 months after last dosed

Pfizer-BioNTech

≥12 years

Monovalent

Purple cap (dilution required) or gray cap (no dilution)

30 mcg per 0.3 mL

2 doses of 0.3 mL separated by 3 to 8 weeksb

0.3 mL given ≥4 weeks after second dose

N/A (use bivalent product for booster dose)

Pfizer-BioNTech

≥12 years

Bivalent

Gray cap (no dilution)

30 mcg per 0.3 mL

N/A (use monovalent product for primary series)

0.3 mL given ≥2 months after last dosed

Canadian recommendations:

Primary series: For children ages 6 to <12 years, Canadian labeling allows for use of the 50 mcg per 0.5 mL product (royal blue vial cap) OR the 100 mcg per 0.5 mL product (red vial cap) for 50 mcg doses (Spikevax Canadian product monograph 2022).

Booster dose: In Canada, both monovalent and bivalent mRNA COVID-19 vaccines are approved for use as booster doses (as age-appropriate), and the Canadian National Advisory Committee on Immunization (NACI) provides different recommendations as compared to the CDC, including longer intervals; see NACI recommendations for details (NACI 2022a; NACI 2022b).

Revaccination: In patients who were vaccinated (primary series or bivalent booster dose) prior to or while receiving a hematopoietic cell transplant (HCT) or chimeric antigen receptor (CAR)–T-cell therapy, revaccination is recommended for patients who are ≥3 months post HCT or CAR-T-cell therapy. In patients who were vaccinated during treatment with B-cell–depleting therapies (eg, rituximab, ocrelizumab) that were administered over a limited period (eg, as part of a treatment regimen for certain malignancies), revaccination with a primary series and bivalent booster dose may be considered ~6 months after completion of B-cell–depleting therapy (CDC 2022c).

Interchangeability:

Primary series with mRNA COVID-19 vaccines: The same vaccine manufacturer should be used for all doses in the primary vaccination series. If the first vaccine product cannot be determined or is unavailable, may administer any age-appropriate mRNA COVID-19 vaccine at a minimum interval of 4 weeks between doses. Patients 6 months to <5 years of age who receive different mRNA products for the first 2 doses should follow a 3-dose schedule, with the third dose (either Moderna monovalent or Pfizer bivalent product) administered ≥8 weeks after the second. In moderately to severely immunocompromised individuals, the additional primary series dose should be the same product as the initial 2-dose series whenever possible; the other mRNA product may be administered if the first product is not available (CDC 2022c).

Primary series with non-mRNA COVID-19 vaccines: In limited, exceptional situations where a patient's first dose was an mRNA vaccine and they are unable to complete the series with the same or different mRNA vaccine (eg, due to a contraindication), then a different, age-appropriate COVID-19 vaccine may be considered at a minimum interval of 4 weeks from the mRNA vaccine dose. If a non–FDA-approved/authorized COVID-19 vaccine (or WHO-listed vaccine) has been administered, allow a minimum interval of 4 weeks between the non–FDA-approved/authorized vaccine (or WHO-listed vaccine) and an FDA-approved/authorized vaccine. See CDC guidelines for detailed recommendations (CDC 2022c).

Premedication: The CDC recommends against prophylactic administration of antipyretic/analgesic medications (eg, acetaminophen, NSAIDs) for the purpose of preventing postvaccination symptoms. Antipyretic/analgesic medications may be taken after vaccination for the treatment of postvaccination local/systemic symptoms, if medically appropriate (CDC 2022c).

Dosing recommendations for deviations in administration, preparation, or storage:

Recommendations for Deviations in COVID-19 Vaccine Usagea

Deviation

Adjustment

a CDC 2022c.

b Unless patient experiences significant or prolonged adverse reactions (assess on a case-by-case basis).

c Some experts suggest a longer interval (8 weeks) after the invalid dose because of the potential for increased reactogenicity and rare risk of myocarditis and pericarditis; consider patient benefit versus risk.

Age

Person <6 months of age received any COVID-19 vaccine product

Do not give another dose until patient is ≥6 months of age.

Person transitioning from age 4 to age 5 who started 3-dose Pfizer-BioNTech primary series with maroon cap product (for ages 6 months to <5 years) and received orange cap product (for ages 5 to <12 years) for dose 2 or 3

Do not repeat the dose. If orange cap product administered for dose 2, administer the bivalent Pfizer-BioNTech maroon cap product (for ages 6 months to <5 years) for the third primary series dose ≥8 weeks after the second primary series dose.

Person 6 months to <18 years of age received Janssen COVID-19 vaccine for primary dose

Do not count dose; begin or continue the age-appropriate mRNA COVID-19 vaccine primary series ≥4 weeks after Janssen dose.

Person 6 months to <12 years of age received Novavax COVID-19 vaccine for primary dose

Do not repeat dose; continue the age-appropriate mRNA COVID-19 vaccine primary series.

Product and dosage

Dose too high (due to incorrect product or dosage administered, including dose volume too high)

Do not repeat dose; administer subsequent dose at appropriate interval.b

Dose too low (due to incorrect product or dosage administered, including dose volume too low)

Repeat dose immediately (no minimum interval) with age-appropriate product and dosage.c

Half-dose volume or formulation administered inadvertently

If same clinic day, administer another half dose (2 doses counted as full dose). If different day, repeat dose.

Bivalent booster vaccine administered as part of primary series

Pfizer-BioNTech: Do not repeat dose.

Moderna: Administer 1 dose of the monovalent vaccine immediately (no minimum interval).c

Monovalent primary series vaccine administered as booster dose

Generally do not repeat dose. May consider administering 1 bivalent booster dose as a repeat dose (≥2 months after last vaccine dose).

Person 6 months to <5 years received monovalent Pfizer-BioNTech vaccine for third primary series dose

Do not repeat dose.

Dosing interval

Primary mRNA series: Dose administered too early (ie, more than 4 days prior to the recommended interval)

Repeat dose at the minimum recommended interval from dose given in error.c

Booster dose: mRNA COVID vaccine booster administered too early (ie, more than 4 days prior to recommended interval)

Repeat dose after the minimum recommended interval from the dose given too early.c

Any COVID-19 vaccine dose administered after recommended interval

Do not repeat dose; no maximum interval.

Tixagevimab/cilgavimab (Evusheld): Administered <14 days after vaccination

Generally do not repeat vaccine dose. May consider administering repeat vaccine dose ≥4 weeks after last vaccine dose.

Preparation (Pfizer-BioNTech products only)

Inappropriate dilution resultant in lower than authorized dose

Repeat dose immediately (no minimum interval).c

Dose undiluted or inappropriate dilution resulted in higher-than-authorized dose

Do not repeat dose.

Wrong diluent use

Contact manufacturer; if no stability data, repeat dose immediately (no minimum interval).

Diluent from single-use vial used for multiple vials

Do not repeat dose.

Premixed vaccine (vial with gray cap) is mixed with diluent

Contact manufacturer; if no stability data, repeat dose immediately (no minimum interval).

Storage

Improper storage or handling of vaccine (eg, temperature excursion, dose administered past expiration date)

Contact manufacturer; if no stability data, repeat dose immediately (no minimum interval).c

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Adult

(For additional information see "COVID-19 mRNA vaccines: Drug information")

COVID-19 prevention

COVID-19 prevention:

Summary of COVID-19 Vaccine (mRNA) Dose Recommendations: FOR PATIENTS ≥18 YEARS OF AGEa

Manufacturer

Composition

Vial description

Total amount of mRNA per dose

Primary series (administer IM)

Booster dose (administer IM)

Primary series dosesb

Additional dose for immunocompromised individualsc

a CDC 2022c. See "Dosing: Pediatric" for pediatric dosing.

b A shorter interval between the first and second dose (Pfizer-BioNTech: 3 weeks; Moderna: 4 weeks) is recommended for persons who are moderately to severely immunocompromised, adults ≥65 years of age, and others who need rapid protection. A longer interval (8 weeks) with an age-appropriate product may be optimal for some persons 6 months to <65 years of age (especially males 12 to 39 years of age) to potentially reduce the small risk for myocarditis and pericarditis while also possibly increasing peak antibody responses and vaccine effectiveness.

c Examples of moderately to severely immunocompromised persons include solid organ transplant or hematopoietic cell transplant recipients, persons receiving immunosuppressing therapies (eg, high-dose corticosteroids, chemotherapeutic agents), persons with HIV infection (advanced or untreated), and persons with moderate or severe primary immunodeficiency. See CDC recommendations for more details.

d Last dose is defined as the last dose of the most recent monovalent mRNA COVID-19 vaccine, including primary series doses or monovalent booster doses received prior to availability of bivalent booster product.

Moderna

Monovalent

Light blue label border and red cap

100 mcg per 0.5 mL

2 doses of 0.5 mL separated by 4 to 8 weeksb

0.5 mL given ≥4 weeks after second dose

N/A (for primary series only)

Moderna

Bivalent

Gray label border and dark blue cap

50 mcg per 0.5 mL

N/A (for booster dose only)

0.5 mL given ≥2 months after last dosed

Pfizer-BioNTech

Monovalent

Purple cap (dilution required) or gray cap (no dilution)

30 mcg per 0.3 mL

2 doses of 0.3 mL separated by 3 to 8 weeksb

0.3 mL given ≥4 weeks after second dose

N/A (for primary series only)

Pfizer-BioNTech

Bivalent

Gray cap (no dilution)

30 mcg per 0.3 mL

N/A (for booster dose only)

0.3 mL given ≥2 months after last dosed

Booster dose: Monovalent mRNA COVID-19 vaccines are no longer authorized as booster doses in the United States. A single bivalent mRNA booster dose is recommended ≥2 months after completion of the primary series or after the last monovalent booster dose (Pfizer-BioNTech [bivalent]: gray cap vial; Moderna: gray label border/dark blue cap) (CDC 2022c).

Canadian recommendations: In Canada, both monovalent and bivalent mRNA COVID-19 vaccines are approved for use as booster doses (as age appropriate), and the Canadian National Advisory Committee on Immunization (NACI) provides different recommendations as compared to the CDC, including longer intervals; see NACI recommendations for details (NACI 2022a; NACI 2022b).

Revaccination: Note: In patients who were vaccinated (primary series or bivalent booster dose) prior to or while receiving a hematopoietic cell transplant (HCT) or chimeric antigen receptor (CAR)–T-cell therapy, revaccination is recommended for patients who are ≥3 months post HCT or CAR-T-cell therapy. In patients who were vaccinated during treatment with B-cell–depleting therapies (eg, rituximab, ocrelizumab) that were administered over a limited period (eg, as part of a treatment regimen for certain malignancies), revaccination with a primary series and bivalent booster dose may be considered ~6 months after completion of B-cell–depleting therapy (CDC 2022c).

Interchangeability:

Primary series with mRNA COVID-19 vaccines: The same vaccine should be used for all doses in the primary vaccination series. If the first vaccine product cannot be determined or is unavailable, may administer any mRNA COVID-19 vaccine at a minimum interval of 4 weeks between doses. In moderately to severely immunocompromised individuals, the additional primary series dose should be the same product as the initial 2-dose series whenever possible; the other mRNA product may be administered if the first product is not available (CDC 2022c).

Primary series with non-mRNA COVID-19 vaccines: In limited, exceptional situations where a patient's first dose was an mRNA vaccine and they are unable to complete the series with the same or different mRNA vaccine (eg, due to a contraindication), then a different, age-appropriate COVID-19 vaccine may be considered at a minimum interval of 4 weeks from the mRNA vaccine dose. If a non–FDA-approved/authorized COVID-19 vaccine (or WHO-listed vaccine) has been administered, allow a minimum interval of 4 weeks between the non–FDA-approved/authorized vaccine (or WHO-listed vaccine) and an FDA-approved/authorized vaccine. See CDC guidelines for detailed recommendations (CDC 2022c).

Booster dose: Following completion of the primary vaccination with an FDA-approved/authorized COVID-19 vaccine, any age-appropriate bivalent mRNA COVID-19 booster vaccine may be used for the booster dose; Novavax monovalent COVID-19 vaccine may be used in limited situations (CDC 2022c).

Premedication: The CDC does not recommend routine prophylactic administration of antipyretic/analgesic medications (eg, acetaminophen, nonsteroidal anti-inflammatory drugs) for the purpose of preventing postvaccination symptoms. These agents may be taken after vaccination for the treatment of postvaccination local/systemic symptoms (if medically appropriate) (CDC 2022c).

Dosing recommendations for deviations in administration, preparation, or storage:

Recommendations for Deviations in COVID-19 Vaccine Usagea

Deviation

Adjustment

a CDC 2022c; refer to CDC guidance documents for additional information.

b Unless patient experiences significant or prolonged adverse reactions (assess on a case-by-case basis).

c Some experts suggest a longer interval (8 weeks) after the invalid dose because of the potential for increased reactogenicity and rare risk of myocarditis and pericarditis; consider patient benefit versus risk.

Product and dosage

Dose too high (due to incorrect product or dosage administered, including dose volume too high)

Do not repeat dose; administer subsequent dose at appropriate interval.b

Dose too low (due to incorrect product or dosage administered, including dose volume too low)

Repeat dose immediately (no minimum interval) with age-appropriate product and dosage.c

Half-dose volume or formulation administered inadvertently

If same clinic day, administer another half dose (2 doses counted as full dose). If different day, repeat dose.

Bivalent booster vaccine administered as part of primary series

Pfizer-BioNTech: Do not repeat dose.

Moderna: Administer 1 dose of the monovalent vaccine immediately (no minimum interval).c

Monovalent primary series vaccine administered as booster dose

Generally, do not repeat dose. May consider administering 1 bivalent booster dose as a repeat dose (≥2 months after last vaccine dose).

Dosing interval

Primary mRNA series: Dose administered too early (ie, more than 4 days prior to the recommended interval)

Repeat dose at the minimum recommended interval from dose given in error.c

Booster dose: mRNA COVID vaccine booster administered too early (ie, more than 4 days prior to recommended interval)

Repeat dose after the minimum recommended interval from the dose given too early.c

Any COVID-19 vaccine dose administered after recommended interval

Do not repeat dose; no maximum interval.

Tixagevimab/cilgavimab (Evusheld): Administered <14 days after vaccination

Generally, do not repeat vaccine dose. May consider administering repeat vaccine dose ≥4 weeks after last vaccine dose.

Preparation (Pfizer-BioNTech product only)

Inappropriate dilution resulted in lower than authorized dose

Repeat dose immediately (no minimum interval).c

Dose undiluted, or inappropriate dilution resulted in higher-than-authorized dose

Do not repeat dose.

Wrong diluent use

Contact manufacturer; if no stability data, repeat dose immediately (no minimum interval).

Diluent from single-use vial used for multiple vials

Do not repeat dose.

Premixed vaccine (vial with gray cap) is mixed with diluent

Contact manufacturer; if no stability data, repeat dose immediately (no minimum interval).

Storage

Improper storage or handling of vaccine (eg, temperature excursion, dose administered past expiration date)

Contact manufacturer; if no stability data, repeat dose immediately (no minimum interval).c

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Suspension, Intramuscular [preservative free]:

Comirnaty: 30 mcg/0.3 mL (1.8 mL) [contains 2-((peg)-2000)-n,n-ditetradecylacetamide]

Moderna COVID-19 Bival Booster: 50 mcg/0.5 mL (2.5 mL) [contains dmg-peg 2000]

Moderna COVID-19 Vac (Booster): 50 mcg/0.5 mL (2.5 mL) [contains dmg-peg 2000]

Moderna COVID-19 Vacc 6m-5y: 25 mcg/0.25 mL (2.5 mL) [contains dmg-peg 2000]

Moderna COVID-19 Vaccine: 100 mcg/0.5 mL (5 mL, 7 mL) [contains dmg-peg 2000]

Pfizer COVID-19 Vac Bival 5-11: 10 mcg/0.2 mL (2 mL) [contains 2-((peg)-2000)-n,n-ditetradecylacetamide]

Pfizer COVID-19 Vac Bivalent: 30 mcg/0.3 mL (0.3 mL, 1.8 mL) [contains 2-((peg)-2000)-n,n-ditetradecylacetamide]

Pfizer COVID-19 Vac-TriS 5-11y: 10 mcg/0.2 mL (2 mL) [contains 2-((peg)-2000)-n,n-ditetradecylacetamide]

Pfizer COVID-19 Vac-TriS 6m-4y: 3 mcg/0.2 mL (2 mL) [contains 2-((peg)-2000)-n,n-ditetradecylacetamide]

Pfizer-BioNT COVID-19 Vac-TriS: 30 mcg/0.3 mL (1.8 mL) [contains 2-((peg)-2000)-n,n-ditetradecylacetamide]

Pfizer-BioNTech COVID-19 Vacc: 30 mcg/0.3 mL (1.8 mL) [contains 2-((peg)-2000)-n,n-ditetradecylacetamide]

Spikevax COVID-19 Vaccine: 100 mcg/0.5 mL (5.5 mL) [contains dmg-peg 2000]

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Suspension, Intramuscular:

Comirnaty: 3 mcg/0.2 mL (2.2 mL); 10 mcg/0.2 mL (1 ea) [contains 2-((peg)-2000)-n,n-ditetradecylacetamide]

Comirnaty (Gray Cap): 30 mcg/0.3 mL (1.8 mL) [contains 2-((peg)-2000)-n,n-ditetradecylacetamide]

Comirnaty (Purple Cap): 30 mcg/0.3 mL (1.8 mL) [contains 2-((peg)-2000)-n,n-ditetradecylacetamide]

Comirnaty Original & Omicron: 30 mcg/0.3 mL (2.25 mL) [contains 2-((peg)-2000)-n,n-ditetradecylacetamide]

Spikevax: 50 mcg/0.5 mL (2.5 mL); 100 mcg/0.5 mL (5 mL) [contains dmg-peg 2000]

Spikevax Bivalent: 50 mcg/0.5 mL (2.5 mL) [contains dmg-peg 2000]

Dosage Forms Considerations

Moderna COVID-19 Vaccine: Vials with magenta label borders and dark blue caps contain monovalent vaccine 25 mcg per 0.25 mL and are for ages 6 months to <6 years. Vials with yellow label borders and dark pink caps contain bivalent vaccine 10 mcg per 0.2 mL for ages 6 months to <6 years. Vials with purple label borders and dark blue caps contain monovalent vaccine 50 mcg per 0.5 mL and are for ages 6 to <12 years. Vials with light blue label borders and red caps contain monovalent vaccine 100 mcg per 0.5 mL and are for ages ≥12 years (primary series). Vials with gray label borders and dark blue caps are bivalent booster doses for ages ≥6 years. Number of doses obtainable from each vial is dependent on the syringes and needles used. Do not pool partial doses remaining in vials into a full dose (FDA 2022a; FDA 2022e; FDA 2022g; FDA 2022h). Note: Canadian labeling allows for use of the 100 mcg per 0.5 mL product (red vial cap) OR the 50 mcg per 0.5 mL (royal vial blue cap) for 50 mcg doses in ages 6 to <12 years (Spikevax Canadian product monograph 2022).

Pfizer-BioNTech COVID-19 Vaccine: Vials with maroon caps contain 3 mcg per 0.2 mL after dilution and are for infants and children 6 months to <5 years of age; both monovalent and bivalent products with maroon caps are available. Some maroon cap vials may state on the label for use in "Ages 2 years to <5 years"; however, these can be used in ages 6 months to <5 years (FDA 2022f). Vials with orange caps contain 10 mcg per 0.2 mL after dilution and are for children 5 to <12 years of age; both monovalent and bivalent products with orange caps are available. Vials with gray or purple caps containing monovalent vaccine are for patients ≥12 years of age and contain doses of 30 mcg per 0.3 mL; both monovalent and bivalent products with gray caps are available. Vials with gray caps should not be diluted, while the other vials (purple, orange, maroon) require dilution. Do not pool partial doses remaining in vials into a full dose.

The buffer used in vials with maroon, orange, or gray caps is tromethamine (Tris); phosphate buffered saline is used in vials with purple caps (FDA 2022a; FDA 2022b; FDA 2022c; FDA 2022d; FDA 2022e; FDA 2022f; FDA 2022g; FDA 2022h).

Prescribing and Access Restrictions

The FDA has granted full approval of the Pfizer-BioNTech COVID-19 vaccine Comirnaty for use in patients ≥12 years of age; the emergency use authorization (EUA) authorizes use in patients ≥6 months of age. The FDA has also granted full approval of the Moderna COVID-19 vaccine Spikevax for use in patients ≥18 years of age; the EUA authorizes use in patients ≥6 months of age. The US federal government, in conjunction with state health departments, allocates vaccine supply to individual sites of care across the United States.

As part of the EUA, information consistent with fact sheets pertaining to emergency use of the COVID-19 vaccines must be provided to health care providers and recipients/caregivers, and certain mandatory requirements for administration under the EUA must be met as outlined in the FDA EUA letter.

Moderna COVID-19 Vaccine:

The health care provider fact sheets are located at:

Monovalent products:

Patients 6 months to <6 years of age (product with magenta label border and dark blue vial cap for primary series): https://www.fda.gov/media/159307/download

Patients 6 to <12 years of age (product with purple label border and dark blue vial cap for primary series): https://www.fda.gov/media/159308/download

Patients ≥12 years of age (product with light blue label border and red vial cap for primary series): https://www.fda.gov/media/157233/download

Bivalent product:

Patients 6 months to <6 years of age (product with yellow label border and dark pink vial cap for booster dose): https://www.fda.gov/media/163785/download

Patients ≥6 years of age (product with gray label border and dark blue cap for booster dose): https://www.fda.gov/media/161318/download

The patient fact sheets for recipients and caregivers are located at:

Patients 6 months to <6 years of age: https://www.fda.gov/media/159309/download

Patients ≥6 years of age: https://www.fda.gov/media/159310/download

Pfizer-BioNTech COVID-19 Vaccine:

The health care provider fact sheets are located at:

Monovalent products:

Patients 6 months to <5 years of age (product with maroon vial cap and label border for first 2 doses of primary series; dilution required): https://www.fda.gov/media/159312/download

Patients 5 to <12 years of age (product with orange vial cap and label border for primary series; dilution required): https://www.fda.gov/media/153714/download

Patients ≥12 years of age:

Product with purple cap and label border for primary series; dilution required: https://www.fda.gov/media/153713/download

Product with gray cap and label border for primary series; no dilution required: https://www.fda.gov/media/153715/download

Bivalent product:

Patients 6 months to <5 years of age (product with maroon vial cap and label border for final dose of primary series; dilution required): https://www.fda.gov/media/159312/download

Patients 5 to <12 years of age (product with orange cap and label border for booster dose; dilution required): https://www.fda.gov/media/162250/download

Patients ≥12 years of age (product with gray cap and label border for booster dose; no dilution required): https://www.fda.gov/media/161327/download

The patient fact sheets for recipients and caregivers are located at:

Patients 6 months to <5 years of age: https://www.fda.gov/media/159313/download

Patients 5 to <12 years of age: https://www.fda.gov/media/153717/download

Patients ≥12 years of age: https://www.fda.gov/media/153716/download

The vaccine provider should include vaccination information in the state/local jurisdiction Immunization Information System (IIS) or other designated system and provide a paper record card as a backup.

Additionally, the vaccination provider is responsible for mandatory reporting of the following to the Vaccine Adverse Event Reporting System (VAERS) (https://vaers.hhs.gov/reportevent.html or 1-800-822-7967):

  • vaccine administration errors whether or not associated with an adverse event

  • serious adverse events (irrespective of attribution to vaccination)

  • cases of multisystem inflammatory syndrome (MIS) in adults and children

  • cases of myocarditis or pericarditis

  • cases of COVID-19 that result in hospitalization or death

The vaccination provider is also responsible for responding to FDA requests for more information. Additional adverse events may be reported to VAERS and the manufacturer. Adverse events related to the Pfizer-BioNTech vaccine may be reported to Pfizer via https://www.pfizersafetyreporting.com, 1-800-438-1985, or via fax at 1-866-635-8337. Adverse events related to the Moderna vaccine may be reported to ModernaTx, Inc. via ModernaPV@modernatx.com (email), 1-866-663-3762, or via fax at 1-866-599-1342.

Administration: Pediatric

Parenteral: IM: Administer IM in the deltoid muscle or anterolateral thigh as appropriate for age (CDC 2022c). Use proper injection technique in the deltoid muscle (eg, injecting in the central, thickest part of the muscle) to reduce the risk of shoulder injury related to vaccine administration (Cross 2016; Foster 2013). Do not inject intravascularly, subcutaneously, or intradermally. To prevent syncope-related injuries, adolescents should be vaccinated while seated or lying down. If administering simultaneously with other vaccines, administer each vaccine at a different injection site (ACIP [Kroger 2022]). US recipients or caregivers should be given a vaccination card that includes the name of the vaccine, lot number, the vaccination date, and name of the health care site or person where the vaccine was administered (FDA 2022a; FDA 2022c).

Moderna vaccine: Prior to use, gently swirl vial; do not shake. The number of doses obtainable from each vial depends on the type of syringe/needle used. Do not puncture the vial stopper of the red cap vial >20 times (maximum number of doses extracted per vial: 20). Do not pool partial doses remaining in vials into a full dose (FDA 2022a; FDA 2022e; FDA 2022g; FDA 2022h; FDA 2022l). Note: The vial with a purple label border and dark blue cap (50 mcg per 0.5 mL) should be used for primary series doses in ages 6 to <12 years, despite statements on cartons and vials indicating use for booster doses only (FDA 2022h).

Pfizer-BioNTech vaccine: Vials with maroon, orange, or purple caps must be diluted prior to use; vial with gray cap must NOT be diluted. Extract doses from vial preferably using a low dead-volume syringe and/or needle. If standard syringes and needles are used, there may not be sufficient volume for full number of stated doses. Do not pool partial doses remaining in vials into a full dose. Note: The vial with a maroon vial cap (3 mcg per 0.2 mL) may be used in ages 6 months to <5 years, despite statements on some cartons and vials indicating use for "Ages 2 years to <5 years" (FDA 2022f).

Inappropriate administration technique: If administered subcutaneously or into a muscle other than the deltoid or anterolateral thigh, do not repeat dose. If additional doses are needed, administer at the recommended interval (CDC 2022c).

Patients at risk for hemorrhage: For patients at risk of hemorrhage following IM injection, the vaccine should be administered IM if, in the opinion of the physician familiar with the patient's bleeding risk, the vaccine can be administered by this route with reasonable safety. If the patient receives antihemophilia or other similar therapy, IM vaccination can be scheduled shortly after such therapy is administered. A fine needle (23-gauge or smaller) can be used for the vaccination and firm pressure applied to the site (without rubbing) for at least 2 minutes. The patient should be instructed concerning the risk of hematoma from the injection. Patients on anticoagulant therapy should be considered to have the same bleeding risks and treated as those with clotting factor disorders (ACIP [Kroger 2022]). For patients with bleeding disorders, specific recommendations are available (eg, US National Hemophilia Foundation, World Federation of Hemophilia).

Administration: Adult

IM: Administer IM in the deltoid muscle or anterolateral thigh (CDC 2022c). Use proper injection technique in the deltoid muscle (eg, injecting in the central, thickest part of the muscle) to reduce the risk of shoulder injury related to vaccine administration (Cross 2016; Foster 2013). Do not inject intravascularly, subcutaneously, or intradermally. To prevent syncope-related injuries, adolescents and adults should be vaccinated while seated or lying down. If administering simultaneously with other vaccines, administer each vaccine at a different injection site (ACIP [Kroger 2022]). US recipients or caregivers should be given a vaccination card that includes the name of the vaccine, lot number, the vaccination date, and name of the health care site or person where the vaccine was administered (FDA 2022a; FDA 2022c; FDA 2022e).

Moderna vaccine: Prior to use, gently swirl vial; do not shake. The number of doses (0.25 or 0.5 mL per dose) obtainable from each vial depends on the type of syringe/needle used. Do not puncture the vial stopper of the red cap vial >20 times (maximum number of doses extracted per vial: 20). Do not pool partial doses remaining in vials into a full dose (FDA 2022a; FDA 2022e).

Pfizer-BioNTech vaccine: Vials with purple caps must be diluted prior to use; vials with gray caps must NOT be diluted. Extract doses from vial preferably using a low dead-volume syringe and/or needle. If standard syringes and needles are used, there may not be sufficient volume for all stated doses. Do not pool partial doses remaining in vials into a full dose (FDA 2022b; FDA 2022c; FDA 2022d).

Inappropriate administration technique: If administered SUBQ or into a muscle other than the deltoid or anterolateral thigh (alternate administration site), do not repeat dose. If additional doses are needed, administer at the recommended interval(s) (CDC 2022c).

Patients at risk for hemorrhage: For patients at risk of hemorrhage following IM injection, the vaccine should be administered IM if, in the opinion of the physician familiar with the patient's bleeding risk, the vaccine can be administered by this route with reasonable safety. If the patient receives antihemophilia or other similar therapy, IM vaccination can be scheduled shortly after such therapy is administered. A fine needle (23-gauge or smaller) can be used for the vaccination and firm pressure applied to the site (without rubbing) for at least 2 minutes. The patient should be instructed concerning the risk of hematoma from the injection. Patients on anticoagulant therapy should be considered to have the same bleeding risks and treated as those with clotting factor disorders (ACIP [Kroger 2022]). For patients with bleeding disorders, specific recommendations are available (eg, US National Hemophilia Foundation, World Federation of Hemophilia).

Storage/Stability

Note: Temperature excursion and extended storage information may be available; contact manufacturer to obtain current recommendations or for guidance if a dose is administered after improper storage and handling or past the expiration/beyond use date. Carton and vial labels may contain different storage information; information in health care provider fact sheet issued as part of emergency use authorization supersedes any information on cartons or vials (FDA 2022a; FDA 2022b; FDA 2022c; FDA 2022d; FDA 2022e; FDA 2022f; FDA 2022g; FDA 2022h; FDA 2022i; FDA 2022j).

Moderna vaccines:

Storage of frozen vials: Store intact vial frozen at −50°C to −15°C (−58°F to 5°F); during storage, minimize exposure to room light (eg, store in original carton to protect from light); avoid exposure to direct sunlight and ultraviolet light.

Thawed vials: May store under refrigeration at 2°C to 8°C (36°F to 46°F) for up to 30 days or for a total of 24 hours at room temperature at 8°C to 25°C (46°F to 77°F) prior to use. Thawed vials can be handled in room light conditions. Do not refreeze thawed vials.

After first use (puncture):

Product with yellow label border and dark pink cap: After first use, may store for up to 8 hours at 2°C to 25°C (36°F to 77°F) (FDA 2022l).

Products with magenta, purple, or gray label border with dark blue cap, or product with blue label border with red cap: After first use, may store for up to 12 hours at 2°C to 25°C (36°F to 77°F) (FDA 2022a; FDA 2022e; FDA 2022g; FDA 2022i). Note: Canadian product information allows storage of in-use vials (after first puncture) for up to 24 hours at 2°C to 25°C (36°F to 77°F).

Transportation of thawed vials: If it is not feasible to transport vials at the recommended freezer temperature, may transport thawed vials at 2°C to 8°C (36°F to 46°F) for up to 12 hours using shipping containers that will maintain 2°C to 8°C (36°F to 46°F) and under routine road and air transport conditions with shaking and vibration minimized. Once thawed and transported at 2°C to 8°C (36°F to 46°F), vials should not be refrozen; store at 2°C to 8°C (36°F to 46°F) until use (up to 30 days total at 2°C to 8°C [36°F to 46°F]).

Storage of pre drawn syringes: Product with light blue label border and red cap: The manufacturer indicates that vaccine may be predrawn in syringes if administered within 12 hours after vial is initially pierced; syringes should be stored refrigerated at 2°C to 8°C (36°F to 46°F) or at room temperature at 15°C to 25°C (59°F to 77°F) and protected from sunlight (data on file [Moderna 2022]). Multidose vials do not contain a preservative. Note: Canadian product information recommends use of predrawn syringes within 24 hours after the vial is first punctured.

Pfizer-BioNTech vaccines:

Note: For all vials, minimize exposure to room light and avoid exposure to direct sunlight and ultraviolet light. Do not refreeze thawed vials (FDA 2022b; FDA 2022c; FDA 2022d).

Vials with purple caps (≥12 years of age) (dilution required) (FDA 2022c):

Storage of vials prior to use: Store intact vials frozen at −90°C to −60°C (−130°F to −76°F) in original carton to protect from light. Alternatively, may store at −25°C to −15°C (−13°F to 5°F) for up to 2 weeks; vials stored under these conditions may be returned one time to the recommended storage of −90°C to −60°C (−130°F to −76°F); ensure that total cumulative time stored at −25°C to −15°C (−13°F to 5°F) does not exceed 2 weeks.

If an ultra-low temperature freezer is not available, the thermal container in which the vaccine arrives may be used as temporary storage when consistently refilled to the top of the container with dry ice; refer to re-icing guidelines in thermal container for more information. Storage 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 full cartons cannot be transported at −90°C to −60°C (−130°F to −76°F), may transport at −25°C to −15°C (−13°F to 5°F). Any hours used for transport at this temperature count against the 2-week limit for storage at −25°C to −15°C (−13°F to 5°F). May return vials one time to the recommended storage condition of −90ºC to −60ºC (−130ºF to −76ºF).

Thawed vials prior to dilution: For frozen vials thawed under refrigeration, may store under refrigeration at 2°C to 8°C (35°F to 46°F) for up to 1 month. For frozen vials thawed at room temperature, may store at room temperature up to 25°C (77°F) for up to 2 hours. Thawed vials can be handled in room light conditions. If transportation of thawed vials is needed, data support transportation of one or more thawed vials at 2°C to 8°C (35°F to 46°F) for up to 12 hours.

Vials after dilution: After dilution, use immediately or may store for up to 6 hours at 2°C to 25°C (35°F to 77°F). Additional studies performed by the manufacturer indicate that diluted vaccine in vials stored at 2°C to 30°C (36°F to 86°F) for up to a cumulative period of 18 hours have been shown to be physically and chemically stable (data on file [Pfizer 2021]). Thawed vials can be handled in room light conditions.

Storage of predrawn syringes : According to the manufacturer, diluted vaccine stored in syringes at 2°C to 30°C (36°F to 86°F) for up to 6 hours has been shown to be physically and chemically stable; consider microbiological risk (data on file [Pfizer 2021]). Multidose vials do not contain a preservative.

Vials with gray caps (≥12 years of age) (no dilution required) (FDA 2022d):

Storage of vials prior to use: For intact vials that arrive frozen, store refrigerated at 2°C to 8°C (35°F to 46°F) for up to 10 weeks. Alternatively, may store frozen at −90°C to −60°C (−130°F to −76°F) for up to 18 months from date of manufacture. Do NOT store at other temperatures. If vials arrive at 2°C to 8°C (35°F to 46°F), they should be stored at 2°C to 8°C (35°F to 46°F) and should not be refrozen.

Storage of vials 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 may be stored at 8°C to 25°C (46°F to 77°F) for up to 12 hours prior to the first puncture. After the first puncture, store at 2°C to 25°C (35°F to 77°F); discard within 12 hours.

Storage of predrawn syringes: According to the manufacturer, vaccine stored in syringes at 2°C to 30°C (35°F to 86°F) for up to 12 hours has been shown to be physically and chemically stable; consider microbiological risk (data on file [Pfizer 2022]). Multidose vials do not contain a preservative.

Vials with orange caps (5 to <12 years of age) or maroon caps (6 months to <5 years of age) (dilution required) (FDA 2022b; FDA 2022f; FDA 2022k):

Storage of vials prior to use: For intact vials that arrive frozen, store refrigerated at 2°C to 8°C (35°F to 46°F) for up to 10 weeks. Alternatively, may store frozen at −90°C to −60°C (−130°F to −76°F) for up to 18 months from date of manufacture. Do NOT store at other temperatures. If vials arrive at 2°C to 8°C (35°F to 46°F), they should be stored at 2°C to 8°C (35°F to 46°F) and should not be refrozen.

Transportation of vials: Undiluted vials may be transported at −90°C to −60°C (−130°F to −76°F) or at 2°C to 8°C (35°F to 46°F).

Thawed vials prior to dilution: 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 may be stored at 8°C to 25°C (46°F to 77°F) for up to 12 hours before dilution.

Vials after dilution: After dilution, use immediately or may store for up to 12 hours at 2°C to 25°C (35°F to 77°F). Note: Vial labels and cartons may indicate a different amount of time (ie, 6 hours) that vial should be discarded after first puncture; however, they may be stored for 12 hours as per the FDA Fact Sheet.

Storage of predrawn syringes: According to the manufacturer, diluted vaccine remains physically and chemically stable when stored in syringes for cumulative time of up to 24 hours post dilution, with no more than 12 hours spent at room temperature (≤30°C [≤86°F]) and the rest at 2°C to 8°C (35°F to 46°F); consider microbiological risk (data on file [Pfizer 2021]). Multidose vials do not contain a preservative.

Use

Active immunization to prevent COVID-19.

Monovalent product:

Pfizer-BioNTech: FDA approved in ages ≥12 years and adults; FDA issued emergency use authorization for ages 6 months to <12 years.

Moderna: FDA approved in ages ≥18 years and adults; FDA issued emergency use authorization for ages 6 months to <18 years.

Bivalent product (Original and Omicron BA.4/BA.5): FDA issued emergency use authorization for ages ≥6 months and adults.

Primary immunization:

The CDC recommends an age-appropriate monovalent mRNA COVID-19 vaccine or Novavax COVID-19 vaccine primary series preferentially to the Janssen COVID-19 vaccine, if no contraindications exist; the Janssen COVID-19 vaccine may be considered in individuals ≥18 years of age in limited situations (eg, patients who had anaphylactic reaction after mRNA COVID-19 vaccine) and is preferable to no COVID-19 vaccine (CDC 2022c).

The CDC recommends a 3-dose mRNA primary series for individuals who are moderately to severely immunocompromised, such as those with the following conditions or treatments (CDC 2022c):

• Active treatment for solid tumor and hematologic malignancies

• Hematologic malignancies associated with poor responses to COVID-19 vaccines (eg, chronic lymphocytic leukemia, non-Hodgkin lymphoma, multiple myeloma, acute leukemia) regardless of current treatment status

• Receipt of solid-organ or islet transplant and taking immunosuppressive therapy

• Receipt of chimeric antigen receptor (CAR)–T-cell or hematopoietic stem cell transplant (within 2 years of transplantation or taking immunosuppressive therapy)

• Moderate or severe primary immunodeficiency (eg, common variable immunodeficiency disease, severe combined immunodeficiency, DiGeorge syndrome, Wiskott-Aldrich syndrome)

• HIV infection (advanced or untreated)

• Active treatment with any of the following: High-dose corticosteroids (ie, ≥20 mg/day prednisone or equivalent for ≥2 weeks), alkylating agents, antimetabolites, transplant-related immunosuppressive drugs, cancer chemotherapeutic agents classified as severely immunosuppressive, tumor necrosis (TNF) blockers, and other biologic agents that are immunosuppressive or immunomodulatory

Booster doses (CDC 2022c):

The CDC recommends a single bivalent mRNA vaccine booster dose for all persons ≥5 years of age (regardless of previous primary series product or number of monovalent booster doses). For persons 6 months to <5 years of age who received a primary series with the Moderna product, a single bivalent mRNA vaccine booster dose is recommended; for persons 6 months to <5 years who received a primary series with the Pfizer product, no booster is currently recommended.

Canadian guidance: The National Advisory Committee on Immunization (NACI) has also made recommendations on the use of COVID-19 vaccines; see recommendations for details (NACI 2022a).

Medication Safety Issues
Sound-alike/look-alike issues:

Multiple formulations from both manufacturers (Pfizer-BioNTech and Moderna) are available; errors related to use of the incorrect formulation have been reported (ISMP [Smetzer 2022a]). Concentrations, dilution requirements, and ingredients vary. Ensure correct formulation, dosage, and preparation prior to administration.

COVID-19 vaccine may be confused with influenza virus vaccine. Medication errors have occurred when COVID-19 vaccine was inadvertently administered instead of influenza virus vaccine (and vice versa). These products may be stored in close proximity to each other. Confirm the correct vaccine has been selected prior to administration (ISMP/NAN 2021).

COVID-19 vaccine may be confused with epinephrine injection. Medication errors have occurred when epinephrine injection was inadvertently administered instead of COVID-19 vaccine. Most mix-ups were due to look-alike, predrawn syringes of epinephrine and the vaccine, which were stored in close proximity (ISMP [Smetzer 2022a]).

Other safety concerns:

Errors related to inaccurate dilution of the Pfizer-BioNTech vaccine formulations have occurred; use caution when diluting the vaccine (Pfizer vaccine with purple, orange, or maroon vial caps). The Moderna vaccines and the Pfizer vaccine with a gray vial cap (multidose vial for ages ≥12 years) do not need to be diluted (FDA 2022a; FDA 2022b; FDA 2022c; FDA 2022d; FDA 2022e; FDA 2022f; FDA 2022g; FDA 2022h; ISMP [Smetzer 2022a]).

Cartons and vials of the Pfizer-BioNTech vaccine formulation for patients 6 months to <5 years of age (product with maroon vial cap) may be labeled "Age 2y to <5" or "For age 2 years to <5 years"; however, all products with the maroon vial cap (3 mcg per 0.2 mL dose) can be used in patients from 6 months to <5 years of age (ISMP 2022; FDA 2022f).

Adverse Reactions (Significant): Considerations
Hypersensitivity reactions

Severe hypersensitivity reactions, including anaphylaxis, have been reported with both the Pfizer-BioNTech (Comirnaty) and Moderna (Spikevax) COVID-19 Vaccines (mRNA) during vaccination outside of clinical trials (Ref). Other hypersensitivity reactions that were commonly present with anaphylaxis included airway obstruction, angioedema, nausea, pruritus, skin rash, and urticaria (Ref). Immediate treatment (including epinephrine 1 mg/mL) for anaphylactoid and/or hypersensitivity reactions should be available during vaccine administration (Ref). Of importance, the polyethylene glycol (PEG) excipient in the COVID-19 mRNA vaccines was initially suspected to be the cause of severe hypersensitivity reactions; however, several case series have documented no severe reactions with COVID-19 mRNA vaccination in patients with known or probable PEG or polysorbate allergy (Ref).

Onset: Rapid; Pfizer: Median onset 10 minutes (range: <1 minute to 19 hours) (Ref). Moderna: Median onset 10 minutes (range: 1 to 45 minutes) (Ref).

Risk factors:

Precautions (but not contraindications) include:

• History of any non-severe, immediate (onset <4 hours) allergic reaction to a previous dose (Ref)

• A history of anaphylaxis to any other vaccine or injectable therapy (eg, IM, IV, or SubQ vaccines or therapies [excluding SubQ immunotherapy for allergies]) (Ref)

• Patients with an allergy-related contraindication to another type of COVID-19 vaccine (eg, adenovirus vector) (certain measures must be taken before a different type of COVID-19 [eg, mRNA] is administered to these patients) (Ref)

Local reactions

Local reactions occur in both adult and pediatric patients (ages ≥6 months) and include erythema at injection site, pain at injection site, and swelling at injection site. In the adult population, injection site pain was reported more frequently in patients 16 to 55 years of age and was more likely to be moderate in severity compared to patients ≥56 years with the Pfizer-BioNTech (Comirnaty) COVID-19 Vaccine (mRNA) primary series. Similarly, injection site pain was reported more frequently in patients 18 to 64 years of age with the Moderna (Spikevax) COVID-19 Vaccine (mRNA). Local reactions were similar to the primary series for the Pfizer-BioNTech COVID-19 Vaccine (mRNA) and the Moderna (Spikevax) COVID-19 Vaccine (mRNA) monovalent and bivalent booster doses. In general, local reactions were mild to moderate in severity and resolved after a mean duration of ~2 to 3 days in both adult and pediatric patients. The proportion of local reactions did not increase after the second dose (Ref). Local hypersensitivity reactions (including rash at injection site and urticaria at injection site) have occurred with the Moderna (Spikevax) COVID-19 Vaccine (mRNA). Swelling at or near the site of dermal fillers (eg, face or lips) may also occur (Ref).

Delayed-onset injection-site reactions (“COVID arm”) have occurred with the Moderna (Spikevax) COVID-19 Vaccine (mRNA) and include erythema, induration, swelling, pain/tenderness, and pruritus (Ref). Delayed-onset local reactions that occur with the first dose are not a contraindication or precaution to the second dose; administer the same vaccine but preferably in the opposite arm (Ref). Delayed-onset local reactions resolved after a median duration of 4 to 6 days (range: 2 to 11 days) (Ref).

Mechanism: Delayed-onset local reactions: Non–dose-related; immunologic (T-cell mediated) (Ref).

Onset: Varied. Local reactions occur within 7 days after either injection (typically within ~1 day) (Ref). Delayed-onset local reactions occur with a median onset on day 7 or 8 after the first dose (range: 2 to 12 days) (Ref). For patients who experienced delayed-onset local reactions with the first dose, delayed-onset local reactions occur more quickly with the second dose with a median onset on day 2 after the second dose (range: 0 to 5 days) (Ref).

Myocarditis and pericarditis

Myocarditis and pericarditis have been reported rarely with both the Pfizer-BioNTech (Comirnaty) and Moderna (Spikevax) COVID-19 Vaccines (mRNA) (Ref). Evidence suggests a possible higher risk for myocarditis with the Moderna COVID-19 Vaccine (mRNA) versus the Pfizer-BioNTech (Comirnaty) Vaccine (mRNA) (Ref). The risk of myocarditis after a booster dose may be similar to or lower than the risk after the second dose of the primary series for the Pfizer-BioNTech COVID-19 and Moderna COVID-19 Vaccines (mRNA) (Ref). Symptoms may include acute chest pain, shortness of breath, or palpitations; younger children may also experience irritability, lethargy, poor feeding, and tachypnea (Ref). Most cases resolved with hospitalization, treatment, and rest within 90 days (Ref).

Mechanism: Unknown; various immune and non-immune hypotheses exist (Ref).

Onset: Varied; usually within 7 days (most often 2 to 4 days) after the second dose or booster dose (Ref).

Risk factors:

• Males <40 years of age (median age of 20 to 30 years of age in most cases) (Ref)

Systemic reactions (excluding hypersensitivity)

Systemic reactions occur in both adult and pediatric patients (ages ≥6 months) and include arthralgia, chills, diarrhea, fatigue, fever, headache, myalgia, nausea, and vomiting. Younger children, especially those <3 years of age, may also experience irritability/crying, drowsiness, and decreased appetite (Ref). In both adult and pediatric patients in general, the frequency and severity of systemic reactions were higher after the second dose with the Pfizer-BioNTech (Comirnaty) COVID-19 Vaccine (mRNA) primary series. In the adult population, frequency and severity of systemic reactions were also higher in patients 16 to 55 years of age than patients ≥56 years with the primary series. Similarly, the frequency and severity of systemic reactions were higher after the second dose and in patients 18 to 64 years of age with the Moderna (Spikevax) COVID-19 Vaccine (mRNA). Systemic reactions were similar to the primary series for the Pfizer-BioNTech COVID-19 Vaccine (mRNA) and the Moderna COVID-19 Vaccine (mRNA) monovalent and bivalent booster doses. Most systemic reactions were mild to moderate in severity and resolved within 1 to 3 days of onset (Ref). Reactions (eg, chills, fever, myalgia) may occur more frequently with the first dose in patients with prior SARS-CoV-2 infection (Ref). An unsolicited systemic reaction possibly attributed to vaccine was lymphadenopathy.

Onset: Rapid; within 3 days after either injection (Ref)

Adverse Reactions

The following adverse reactions and incidences are derived from product labeling and the FDA issued emergency use authorizations (EUAs) for the Pfizer BioNTech COVID-19 Vaccine mRNA (Comirnaty) (ages ≥6 months) (primary series and monovalent booster doses), the Moderna COVID-19 Vaccine (Spikevax) (ages ≥6 months) (primary series and monovalent booster doses), the Pfizer BioNTech COVID-19 Vaccine mRNA (ages ≥12 years) (bivalent booster dose), and the Moderna COVID-19 Vaccine (ages ≥18 years) (bivalent booster dose), unless otherwise specified. Refer to product labeling and EUAs for specific vaccines for information regarding reporting adverse reactions (FDA 2022b, FDA 2022c, FDA 2022d, FDA 2022i, FDA 2022j).

>10%:

Gastrointestinal: Decreased appetite (infants and children: 20% to 32%) (table 1), diarrhea (Pfizer: 4% to 11%) (table 2), nausea and vomiting (Moderna: 5% to 24%) (table 3)

COVID-19 Vaccine (mRNA): Adverse Reaction: Decreased Appetite

Drug (COVID-19 Vaccine [mRNA])

Placebo

Population

Number of Patients (COVID-19 Vaccine [mRNA])

Number of Patients (Placebo)

Comments

Manufacturer

30%

26%

6 to 23 months of age

1,746

582

Dose 1

Moderna

32%

25%

6 to 23 months of age

1,596

526

Dose 2

Moderna

24%

22%

2 to 3 years of age

944

320

Dose 1

Moderna

31%

21%

2 to 3 years of age

963

330

Dose 2

Moderna

22%

21%

6 to 23 months of age

1,159 to 1,173

591 to 595

Dose 1

Pfizer

22%

18%

6 to 23 months of age

1,137 to 1,147

590 to 591

Dose 2

Pfizer

20%

14%

6 to 23 months of age

362 to 365

170

Dose 3

Pfizer

COVID-19 Vaccine (mRNA): Adverse Reaction: Diarrhea

Drug (COVID-19 Vaccine [mRNA])

Placebo

Population

Number of Patients (COVID-19 Vaccine [mRNA])

Number of Patients (Placebo)

Comments

Manufacturer

8%

8%

2 to 4 years of age

1,813 to 1,824

905 to 909

Dose 1

Pfizer

7%

7%

2 to 4 years of age

1,772 to 1,779

877 to 878

Dose 2

Pfizer

5%

5%

2 to 4 years of age

547 to 552

262

Dose 3

Pfizer

6%

4%

5 to 11 years of age

1,511

748

Dose 1

Pfizer

5%

5%

5 to 11 years of age

1,501

740

Dose 2

Pfizer

5%

N/A

5 to 11 years of age

371

N/A

Monovalent booster dose

Pfizer

8%

7%

12 to 15 years of age

1,127

1,127

Dose 1

Pfizer

6%

4%

12 to 15 years of age

1,097

1,078

Dose 2

Pfizer

11%

11%

16 to 55 years of age

2,899

2,908

Dose 1

Pfizer

10%

8%

16 to 55 years of age

2,682

2,684

Dose 2

Pfizer

9%

N/A

18 to 55 years of age

289

N/A

Monovalent booster dose

Pfizer

8%

7%

≥56 years of age

2,008

1,989

Dose 1

Pfizer

8%

6%

≥56 years of age

1,860

1,833

Dose 2

Pfizer

4%

N/A

>55 years of age

298

N/A

Monovalent booster dose

Pfizer

9%

N/A

>55 years of age

301

N/A

Bivalent booster dose

Pfizer

COVID-19 Vaccine (mRNA): Adverse Reaction: Nausea and Vomiting

Drug (COVID-19 Vaccine [mRNA])

Placebo

Population

Number of Patients (COVID-19 Vaccine [mRNA])

Number of Patients (Placebo)

Comments

Manufacturer

7%

8%

37 months to 5 years of age

2,013

650

Dose 1

Moderna

10%

5%

37 months to 5 years of age

1,975

629

Dose 2

Moderna

11%

11%

6 to 11 years of age

3,004

993

Dose 1

Moderna

24%

10%

6 to 11 years of age

2,988

969

Dose 2

Moderna

11%

9%

12 to 17 years of age

2,482

1,238

Dose 1

Moderna

24%

9%

12 to 17 years of age

2,478

1,220

Dose 2

Moderna

9%

8%

18 to 64 years of age

11,406

11,407

Dose 1

Moderna

21%

7%

18 to 64 years of age

10,985

10,918

Dose 2

Moderna

12%

N/A

18 to 64 years of age

129

N/A

Monovalent booster dose

Moderna

13%

N/A

18 to 64 years of age

211

N/A

Monovalent booster dose

Moderna

13%

N/A

18 to 64 years of age

263

N/A

Bivalent booster dose

Moderna

5%

4%

≥65 years of age

3,762

3,748

Dose 1

Moderna

12%

4%

≥65 years of age

3,692

3,648

Dose 2

Moderna

8%

N/A

≥65 years of age

38

N/A

Monovalent booster dose

Moderna

6%

N/A

≥65 years of age

140

N/A

Monovalent booster dose

Moderna

6%

N/A

≥65 years of age

174

N/A

Bivalent booster dose

Moderna

Local: Erythema at injection site (2% to 20%) (table 4), pain at injection site (27% to 95%) (table 5), swelling at injection site (3% to 21%) (table 6), tenderness at injection site (infants and children: Pfizer: 15% to 17%) (table 7)

COVID-19 Vaccine (mRNA): Adverse Reaction: Erythema at Injection Site

Drug (COVID-19 Vaccine [mRNA])

Placebo

Population

Number of Patients (COVID-19 Vaccine [mRNA])

Number of Patients (Placebo)

Comments

Manufacturer

9%

4%

6 to 23 months of age

1,746

582

Dose 1

Moderna

14%

4%

6 to 23 months of age

1,596

526

Dose 2

Moderna

10%

4%

2 to 3 years of age

944

320

Dose 1

Moderna

12%

3%

2 to 3 years of age

963

330

Dose 2

Moderna

4%

0.2%

37 months to 5 years of age

2,013

650

Dose 1

Moderna

7%

0.8%

37 months to 5 years of age

1,975

629

Dose 2

Moderna

12%

1%

6 to 11 years of age

3,004

993

Dose 1

Moderna

19%

1%

6 to 11 years of age

2,988

969

Dose 2

Moderna

14%

0.6%

12 to 17 years of age

2,482

1,238

Dose 1

Moderna

20%

0.9%

12 to 17 years of age

2,478

1,220

Dose 2

Moderna

3%

0.5%

18 to 64 years of age

11,406

11,407

Dose 1

Moderna

9%

0.5%

18 to 64 years of age

10,985

10,918

Dose 2

Moderna

5%

N/A

18 to 64 years of age

129

N/A

Monovalent booster dose

Moderna

5%

N/A

18 to 64 years of age

211

N/A

Monovalent booster dose

Moderna

8%

N/A

18 to 64 years of age

263

N/A

Bivalent booster dose

Moderna

2%

0.5%

≥65 years of age

3,762

3,748

Dose 1

Moderna

8%

0.4%

≥65 years of age

3,692

3,648

Dose 2

Moderna

3%

N/A

≥65 years of age

38

N/A

Monovalent booster dose

Moderna

2%

N/A

≥65 years of age

140

N/A

Monovalent booster dose

Moderna

6%

N/A

≥65 years of age

174

N/A

Bivalent booster dose

Moderna

11%

7%

6 to 23 months of age

1,159 to 1,173

591 to 595

Dose 1

Pfizer

9%

7%

6 to 23 months of age

1,137 to 1,147

590 to 591

Dose 2

Pfizer

7%

5%

6 to 23 months of age

362 to 365

170

Dose 3

Pfizer

9%

9%

2 to 4 years of age

1,814 to 1,825

905 to 909

Dose 1

Pfizer

11%

6%

2 to 4 years of age

1,772 to 1,779

877 to 878

Dose 2

Pfizer

11%

3%

2 to 4 years of age

547 to 552

262

Dose 3

Pfizer

15%

6%

5 to 11 years of age

1,511

748

Dose 1

Pfizer

19%

5%

5 to 11 years of age

1,501

740

Dose 2

Pfizer

16%

N/A

5 to 11 years of age

371

N/A

Monovalent booster dose

Pfizer

6%

1%

12 to 15 years of age

1,127

1,127

Dose 1

Pfizer

5%

0.9%

12 to 15 years of age

1,097

1,078

Dose 2

Pfizer

5%

1%

16 to 55 years of age

2,899

2,908

Dose 1

Pfizer

6%

0.7%

16 to 55 years of age

2,682

2,684

Dose 2

Pfizer

6%

N/A

18 to 55 years of age

289

N/A

Monovalent booster dose

Pfizer

5%

1%

≥56 years of age

2,008

1,989

Dose 1

Pfizer

7%

0.8%

≥56 years of age

1,860

1,833

Dose 2

Pfizer

6%

N/A

>55 years of age

298

N/A

Monovalent booster dose

Pfizer

7%

N/A

>55 years of age

301

N/A

Bivalent booster dose

Pfizer

COVID-19 Vaccine (mRNA): Adverse Reaction: Pain at Injection Site

Drug (COVID-19 Vaccine [mRNA])

Placebo

Population

Number of Patients (COVID-19 Vaccine [mRNA])

Number of Patients (Placebo)

Comments

Manufacturer

37%

30%

6 to 23 months of age

1,746

582

Dose 1

Moderna

46%

26%

6 to 23 months of age

1,596

526

Dose 2

Moderna

53%

37%

2 to 3 years of age

944

320

Dose 1

Moderna

68%

44%

2 to 3 years of age

963

330

Dose 2

Moderna

65%

41%

37 months to 5 years of age

2,013

650

Dose 1

Moderna

73%

40%

37 months to 5 years of age

1,975

629

Dose 2

Moderna

93%

47%

6 to 11 years of age

3,004

993

Dose 1

Moderna

95%

50%

6 to 11 years of age

2,988

969

Dose 2

Moderna

93%

35%

12 to 17 years of age

2,482

1,238

Dose 1

Moderna

93%

30%

12 to 17 years of age

2,478

1,220

Dose 2

Moderna

87%

19%

18 to 64 years of age

11,406

11,407

Dose 1

Moderna

90%

19%

18 to 64 years of age

10,985

10,918

Dose 2

Moderna

86%

N/A

18 to 64 years of age

129

N/A

Monovalent booster dose

Moderna

83%

N/A

18 to 64 years of age

211

N/A

Monovalent booster dose

Moderna

88%

N/A

18 to 64 years of age

263

N/A

Bivalent booster dose

Moderna

74%

13%

≥65 years of age

3,762

3,748

Dose 1

Moderna

83%

12%

≥65 years of age

3,692

3,648

Dose 2

Moderna

76%

N/A

≥65 years of age

38

N/A

Monovalent booster dose

Moderna

67%

N/A

≥65 years of age

140

N/A

Monovalent booster dose

Moderna

62%

N/A

≥65 years of age

174

N/A

Bivalent booster dose

Moderna

31%

21%

2 to 4 years of age

1,814 to 1,825

905 to 909

Dose 1

Pfizer

31%

20%

2 to 4 years of age

1,772 to 1,779

877 to 878

Dose 2

Pfizer

27%

13%

2 to 4 years of age

547 to 552

262

Dose 3

Pfizer

74%

31%

5 to 11 years of age

1,511

748

Dose 1

Pfizer

71%

30%

5 to 11 years of age

1,501

740

Dose 2

Pfizer

74%

N/A

5 to 11 years of age

371

N/A

Monovalent booster dose

Pfizer

86%

23%

12 to 15 years of age

1,127

1,127

Dose 1

Pfizer

79%

18%

12 to 15 years of age

1,097

1,078

Dose 2

Pfizer

84%

14%

16 to 55 years of age

2,899

2,908

Dose 1

Pfizer

78%

12%

16 to 55 years of age

2,682

2,684

Dose 2

Pfizer

83%

N/A

18 to 55 years of age

289

N/A

Monovalent booster dose

Pfizer

70%

9%

≥56 years of age

2,008

1,989

Dose 1

Pfizer

66%

8%

≥56 years of age

1,860

1,833

Dose 2

Pfizer

60%

N/A

>55 years of age

298

N/A

Monovalent booster dose

Pfizer

58%

N/A

>55 years of age

301

N/A

Bivalent booster dose

Pfizer

COVID-19 Vaccine (mRNA): Adverse Reaction: Swelling at Injection Site

Drug (COVID-19 Vaccine [mRNA])

Placebo

Population

Number of Patients (COVID-19 Vaccine [mRNA])

Number of Patients (Placebo)

Comments

Manufacturer

8%

3%

6 to 23 months of age

1,746

582

Dose 1

Moderna

15%

2%

6 to 23 months of age

1,596

526

Dose 2

Moderna

8%

3%

2 to 3 years of age

944

320

Dose 1

Moderna

12%

2%

2 to 3 years of age

963

330

Dose 2

Moderna

3%

0.9%

37 months to 5 years of age

2,013

650

Dose 1

Moderna

7%

0.6%

37 months to 5 years of age

1,975

629

Dose 2

Moderna

12%

1%

6 to 11 years of age

3,004

993

Dose 1

Moderna

17%

1%

6 to 11 years of age

2,988

969

Dose 2

Moderna

16%

1%

12 to 17 years of age

2,482

1,238

Dose 1

Moderna

21%

1%

12 to 17 years of age

2,478

1,220

Dose 2

Moderna

7%

0.3%

18 to 64 years of age

11,406

11,407

Dose 1

Moderna

13%

0.3%

18 to 64 years of age

10,985

10,918

Dose 2

Moderna

6%

N/A

18 to 64 years of age

129

N/A

Monovalent booster dose

Moderna

7%

N/A

18 to 64 years of age

211

N/A

Monovalent booster dose

Moderna

8%

N/A

18 to 64 years of age

263

N/A

Bivalent booster dose

Moderna

4%

0.5%

≥65 years of age

3,762

3,748

Dose 1

Moderna

11%

0.4%

≥65 years of age

3,692

3,648

Dose 2

Moderna

3%

N/A

≥65 years of age

38

N/A

Monovalent booster dose

Moderna

6%

N/A

≥65 years of age

140

N/A

Monovalent booster dose

Moderna

5%

N/A

≥65 years of age

174

N/A

Bivalent booster dose

Moderna

4%

3%

6 to 23 months of age

1,159 to 1,173

591 to 595

Dose 1

Pfizer

4%

2%

6 to 23 months of age

1,137 to 1,147

590 to 591

Dose 2

Pfizer

3%

2%

6 to 23 months of age

362 to 365

170

Dose 3

Pfizer

4%

3%

2 to 4 years of age

1,814 to 1,825

905 to 909

Dose 1

Pfizer

6%

2%

2 to 4 years of age

1,772 to 1,779

877 to 878

Dose 2

Pfizer

3%

1%

2 to 4 years of age

547 to 552

262

Dose 3

Pfizer

11%

3%

5 to 11 years of age

1,511

748

Dose 1

Pfizer

15%

3%

5 to 11 years of age

1,501

740

Dose 2

Pfizer

16%

N/A

5 to 11 years of age

371

N/A

Monovalent booster dose

Pfizer

7%

1%

12 to 15 years of age

1,127

1,127

Dose 1

Pfizer

5%

0.6%

12 to 15 years of age

1,097

1,078

Dose 2

Pfizer

6%

0.6%

16 to 55 years of age

2,899

2,908

Dose 1

Pfizer

7%

0.2%

16 to 55 years of age

2,682

2,684

Dose 2

Pfizer

8%

N/A

18 to 55 years of age

289

N/A

Monovalent booster dose

Pfizer

7%

1%

≥56 years of age

2,008

1,989

Dose 1

Pfizer

8%

0.7%

≥56 years of age

1,860

1,833

Dose 2

Pfizer

6%

N/A

>55 years of age

298

N/A

Monovalent booster dose

Pfizer

7%

N/A

>55 years of age

301

N/A

Bivalent booster dose

Pfizer

COVID-19 Vaccine (mRNA): Adverse Reaction: Tenderness at Injection Site

Drug (COVID-19 Vaccine [mRNA])

Placebo

Population

Number of Patients (COVID-19 Vaccine [mRNA])

Number of Patients (Placebo)

Comments

Manufacturer

17%

11%

6 to 23 months of age

1,159 to 1,173

591 to 595

Dose 1

Pfizer

15%

9%

6 to 23 months of age

1,137 to 1,147

590 to 591

Dose 2

Pfizer

16%

12%

6 to 23 months of age

362 to 365

170

Dose 3

Pfizer

Nervous system: Chills (2% to 49%) (table 8), drowsiness (infants and children: 20% to 37%) (table 9), fatigue (25% to 68%) (table 10), headache (5% to 70%) (table 11), irritability (and/or crying; infants and children: 44% to 68%) (table 12)

COVID-19 Vaccine (mRNA): Adverse Reaction: Chills

Drug (COVID-19 Vaccine [mRNA])

Placebo

Population

Number of Patients (COVID-19 Vaccine [mRNA])

Number of Patients (Placebo)

Comments

Manufacturer

6%

6%

37 months to 5 years of age

2,013

650

Dose 1

Moderna

12%

5%

37 months to 5 years of age

1,975

629

Dose 2

Moderna

10%

7%

6 to 11 years of age

3,004

993

Dose 1

Moderna

30%

8%

6 to 11 years of age

2,988

969

Dose 2

Moderna

18%

11%

12 to 17 years of age

2,482

1,238

Dose 1

Moderna

43%

8%

12 to 17 years of age

2,478

1,220

Dose 2

Moderna

9%

6%

18 to 64 years of age

11,406

11,407

Dose 1

Moderna

49%

6%

18 to 64 years of age

10,985

10,918

Dose 2

Moderna

40%

N/A

18 to 64 years of age

129

N/A

Monovalent booster dose

Moderna

26%

N/A

18 to 64 years of age

211

N/A

Monovalent booster dose

Moderna

24%

N/A

18 to 64 years of age

263

N/A

Bivalent booster dose

Moderna

5%

4%

≥65 years of age

3,762

3,748

Dose 1

Moderna

31%

4%

≥65 years of age

3,692

3,648

Dose 2

Moderna

18%

N/A

≥65 years of age

38

N/A

Monovalent booster dose

Moderna

14%

N/A

≥65 years of age

140

N/A

Monovalent booster dose

Moderna

23%

N/A

≥65 years of age

174

N/A

Bivalent booster dose

Moderna

2%

2%

2 to 4 years of age

1,813 to 1,824

905 to 909

Dose 1

Pfizer

3%

3%

2 to 4 years of age

1,772 to 1,779

877 to 878

Dose 2

Pfizer

3%

3%

2 to 4 years of age

547 to 552

262

Dose 3

Pfizer

5%

5%

5 to 11 years of age

1,511

748

Dose 1

Pfizer

10%

4%

5 to 11 years of age

1,501

740

Dose 2

Pfizer

11%

N/A

5 to 11 years of age

371

N/A

Monovalent booster dose

Pfizer

28%

10%

12 to 15 years of age

1,127

1,127

Dose 1

Pfizer

42%

7%

12 to 15 years of age

1,097

1,078

Dose 2

Pfizer

17%

7%

16 to 55 years of age

2,899

2,908

Dose 1

Pfizer

38%

4%

16 to 55 years of age

2,682

2,684

Dose 2

Pfizer

29%

N/A

18 to 55 years of age

289

N/A

Monovalent booster dose

Pfizer

7%

4%

≥56 years of age

2,008

1,989

Dose 1

Pfizer

23%

3%

≥56 years of age

1,860

1,833

Dose 2

Pfizer

16%

N/A

>55 years of age

298

N/A

Monovalent booster dose

Pfizer

13%

N/A

>55 years of age

301

N/A

Bivalent booster dose

Pfizer

COVID-19 Vaccine (mRNA): Adverse Reaction: Drowsiness

Drug (COVID-19 Vaccine [mRNA])

Placebo

Population

Number of Patients (COVID-19 Vaccine [mRNA])

Number of Patients (Placebo)

Comments

Manufacturer

37%

37%

6 to 23 months of age

1,746

582

Dose 1

Moderna

35%

33%

6 to 23 months of age

1,596

526

Dose 2

Moderna

30%

29%

2 to 3 years of age

944

320

Dose 1

Moderna

36%

27%

2 to 3 years of age

963

330

Dose 2

Moderna

27%

29%

6 to 23 months of age

1,159 to 1,173

591 to 595

Dose 1

Pfizer

24%

21%

6 to 23 months of age

1,137 to 1,147

590 to 591

Dose 2

Pfizer

20%

13%

6 to 23 months of age

362 to 365

170

Dose 3

Pfizer

COVID-19 Vaccine (mRNA): Adverse Reaction: Fatigue

Drug (COVID-19 Vaccine [mRNA])

Placebo

Population

Number of Patients (COVID-19 Vaccine [mRNA])

Number of Patients (Placebo)

Comments

Manufacturer

40%

36%

37 months to 5 years of age

2,013

650

Dose 1

Moderna

48%

29%

37 months to 5 years of age

1,975

629

Dose 2

Moderna

43%

34%

6 to 11 years of age

3,004

993

Dose 1

Moderna

65%

35%

6 to 11 years of age

2,988

969

Dose 2

Moderna

48%

37%

12 to 17 years of age

2,482

1,238

Dose 1

Moderna

68%

29%

12 to 17 years of age

2,478

1,220

Dose 2

Moderna

39%

29%

18 to 64 years of age

11,406

11,407

Dose 1

Moderna

68%

25%

18 to 64 years of age

10,985

10,918

Dose 2

Moderna

62%

N/A

18 to 64 years of age

129

N/A

Monovalent booster dose

Moderna

55%

N/A

18 to 64 years of age

211

N/A

Monovalent booster dose

Moderna

59%

N/A

18 to 64 years of age

263

N/A

Bivalent booster dose

Moderna

33%

23%

≥65 years of age

3,762

3,748

Dose 1

Moderna

58%

20%

≥65 years of age

3,692

3,648

Dose 2

Moderna

47%

N/A

≥65 years of age

38

N/A

Monovalent booster dose

Moderna

47%

N/A

≥65 years of age

140

N/A

Monovalent booster dose

Moderna

49%

N/A

≥65 years of age

174

N/A

Bivalent booster dose

Moderna

30%

31%

2 to 4 years of age

1,813 to 1,824

905 to 909

Dose 1

Pfizer

26%

23%

2 to 4 years of age

1,772 to 1,779

877 to 878

Dose 2

Pfizer

25%

22%

2 to 4 years of age

547 to 552

262

Dose 3

Pfizer

34%

31%

5 to 11 years of age

1,511

748

Dose 1

Pfizer

39%

24%

5 to 11 years of age

1,501

740

Dose 2

Pfizer

46%

N/A

5 to 11 years of age

371

N/A

Monovalent booster dose

Pfizer

60%

41%

12 to 15 years of age

1,127

1,127

Dose 1

Pfizer

66%

25%

12 to 15 years of age

1,097

1,078

Dose 2

Pfizer

49%

33%

16 to 55 years of age

2,899

2,908

Dose 1

Pfizer

62%

23%

16 to 55 years of age

2,682

2,684

Dose 2

Pfizer

64%

N/A

18 to 55 years of age

289

N/A

Monovalent booster dose

Pfizer

34%

23%

≥56 years of age

2,008

1,989

Dose 1

Pfizer

51%

17%

≥56 years of age

1,860

1,833

Dose 2

Pfizer

45%

N/A

>55 years of age

298

N/A

Monovalent booster dose

Pfizer

49%

N/A

>55 years of age

301

N/A

Bivalent booster dose

Pfizer

COVID-19 Vaccine (mRNA): Adverse Reaction: Headache

Drug (COVID-19 Vaccine [mRNA])

Placebo

Population

Number of Patients (COVID-19 Vaccine [mRNA])

Number of Patients (Placebo)

Comments

Manufacturer

12%

12%

37 months to 5 years of age

2,013

650

Dose 1

Moderna

16%

8%

37 months to 5 years of age

1,975

629

Dose 2

Moderna

31%

31%

6 to 11 years of age

3,004

993

Dose 1

Moderna

54%

28%

6 to 11 years of age

2,988

969

Dose 2

Moderna

45%

39%

12 to 17 years of age

2,482

1,238

Dose 1

Moderna

70%

30%

12 to 17 years of age

2,478

1,220

Dose 2

Moderna

35%

29%

18 to 64 years of age

11,406

11,407

Dose 1

Moderna

63%

25%

18 to 64 years of age

10,985

10,918

Dose 2

Moderna

59%

N/A

18 to 64 years of age

129

N/A

Monovalent booster dose

Moderna

47%

N/A

18 to 64 years of age

211

N/A

Monovalent booster dose

Moderna

49%

N/A

18 to 64 years of age

263

N/A

Bivalent booster dose

Moderna

25%

19%

≥65 years of age

3,762

3,748

Dose 1

Moderna

46%

18%

≥65 years of age

3,692

3,648

Dose 2

Moderna

42%

N/A

≥65 years of age

38

N/A

Monovalent booster dose

Moderna

32%

N/A

≥65 years of age

140

N/A

Monovalent booster dose

Moderna

36%

N/A

≥65 years of age

174

N/A

Bivalent booster dose

Moderna

5%

5%

2 to 4 years of age

1,813 to 1,824

905 to 909

Dose 1

Pfizer

5%

4%

2 to 4 years of age

1,772 to 1,779

877 to 878

Dose 2

Pfizer

5%

4%

2 to 4 years of age

547 to 552

262

Dose 3

Pfizer

22%

24%

5 to 11 years of age

1,511

748

Dose 1

Pfizer

28%

19%

5 to 11 years of age

1,501

740

Dose 2

Pfizer

34%

N/A

5 to 11 years of age

371

N/A

Monovalent booster dose

Pfizer

55%

35%

12 to 15 years of age

1,127

1,127

Dose 1

Pfizer

65%

24%

12 to 15 years of age

1,097

1,078

Dose 2

Pfizer

44%

34%

16 to 55 years of age

2,899

2,908

Dose 1

Pfizer

54%

24%

16 to 55 years of age

2,682

2,684

Dose 2

Pfizer

48%

N/A

18 to 55 years of age

289

N/A

Monovalent booster dose

Pfizer

25%

18%

≥56 years of age

2,008

1,989

Dose 1

Pfizer

39%

14%

≥56 years of age

1,860

1,833

Dose 2

Pfizer

27%

N/A

>55 years of age

298

N/A

Monovalent booster dose

Pfizer

34%

N/A

>55 years of age

301

N/A

Bivalent booster dose

Pfizer

COVID-19 Vaccine (mRNA): Adverse Reaction: Irritability

Drug (COVID-19 Vaccine [mRNA])

Placebo

Population

Number of Patients (COVID-19 Vaccine [mRNA])

Number of Patients (Placebo)

Comments

Manufacturer

Comments

68%

62%

6 to 23 months of age

1,746

582

Dose 1

Moderna

Described as "irritability/crying"

64%

59%

6 to 23 months of age

1,596

526

Dose 2

Moderna

55%

51%

2 to 3 years of age

944

320

Dose 1

Moderna

54%

45%

2 to 3 years of age

963

330

Dose 2

Moderna

51%

47%

6 to 23 months of age

1,159 to 1,173

591 to 595

Dose 1

Pfizer

N/A

47%

41%

6 to 23 months of age

1,137 to 1,147

590 to 591

Dose 2

Pfizer

44%

38%

6 to 23 months of age

362 to 365

170

Dose 3

Pfizer

Neuromuscular & skeletal: Arthralgia (Moderna: 6% to 46%; Pfizer: ≤25%) (table 13), axillary swelling (Moderna: Including axillary tenderness; 5% to 25%), myalgia (Moderna: 10% to 62%; Pfizer: 2% to 39%) (table 14)

COVID-19 Vaccine (mRNA): Adverse Reaction: Arthralgia

Drug (COVID-19 Vaccine [mRNA])

Placebo

Population

Number of Patients (COVID-19 Vaccine [mRNA])

Number of Patients (Placebo)

Comments

Manufacturer

6%

5%

37 months to 5 years of age

2,013

650

Dose 1

Moderna

9%

5%

37 months to 5 years of age

1,975

629

Dose 2

Moderna

9%

8%

6 to 11 years of age

3,004

993

Dose 1

Moderna

16%

9%

6 to 11 years of age

2,988

969

Dose 2

Moderna

15%

12%

12 to 17 years of age

2,482

1,238

Dose 1

Moderna

29%

9%

12 to 17 years of age

2,478

1,220

Dose 2

Moderna

17%

12%

18 to 64 years of age

11,406

11,407

Dose 1

Moderna

46%

11%

18 to 64 years of age

10,985

10,918

Dose 2

Moderna

42%

N/A

18 to 64 years of age

129

N/A

Monovalent booster dose

Moderna

33%

N/A

18 to 64 years of age

211

N/A

Monovalent booster dose

Moderna

33%

N/A

18 to 64 years of age

263

N/A

Bivalent booster dose

Moderna

16%

12%

≥65 years of age

3,762

3,748

Dose 1

Moderna

35%

11%

≥65 years of age

3,692

3,648

Dose 2

Moderna

40%

N/A

≥65 years of age

38

N/A

Monovalent booster dose

Moderna

30%

N/A

≥65 years of age

140

N/A

Monovalent booster dose

Moderna

28%

N/A

≥65 years of age

174

N/A

Bivalent booster dose

Moderna

0.8%

2%

2 to 4 years of age

1,813 to 1,824

905 to 909

Dose 1

Pfizer

1%

1%

2 to 4 years of age

1,772 to 1,779

877 to 878

Dose 2

Pfizer

1%

0.8%

2 to 4 years of age

547 to 552

262

Dose 3

Pfizer

3%

6%

5 to 11 years of age

1,511

748

Dose 1

Pfizer

5%

4%

5 to 11 years of age

1,501

740

Dose 2

Pfizer

7%

N/A

5 to 11 years of age

371

N/A

Monovalent booster dose

Pfizer

10%

7%

12 to 15 years of age

1,127

1,127

Dose 1

Pfizer

16%

5%

12 to 15 years of age

1,097

1,078

Dose 2

Pfizer

12%

6%

16 to 55 years of age

2,899

2,908

Dose 1

Pfizer

24%

6%

16 to 55 years of age

2,682

2,684

Dose 2

Pfizer

25%

N/A

18 to 55 years of age

289

N/A

Monovalent booster dose

Pfizer

9%

6%

≥56 years of age

2,008

1,989

Dose 1

Pfizer

19%

4%

≥56 years of age

1,860

1,833

Dose 2

Pfizer

9%

N/A

>55 years of age

298

N/A

Monovalent booster dose

Pfizer

11%

N/A

>55 years of age

301

N/A

Bivalent booster dose

Pfizer

COVID-19 Vaccine (mRNA): Adverse Reaction: Myalgia

Drug (COVID-19 Vaccine [mRNA])

Placebo

Population

Number of Patients (COVID-19 Vaccine [mRNA])

Number of Patients (Placebo)

Comments

Manufacturer

10%

9%

37 months to 5 years of age

2,013

650

Dose 1

Moderna

16%

8%

37 months to 5 years of age

1,975

629

Dose 2

Moderna

15%

10%

6 to 11 years of age

3,004

993

Dose 1

Moderna

28%

11%

6 to 11 years of age

2,988

969

Dose 2

Moderna

27%

17%

12 to 17 years of age

2,482

1,238

Dose 1

Moderna

47%

13%

12 to 17 years of age

2,478

1,220

Dose 2

Moderna

24%

14%

18 to 64 years of age

11,406

11,407

Dose 1

Moderna

62%

13%

18 to 64 years of age

10,985

10,918

Dose 2

Moderna

50%

N/A

18 to 64 years of age

129

N/A

Monovalent booster dose

Moderna

43%

N/A

18 to 64 years of age

211

N/A

Monovalent booster dose

Moderna

43%

N/A

18 to 64 years of age

263

N/A

Bivalent booster dose

Moderna

20%

12%

≥65 years of age

3,762

3,748

Dose 1

Moderna

47%

11%

≥65 years of age

3,692

3,648

Dose 2

Moderna

47%

N/A

≥65 years of age

38

N/A

Monovalent booster dose

Moderna

32%

N/A

≥65 years of age

140

N/A

Monovalent booster dose

Moderna

35%

N/A

≥65 years of age

174

N/A

Bivalent booster dose

Moderna

2%

2%

2 to 4 years of age

1,813 to 1,824

905 to 909

Dose 1

Pfizer

3%

2%

2 to 4 years of age

1,772 to 1,779

877 to 878

Dose 2

Pfizer

2%

2%

2 to 4 years of age

547 to 552

262

Dose 3

Pfizer

9%

7%

5 to 11 years of age

1,511

748

Dose 1

Pfizer

12%

7%

5 to 11 years of age

1,501

740

Dose 2

Pfizer

18%

N/A

5 to 11 years of age

371

N/A

Monovalent booster dose

Pfizer

24%

13%

12 to 15 years of age

1,127

1,127

Dose 1

Pfizer

32%

8%

12 to 15 years of age

1,097

1,078

Dose 2

Pfizer

23%

11%

16 to 55 years of age

2,899

2,908

Dose 1

Pfizer

39%

9%

16 to 55 years of age

2,682

2,684

Dose 2

Pfizer

39%

N/A

18 to 55 years of age

289

N/A

Monovalent booster dose

Pfizer

14%

8%

≥56 years of age

2,008

1,989

Dose 1

Pfizer

29%

5%

≥56 years of age

1,860

1,833

Dose 2

Pfizer

20%

N/A

>55 years of age

298

N/A

Monovalent booster dose

Pfizer

22%

N/A

>55 years of age

301

N/A

Bivalent booster dose

Pfizer

Miscellaneous: Fever (≤24%) (table 15)

COVID-19 Vaccine (mRNA): Adverse Reaction: Fever

Drug (COVID-19 Vaccine [mRNA])

Placebo

Population

Number of Patients (COVID-19 Vaccine [mRNA])

Number of Patients (Placebo)

Comments

Manufacturer

11%

8%

6 to 23 months of age

1,746

582

Dose 1

Moderna

15%

8%

6 to 23 months of age

1,596

526

Dose 2

Moderna

11%

8%

2 to 3 years of age

944

320

Dose 1

Moderna

19%

11%

2 to 3 years of age

963

330

Dose 2

Moderna

8%

5%

37 months to 5 years of age

2,013

650

Dose 1

Moderna

16%

5%

37 months to 5 years of age

1,975

629

Dose 2

Moderna

3%

2%

6 to 11 years of age

3,004

993

Dose 1

Moderna

24%

2%

6 to 11 years of age

2,988

969

Dose 2

Moderna

3%

1%

12 to 17 years of age

2,482

1,238

Dose 1

Moderna

12%

1%

12 to 17 years of age

2,478

1,220

Dose 2

Moderna

0.9%

0.3%

18 to 64 years of age

11,406

11,407

Dose 1

Moderna

17%

0.3%

18 to 64 years of age

10,985

10,918

Dose 2

Moderna

7%

N/A

18 to 64 years of age

129

N/A

Monovalent booster dose

Moderna

5%

N/A

18 to 64 years of age

211

N/A

Monovalent booster dose

Moderna

4%

N/A

18 to 64 years of age

263

N/A

Bivalent booster dose

Moderna

0.3%

0.2%

≥65 years of age

3,762

3,748

Dose 1

Moderna

10%

0.1%

≥65 years of age

3,692

3,648

Dose 2

Moderna

5%

N/A

≥65 years of age

38

N/A

Monovalent booster dose

Moderna

1%

N/A

≥65 years of age

140

N/A

Monovalent booster dose

Moderna

5%

N/A

≥65 years of age

174

N/A

Bivalent booster dose

Moderna

7%

7%

6 to 23 months of age

1,159 to 1,173

591 to 595

Dose 1

Pfizer

7%

6%

6 to 23 months of age

1,137 to 1,147

590 to 591

Dose 2

Pfizer

7%

6%

6 to 23 months of age

362 to 365

170

Dose 3

Pfizer

5%

5%

2 to 4 years of age

1,813 to 1,824

905 to 909

Dose 1

Pfizer

5%

5%

2 to 4 years of age

1,772 to 1,779

877 to 878

Dose 2

Pfizer

5%

4%

2 to 4 years of age

547 to 552

262

Dose 3

Pfizer

3%

1%

5 to 11 years of age

1,511

748

Dose 1

Pfizer

7%

1%

5 to 11 years of age

1,501

740

Dose 2

Pfizer

7%

N/A

5 to 11 years of age

371

N/A

Monovalent booster dose

Pfizer

10%

1%

12 to 15 years of age

1,127

1,127

Dose 1

Pfizer

20%

0.6%

12 to 15 years of age

1,097

1,078

Dose 2

Pfizer

4%

0.9%

16 to 55 years of age

2,899

2,908

Dose 1

Pfizer

16%

0.4%

16 to 55 years of age

2,682

2,684

Dose 2

Pfizer

9%

N/A

18 to 55 years of age

289

N/A

Monovalent booster dose

Pfizer

1%

0.4%

≥56 years of age

2,008

1,989

Dose 1

Pfizer

12%

0.2%

≥56 years of age

1,860

1,833

Dose 2

Pfizer

4%

N/A

>55 years of age

298

N/A

Monovalent booster dose

Pfizer

5%

N/A

>55 years of age

301

N/A

Bivalent booster dose

Pfizer

1% to 10%:

Gastrointestinal: Abdominal pain (Moderna: 1%), nausea (Pfizer: ≤1%), vomiting (Pfizer: ≤3%) (table 16)

COVID-19 Vaccine (mRNA): Adverse Reaction: Vomiting

Drug (COVID-19 Vaccine [mRNA])

Placebo

Population

Number of Patients (COVID-19 Vaccine [mRNA])

Number of Patients (Placebo)

Comments

Manufacturer

3%

3%

2 to 4 years of age

1,813 to 1,824

905 to 909

Dose 1

Pfizer

3%

3%

2 to 4 years of age

1,772 to 1,779

877 to 878

Dose 2

Pfizer

2%

4%

2 to 4 years of age

547 to 552

262

Dose 3

Pfizer

2%

2%

5 to 11 years of age

1,511

748

Dose 1

Pfizer

2%

0.8%

5 to 11 years of age

1,501

740

Dose 2

Pfizer

2%

N/A

5 to 11 years of age

371

N/A

Monovalent booster dose

Pfizer

3%

0.9%

12 to 15 years of age

1,127

1,127

Dose 1

Pfizer

3%

1%

12 to 15 years of age

1,097

1,078

Dose 2

Pfizer

1%

1%

16 to 55 years of age

2,899

2,908

Dose 1

Pfizer

2%

1%

16 to 55 years of age

2,682

2,684

Dose 2

Pfizer

2%

N/A

18 to 55 years of age

289

N/A

Monovalent booster dose

Pfizer

0.5%

0.5%

≥56 years of age

2,008

1,989

Dose 1

Pfizer

0.7%

0.3%

≥56 years of age

1,860

1,833

Dose 2

Pfizer

1%

N/A

>55 years of age

298

N/A

Monovalent booster dose

Pfizer

2%

N/A

>55 years of age

301

N/A

Bivalent booster dose

Pfizer

Hematologic & oncologic: Lymphadenopathy (≤5%; unsolicited)

Hypersensitivity: Hypersensitivity reaction (Moderna: 2% to 5%; including rash at injection site, urticaria at injection site, and severe hypersensitivity reaction) (table 17)

COVID-19 Vaccine (mRNA): Adverse Reaction: Hypersensitivity Reaction

Drug (COVID-19 Vaccine [mRNA])

Placebo

Population

Manufacturer

4%

5%

6 to 23 months of age

Moderna

4%

2%

6 to 11 years of age

Moderna

5%

3%

6 to 11 years of age

Moderna

2%

0.6%

12 to 17 years of age

Moderna

2%

1%

≥18 years of age

Moderna

Local: Injection-site reaction (Moderna: Delayed-onset: 1% to 3%)

<1%:

Dermatologic: Hyperhidrosis (Pfizer), night sweats (Pfizer)

Hypersensitivity: Angioedema (Shimabukuro 2021a)

Infection: Herpes zoster infection (Moderna)

Local: Local swelling (at or near the site of dermal fillers [eg, face or lips]) (CDC 2022c)

Nervous system: Asthenia (Pfizer), facial nerve paralysis (including Bell palsy, hypoesthesia, paresthesia; unsolicited, data insufficient to determine causal relationship), lethargy (Pfizer), malaise (Pfizer)

Frequency not defined:

Gastrointestinal: Appendicitis (Pfizer; unsolicited; data insufficient to determine causal relationship)

Neuromuscular & skeletal: Joint injury (shoulder; unsolicited) (Polack 2020)

Post-authorization/postmarketing:

Cardiovascular: Myocarditis, pericarditis, syncope (adolescents in particular)

Dermatologic: Erythema multiforme (Moderna), pruritus (Shimabukuro 2021a), skin rash (Shimabukuro 2021a), urticaria (Shimabukuro 2021a)

Endocrine & metabolic: Graves disease (new onset or exacerbation) (Chee 2022)

Hypersensitivity: Anaphylaxis, hypersensitivity reaction (Pfizer: Including severe hypersensitivity reactions)

Nervous system: Dizziness (CDC 2021a)

Neuromuscular & skeletal: Upper extremity pain (arm) (Pfizer)

Respiratory: Airway obstruction (Shimabukuro 2021a)

Contraindications

History of a severe allergic reaction (eg, anaphylaxis) after a previous dose or to a component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Shoulder injury related to vaccine administration: Vaccine administration that is too high on the upper arm may cause shoulder injury (eg, shoulder bursitis, tendinopathy) resulting in shoulder pain and reduced range of motion following injection. Use proper injection technique for vaccines administered in the deltoid muscle (eg, injecting in the central, thickest part of the muscle) to reduce the risk of shoulder injury related to vaccine administration (Cross 2016; Foster 2013).

• Syncope: Syncope has been reported with use of injectable vaccines and may result in serious secondary injury (eg, skull fracture, cerebral hemorrhage); typically reported in adolescents and young adults and within 15 minutes after vaccination. Procedures should be in place to avoid injuries from falling and to restore cerebral perfusion if syncope occurs (ACIP [Kroger 2022]).

Disease-related concerns:

• Acute illness: The decision to administer or delay vaccination because of current or recent febrile illness depends on the severity of symptoms and the etiology of the disease. In general, it is recommended to defer vaccine administration in patients with moderate or severe acute febrile illness (with or without fever) and to provide vaccination in patients with mild acute illness (with or without fever) (ACIP [Kroger 2022]). Although not included in the Pfizer or Moderna documentation from the FDA, the Canadian product information for the Pfizer vaccine recommends postponing vaccination in patients with acute severe febrile illness. In addition, the Canadian product information for the Moderna vaccine states to consider postponing vaccination in patients with acute severe febrile illness or severe acute infection.

• Bleeding disorders: Use with caution in patients with bleeding disorders (including thrombocytopenia); bleeding or hematoma may occur from IM administration; if the patient receives antihemophilia or other similar therapy, IM injection can be scheduled shortly after such therapy is administered (ACIP [Kroger 2022]). For more information on administering the COVID-19 vaccine in patients with bleeding disorders, see society recommendations (eg, US National Hemophilia Foundation, World Federation of Hemophilia).

• Multisystem inflammatory syndrome: In patients with a history of multisystem inflammatory syndrome (MIS), it is typically recommended to delay COVID-19 vaccination until clinical recovery from MIS and until ≥90 days after diagnosis. Data on the safety of COVID-19 vaccination following MIS in children (MIS-C) or MIS in adults (MIS-A) are limited; risks and benefits should be weighed with consideration given to patient-specific factors (eg, recovery from illness [including return to baseline cardiac function], risk of severe COVID-19). In patients who developed MIS within 90 days following a dose of COVID-19 mRNA vaccine, subsequent doses should be deferred, but may be offered on a case-by-case basis per provider discretion. In patients who developed MIS ≥90 days after a previous dose of COVID-19 mRNA vaccine, subsequent doses should be considered ≥90 days after MIS diagnosis for patients who have clinically recovered (including return to baseline cardiac function) (CDC 2022c).

• Myocarditis/pericarditis (CDC 2022c):

- Persons who experience myocarditis/pericarditis after a dose of the vaccine: For persons who developed myocarditis or pericarditis after a dose of the mRNA vaccine, subsequent doses of any COVID-19 vaccine are generally not recommended. If a subsequent dose is desired by the patient (or caregiver) and clinically appropriate, wait until complete resolution of signs/symptoms of myocarditis or pericarditis as determined by clinical team and cardiac testing. For males ≥18 years of age, consider the Janssen vaccine instead of mRNA vaccine.

- Persons with history of myocarditis or pericarditis prior to vaccination: Persons with history of myocarditis or pericarditis unrelated to mRNA COVID-19 vaccination may receive any FDA-approved or FDA-authorized COVID-19 vaccine after complete resolution of signs/symptoms of myocarditis or pericarditis as determined by clinical team and cardiac testing.

• SARS-CoV-2 infection or exposure (CDC 2022c):

- Persons with history of COVID-19 or asymptomatic SARS-CoV-2 infection: Vaccination is recommended for everyone ≥6 months of age, regardless of history of symptomatic or asymptomatic SARS-CoV-2 infection. Persons who recently had SARS-CoV-2 infection may consider delaying vaccine doses by 3 months from symptom onset or positive test (if asymptomatic); increased time between infection and vaccination may improve vaccination immune response.

- Persons with current SARS-CoV-2 infection (including asymptomatic): In persons with known current SARS-CoV-2 infection, defer vaccination until the person has recovered from acute illness (if symptomatic) and no longer requires isolation. Persons who recently had SARS-CoV-2 infection may consider delaying vaccine doses by 3 months from symptom onset or positive test (if asymptomatic); increased time between infection and vaccination may improve vaccination immune response.

- Persons who received passive antibody COVID-19 therapy: Vaccination does not need to be delayed for persons who previously received COVID-19 monoclonal antibody therapy or convalescent plasma (postexposure prophylaxis or treatment). For persons who are to receive tixagevimab/cilgavimab for pre-exposure prophylaxis, delay tixagevimab/cilgavimab administration until ≥2 weeks after COVID-19 vaccination.

- Persons with known SARS-CoV-2 exposure: Persons with recent known exposure may be vaccinated if they do not have symptoms consistent with SARS-CoV-2 infection; follow CDC’s postexposure guidance. Vaccination for postexposure prophylaxis is not recommended.

Concurrent drug therapy issues:

• Anticoagulant therapy: Clinicians administering vaccine should be aware of potential bleeding or hematoma that could occur due to IM administration (ACIP [Kroger 2022]).

• Medications for postvaccination adverse reactions: Antipyretic or analgesic medications (eg, acetaminophen, nonsteroidal anti-inflammatory drugs) may be taken for the treatment of postvaccination local/systemic symptoms (if medically appropriate) but should not be used prophylactically to prevent postvaccination symptoms (CDC 2022c).

• Vaccines: The CDC and American Academy of Pediatrics recommend simultaneous administration of the COVID-19 vaccine with other vaccines or administration in the days before and after receipt of other vaccines (AAP 2022; CDC 2022c). Because of the risk for myocarditis and pericarditis related to the mRNA COVID-19 vaccine and smallpox vaccine (ACAM2000) and the unknown myocarditis and pericarditis risk related to smallpox and monkeypox vaccine (Jynneos or Imvamune), consider waiting 4 weeks after orthopoxvirus vaccine (ACAM2000; Jynneos or Imvamune) administration before administering a COVID-19 mRNA vaccine (especially for adolescent/young adult males). There is no minimum interval after COVID-19 vaccination before orthopoxvirus vaccines may be administered (CDC 2022c; CDC/ACIP [Rao 2022]).

Dosage form specific issues:

• Traceability: The vaccine name, batch/lot number, expiration date, and other administration details must be recorded for each patient in order to improve traceability.

Special populations:

• Altered immunocompetence: COVID-19 vaccines can be safely administered to immunocompromised persons (including those with HIV or receiving immunosuppressant therapy) if no contraindications exist; as with the general population, mRNA vaccines are preferred. Immunocompromised persons may have a diminished immune response to the vaccine, but the potential benefit of the vaccine outweighs the uncertainties. Persons who are moderately or severely immunocompromised should receive a 3-dose mRNA primary series to enhance antibody response; booster doses should be administered as appropriate for age and medical conditions. If possible, complete COVID-19 vaccination ≥2 weeks prior to initiation or resumption of immunosuppressive therapy (CDC 2022c; NACI 2021). For more information on administering the COVID-19 vaccine in specific disease states, see society recommendations (eg, American Cancer Society, National Multiple Sclerosis Society).

• Persons who had received dermal fillers: Temporary swelling at or near the site of filler injection has been infrequently reported after COVID-19 (mRNA) vaccination (CDC 2022c).

• Pediatric: Multiple formulations from both manufacturers (Pfizer-BioNTech and Moderna) are available and the ages for which each product is authorized differs. Additionally, the number of doses to complete primary series differs between manufacturers for some age groups. Monovalent and bivalent products may look similar. Use extra caution when selecting formulation, dosage, and preparation prior to administration (ISMP [Smetzer 2022b]).

Other warnings/precautions:

• Effective immunity: Vaccination may not result in effective immunity in all patients. Response depends upon multiple factors (eg, type of vaccine, age of patient) and may be improved by administering the vaccine at the recommended dose, route, and interval (ACIP [Kroger 2022]). Vaccines may not be effective if administered during periods of altered immune competence (ACIP [Kroger 2022]; CDC 2022c).

• Mammograms: Temporary contralateral or ipsilateral lymphadenopathy after a COVID-19 vaccination has been reported. To avoid possible misinterpretation of mammogram screening, mammograms are recommended prior to vaccination or 4 to 6 weeks after the second dose. When this is not possible, the mammogram technologist or radiologist should be informed when and which vaccine was administered, and what arm the injection was given (ACOG 2022). Imaging needed for acute symptoms, or urgent treatment planning or complications, should not be delayed (Becker 2021).

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program

Abatacept: May diminish the therapeutic effect of COVID-19 Vaccines. Management: Rheumatology guidelines recommend holding SQ abatacept for 1 to 2 weeks after each vaccine dose and timing vaccine dose so that it is given 1 week prior to the next IV abatacept dose. Risk D: Consider therapy modification

Acetaminophen: May diminish the therapeutic effect of Vaccines. Management: Consider avoiding routine prophylactic use of acetaminophen before or during vaccine administration when possible. Acetaminophen is still recommended to treat fevers and/or pain that occurs after vaccination. Risk D: Consider therapy modification

Anti-CD20 B-Cell Depleting Therapies: May diminish the therapeutic effect of COVID-19 Vaccines. Management: Administer COVID-19 vaccine 2 to 4 weeks prior to the next scheduled dose of anti-CD20 therapy, if used chronically for the treatment of autoimmune disease. Revaccinate 6 months after completion of anti-CD20 therapy if used over a limited period. Risk D: Consider therapy modification

Apremilast: May diminish the therapeutic effect of COVID-19 Vaccines. Management: Rheumatology guidelines recommend holding apremilast for 1 to 2 weeks after vaccine administration as permitted by the underlying disease. These guidelines consider apremilast to be an immunomodulatory or immunosuppressive medication. Risk D: Consider therapy modification

AzaTHIOprine: May diminish the therapeutic effect of COVID-19 Vaccines. Management: Rheumatology guidelines recommend holding azathioprine for 1 to 2 weeks after each vaccine dose as permitted by the underlying disease. This recommendation is specific to patients using azathioprine for rheumatic and musculoskeletal disease. Risk D: Consider therapy modification

Baricitinib: May diminish the therapeutic effect of COVID-19 Vaccines. Management: Rheumatology guidelines recommend holding baricitinib, tofactinib, or upadacitinib for 1 to 2 weeks after vaccine administration as permitted by the underlying disease. Risk D: Consider therapy modification

Belimumab: May diminish the therapeutic effect of COVID-19 Vaccines. Management: Rheumatology guidelines recommend holding subcutaneous belimumab doses for 1 to 2 weeks after each COVID-19 vaccine dose as disease activity permits. The recommendation specifies subcutaneous belimumab and does not mention intravenous belimumab. Risk D: Consider therapy modification

Calcineurin Inhibitors (Systemic): May diminish the therapeutic effect of COVID-19 Vaccines. Management: Rheumatology guidelines recommend holding calcineurin inhibitors for 1 to 2 weeks after each vaccine dose as permitted by the underlying disease. This is specific to the use of calcineurin inhibitors for rheumatologic or musculoskeletal disease. Risk D: Consider therapy modification

CAR-T Cell Immunotherapy: May diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: The CDC recommends that CAR-T-cell recipients who received COVID-19 vaccine prior to or during treatment with CAR-T-cell therapy should be revaccinated with a primary vaccine series at least 3 months (12 weeks) after CAR-T-cell therapy. Risk D: Consider therapy modification

Corticosteroids (Systemic): May diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification

Cyclophosphamide: May diminish the therapeutic effect of COVID-19 Vaccines. Management: Adjust timing of intravenous cyclophosphamide so that administration occurs 1 week after each vaccine dose, if feasible; hold oral cyclophosphamide for 1 to 2 weeks after vaccine administration as permitted by the underlying disease. Risk D: Consider therapy modification

Dermal Fillers: COVID-19 Vaccine (mRNA) may enhance the adverse/toxic effect of Dermal Fillers. Specifically, the risk for swelling at or near the site of dermal filler injection (usually face or lips) may be increased. Risk C: Monitor therapy

Elivaldogene Autotemcel: May enhance the adverse/toxic effect of Vaccines. Specifically, there may be a greater risk for contracting an infection from any live vaccine. Elivaldogene Autotemcel may diminish the therapeutic effect of Vaccines. Management: Administration of vaccines is not recommended in the 6 weeks before myeloablative conditioning, and until hematologic recovery after elivaldogene autotemcel treatment. Risk X: Avoid combination

Immunosuppressants (Cytotoxic Chemotherapy): May diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification

Immunosuppressants (Miscellaneous Oncologic Agents): May diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification

Immunosuppressants (Therapeutic Immunosuppressant Agents): May diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification

Leflunomide: May diminish the therapeutic effect of COVID-19 Vaccines. Management: Rheumatology guidelines recommend holding leflunomide for 1 to 2 weeks after vaccine administration as permitted by the underlying disease. Risk D: Consider therapy modification

Methotrexate: May diminish the therapeutic effect of COVID-19 Vaccines. Management: Rheumatology guidelines recommend holding methotrexate for 1 to 2 weeks after vaccine administration as permitted by underlying disease. This is specific to patients using methotrexate for rheumatic and musculoskeletal disease. Risk D: Consider therapy modification

Mycophenolate: May diminish the therapeutic effect of COVID-19 Vaccines. Management: Rheumatology guidelines recommend holding mycophenolate for 1 to 2 weeks after each vaccine dose as permitted by the underlying disease. This recommendation is specific to patients using mycophenolate for rheumatic and musculoskeletal diseases. Risk D: Consider therapy modification

Propacetamol: May diminish the therapeutic effect of Vaccines. Management: Consider avoiding routine prophylactic use of propacetamol before or during vaccine administration when possible. Propacetamol is still recommended to treat fevers and/or pain that occurs after vaccination. Risk D: Consider therapy modification

Smallpox and Monkeypox Vaccine (Live): May enhance the adverse/toxic effect of COVID-19 Vaccine (mRNA). Specifically, the risk of myocarditis may be increased. Management: Consider waiting 4 weeks after receipt of the smallpox and monkeypox vaccine before receiving an mRNA COVID-19 vaccine. No minimum interval is necessary between receipt of an mRNA COVID-19 vaccine and the smallpox and monkeypox vaccine. Risk D: Consider therapy modification

Smallpox Vaccine Live: May enhance the adverse/toxic effect of COVID-19 Vaccine (mRNA). Specifically, the risk for myocarditis may be increased. Management: Consider waiting 4 weeks after receipt of the smallpox vaccine before receiving an mRNA COVID-19 vaccine. No minimum interval is necessary between receipt of an mRNA COVID-19 vaccine and the smallpox vaccine. Risk D: Consider therapy modification

SulfaSALAzine: May diminish the therapeutic effect of COVID-19 Vaccines. Management: Rheumatology guidelines recommend holding sulfasalazine for 1 to 2 weeks after vaccine administration as permitted by the underlying disease. These guidelines consider sulfasalazine to be an immunomodulatory or immunosuppressive medication. Risk D: Consider therapy modification

Teplizumab: May diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: mRNA vaccines are not recommended during the 2 weeks before teplizumab, during treatment, or for 6 weeks afterward. The CDC recommends a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Risk D: Consider therapy modification

Tixagevimab and Cilgavimab: May diminish the therapeutic effect of COVID-19 Vaccines. Management: Wait at least 2 weeks after receipt of a COVID-19 vaccine before administering tixagevimab and cilgavimab for pre-exposure prophylaxis. Risk D: Consider therapy modification

Tofacitinib: May diminish the therapeutic effect of COVID-19 Vaccines. Management: Rheumatology guidelines recommend holding baricitinib, tofactinib, or upadacitinib for 1 to 2 weeks after vaccine administration as permitted by the underlying disease. Risk D: Consider therapy modification

Upadacitinib: May diminish the therapeutic effect of COVID-19 Vaccines. Management: Rheumatology guidelines recommend holding baricitinib, tofactinib, or upadacitinib for 1 to 2 weeks after vaccine administration as permitted by the underlying disease. Risk D: Consider therapy modification

Reproductive Considerations

Pregnancy testing is not required prior to vaccination. Pregnancy does not need to be delayed following vaccination (ACOG 2022).

There is no evidence that COVID-19 vaccines affect the fertility of either partner among couples trying to conceive (ACOG 2022; CDC 2022d).

- Semen parameters are not affected following COVID-19 vaccination for healthy sperm donors or in patients undergoing assisted reproduction technology (Barda 2022; Gonzalez 2021; Lifshitz 2022; Reschini 2022; Safrai 2022). In one study, semen parameters were evaluated prior to and after vaccination. The study included 106 men (median age: 39 years); 73 received the Pfizer-BioNTech COVID-19 Vaccine and 20 received the Moderna COVID-19 Vaccine. COVID-19 vaccines did not decrease sperm volume, concentration, motility, or morphology. In addition, the fertilization rate was not different prior to or after vaccination (Reschini 2022). Although COVID-19 vaccination does not impair semen parameters, COVID-19 infection has been shown to decrease sperm quality and may temporarily impair fertility (Donders 2022; Enikeev 2022; Wesselink 2022).

- COVID-19 vaccines did not affect the ability to conceive in 2,123 couples planning a pregnancy. Couples were not using fertility treatments and prospectively provided information via an online questionnaire related to vaccine status, COVID-19 infection, menstrual cycles, and pregnancy status for 12 months. Outcome data were available for the female partner administered the Pfizer-BioNTech COVID-19 Vaccine (n = 713), Moderna COVID-19 Vaccine (n = 446), Janssen COVID-19 (adenovirus vector) Vaccine (n = 67), or unvaccinated (n = 897); vaccine status was known for 1,369 male partners. Female patients, vaccinated with one dose of a vaccine prior to their last menstrual period, had a similar probability (fecundability ratio [FR]) of conceiving during that cycle compared to the unvaccinated females (FR vaccinated 1.08, unvaccinated 1). The FR was also similar in fully vaccinated females (FR 1.07; 2 doses of an mRNA vaccine or 1 dose of the adenovirus vector). The FR in couples with vaccinated males was 0.95 (1 dose) and 1 (fully vaccinated). The FR did not vary by brand of vaccine (Wesselink 2022).

- The Pfizer-BioNTech COVID-19 Vaccine and the Moderna COVID-19 Vaccine were not found to effect embryo implantation in a large retrospective study which compared nonvaccinated (n = 3,773) and vaccinated (n = 890) single euploid embryo transfers. Clinical pregnancy rates and the sustained implantation rates were not significantly different between vaccinated and nonvaccinated women in the study. In addition, the number of mRNA doses (1 or 2) and the time interval between vaccination and embryo transfer did not influence the study outcomes (Brandão 2022).

- Based on available data, egg quality, embryo quality and development, and pregnancy rates are not impaired following COVID-19 vaccination (ACOG 2022).

There have been anecdotal reports of temporary menstrual changes following vaccination. Vaccines have not previously been associated with menstrual disturbances. Environmental stresses can impact menses. COVID-19 vaccines may be given to patients who are menstruating, and vaccination does not need to be scheduled based on menstrual cycle. Based on available data, any effect of the COVID-19 vaccine on menstruation is minimal and temporary, not a reason to avoid vaccination (ACOG 2022).

- Menstrual cycle length was evaluated in a retrospective analysis of prospectively collected data from vaccinated (n = 2,403) and unvaccinated individuals (n = 1,556) who were tracking menstrual cycles for nonhormonal pregnancy prevention or planning. Included were persons 18 to 45 years of age who had normal menstrual cycle lengths (24 to 38 days), provided 6 consecutive cycles of data, and had not been pregnant nor used hormonal contraception for ≥3 cycles. Data was collected from persons residing in the United States between December 2020 and July 2021. Vaccinated patients received the Pfizer-BioNTech COVID-19 Vaccine (55%), Moderna COVID-19 Vaccine (35%), or the Janssen COVID-19 (adenovirus vector) Vaccine (7%). When adjusting for age, race, BMI, education, parity, and relationship status, the length of a menstrual cycle differed by less than 1 day following vaccination. This was not considered clinically significant. A small subgroup of patients (n = 358) received 2 vaccine doses within the same cycle; these patients had an increase in cycle length by 2 days (Edelman 2022a). A second prospective study included data from an international cohort between October 2020 and November 2021, following vaccination between January and October 2021. Included were 14,936 vaccinated and 4,686 unvaccinated persons. Vaccinated patients received the Pfizer-BioNTech COVID-19 Vaccine (66.48%), Moderna COVID-19 Vaccine (17.46%), or the Janssen COVID-19 (adenovirus vector) Vaccine (1.89%). As in the previous study, the length of a menstrual cycle differed by less than 1 day following vaccination. In addition, a subgroup of persons had an increase in cycle length of 3.7 days when 2 doses of the vaccine were received within a single cycle, compared to persons who were not vaccinated. Any changes in cycle length were temporary (Edelman 2022b).

- Menstrual cycle length, menstrual bleeding, and other parameters were evaluated in a prospective study including 76 women tracking their menstrual cycles for natural family planning (fertility monitoring). All women in the study had regular menstrual cycles (21 to 42 days) prior to vaccination and recorded data for at least 3 months after receiving the vaccine (primarily an mRNA vaccine: Pfizer-BioNTech COVID-19 Vaccine n = 48 or Moderna COVID-19 Vaccine n = 23). Outcome data were obtained using reports generated by the tracking method used by the participant and available for 227 cycles prior to vaccination, 145 cycles between the first and second doses, and 216 post-vaccine cycles. Based on the recorded data, cycle length did not change as a result of vaccination, although a subset of women (22%) perceived a change. Depending on the tracking method, the study was also able to evaluate bleeding volume, signs of ovulation, and hormonal changes; no differences in these parameters were observed (Bouchard 2022).

- A meta-analysis of 14 observational studies evaluated menstrual irregularities following vaccination with various COVID-19 vaccines (AstraZenica, CoronaVax, CoVac, Janssen, Moderna, Novavax, Pfizer, Sinopharm, Sinovac). Changes to menstrual flow were among the outcomes reported; changes were considered intermittent and self-limiting. Until data are available from prospective cohort studies, individualized counseling is suggested, particularly for patients who already have menstrual irregularities or fertility issues (Nazir 2022).

Due to the risk of severe illness, pregnancy complications, and death from COVID-19 infection during pregnancy, vaccination with an appropriate vaccine is strongly recommended for all patients planning a pregnancy, patients trying to become pregnant now, and patients who might become pregnant in the future, including those patients previously diagnosed with COVID-19 infection (ACOG 2022; CDC 2022d).

Monovalent mRNA COVID-19 vaccines are recommended for the primary series in eligible patients who do not otherwise have contraindications to the vaccine. Bivalent mRNA COVID-19 vaccines are recommended for booster doses (ACOG 2022; CDC 2022d)

Pregnancy Considerations

Antibodies generated following vaccination of pregnant patients can be detected in cord blood. Placental transfer of IgG antibodies to the neonate increases from time of vaccination to delivery following administration of an mRNA COVID-19 vaccine during pregnancy (Fu 2022; Rawal 2022). Antibodies generated in response to the vaccine persist in the infant serum for up to 6 months of age and are higher than those in infants born to infected mothers (Rawal 2022; Shook 2022). Completion of a 2-dose mRNA vaccine series during pregnancy decreases hospitalization due to COVID-19 infection in infants <6 months of age (Halasa 2022a; Halasa 2022b). When patients received the second or third dose of a monovalent mRNA vaccine during the second or third trimesters of pregnancy, the risk of the infant testing positive for COVID-19 infection was decreased within the first 4 months of life (Carlsen 2022). The optimal time of maternal vaccination for neonatal protection requires additional study (Fu 2022).

There was no increased risk of congenital fetal anomalies (identified via ultrasonography) based on data collected from 1,149 pregnant patients vaccinated within 30 days prior to conception until 14 weeks' gestation when compared to nonvaccinated pregnant patients (n=534) or pregnant patients vaccinated outside of this time period (n=1,473) (ACOG 2022; Ruderman 2022). Meta-analyses, one which included data from the V-safe Surveillance System and pregnancy registry and the Vaccine Adverse Event Reporting System (VAERS), found the rates of small for gestational age, stillbirth, preterm birth, miscarriage, and congenital anomalies to be similar following COVID-19 vaccination when compared to the general population (Ma 2022; Rawal 2022). The rates of gestational diabetes, gestational hypertension, preeclampsia, or eclampsia following COVID-19 vaccination are also within the known background rate (ACOG 2022; Ma 2022; Rawal 2022).

The immune response generated by the COVID-19 (mRNA) vaccine in pregnant patients is comparable to the immune response in patients who are not pregnant (ACOG 2022). Meta-analyses of available studies have found the antibody response in pregnant patients provided by vaccination to be higher than that following natural infection (Fu 2022; Rawal 2022). The highest antibody levels are found following a full vaccination series plus a booster dose (Rawal 2022). The rates of injection-site pain, injection-site soreness, and fatigue occurred at rates similar to nonpregnant patients and occurred more frequently after the second dose in both pregnant and nonpregnant patients (Fu 2022; Rawal 2022). Using data from the VAERS, reports of acute adverse events requiring medical attention following vaccination during pregnancy are uncommon (DeSilva 2022). A large observational cohort study evaluating the COVID-19 (mRNA) vaccine found the incidence of significant adverse health events to be lower in vaccinated pregnant patients compared to age-matched unvaccinated pregnant persons (Sadarangani 2022). COVID-19 vaccination effectively prevents COVID-19 infection and hospitalization in pregnant patients (Ma 2022; Rawal 2022). If severe infection and hospitalization occur, pregnant patients who are vaccinated are significantly less likely to require ICU admission, intubation, or die (de Freitas Paganoti 2022). Based on available data, mRNA vaccines are likely to have the same safety and efficacy in pregnant and nonpregnant patients (ACOG 2022).

The risk of severe illness from COVID-19 infection is increased in symptomatic pregnant patients compared to nonpregnant patients. Pregnant and recently pregnant patients with moderate or severe infection are at increased risk of complications such as hypertensive disorders of pregnancy, postpartum hemorrhage, or other infections compared to pregnant patients without COVID-19. Pregnant patients with symptoms may require ICU admission, mechanical ventilation, or ventilatory support (ECMO) compared to symptomatic nonpregnant patients. Other adverse pregnancy outcomes include preterm birth and stillbirth. The risk of coagulopathy, cesarean delivery, and maternal death may be increased; neonates have an increased risk for NICU admission. Maternal age and comorbidities such as diabetes, hypertension, lung disease, and obesity may also increase the risk of severe illness in pregnant and recently pregnant patients (ACOG FAQ 2022; NIH 2022).

Due to the risk of severe illness, pregnancy complications, and death from COVID-19 infection during pregnancy, vaccination with an appropriate vaccine is strongly recommended. A COVID-19 vaccine is recommended for all pregnant patients who otherwise meet the criteria for vaccination, including those previously diagnosed with COVID-19 infection (ACOG 2022; CDC 2022d). Monovalent mRNA COVID-19 vaccines are recommended for the primary series in eligible pregnant patients who do not otherwise have contraindications to the vaccine. Bivalent mRNA COVID-19 vaccines are recommended for booster doses (ACOG 2022; CDC 2022d). Infants of mothers who were vaccinated during pregnancy or had COVID-19 infection during pregnancy should be vaccinated according to recommended schedules (CDC 2022d).

Vaccination of pregnant patients may be done in any setting authorized to administer the vaccine. The COVID-19 vaccine may be administered in any trimester and should be given as soon as possible to maximize maternal health. COVID-19 vaccines may be administered simultaneously with other vaccines routinely administered during pregnancy. Vaccination status should be documented for all pregnant patients; for patients who do not receive the COVID-19 vaccine, the discussion should be documented in the medical record and vaccination offered again at subsequent visits (ACOG 2022).

Rho(D) immune globulin is not expected to interfere with an immune response to the COVID-19 vaccine. Treatment should not be withheld in patients planning to be vaccinated or who recently received the COVID-19 vaccine (ACOG 2022).

Information related to COVID-19 vaccines continues to emerge; refer to current guidelines for vaccinating pregnant patients.

Data collection to monitor maternal and infant outcomes following exposure to COVID-19 vaccines during pregnancy is ongoing:

- Health care providers are encouraged to enroll patients exposed to the Moderna COVID-19 Vaccine during pregnancy in the Moderna Pregnancy Registry (1-866-663-3762).

- All patients who receive a COVID-19 vaccine are encouraged to enroll in the CDC V-SAFE monitoring program (https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/vsafe.html) (ACOG 2022).

- Health care providers are encouraged to enroll pregnant patients exposed to COVID-19 vaccines in the Organization of Teratology Information Specialists (OTIS) pregnancy registry (1-877-311-8972; https://mothertobaby.org/join-study/).

Monitoring Parameters

Observe for hypersensitivity and syncope for 15 minutes following administration (ACIP [Kroger 2022]; CDC 2022c). Observe patients for 30 minutes after vaccination in those patients with the following: a history of nonsevere, immediate (within 4 hours) allergic reaction after receipt of a COVID-19 vaccine; a history of anaphylaxis following receipt of a non–COVID-19 vaccine or injectable therapy, or an allergy-related contraindication to a different type of COVID-19 vaccine (CDC 2022c). If seizure-like activity associated with syncope occurs, maintain patient in supine or Trendelenburg position to reestablish adequate cerebral perfusion.

Antibody testing to assess for SARS-CoV-2 immunity before or following vaccination is not currently recommended (CDC 2022c).

Mechanism of Action

Promotes active immunization against COVID-19 caused by SARS-CoV-2 virus. The modified messenger RNA (mRNA) in the vaccine is formulated in lipid particles that enable delivery of the RNA into host cells to allow expression of the SARS-CoV-2 spike (S) antigen. The vaccine elicits both neutralizing antibody and cellular immune responses to the S antigen, which protects against COVID-19 disease.

Pharmacokinetics (Adult data unless noted)

Onset of action:

Moderna vaccine: Vaccine efficacy assessment was based on disease cases occurring 14 days or more after dose 2 (Baden 2020). Virus-neutralizing antibody activity was detected in all patients by day 15 following the second dose (Jackson 2020).

Pfizer-BioNTech vaccine: Vaccine efficacy assessment was based on disease cases occurring 7 days or more after dose 2 (Polack 2020). Virus-neutralizing antibody activity peaked 7 to 14 days following the second dose (Walsh 2020).

Pricing: US

Suspension (Comirnaty Intramuscular)

30 mcg/0.3 ml (per mL): $0.00

Suspension (Spikevax COVID-19 Vaccine Intramuscular)

100 mcg/0.5 mL (per mL): $0.00

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

  1. Aharon D, Lederman M, Ghofranian A, et al. In vitro fertilization and early pregnancy outcomes after coronavirus disease 2019 (COVID-19) vaccination. Obstet Gynecol. Published online January 25, 2022. doi:10.1097/AOG.0000000000004713 [PubMed 35080199]
  2. American Academy of Pediatrics (AAP) Committee on Infectious Diseases. COVID-19 vaccines in infants, children, and adolescents. Pediatrics. Published online June 18, 2022. doi:10.1542/peds.2022-058700. https://publications.aap.org/pediatrics/article/doi/10.1542/peds.2022-058700/188297/COVID-19-Vaccines-in-Infants-Children-and [PubMed 35716376]
  3. American College of Obstetricians and Gynecologists (ACOG). COVID-19 vaccination considerations for obstetric–gynecologic care. https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2020/12/vaccinating-pregnant-and-lactating-patients-against-covid-19. Updated November 16, 2022. Accessed November 28, 2022.
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