COVID-19 Vaccines

(Updated January 24, 2021)

“More about COVID-19 vaccine operational considerations is available in USP’s COVID-19 Vaccine Handling Toolkit”

The chart below provides dosing, storage, adverse effects, and efficacy information for COVID-19 vaccines available or submitted for approval in the U.S. and/or Canada. The American Society of Health System Pharmacists has resources related to COVID-19 vaccines at https://www.ashp.org/COVID-19/Vaccines?loginreturnUrl=SSOCheckOnly. See end of chart for links to the fact sheets and product labelling.

Vaccine/Type/Status

Dosing

Storage/Stabilitye

Adverse Effects

Efficacyd

BNT162b2
(Pfizer-BioNTech)/mRNA

U.S.: Emergency Use Authorization

Canada: authorized by interim order.

Two 0.3 mL doses (0, 21 days) IM for ≥16 years of age18,19

Requires dilution with 1.8 mL of NS per vial.18,19

Special dry ice shipper: see footnote b for storage/handling

Ultracold freezer (-70oC±10oC): Mfr expiration date (undiluted)7

Thawing (required before diluting): may take two to three hours in the refrigerator,18,19 or 30 minutes at room temperature.19 Allow vial to reach room temperature before diluting.19 Do not refreeze.18,19

Refrigerator (2oC to 8oC): 5 days undiluted; 6 hours once diluted18,19

Room Temp (up to 25oC): 2 hours, undiluted, 6 hours once diluted, minimizing light exposure18,19

Most (>95%) adverse effects were mild to moderate.5

Local/injection site: mild to moderate pain in >65% of patients. Severe pain in <1%. Redness and swelling much less common.5

Systemic: fatigue (<60%), headache (≤52%), myalgia (≤37%), chills (≤35%), arthralgia (≤22%), fever ≥38oC (≤16%).5 Less common: diarrhea (<11%), vomiting.17 Any severe event after first dose ≤0.9%, and <2% after the second dose, except fatigue (3.8%) and headache (2%).5

Recipients can expect local adverse effects to resolve within one to two days.5 Systemic effects occur within the first one to two days, then resolve quickly.5 Participants were allowed to use analgesics/antipyretics.5

Appears better tolerated in older (>55 years of age) vs younger adults.5

Four cases of Bell’s palsy occurred in the vaccine group.17

Severe allergic reactions have been reported outside of clinical trials.19 Treatment for severe allergic reactions must be immediately available.19

54.2% effective between dose one and two, starting ~14 days after the first dose.17

95% effective (95% CI 90.3% to 97.6%) seven days after the second dose (n=43,448).5 NNV =71. 94.7% effective in adults ≥65 years of age.5

One severe COVID-19 case (nonhospitalized) in the vaccine group vs nine in the placebo group.17

Immunocompromised patients were excluded from trials.5

Approval in 16- and 17-year-olds was extrapolated from data in adults, but safety data (n=103) was reviewed.17,19 Pediatric studies ongoing.17

Immunogenicity (Phase I study):a produced neutralizing antibody response ≥natural infection in adults 18 to 85 years of age.1

mRNA-1273
(Moderna)/mRNA

U.S.: Emergency Use Authorization

Canada: authorized by interim order

Two 0.5 mL doses (0, 1 month) IM for ≥18 years of age21,22

Does not require dilution.21,22

Shipping and long-term storage: -25oC to -15oC for ≤6 months6

Refrigerator (2oC to 8oC): 30 days after thawing (prior to first use), within the 6-month shelf-life6,21,22

Room temperature: 12 hours (6 hours after the first dose is withdrawn, in vial or syringe)21,22,23

>90% of adverse effects mild to moderate.4

Local/injection site: mild to moderate pain in >80% of patients. Severe pain in 2.8% of patients after the first dose and in 4.1% after the second dose.4

Systemic: fatigue (68.5%), headache (63%), myalgia (59.6%), chills (43.4%), arthralgia (44.8%), fever (14.8%). Less common: nausea, vomiting, diarrhea. Severe adverse events after 2nd dose: fatigue (9.7%), myalgia (8.6%), arthralgia (5.1%), headache (5.5%).4

Median duration of adverse effects was two days (three for local effects after 2nd dose).4 Participants were allowed to use analgesics/antipyretics.4

Appears better tolerated in older (≥65 years of age) vs younger patients.4

Three cases of Bell’s palsy occurred in the vaccine group, one in the placebo group.4

92.1% effective between dose one and two, starting ~14 days after the first dose.4 Protection beyond 28 days after a single dose unknown.4

94.1% effective (95% CI 89.3% to 96.8%) 14 days after second dose (n=27,817).4 NNV = 80. No cases of severe COVID-19 in the vaccine group vs 11 in the placebo group.4

~25% of patients were ≥65 years of age, 9.4% had diabetes, ~6.5% had severe obesity, ~5% had significant heart disease, and ~5% had chronic lung disease.4

Immunogenicity (Phase I study):a produced neutralizing antibody response in adults comparable to natural infection, even in patients >70 years of age.2,13 Minimal Th2 response.2,13

AZD1222
(AstraZeneca)/Viral vector (non-replicating)

Phase III data published.

Canada: approval pending

Two doses IM (0, 28 days)3,8

Refrigerator (2oC to 8oC) for ≤6 months9

Meningococcal conjugate (MenACWY) vaccine used as comparator to maintain blinding in regard to adverse effects.3

Transverse myelitis occurred in three patients (one placebo). A possible vaccine relationship was not ruled out in one case.20

Local/injection site (Phase II/III study): pain and tenderness occurred most often.15

Systemic (Phase II/III study): occurred in most patients. Fatigue, headache, feverishness, and myalgia.15 Other systemic side effects were malaise and chills. Few patients had objectively documented fever.15

Better tolerated in older patients.15

Adverse effects peaked day after vaccination.3

Interim analysis of Phase I-III data:

  • Half dose,c followed by full dose (n=2,741): 90% (≥14 days after second dose)20
  • Two full doses (n=8,895): 62.1% (≥14 days after second dose)20
  • Combined results: 70.4% effective20
  • No cases of severe COVID-19 occurred in the COVID-19 vaccine group.20

Immunogenicity:a produced neutralizing antibody response in adults 18 to ≥70 years of age.15 Immunogenicity was not affected by acetaminophen.3

JNJ-78436735
Johnson & Johnson
/Viral vector (non-replicating)

Phase III underway14

Canada: approval pending

One IM dose8,10 (two-dose regimen also being studied)

2 years at -20oC and at least 3 months at 2oC to 8oC11

Phase I/IIa data:

  • Most adverse effects were mild to moderate.10
  • Local/injection site: occurred in 64% of patients 18 to 55 years of age, and in 41% of patients ≥65 years of age, most commonly injection site pain.10 None were severe.10
  • Systemic: occurred in 65% of patients 18 to 55 years of age, and in 46% of patients ≥65 years of age, most commonly fatigue, headache, and myalgia.10 Fever occurred in <20% of patients within two days of immunization but resolved within one to two days.10

Immunogenicity (Phase I/IIa study):a Producing neutralizing antibody response in 100% of patients.10 No or minimal Th2 response.10 Robust CD8+ response.10

  1. Neutralizing antibodies and Th1 CD4+ polarization are thought to be desirable. Neutralizing antibodies were associated with protection in non-human primate studies. Th1 polarization means that there is more of a response by Th1 CD4+ helper T cells than Th2 CD4+ helper T cells. Th2>Th1 response was associated with immunopathologic lung damage (“enhanced respiratory disease”) in preclinical SARS-CoV-1 and MERS vaccine studies.12
  2. Pfizer vaccine storage and dry ice safety handling resources at https://www.cvdvaccine-us.com/product-storage-and-dry-ice.
  3. Half-dose used due to manufacturing error.16
  4. Efficacy = Based on reduction of documented COVID-19 infections (COVID-19 symptoms plus confirmatory test for SARS-CoV2 test [polymerase chain reaction]).17,19,20 This means we do not know if the vaccine prevents asymptomatic infection.
  5. USP: Vaccines should be prepared in accordance with the manufacturer’s labeling. This means that USP engineering controls, risk levels, and beyond-use dating is not required. See https://www.usp.org/compounding.

Abbreviations: IM = intramuscular; NS = normal saline

Fact Sheets and Product Labeling

Prepared by the Editors of Therapeutic Research Center (370101); last modified January 8, 2021.

References

  1. Walsh EE, Frenck RW Jr, Falsey AR, et al. Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates. N Engl J Med 2020;383:2439-50.
  2. Jackson LA, Anderson EJ, Rouphael NG, et al. An mRNA vaccine against SARS-CoV-2: preliminary report. New Engl J Med 2020;383:1920-31.
  3. Folegatti PM, Ewer KJ, Aley PK, et al. Safety and immunogenicity of the ChAdOx1 nCOV-19 vaccine against SARS-CoV-2: a preliminary report of a phase1/2, single-blind, randomised controlled trial. Lancet 2020;396:467-78.
  4. FDA. FDA Briefing document. Moderna COVID-19 vaccine. Vaccines and Related Biological Products Advisory Committee Meeting. December 17, 2020. https://www.fda.gov/media/144434/download. (Accessed December 16, 2020).
  5. Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med 2020 Dec 10. doi: 10.1056/NEJMoa2034577.
  6. Moderna. Moderna announces longer shelf life for its COVID-19 vaccine candidate at refrigerated temperatures. November 16, 2020. https://investors.modernatx.com/node/10311/pdf. (Accessed November 26, 2020).
  7. CDC. Pfizer-BioNTech COVID-19 vaccine. Storing in an ultra-cold freezer. Last reviewed January 4, 2021. https://www.cdc.gov/vaccines/covid-19/info-by-product/pfizer/index.html. (Accessed January 24, 2021).
  8. CDC. ACIP COVID-19 vaccines work group. November 23, 2020. https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2020-11/COVID-01-Bell.pdf. (Accessed November 27, 2020).
  9. AstraZeneca press release. AZD1222 vaccine met primary efficacy endpoint in preventing COVID-19. https://www.astrazeneca.com/media-centre/press-releases/2020/azd1222hlr.html. (Accessed November 27, 2020).
  10. Sadoff J, Le Gars M, Shukarev G, et al. Interim results of a phase 1a-2 trial of Ad26.COV2.S. N Engl J Med 2021 Jan 13.. doi: 10.1056/NEJMoa2034201.
  11. Johnson & Johnson. Johnson& Johnson initiates pivotal global phase 3 clinical trial of Janssen’s COVID-19 vaccine candidate. September 23, 2020. https://www.jnj.com/johnson-johnson-initiates-pivotal-global-phase-3-clinical-trial-of-janssens-covid-19-vaccine-candidate. (Accessed November 28, 2020).
  12. FDA. Development and Licensure of Vaccines to Prevent COVID-19; Guidance for Industry. June 20, 2020. https://www.fda.gov/media/139638/download. (Accessed November 28, 2020).
  13. Anderson EJ, Rouphael NG, Widge AT, et al. Safety and immunogenicity of SARS-CoV-2 mRNA-1273 vaccine in older adults. N Engl J Med 2020;383:2427-38.
  14. Johnson & Johnson. Johnson & Johnson announces the initiation of a rolling submission for its single-dose Janssen COVID-19 vaccine candidate with Health Canada. December 1, 2020. https://www.jnj.com/our-company/johnson-johnson-announces-the-initiation-of-a-rolling-submission-for-its-single-dose-janssen-covid-19-vaccine-candidate-with-health-canada. (Accessed December 12, 2020).
  15. Ramasamy MN, Minassian AM, Ewer KJ, et al. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial. Lancet 2020;396:1979-93.
  16. Anon. AstraZeneca, Oxford acknowledge manufacturing error in potential COVID-19 vaccine. November 26, 2020. https://www.nasdaq.com/articles/astrazeneca-oxford-acknowledge-manufacturing-error-in-potential-covid-19-vaccine-2020-11. (Accessed December 1, 2020).
  17. FDA. FDA Briefing document. Pfizer-BioNTech COVID-19 vaccine. Vaccines and Related Biological Products Advisory Committee meeting. December 10, 2020. https://www.fda.gov/media/144245/download. (Accessed December 16, 2020).
  18. Product monograph for Pfizer-Biontech COVID-19 vaccine. Pfizer Canada. Kirkland, QC H9J 2M5. December 9, 2020.
  19. FDA. Fact sheet for health care providers emergency use authorization (EUA) of the Pfizer-Biontech COVID-19 vaccine to prevent coronavirus disease 2019 (COVID-19). January 2021. https://www.fda.gov/media/144413/download. (Accessed January 20, 2021).
  20. Voysey M, Costa Clemens SA, Madhi SA, et al. Safety and efficacy of the ChAdOx1CoV-19 vaccine (AZS1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet 2020 Dec 8. doi: 10.1016/S0140-6736(20)32661-1.
  21. FDA. Fact sheet for healthcare providers administering vaccine (vaccination providers). Emergency use authorization (EUA) of the Moderna COVID-19 vaccine to prevent coronavirus disease 2019 (COVID-19). December 2020. https://www.fda.gov/media/144637/download. (Accessed December 18, 2020).
  22. Product monograph for Moderna COVID-19 vaccine (Canada). Moderna Therapeutics. Cambridge, MA 02139. December 2020.
  23. Personal communication (written). P. Raper. Medical Information. Moderna. Cambridge, MA 02139. January 5, 2021.

Cite this document as follows: Clinical Resource, COVID-19 Vaccines. Pharmacist’s Letter/Prescriber’s Letter. January 2021.

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