Consumer medicine information

COVID-19 Vaccine AstraZeneca

COVID-19 (ChAdOx1-S) vaccine

BRAND INFORMATION

Brand name

COVID-19 Vaccine AstraZeneca

Active ingredient

COVID-19 (ChAdOx1-S) vaccine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using COVID-19 Vaccine AstraZeneca.

1. Why am I being given COVID-19 Vaccine AstraZeneca?

COVID-19 Vaccine AstraZeneca contains the active ingredient ChAdOx1-S. This vaccine is used to protect people aged 18 years and older against COVID-19.

COVID-19 is caused by a virus called coronavirus (SARSCoV-2).

COVID-19 Vaccine AstraZeneca stimulates the body’s natural defences (immune system). It causes the body to produce its own protection (antibodies) against the virus. This will help to protect you against COVID-19 in the future. None of the ingredients in this vaccine can cause COVID-19.

2. What should I know before I am given this COVID-19 vaccine

Warnings

You should not receive COVID-19 Vaccine AstraZeneca if:

  • you are allergic to this vaccine or any of the ingredients listed at the end of this leaflet.
  • Always check the ingredients to make sure you can use this vaccine.

Check with your healthcare provider before vaccination if:

  • You have ever had a severe allergic reaction (anaphylaxis) after any other vaccine injection;
  • Your immune system does not work properly (immunodeficiency) or are taking medicines that weaken the immune system (such as high-dose corticosteroids, immunosuppressants or cancer medicines);
  • You currently have a severe infection with a high temperature (over 38°C);
  • You have a problem with bleeding or bruising, or if you are taking a blood thinning medicine (anticoagulant);
  • You have any other medical conditions
  • You take any medicines for any other condition including any recent or planned vaccines

After vaccination you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your healthcare provider if you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby. There are limited data on the use of COVID-19 Vaccine AstraZeneca in pregnant or breastfeeding women. Your healthcare provider will discuss with you whether you can be given the vaccine.

Children and adolescents

No data are currently available on the use of COVID-19 Vaccine AstraZeneca in children and adolescents younger than 18 years of age.

3. What if I am taking, have recently taken or might take other medicines or vaccines?

Tell your healthcare provider if you are taking, have recently taken, or might take, any other vaccines or medicines including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Medicines (including other vaccines) that may impact whether you should be given this vaccine or not include the following (see also Section 2 above):

  • medicines that weaken the immune system (such as high-dose corticosteroids, immunosuppressants or cancer medicines);
  • blood thinning medicines (anticoagulant)
  • any other vaccine including any other COVID-19 vaccines

Check with your healthcare provider if you are not sure about what vaccines, medicines, vitamins or supplements you are taking or have recently taken and if these may affect this COVID-19 Vaccine.

4. How I am given this COVID-19 Vaccine?

How COVID-19 Vaccine AstraZeneca is given

COVID-19 Vaccine AstraZeneca will be given to you by a healthcare provider. It is injected into a muscle (usually in the upper arm).

You will receive 2 (0.5 mL per dose) injections. You will be told when you need to return for your second injection of COVID-19 Vaccine AstraZeneca.

The second injection can be given between 4 and 12 weeks after the first injection.

When COVID-19 Vaccine AstraZeneca is given for the first injection, COVID-19 Vaccine AstraZeneca (and not another vaccine against COVID-19) should be given for the second injection to complete vaccination course.

If you forget to get your second injection

If you forget to go back at the scheduled time, ask your healthcare provider for advice. It is important that you return for your second injection of COVID-19 Vaccine AstraZeneca. If you miss a scheduled second injection you may not achieve maximum protection.

If you use too much COVID-19 Vaccine AstraZeneca

As COVID-19 Vaccine AstraZeneca is given under the close supervision of a healthcare provider it is unlikely that you will be given too much.

If you are concerned that you have been given too much COVID-19 Vaccine AstraZeneca, tell your healthcare provider immediately.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know about being given this COVID-19 Vaccine?

As with any vaccine, COVID-19 Vaccine AstraZeneca may not protect everyone who is vaccinated from COVID-19. It is not yet known how long people who receive the vaccine will be protected for.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how this vaccine affects you.

COVID-19 Vaccine AstraZeneca has no known effect on the ability to drive and use machines. However, side effects listed in section 6 may impact your ability to drive and use machines. If you feel unwell, do not drive or use machines.

Looking after your vaccine

Your healthcare provider is responsible for storing this vaccine and disposing of any unused product correctly.

6. Are there any side effects?

All vaccines can have side effects. If you do experience any side effects, most of them are mild to moderate in nature and resolve within a few days. However, some side effects may need medical attention.

See the information below and, if you need to, ask your healthcare provider if you have any further questions about side effects.

Less serious side effects

Serious side effects

Tell your healthcare provider if you notice anything else that may be making you feel unwell. Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/ reporting-problems and include the vaccine name (COVID-19 Vaccine AstraZeneca) and batch/lot number if available. By reporting side effects, you can help provide more information on the safety of this vaccine.

7. Product details

This vaccine is only available with a doctor's prescription.

What COVID-19 Vaccine AstraZeneca contains

* Recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS-CoV-2 Spike glycoprotein. The vaccine is manufactured using material originally sourced from a human embryo (Human Embryo Kidney cells: HEK293).

Do not take this vaccine if you are allergic to any of these ingredients.

This product contains genetically modified organisms (GMOs).

COVID-19 Vaccine AstraZeneca does not contain any preservatives and the vial stopper is not made with natural rubber latex.

What this vaccine looks like

COVID-19 Vaccine AstraZeneca is approved^ for the following multidose vial packs (Aust R 349072):

  • 4mL (8 dose) vial in packs of 10 vials
  • 5mL (10 dose) vial in packs of 10 vials.

^not all pack sizes may be available in Australia

Sponsor

AstraZeneca Pty Ltd
ABN 54 009 682 311
66 Talavera Road
MACQUARIE PARK NSW 2113

For COVID-19 Vaccine AstraZeneca enquiries contact1800 343 949

This leaflet was prepared on 25 February 2021.

© AstraZeneca, 2021

Doc ID-004490139 v4

Published by MIMS April 2021

BRAND INFORMATION

Brand name

COVID-19 Vaccine AstraZeneca

Active ingredient

COVID-19 (ChAdOx1-S) vaccine

Schedule

S4

 

1 Name of Medicine

ChAdOx1-S.

2 Qualitative and Quantitative Composition

One dose (0.5 mL) contains 5x1010 viral particles (vp) of ChAdOx1-Sa, b, c.
a Recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS-CoV-2 Spike (S) glycoprotein (GP).
b The vaccine is manufactured using material originally sourced from a human embryo (Human Embryonic Kidney cells: HEK293).
c Corresponding to not less than 2.5 x 108 infectious units (Inf.U).
There are two multi-dose vial presentations:
8 dose: 4x1011 vp of ChAdOx1-S in 4 mL.
10 dose: 5x1011 vp of ChAdOx1-S in 5 mL.
This product contains genetically modified organisms (GMOs).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Solution for injection.
Clear to slightly opaque, colourless to slightly brown, particle free with a pH of 6.1 - 7.1.

4 Clinical Particulars

4.1 Therapeutic Indications

COVID-19 Vaccine AstraZeneca has provisional approval for the indication:
Active immunisation of individuals ≥ 18 years old for the prevention of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2.
The use of this vaccine should be in accordance with official recommendations.
The decision has been made on the basis of short term efficacy and safety data. Continued approval is dependent upon the evidence of longer-term efficacy and safety from ongoing clinical trials and post-market assessment.

4.2 Dose and Method of Administration

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 Pharmacodynamic Properties).
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 Special Warnings and Precautions for Use).

Special patient populations.

Use in the elderly.

No dosage adjustment is required in elderly individuals ≥ 65 years of age (see Section 4.4 Special Warnings and Precautions for Use).

Paediatric use.

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.

Method of administration.

COVID-19 Vaccine AstraZeneca is for intramuscular (IM) injection only, preferably in the deltoid muscle.
To facilitate the traceability of the vaccine, the name and the batch number of the administered product should be clearly recorded for each recipient.
COVID-19 Vaccine AstraZeneca is a colourless to slightly brown, clear to slightly opaque solution. The vaccine should be inspected visually for particulate matter and discolouration prior to administration. Discard the vial if the solution is discoloured or visible particles are observed. Do not shake.
Using an aseptic technique, each vaccine dose of 0.5 mL is withdrawn into a syringe for injection to be administered intramuscularly. Use a separate sterile needle and syringe for each individual.
Each vial contains at least the number of doses stated. It is normal for liquid to remain in the vial after withdrawing the final dose. When low dead volume syringes and/or needles are used, the amount remaining in the vial may be sufficient for an additional dose. Care should be taken to ensure a full 0.5 mL dose is administered. Where a full 0.5 mL dose cannot be extracted, the remaining volume should be discarded. Do not pool excess vaccine from multiple vials.
The vaccine does not contain any preservative. After first opening, use the vial within:
6 hours when stored at room temperature (up to 30°C), or
48 hours when stored in a refrigerator (2°C to 8°C).
The vial can be re-refrigerated, but after first opening the cumulative storage time at room temperature must not exceed 6 hours, and the total cumulative storage time must not exceed 48 hours. After this time, the vial must be discarded.
There is limited information available in relation to the storage of the vaccine in syringes. For practical reasons, if the contents of the vial are to be used within a short period of time, drawing up the content in multiple syringes at once may be considered. Vaccine in syringes may be kept for up to 6 hours when stored at room temperature (up to 30°C). However, ensure that the cumulative storage time at room temperature from the first vial puncture to last dose administration does not exceed 6 hours. After this time, the syringe must be discarded. For more details in relation to administration, please refer to Department of Health Guidance Documents.
The vials, needles, syringes should be disposed of in the clinical waste bin (see Section 6.6 Special Precautions for Disposal).

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed, see Section 6.1 List of Excipients.
Patients who have experienced major venous and/or arterial thrombosis in combination with thrombocytopenia following vaccination with any COVID-19 vaccine.
Individuals who have previously experienced episodes of capillary leak syndrome (also see Section 4.4 Special Warnings and Precautions for Use).

4.4 Special Warnings and Precautions for Use

As with any vaccine, vaccination with COVID-19 Vaccine AstraZeneca may not protect all vaccine recipients. Vaccination does not mitigate the need to follow other official recommendations to prevent the spread of COVID-19.

Hypersensitivity including anaphylaxis.

Hypersensitivity reactions including anaphylaxis and angioedema have occurred following administration of COVID-19 Vaccine AstraZeneca.
Appropriate medical treatment and supervision should always be readily available in case of an anaphylactic event following the administration of the vaccine.
A second dose of the vaccine should not be given to those who have experienced a severe hypersensitivity reaction to the first dose of COVID-19 Vaccine AstraZeneca.

Concurrent illness.

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.

Thrombosis and thrombocytopenia.

A very rare and serious combination of thrombosis and thrombocytopenia including thrombosis with thrombocytopenia syndrome (TTS), in some cases accompanied by bleeding, has been observed following vaccination with COVID-19 Vaccine AstraZeneca during post-marketing use. This includes cases presenting as venous thrombosis, including unusual sites such as cerebral venous sinus thrombosis, splanchnic vein thrombosis, as well as arterial thrombosis, concomitant with thrombocytopenia. The majority of the events occurred within the first 21 days following vaccination but have also been reported after this period. Some events had a fatal outcome.
Whilst specific risk factors for thromboembolism in combination with thrombocytopenia have not been identified, cases have occurred in patients with a previous history of thrombosis, as well as in patients with autoimmune disorders, including immune thrombocytopenia. The benefits and risks of vaccination should be considered in these patients. Cases have also occurred in patients without other risk factors for thrombosis and thrombocytopenia. As a precautionary measure, administration of the COVID-19 Vaccine AstraZeneca in patients with a history of cerebral venous sinus thrombosis with thrombocytopenia or heparin induced thrombocytopenia (HIT) should only be considered when the benefit outweighs any potential risks.
Healthcare professionals should be alert to the signs and symptoms of thrombosis and thrombocytopenia as well as coagulopathies. Vaccinated individuals should be instructed to seek immediate medical attention if they develop symptoms such as a severe or persistent headache, blurred vision, confusion, seizures, shortness of breath, chest pain, leg swelling, leg pain, persistent abdominal pain or unusual skin bruising and/or petechia a few days after vaccination.
Individuals diagnosed with thrombocytopenia within 21 days of vaccination with COVID-19 Vaccine AstraZeneca, should be actively investigated for signs of thrombosis. Similarly, individuals who present with thrombosis within 21 days of vaccination should be evaluated for thrombocytopenia.
Since medical management of a post-vaccine thrombosis with thrombocytopenia may be different from medical management of other thromboses, if a patient presents with thrombosis and/or thrombocytopenia after receiving a vaccine, healthcare professionals should consult applicable guidance and seek advice from a specialist haematologist to diagnose and treat this condition.

Risk of bleeding with intramuscular administration.

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.

Capillary leak syndrome.

Very rare cases of capillary leak syndrome (CLS) have been reported in the first days after vaccination with COVID-19 Vaccine AstraZeneca. A history of CLS was apparent in some of these cases. Fatal outcome has been reported. CLS is a rare disorder characterised by acute episodes of oedema mainly affecting the limbs, hypotension, haemoconcentration and hypoalbuminaemia. Patients with an acute episode of CLS following vaccination require prompt recognition and treatment. Intensive support therapy is usually warranted. Individuals with a known history of CLS should not be vaccinated with this vaccine (see Section 4.3 Contraindications).

Neurological events.

Very rare events of demyelinating disorders have been reported following vaccination with COVID-19 Vaccine AstraZeneca. A causal relationship has not been established.
As with other vaccines, the benefits and potential risks of vaccinating individuals with COVID-19 Vaccine AstraZeneca should be considered.

Immunocompromised individuals.

The immunogenicity, efficacy and safety of COVID-19 Vaccine AstraZeneca has not been assessed in immunocompromised individuals, including those receiving immunosuppressive therapy. The immunogenicity of vaccines may be lower in immunosuppressed patients.

Duration of protection.

The duration of protection has not yet been established. Studies are ongoing.

Interchangeability.

There are no safety, immunogenicity or efficacy data to support interchangeability of COVID-19 Vaccine AstraZeneca with other COVID-19 vaccines.

Use in the elderly.

There are currently limited data available for the efficacy and safety in individuals over 65 years of age. Further information will be collected from ongoing clinical studies and post-market monitoring. The decision to immunise an elderly patient should be decided on a case-by-case basis with consideration of age, co-morbidities, their environment, potential benefits and potential risks.

Use in individuals with significant co-morbidities.

There are currently limited data available for the efficacy and safety in individuals with significant co-morbidities. The decision to immunise an individual should be made on the basis of potential benefits over risks to that individual.

Paediatric use.

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.

Effects on laboratory tests.

Vaccination with COVID-19 Vaccine AstraZeneca leads to the development of antibodies to the SARS-CoV-2 S protein. This does not interfere with results from SARS-CoV-2 PCR testing.

4.5 Interactions with Other Medicines and Other Forms of Interactions

The safety, immunogenicity and efficacy of co-administration of COVID-19 Vaccine AstraZeneca with other vaccines have not been evaluated.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

It is unknown whether COVID-19 Vaccine AstraZeneca may impact fertility. No data are available.
(Category B2)
There are a limited amount of data from the use of COVID-19 Vaccine AstraZeneca in pregnant women, or women who became pregnant after receiving the vaccine. The data are insufficient to inform on vaccine associated risk.
Animal reproductive toxicity studies have not been completed.
As a precautionary measure, vaccination with COVID-19 Vaccine AstraZeneca is not recommended during pregnancy. Use of COVID-19 Vaccine AstraZeneca in pregnant women should be based on an assessment of whether the benefits of vaccination outweigh the potential risks.
There are no or limited data from the use of COVID-19 Vaccine AstraZeneca in lactating women.
A risk to breastfed newborns/infants cannot be excluded.

4.7 Effects on Ability to Drive and Use Machines

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 Adverse Effects (Undesirable Effects) may temporarily affect the ability to drive or use machines.

4.8 Adverse Effects (Undesirable Effects)

Clinical trials.

Overall summary of the safety profile.

The overall safety of COVID-19 Vaccine AstraZeneca is based on an interim analysis (data lock: 4 November 2020) 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.
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.
Following vaccination, recipients may experience multiple adverse reactions occurring at the same time (for example, myalgia/arthralgia, headache, chills, pyrexia and malaise). If a recipient reports persistent symptoms, alternative causes should be considered.
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).
Analgesic and/or anti-pyretic medicinal products (e.g. paracetamol-containing products) may be used to provide symptomatic relief from post-vaccination adverse reactions.
Safety in subgroups including the frail elderly, immunosuppressed, and pregnancy is unknown due to the low number of representative participants from these groups. Further information will become available from ongoing clinical studies and pharmacovigilance programmes.

Adverse drug 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). See Table 1.
Table 2 provides new ADR reported from the primary analysis of the pooled data from the four clinical trials (data lock: 7 December 2020; medium duration of follow-up of 4.5 months).

Post-marketing experience.

The following adverse reactions were not observed during clinical trials and have been spontaneously reported during worldwide post-authorisation use of COVID-19 Vaccine AstraZeneca.

Immune system disorders.

*Anaphylactic reaction.

Skin and subcutaneous tissue disorders.

*Angioedema.

Vascular disorders.

A very rare and serious combination of thrombosis and thrombocytopenia including thrombosis with thrombocytopenia syndrome (TTS), in some cases accompanied by bleeding, has been observed. This includes cases presenting as venous thrombosis, including unusual sites such as cerebral venous sinus thrombosis, splanchnic vein thrombosis, as well as arterial thrombosis, concomitant with thrombocytopenia (see Section 4.4 Special Warnings and Precautions for Use).
Capillary leak syndrome (see Section 4.4 Special Warnings and Precautions for Use).

Blood and lymphatic system disorders.

Thrombocytopenia (frequency very rare). The majority of reported events occurred in individuals aged 18-59 years old.
* The frequency of these adverse reactions is 'not known' (cannot be estimated from available data as the reports come from a population of unknown size).

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

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.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

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 neutralizing antibody and cellular immune responses.

Clinical trials.

This section will be updated as evidence emerges from ongoing clinical studies.

Interim analysis of pooled data from COV001, COV002, COV003, and COV005.

The efficacy and safety of COVID-19 Vaccine AstraZeneca has been evaluated based on an interim analysis (data lock: 4 November 2020) of pooled data from four on-going randomised, blinded, controlled trials: a Phase I/II Study, COV001 (NCT04324606), in healthy adults 18 to 55 years of age in the UK; a Phase II/III Study, COV002 (NCT04400838), in adults ≥ 18 years of age (including the elderly) in the UK; a Phase III Study, COV003 (ISRCTN89951424), in adults ≥ 18 years of age (including the elderly) in Brazil; and a Phase I/II study, COV005 (NCT04444674), in adults aged 18 to 65 years of age in South Africa. The studies excluded participants with severe and/or uncontrolled cardiovascular, gastrointestinal, liver, renal, endocrine/metabolic disease, and neurological illnesses; as well as those with severe 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. These studies are ongoing.
The interim efficacy analysis was based upon the results of COV002 and COV003, as at that time studies COV001 and COV005 had < 5 virologically confirmed COVID-19 cases per study and therefore did not meet the predefined statistical threshold to be included in the efficacy analysis.
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). Participants randomised to COVID-19 Vaccine AstraZeneca received either two standard doses [SD] (5 x 1010 vp per dose) or one low dose [LD] (2.2 x 1010 vp) followed by one SD (5 x 1010 vp), administered via IM injection.
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. In the pooled analysis, 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 mild comorbidity (defined as a BMI ≥ 30 kg/m2, cardiovascular disorder, respiratory disease or diabetes). At the time of interim analysis, the median follow up time post-dose 1 was 4.7 months and post-dose 2 was 2.2 months.
The primary efficacy endpoint was symptomatic COVID-19 infection, defined as objective fever (≥ 37.8°C), cough, shortness of breath, anosmia, or ageusia with virologically confirmed COVID-19 occurring ≥ 15 days post second dose, in participants without serological evidence of previous SARS-CoV-2 infection. 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 met the primary efficacy endpoint criteria. COVID-19 Vaccine AstraZeneca significantly decreased the incidence of COVID-19 compared to control (see Table 3).
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]).
An exploratory analyses of the impact of duration between doses and efficacy demonstrated greater efficacy with increasing duration between vaccine doses (Table 4). This was supported by the immunogenicity data (see Immunogenicity, Table 5).
COVID-19 Vaccine AstraZeneca reduced COVID-19 hospitalisation (WHO Severity grading ≥ 4).
In all participants who received SD as a first dose, as from 22 days post dose 1, there were 0 (0.0%, N = 6,307) cases of COVID-19 hospitalisation in participants who received COVID-19 Vaccine AstraZeneca (N = 6,307), as compared to 9 (0.14%, N = 6,297) reported for control.
Participants who had one or more mild 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 in the subgroup of participants ≥ 65 years old were too few to draw conclusions on efficacy. In this sub-population, efficacy has been inferred from immunogenicity data and efficacy demonstrated in the general population.
Limited data are available on the impact of emerging SARS-CoV-2 variants of concern on vaccine efficacy. Further information will be collected throughout the AZD1222 clinical development program by clinical and surveillance virology monitoring.

Immunogenicity.

Interim analysis of pooled data from COV001, COV002, COV003, and COV005.

An immunological correlate of protection has not been established; therefore, the level of immune response that provides protection against COVID-19 is unknown.
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 (see Table 5).
Generally similar trends were observed between analyses of neutralising antibodies and S-binding antibodies.
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 SD (97.8% [N = 136, 95% CI: 93.7; 99.5]) and the second SD (100.0% [N = 111, 95% CI: 96.7; NE]). The increase in S-binding antibodies was numerically lower for participants ≥ 65 years old (28 days after second SD: Geometric mean titre (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 SD: 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 numerically 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-γ enzyme-linked immunospot (ELISpot) assay are induced 14 days after a first dose of COVID-19 Vaccine AstraZeneca. These do not rise further after a second dose.

5.2 Pharmacokinetic Properties

Not applicable.

5.3 Preclinical Safety Data

Toxicity and local tolerance studies.

Non-clinical data obtained from toxicology and local tolerance studies with investigational vaccines utilising the same ChAdOx1 adenoviral vector vaccine technology as COVID-19 Vaccine AstraZeneca, concluded that the ChAdOx1 technology was well tolerated in mice and was not associated with any adverse effects.

Genotoxicity.

COVID-19 Vaccine AstraZeneca is a vaccine, as such, genotoxicity (mutagenicity) studies have not been conducted.

Carcinogenicity.

COVID-19 Vaccine AstraZeneca is a vaccine, as such, carcinogenicity studies have not been conducted.

6 Pharmaceutical Particulars

6.1 List of Excipients

COVID-19 Vaccine AstraZeneca contains the excipients histidine, histidine hydrochloride monohydrate, sodium chloride, magnesium chloride hexahydrate, disodium edetate (EDTA), sucrose, ethanol absolute, polysorbate 80 and water for injections.
COVID-19 Vaccine AstraZeneca does not contain any preservatives and the vial stopper is not made with natural rubber latex.

6.2 Incompatibilities

In the absence of compatibility studies, this vaccine must not be mixed with other medicinal products.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Unopened multidose vial.

Store at 2°C to 8°C (Refrigerate. Do not freeze).
Store in outer carton in order to protect from light.

Opened multidose vial.

After first opening, chemical and physical in-use stability has been demonstrated from the time of vial puncture to administration for no more than:
6 hours at room temperature up to 30°C, or
48 hours in a refrigerator (2°C to 8°C).
The vial can be re-refrigerated, but after first opening the cumulative storage time at room temperature must not exceed 6 hours, and the total cumulative storage time must not exceed 48 hours.
See Section 4.2 Dose and Method of Administration, Method of administration for details on the storage of the vaccine in syringes.

6.5 Nature and Contents of Container

4 mL of solution in a 8-dose vial (clear type I glass) with stopper (elastomeric with aluminium overseal). Packs of 10 multidose vials.
5 mL of solution in a 10-dose vial (clear type I glass) with stopper (elastomeric with aluminium overseal). Packs of 10 multidose vials.

6.6 Special Precautions for Disposal

COVID-19 Vaccine AstraZeneca contains genetically modified organisms (GMOs). Any unused vaccine or waste material should be disposed of in accordance with local requirements in a clinical waste bin. Spills should be disinfected with an appropriate antiviral disinfectant.

6.7 Physicochemical Properties

CAS number.

2420395-83-9.

7 Medicine Schedule (Poisons Standard)

Prescription only medicine (Schedule 4).

Summary Table of Changes