§ January 4th, 2021 § Filed under Genetically Modified Humans Comments Off on Information for Healthcare Professionals on COVID-19 Vaccine AstraZeneca – GOV.UK
Regulation 174 Information for UK healthcare professionals
This medicinal product has been given authorisation for temporary supply by the UK Department of Health and Social Care and the Medicines and Healthcare products Regulatory Agency. It does not have a marketing authorisation, but this temporary authorisation grants permission for the medicine to be used for active immunisation of individuals aged 18 years and older for the prevention of coronavirus disease 2019 (COVID-19).
As with any new medicine in the UK, this product will be closely monitored to allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions.
COVID-19 Vaccine AstraZeneca, solution for injection in multidose container
COVID-19 Vaccine (ChAdOx1 S [recombinant])
One dose (0.5 ml) contains:
COVID-19 Vaccine (ChAdOx1-S* recombinant) 5 1010 viral particles (vp)
*Recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS CoV 2 Spike (S) glycoprotein. Produced in genetically modified human embryonic kidney (HEK) 293 cells.
This product contains genetically modified organisms (GMOs).
For the full list of excipients, see section 6.1.
Solution for injection.
The solution is colourless to slightly brown, clear to slightly opaque and particle free with a pH of 6.6.
COVID-19 Vaccine AstraZeneca is indicated for active immunisation of individuals 18 years old for the prevention of coronavirus disease 2019 (COVID-19).
The use of COVID-19 Vaccine AstraZeneca should be in accordance with official guidance.
The COVID-19 Vaccine AstraZeneca vaccination course consists of two separate doses of 0.5 ml each. The second dose should be administered between 4 and 12 weeks after the first dose (see section 5.1).
It is recommended that individuals who receive a first dose of COVID-19 Vaccine AstraZeneca complete the vaccination course with COVID-19 Vaccine AstraZeneca (see section 4.4).
Efficacy and safety data are currently limited in individuals 65 years of age (see sections 4.8 and 5.1). No dosage adjustment is required.
The safety and efficacy of COVID-19 Vaccine AstraZeneca in children and adolescents (aged <18 years old) have not yet been established. No data are available.
COVID-19 Vaccine AstraZeneca is for intramuscular (IM) injection only, preferably in the deltoid muscle.
For instructions on administration, see section 6.6.
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of an anaphylactic event following the administration of the vaccine.
As with other vaccines, administration of COVID-19 Vaccine AstraZeneca should be postponed in individuals suffering from an acute severe febrile illness. However, the presence of a minor infection, such as cold, and/or low-grade fever should not delay vaccination.
As with other intramuscular injections, COVID-19 Vaccine AstraZeneca should be given with caution to individuals with thrombocytopenia, any coagulation disorder or to persons on anticoagulation therapy, because bleeding or bruising may occur following an intramuscular administration in these individuals.
It is not known whether individuals with impaired immune responsiveness, including individuals receiving immunosuppressant therapy, will elicit the same response as immunocompetent individuals to the vaccine regimen.
The duration of protection has not yet been established. As with any vaccine, vaccination with COVID-19 Vaccine AstraZeneca may not protect all vaccine recipients.
No data are available on the use of COVID-19 Vaccine AstraZeneca in persons that have previously received a full or partial vaccine series with another COVID-19 vaccine.
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, and is considered to be essentially sodium-free.
No interaction studies have been performed.
Concomitant administration of COVID-19Vaccine AstraZeneca with other vaccines has not been studied (see section 5.1).
There is a limited experience with the use of COVID-19 Vaccine AstraZeneca in pregnant women.
Preliminary animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryofetal development, parturition or post natal development; definitive animal studies have not been completed yet. The full relevance of animal studies to human risk with vaccines for COVID-19 remains to be established.
Administration of COVID-19 Vaccine AstraZeneca in pregnancy should only be considered when the potential benefits outweigh any potential risks for the mother and fetus.
It is unknown whether COVID-19 Vaccine AstraZeneca is excreted in human milk.
Preliminary animal studies do not indicate direct or indirect harmful effects with respect to fertility.
COVID-19 Vaccine AstraZeneca has no or negligible influence on the ability to drive and use machines. However, some of the adverse reactions mentioned under section 4.8 may temporarily affect the ability to drive or use machines.
The overall safety of COVID-19 Vaccine AstraZeneca is based on an interim analysis of pooled data from four clinical trials conducted in the United Kingdom, Brazil, and South Africa. At the time of analysis, 23,745 participants 18 years old had been randomised and received either COVID-19 Vaccine AstraZeneca or control. Out of these, 12,021 received at least one dose of COVID-19 Vaccine AstraZeneca. The median duration of follow-up in the COVID-19 Vaccine AstraZeneca group was 105 days post dose 1, and 62 days post dose 2.
Demographic characteristics were generally similar among participants who received COVID-19 Vaccine AstraZeneca and those who received control. Overall, among the participants who received COVID-19 Vaccine AstraZeneca, 90.3% were aged 18 to 64 years and 9.7% were 65 years of age or older. The majority of recipients were White (75.5%), 10.1% were Black and 3.5% were Asian; 55.8% were female and 44.2% male.
The most frequently reported adverse reactions were injection site tenderness (>60%); injection site pain, headache, fatigue (>50%); myalgia, malaise (>40%); pyrexia, chills (>30%); and arthralgia, nausea (>20%). The majority of adverse reactions were mild to moderate in severity and usually resolved within a few days of vaccination. By day 7 the incidence of subjects with at least one local or systemic reaction was 4% and 13% respectively. When compared with the first dose, adverse reactions reported after the second dose were milder and reported less frequently.
Adverse reactions were generally milder and reported less frequently in older adults (65 years old).
If required, analgesic and/or anti-pyretic medicinal products (e.g. paracetamol-containing products) may be used to provide symptomatic relief from post-vaccination adverse reactions.
Adverse drug reactions (ADRs) are organised by MedDRA System Organ Class (SOC). Within each SOC, preferred terms are arranged by decreasing frequency and then by decreasing seriousness. Frequencies of occurrence of adverse reactions are defined as: very common (1/10); common (1/100 to <1/10); uncommon (1/1,000 to <1/100); rare (1/10,000 to <1/1000); very rare (<1/10,000) and not known (cannot be estimated from available data).
MedDRA SOC: Blood and lymphatic system disorders
MedDRA SOC: Metabolism and nutrition disorders
MedDRA SOC: Nervous system disorders
MedDRA SOC: Nervous system disorders
MedDRA SOC: Gastrointestinal disorders
MedDRA SOC: Gastrointestinal disorders
MedDRA SOC: Gastrointestinal disorders
MedDRA SOC: Skin and subcutaneous tissue disorders
MedDRA SOC: Musculoskeletal and connective tissue disorders
MedDRA SOC: General disorders and administration site conditions
MedDRA SOC: General disorders and administration site conditions
(a) Unsolicited adverse reaction
(b) Injection site bruising includes injection site haematoma (uncommon, unsolicited adverse reaction)
(c) Pyrexia includes feverishness (very common) and fever 38C (common)
Very rare events of neuroinflammatory disorders have been reported following vaccination with COVID-19 Vaccine AstraZeneca. A causal relationship has not been established.
If you are concerned about an adverse event, it should be reported on a Yellow Card. Reporting forms and information can be found at the Coronavirus Yellow Card reporting site search for MHRA Yellow Card in the Google Play or Apple App Store and include the vaccine brand and batch/Lot number if available.
Alternatively, adverse events of concern in association with COVID-19 Vaccine AstraZeneca can be reported to AstraZeneca on 08000541028 or via the AstraZeneca website.
Please do not report the same adverse event(s) to both systems as all reports will be shared between AstraZeneca and the MHRA (in an anonymised form) and dual reporting will create unnecessary duplicates.
Experience of overdose is limited.
There is no specific treatment for an overdose with COVID-19 Vaccine AstraZeneca. In the event of an overdose, the individual should be monitored and provided with symptomatic treatment as appropriate.
Pharmacotherapeutic group: Vaccine, other viral vaccines, ATC code: J07BX03
COVID-19 Vaccine AstraZeneca is a monovalent vaccine composed of a single recombinant, replication-deficient chimpanzee adenovirus (ChAdOx1) vector encoding the S glycoprotein of SARS CoV 2. Following administration, the S glycoprotein of SARS CoV 2 is expressed locally stimulating neutralising antibody and cellular immune responses.
COVID-19 Vaccine AstraZeneca has been evaluated based on an interim analysis of pooled data from four on-going randomised, blinded, controlled trials: a Phase I/II Study, COV001, in healthy adults 18 to 55 years of age in the UK; a Phase II/III Study, COV002, in adults 18 years of age (including the elderly) in the UK; a Phase III Study, COV003, in adults 18 years of age (including the elderly) in Brazil; and a Phase I/II study, COV005, in adults aged 18 to 65 years of age in South Africa. The studies excluded participants with history of anaphylaxis or angioedema; participants with severe and/or uncontrolled cardiovascular, gastrointestinal, liver, renal, endocrine/metabolic disease, and neurological illnesses; as well as those with immunosuppression. In studies COV001 and COV002, licensed seasonal influenza and pneumococcal vaccinations were permitted (at least 7 days before or after their study vaccine).
All participants are planned to be followed for up to 12 months, for assessments of safety and efficacy against COVID-19 disease.
Based on the pre-defined criteria for interim efficacy analysis, COV002 and COV003 exceeded the threshold of 5 virologically confirmed COVID-19 cases per study and therefore contributed to the efficacy analysis; COV001 and COV005 were excluded.
In the pooled analysis for efficacy (COV002 and COV003), participants 18 years of age received two doses of COVID-19 Vaccine AstraZeneca (N=5,807) or control (meningococcal vaccine or saline) (N=5,829). Because of logistical constraints, the interval between dose 1 and dose 2 ranged from 4 to 26 weeks.
Baseline demographics were well balanced across COVID-19 Vaccine AstraZeneca and control treatment groups. Overall, among the participants who received COVID-19 Vaccine AstraZeneca, 94.1% of participants were 18 to 64 years old (with 5.9% aged 65 or older); 60.7% of subjects were female; 82.8% were White, 4.6% were Asian, and 4.4% were Black. A total of 2,070 (35.6%) participants had at least one pre-existing comorbidity (defined as a BMI 30 kg/m2, cardiovascular disorder, respiratory disease or diabetes). The median follow-up time post-dose 1 and post-dose 2 was 132 days and 63 days, respectively.
Final determination of COVID-19 cases were made by an adjudication committee, who also assigned disease severity according to the WHO clinical progression scale. A total of 131 participants had SARS CoV 2 virologically confirmed (by nucleic acid amplification tests) COVID-19 occurring 15 days post dose 2 with at least one COVID-19 symptom (objective fever (defined as 37.8C), cough, shortness of breath, anosmia, or ageusia) and were without evidence of previous SARS CoV 2 infection. COVID-19 Vaccine AstraZeneca significantly decreased the incidence of COVID-19 compared to control (see Table 2).
N = Number of subjects included in each group
n = Number of subjects having a confirmed event
CI = Confidence Interval
a 95.84% CI
b WHO severity grading 4
c WHO severity grading 6
d 95% CI
e Two cases of hospitalisation occurred on Days 1 and 10 post vaccination.
The level of protection gained from a single dose of COVID-19 Vaccine AstraZeneca was assessed in an exploratory analysis that included participants who had received one dose. Participants were censored from the analysis at the earliest time point of when they received a second dose or at 12 weeks post dose 1. In this population, vaccine efficacy from 22 days post dose 1 was 73.00% (95% CI: 48.79; 85.76 [COVID-19 Vaccine AstraZeneca 12/7,998 vs control 44/7,982]).
Exploratory analyses showed that increased immunogenicity was associated with a longer dose interval (see Immunogenicity Table 3). Efficacy is currently demonstrated with more certainty for dose intervals from 8 to 12 weeks. Data for intervals longer than 12 weeks are limited.
Participants who had one or more comorbidities had a vaccine efficacy of 73.43% [95% CI: 48.49; 86.29]; 11 (0.53%) vs 43 (2.02%) for COVID-19 Vaccine AstraZeneca (N=2,070) and control (N=2,113), respectively; which was similar to the vaccine efficacy observed in the overall population.
The number of COVID-19 cases (2) in 660 participants 65 years old were too few to draw conclusions on efficacy. However, in this subpopulation, immunogenicity data are available, see below.
Following vaccination with COVID-19 Vaccine AstraZeneca, in participants who were seronegative at baseline, seroconversion (as measured by a 4 fold increase from baseline in S binding antibodies) was demonstrated in 98% of participants at 28 days after the first dose and >99% at 28 days after the second. Higher S binding antibodies were observed with increasing dose interval (Table 3).
Generally similar trends were observed between analyses of neutralising antibodies and S binding antibodies. An immunological correlate of protection has not been established; therefore the level of immune response that provides protection against COVID-19 is unknown.
N = Number of subjects included in each group
GMT = Geometric mean titre
CI = Confidence interval
S = Spike
a Immune response evaluated using a multiplex immunoassay
b in individuals who received two recommended doses of vaccine.
The immune response observed in participants with one or more comorbidities was consistent with the overall population.
High seroconversion rates were observed in older adults (65 years) after the first (97.8%; N=136) and the second recommended dose (100.0%; N=111). The increase in S binding antibodies was lower for participants 65 years old (28 days after second dose: GMT=20,727.02 [N=116, 95% CI: 17,646.6; 24,345.2]) when compared to participants aged 18 64 years (28 days after second dose: GMT=30,695.30 [N=703, 95% CI: 28,496.2; 33,064.1]). The majority of participants 65 years old had a dose interval of <6 weeks, which may have contributed to the lower titres observed.
In participants with serological evidence of prior SARS CoV 2 infection at baseline (GMT=13,137.97 [N=29; 95% CI: 7,441.8; 23,194.1]), S antibody titres peaked 28 days after dose 1 (GMT=175,120.84 [N=28; 95% CI: 120,096.9; 255,354.8]).
Spike specific T cell responses as measured by IFN enzyme-linked immunospot (ELISpot) assay were induced after a first dose of COVID-19 Vaccine AstraZeneca. These did not rise further after a second dose.
Not applicable.
Non-clinical data reveal no special hazard for humans based on a conventional study of repeat dose toxicity. Animal studies into potential toxicity to reproduction and development have not yet been completed.
In the absence of compatibility studies, this vaccine must not be mixed with other medicinal products.
6 months
Use as soon as practically possible and within 6 hours. The vaccine may be stored between 2C and 25C during the in-use period.
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Information for Healthcare Professionals on COVID-19 Vaccine AstraZeneca - GOV.UK
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