Consumer medicine information

Vaxzevria

COVID-19 (ChAdOx1-S) vaccine

BRAND INFORMATION

Brand name

Vaxzevria

Active ingredient

COVID-19 (ChAdOx1-S) vaccine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Vaxzevria.

SUMMARY CMI

VAXZEVRIA®

Consumer Medicine Information (CMI) summary

This vaccine has provisional approval in Australia to protect people aged 18 years and older against COVID-19 disease. The approval has been granted on the basis of short-term efficacy and safety data. Evidence of longer term efficacy and safety from ongoing clinical trials and vaccination in the community continues to be gathered and assessed.

The full CMI on the next page has more details. If you are worried about using this vaccine, speak to your healthcare provider (e.g. doctor, nurse or pharmacist).

▼ This vaccine is new. Please report side effects. See the full CMI for further details.

1. Why am I being given VAXZEVRIA?

VAXZEVRIA contains the active ingredient ChAdOx1-S. This vaccine is used to protect people aged 18 years and older against COVID-19. For more information, see Section 1. Why am I being given VAXZEVRIA? in the full CMI.

2. What should I know before I am given VAXZEVRIA?

You should not receive VAXZEVRIA if you have ever had an allergic reaction to VAXZEVRIA or any of the ingredients listed at the end of the CMI, have had a major blood clot occurring at the same time as having low levels of platelets (thrombocytopenia) after receiving any COVID-19 vaccine or have had capillary leak syndrome (a condition causing fluid leakage from small blood vessels).

Talk to your healthcare provider if you have or have had any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

VAXZEVRIA should not be given to children under 18 years.

For more information, see Section 2. What should I know before I am given VAXZEVRIA? in the full CMI.

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

Medicines (including other vaccines) that may impact whether you should be given this vaccine or not are listed in Section 3. What if I am taking, have recently taken or might take other medicines or vaccines? in the full CMI.

4. How am I given VAXZEVRIA?

VAXZEVRIA will be given to you by a healthcare provider. It is injected into a muscle (usually in the upper arm). You will receive 2 injections with the second injection given 4-12 weeks after the first injection. You may receive a booster dose (third dose) at least 3 months after the second injection of the primary course with VAXZEVRIA or another approved COVID-19 vaccine. More instructions can be found in Section 4. How am I given VAXZEVRIA? in the full CMI.

5. What should I know about being given VAXZEVRIA?

General

As with any vaccine, VAXZEVRIA 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

VAXZEVRIA has no known effect on the ability to drive/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/use machines.

For more information, see Section 5. What should I know about being given VAXZEVRIA? in the full CMI.

6. Are there any side effects?

Most side effects are mild to moderate in nature and resolve within a few days. Fewer side effects were reported after the second dose. These include tenderness, pain, warmth, redness, itching or swelling where the injection is given; Generally feeling unwell or tired; Flu like symptoms such as fever/feeling feverish, sore throat, runny nose, cough and/or chills; Headache; Feeling/being sick or diarrhoea; Muscle pain/ache, joint pain, pain in legs or arms; ringing in the ears, inflammation of blood vessels in the skin, often with a rash and small red or purple spots.

Some very rare serious side effects, such as major blood clots in combination with low levels of blood platelets, very low levels of blood platelets with or without bleeding, capillary leak syndrome, inflammation of the nerves and/or spinal cord (or allergic reactions, may require urgent medical attention or hospitalisation.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

▼ This vaccine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. You can report side effects to your doctor or other healthcare provider, or directly at www.tga.gov.au/reporting-problems.



FULL CMI

VAXZEVRIA® (previously COVID-19 Vaccine AstraZeneca)

Active ingredient: ChAdOx1-S

This vaccine has provisional approval in Australia to protect people aged 18 years and older against COVID-19 disease. This approval has been granted on the basis of short term efficacy and safety data. Evidence of longer term efficacy and safety from ongoing clinical trials and vaccination in the community continues to be gathered and assessed.

Consumer Medicine Information (CMI)

This leaflet provides important information about VAXZEVRIA. You should also speak to your healthcare provider (e.g. doctor, nurse or pharmacist) if you would like further information or if you have any concerns or questions about using VAXZEVRIA.

Where to find information in this leaflet:

1. Why am I being given VAXZEVRIA?
2. What should I know before I am given VAXZEVRIA?
3. What if I am taking, have recently taken or might take other medicines or vaccines?
4. How am I given VAXZEVRIA?
5. What should I know about being given VAXZEVRIA?
6. Are there any side effects?
7. Product details

1. Why am I being given VAXZEVRIA?

VAXZEVRIA 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 (SARS-CoV-2).

VAXZEVRIA 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 VAXZEVRIA?

Warnings

You should not receive VAXZEVRIA 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.
  • Have had a major blood clot occurring at the same time as having low levels of platelets (thrombocytopenia) after receiving any COVID-19 vaccine.
  • Have had capillary leak syndrome (CLS; a condition causing fluid leakage from small blood vessels).

Check with your healthcare provider before vaccination if:

  • You have ever had a severe allergic reaction after any other vaccine injection or after you were given VAXZEVRIA in the past;
  • 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 ever had a blood clot in the past or if you have an autoimmune disorder (illness where the body's immune system attacks its own cells) including immune thrombocytopenia (ITP; previously known as idiopathic thrombocytopenic purpura);
  • You have ever had a serious medical condition (heparin induced thrombocytopenia; HIT) where your blood platelet levels became very low (thrombocytopenia) after taking heparin (a blood thinning medicine)
  • You have a problem with bleeding or bruising, or if you are taking a blood thinning medicine (anticoagulant);
  • You have ever had capillary leak syndrome (CLS; a condition causing fluid leakage from small blood vessels)
  • You have ever fainted or felt stressed (eg dizziness, increased heart rate, difficulty in breathing, sweating, tingling feeling and/or feeling anxious) when you have been given an injection including other vaccines.
  • You have any other medical conditions
  • You take any medicines for any other condition including any recent or planned vaccines

Blood disorders

Very rare cases of blood clots with low levels of blood platelets have been observed following vaccination with VAXZEVRIA. The majority of these cases occurred within the first 21 days following vaccination but have also been reported after this period. Some had a fatal outcome.

Blood clots, including clots in the brain, not associated with low levels of blood platelets have been observed following vaccination with VAXZEVRIA. However, it has not been determined whether these events were due to the vaccine. Some had a fatal outcome.

Very low levels of blood platelets (immune thrombocytopenia), that can be associated with bleeding, have been reported very rarely, usually within the first four weeks following vaccination with Vaxzevria.

Seek urgent medical attention if from a few days following vaccination you:

  • Experience a severe or persistent headache, blurred vision, confusion or seizures (fits)
  • Develop shortness of breath, chest pain, leg swelling, leg pain or persistent abdominal pain
  • Notice unexplained bleeding, unusual skin bruising or pinpoint round spots beyond the site of vaccination

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 VAXZEVRIA 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 VAXZEVRIA 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 VAXZEVRIA.

4. How am I given VAXZEVRIA?

How VAXZEVRIA is given

VAXZEVRIA will be given to you by a healthcare provider. It is injected into a muscle (usually in the upper arm).

Primary vaccination course

You will receive 2 (0.5 mL per dose) injections as part of the primary vaccination course. You will be told when you need to return for your second injection of VAXZEVRIA.

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

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

Booster dose

You may also receive a third booster injection of VAXZEVRIA. The booster injection may be given at least 3 months after the second injection of your primary vaccination course with VAXZEVRIA or another approved COVID-19 vaccine (eg mRNA vaccine).

If you forget to get your second injection or booster injection

If you forget to go back at the scheduled time for your second injection or your booster injection, ask your healthcare provider for advice. It is important that you return for your second injection and/or any recommended booster injections of VAXZEVRIA. If you miss a scheduled second or booster injections you may not achieve maximum protection.

If you use too much VAXZEVRIA

As VAXZEVRIA 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 VAXZEVRIA, 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 VAXZEVRIA?

As with any vaccine, VAXZEVRIA 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.

VAXZEVRIA 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. Fewer side effects were reported after the second dose However, some side effects may need medical attention.

After vaccination, you may have more than one side effect at the same time (for example, muscle pain/ache, joint pain, headaches, chills and generally feeling unwell).

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

Less serious side effectsWhat to do
  • Tenderness, pain, warmth, redness, itching or swelling where the injection is given
  • Generally feeling unwell
  • Feeling tired (fatigue)
  • Flu like symptoms such as fever/feeling feverish (high temperatures), sore throat, runny nose, cough and/or chills
  • Headache
  • Feeling sick (nausea), being sick (vomiting) or diarrhoea
  • Muscle pain/ache, joint pain, pain in legs or arms
  • ringing in the ears (tinnitus)
  • inflammation of blood vessels in the skin, often with a rash and small red or purple spots (cutaneous vasculitis)
Speak to your healthcare provider if you have any of these less serious side effects and they worry you.
Medicines containing paracetamol can be taken if you need relief from side effects such as pain and/or fever.

Serious side effects

Serious side effectsWhat to do
Low levels of blood platelets (with or without major blood clots or bleeding (thrombocytopenia or immune thrombocytopenia) have been observed very rarely.
Get medical attention immediately if from a few days following vaccination you get any of the following symptoms:
  • experience a severe or persistent headache, blurred vision, confusion or seizures (fits)
  • develop shortness of breath, chest pain, leg swelling, leg pain or persistent abdominal pain
  • notice unexplained bleeding, unusual skin bruising or pinpoint round spots beyond the site of vaccination
Tell your healthcare provider straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.
You may need urgent medical attention or hospitalisation.
Very rare cases of capillary leak syndrome (CLS) have been reported.
Get medical attention immediately if you get any of the following symptoms in the days following vaccination:
  • rapid swelling of the arms and legs,
  • sudden weight gain, and
  • feeling faint (low blood pressure)
Tell your healthcare provider straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.
You may need urgent medical attention or hospitalisation.
Very rare cases of Guillain-Barré syndrome (GBS) and Acute Disseminated Encephalomyelitis (ADEM) have been reported. GBS and ADEM are rare immune disorders that can cause inflammation in the brain and spinal cord that damages myelin - the protective covering of nerve fibres.
Get medical attention immediately if you get any of the following symptoms: Pain, numbness, paralysis, confusion, difficulty breathing, muscle weakness in the arms and legs, which may progress to the chest and face.
Very rare cases of transverse myelitis (inflammation of the spinal cord) have been reported.
Get medical attention immediately if you get any of the following symptoms: weakness in the arms or legs, sensory symptoms (such as tingling, numbness, pain or loss of pain sensation), localized or radiating back pain, bladder and bowel symptoms.		Tell your healthcare provider straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.
You may need urgent medical attention or hospitalisation.
All injectable vaccines have the potential for an allergic reaction after you are injected.
Some of the symptoms of an allergic reaction may include:
  • swelling of the face, lips, tongue, mouth, throat and/or other parts of the body
  • shortness of breath, wheezing or difficulty breathing
  • fainting, dizziness, feeling lightheaded (due to a drop in blood pressure)
  • changes in your heartbeat
  • rash, itching or hives on the skin
Tell your healthcare provider straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.
You may need urgent medical attention or hospitalisation.

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 (VAXZEVRIA) 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 VAXZEVRIA contains

Active ingredient
(main ingredient)		One dose (0.5 mL) contains:
ChAdOx1-S* 5 x 1010 viral particles (vp) [corresponding to not less than 2.5 x 108 infectious units (Inf.U)]
Other ingredients
(inactive ingredients)		histidine, histidine hydrochloride monohydrate, sodium chloride, magnesium chloride hexahydrate, disodium edetate, sucrose, ethanol absolute, polysorbate 80 and water for injections.

* 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).

VAXZEVRIA does not contain any preservatives and the vial stopper is not made with natural rubber latex.

What this vaccine looks like

VAXZEVRIA is approved for the following multidose vial packs (Aust R 349072):

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

Sponsor

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

For VAXZEVRIA enquiries contact 1800 343 949

This leaflet was prepared on 6 February 2023

Vaxzevria is a registered trade mark of the AstraZeneca group of companies.

© AstraZeneca, 2023

Doc ID-004490139 v21

Published by MIMS March 2023

BRAND INFORMATION

Brand name

Vaxzevria

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 5 x 1010 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: 4 x 1011 vp of ChAdOx1-S in 4 mL.
10 dose: 5 x 1011 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

Vaxzevria 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 Vaxzevria primary 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 Vaxzevria receive a second dose of Vaxzevria (see Section 4.4 Special Warnings and Precautions for Use).
A third (booster) dose of 0.5 mL may be given if clinically indicated with reference to official guidance regarding the use of a heterologous third dose (e.g. mRNA vaccine).
A third (booster) dose of Vaxzevria should be administered at least 3 months after a second dose of Vaxzevria.

Special patient populations.

Use in the elderly.

No dosage adjustment is required in elderly individuals ≥ 65 years of age (see Section 5.1 Pharmacodynamic Properties).

Paediatric use.

The safety and efficacy of Vaxzevria in children and adolescents (aged < 18 years old) have not yet been established. No data are available.

Method of administration.

Vaxzevria 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.
Vaxzevria 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 in 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 Vaxzevria 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 Vaxzevria.
Appropriate medical treatment and supervision should always be readily available in case of an anaphylactic event following the administration of the vaccine.
An additional dose of the vaccine should not be given to those who have experienced a severe hypersensitivity reaction to a previous dose of Vaxzevria.

Anxiety-related reactions.

Anxiety-related reactions, including vasovagal reactions (syncope (fainting)), hyperventilation or stress-related reactions may occur in association with vaccination as a psychogenic response to the needle injection or with the process of vaccination itself. It is important that precautions are in place to avoid injury from fainting.

Concurrent illness.

As with other vaccines, administration of Vaxzevria 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.

Coagulation disorders.

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 Vaxzevria 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. The reporting rates after the second dose are lower compared to after the first dose. Also see Section 4.3 Contraindications.
The incidence of TTS following a third dose of Vaxzevria has not yet been determined, including in people who have received a third dose of Vaxzevria following another type COVID-19 vaccine.
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 Vaxzevria 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.

Venous thromboembolic events without thrombocytopenia.

Venous thromboembolic events without accompanying thrombocytopenia, including events of cerebrovascular venous and sinus thrombosis (CVST) have been reported following vaccination with Vaxzevria. Although a causal relationship has not been established, these events can be fatal and may require different treatment approaches than TTS. Healthcare professionals should consult applicable guidance.

Thrombocytopenia.

Cases of thrombocytopenia, including immune thrombocytopenia (ITP), have been reported after receiving Vaxzevria, typically within the first four weeks after vaccination. Very rarely, these presented with very low platelet levels (< 20 x109 per L) and/or were associated with bleeding. Cases with fatal outcome have been reported.
Some of these cases occurred in individuals with a history of ITP or thrombocytopenia. If an individual has a history of a thrombocytopenic disorder, such as ITP, the risk of developing low platelet levels should be considered before administering the vaccine and platelet monitoring is recommended after vaccination.
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, spontaneous bleeding or unusual skin bruising and/or petechia a few days after vaccination.
Individuals diagnosed with thrombocytopenia within 21 days of vaccination with Vaxzevria, 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, Vaxzevria 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 Vaxzevria. 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.

Guillain-Barré Syndrome (GBS) has been reported very rarely following vaccination with Vaxzevria.
Transverse myelitis (TM) has been reported very rarely following vaccination with Vaxzevria. Healthcare professionals should be alert of TM signs and symptoms to ensure correct diagnosis, in order to initiate adequate supportive care and treatment, and to rule out other causes.
Very rare events of demyelinating disorders, including acute disseminated encephalomyelitis, have been reported following vaccination with Vaxzevria. A causal relationship has not been established. Healthcare professionals should be alert of signs and symptoms of demyelinating disorders to ensure correct diagnosis, in order to initiate adequate supportive care and treatment, and to rule out other causes.

Risk of very rare events after a booster dose.

The risk of very rare events (such as coagulation disorders including thrombosis with thrombocytopenia syndrome, CLS, GBS and TM) after a booster dose of Vaxzevria has not yet been characterised.

Immunocompromised individuals.

The immunogenicity, efficacy and safety of Vaxzevria 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.

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 Vaxzevria in children and adolescents (aged < 18 years old) have not yet been established. No data are available.

Effects on laboratory tests.

Vaccination with Vaxzevria 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 Vaxzevria with other vaccines have not been evaluated.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

In a combined fertility and developmental toxicity study, female mice were intramuscularly administered 3.71 x 1010 virus particles (> 1000 times the clinical dose of virus particles/kg) of Vaxzevria 13 days before mating and on gestation day 6. SARS COV-2 glycoprotein antibodies were present in maternal animals from prior to mating to the end of the study on gestational day 17.5 as well as in fetuses. There were no vaccine-related effects on female fertility and pregnancy rate. A biodistribution study conducted in mice did not show quantifiable distribution of virus particles to the gonads (testes, ovaries) following IM injection.
(Category B1)
There are a limited amount of data from the use of Vaxzevria in pregnant women, or women who became pregnant after receiving the vaccine. The data are insufficient to inform on vaccine associated risk.
Animal studies did not indicate harmful effects with respect to reproductive toxicity. In a combined fertility and developmental toxicity study, female mice were intramuscularly administered Vaxzevria before the start of mating (premating day 13) and gestation day 6 or twice during gestation (gestation days 6 and 15) with 3.71 x 1010 virus particles (> 1000 times the clinical dose on a virus particle/kg basis). There were no significant vaccine-related adverse effects on embryofetal development or parturition. In this study, vaccine elicited detectable anti-SARS-CoV-2 S-glycoprotein maternal antibodies were transferred to the fetuses and pups indicating placental transfer.
Use of Vaxzevria in pregnant women should only be considered when the potential benefits of vaccination outweigh the potential risks for the mother and fetus.
 There are limited data from the use of Vaxzevria in lactating women. It is unknown whether Vaxzevria is excreted in human milk. A risk to breastfed newborns/infants cannot be excluded.
In animal studies, lactational transfer of anti-SARS-CoV-2 S antibodies from maternal female mice to pups was observed. In a reproductive and development toxicity study, Vaxzevria did not induce maternal or developmental toxicity following two vaccine doses during gestation. In this study, vaccine elicited detectable anti-SARS-CoV-2 S-glycoprotein maternal antibodies were transferred to the fetuses and pups indicating lactational transfer.

4.7 Effects on Ability to Drive and Use Machines

Vaxzevria has no or negligible influence on the ability to drive and use machines. However, some of the adverse reactions mentioned under Section 4.8 Adverse Effects (Undesirable Effects) may temporarily affect the ability to drive or use machines.

4.8 Adverse Effects (Undesirable Effects)

Clinical trials.

Primary vaccination course.

Overall summary of the safety profile from the pivotal Oxford clinical trials.

The overall safety of Vaxzevria is based on an analysis (data lock: 7 December 2020) of pooled data from four clinical trials (COV001, COV002, COV003 and COV005) conducted in the United Kingdom, Brazil, and South Africa. At the time of analysis, 24,244 participants ≥ 18 years old had been randomised and received either Vaxzevria or control. Out of these, 12,282 received at least one dose of Vaxzevria, with a median duration of follow-up of 4.5 months.
Demographic characteristics were generally similar among participants who received Vaxzevria and those who received control. Overall, among the participants who received Vaxzevria, 89.8% were aged 18 to 64 years and 10.2% were 65 years of age or older. The majority of recipients were White (75.5%), 9.8% were Black and 3.7% 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.

Adverse drug reactions from the pivotal Oxford clinical trials.

See Table 1.
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).

Summary of the safety data from phase III clinical trial D8110C00001.

Additional safety of Vaxzevria was established in a randomised Phase III clinical trial conducted in the United States, Peru and Chile. At the time of the analysis, 32,379 participants ≥ 18 years old had received at least one dose, including 21,587 in the Vaxzevria group and 10,792 in the placebo group.
Demographic characteristics were generally similar among participants who received Vaxzevria and those who received placebo. Overall, among the participants who received Vaxzevria 77.6% were 18 to 64 years and 22.4% were ≥ 65 years of age. Seventy-nine percent (79%) of the participants were White, 8.3% were Black, 4.4% were Asian, 4.0% were American Indian or Alaska Native, 0.3% were Native Hawaiian or Other Pacific Islander, 2.4% were of multiple races and 1.7% were not reported or unknown; 44.4% were female and 55.6% male.
The safety profile observed in this Phase III clinical trial was consistent with pooled analysis of data from the United Kingdom, Brazil and South Africa (pivotal Oxford clinical trials - COV001, COV002, COV003 and COV005). Adverse reactions seen in this Phase 3 clinical trial were observed at similar frequencies as seen in the pooled analysis except the following: feverishness (pyrexia) (0.7%), arthralgia (1.1%), injection site warmth (< 0.1%) and injection site pruritus (0.2%). These adverse reactions were solicited adverse events in the COV001, COV002, COV003 and COV005 studies whereas the D8110C00001 clinical trial did not include these as solicited symptoms to report.
Booster dose (third dose). The safety profile observed in individuals who received a booster dose (third dose) was consistent with the known safety profile of Vaxzevria. No new safety concerns, as compared with adverse reactions reported for the primary vaccination course with Vaxzevria, have been identified in individuals receiving a booster dose of Vaxzevria.

Booster dose (third dose) following primary vaccination with Vaxzevria.

In Study D7220C00001, 367 participants who had previously received a 2-dose primary vaccination course with Vaxzevria received a single booster dose (third dose) of Vaxzevria. Median time between the second dose and the booster dose was 8.6 months (263 days).
The most frequently reported adverse reactions in previously Vaxzevria vaccinated participants were injection site tenderness (54%), fatigue (43%), injection site pain (38%), headache (34%), myalgia (23%), and malaise (22%). The majority of these adverse reactions were mild to moderate in severity and usually resolved within a few days of vaccination.

Booster dose (third dose) following primary vaccination with an approved COVID-19 mRNA vaccine.

In Study D7220C00001, 322 participants who had previously received a 2-dose primary vaccination course with an approved COVID-19 mRNA vaccine received a single booster dose (third dose) of Vaxzevria. Median time between the second dose and the booster dose was 3.9 months (119 days).
The most frequently reported adverse reactions in previously mRNA vaccinated participants were injection site tenderness (71%), fatigue (58%), headache (52%), injection site pain (50%), myalgia (47%), malaise (42%), chills (31%), and nausea (21%). The majority of these adverse reactions were mild to moderate in severity and usually resolved within a few days of vaccination.
In the COV001 study, the observed reactogenicity in participants who received a booster dose (third dose) following a 2 dose primary vaccination course was consistent with the known reactogenicity profile of Vaxzevria, and was lower after the third dose compared with after the first dose.
No new safety concerns, as compared with adverse reactions reported for the primary vaccination course with Vaxzevria, have been identified in individuals receiving a booster dose of Vaxzevria.

Post-marketing experience.

The following adverse reactions were not observed during clinical trials and have been spontaneously reported during worldwide post-authorisation use of Vaxzevria. See Table 2.

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 Vaxzevria. 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.

Vaxzevria 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.
Efficacy of two doses of Vaxzevria.

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

The efficacy and safety of Vaxzevria has been evaluated based on the primary analysis (data lock: 7 December 2020) of pooled data from four pivotal on-going randomised, blinded, controlled Oxford clinical 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.
In the pooled analysis for efficacy, participants ≥ 18 years of age received two doses of Vaxzevria (N = 8,597) or control (meningococcal vaccine or saline) (N = 8,581). Participants randomised to Vaxzevria 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 3 to 28 weeks, with 77.0% of participants receiving their two doses within the interval of 4 to 12 weeks.
Baseline demographics were well balanced across Vaxzevria and control treatment groups. In the pooled analysis, among the participants who received Vaxzevria, 91.8% of participants were 18 to 64 years old (with 8.2% aged 65 or older); 56.0% of subjects were female; 74.9% were White, 10.1% were Black and 3.7% were Asian. A total of 3,056 (35.5%) 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 primary analysis the median follow-up time post-dose 1 was 4.7 months and post-dose 2 was 2.7 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 332 participants met the primary efficacy endpoint criteria. Vaxzevria significantly decreased the incidence of COVID-19 compared to control (see Table 3).
The level of protection gained from a single dose of Vaxzevria 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 71.42% (95% CI: 51.11; 84.08 [Vaxzevria 18/9,335 vs control 63/9,312]).
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 6).

Efficacy against COVID-19 hospital admission and severe COVID-19 disease.

Vaxzevria 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, the vaccine efficacy was 100% (97.5% CI: 69.92; not evaluable) with 0 (N = 9, 335) cases of COVID-19 hospitalisation in participants who received Vaxzevria when compared to 14 (0.15%, N = 9,312) cases reported for control. Two of the COVID-19 cases reported for control (≥ 22 days post-dose 1) were severe (WHO severity grading ≥ 6).

Efficacy in sub-groups.

Participants who had one or more mild comorbidities had a vaccine efficacy of 62.71% [95% CI: 44.79; 74.82]; 34 (1.11%) vs 93 (3.00%) cases of COVID-19 for Vaxzevria (SDSD+LDSD, ≥ 15 days post-dose 2; N = 3,056) and control (N = 3,102), respectively; which was similar to the vaccine efficacy observed in the overall population.
In participants ≥ 65 years old who had received 2 doses of Vaxzevria (SDSD+LDSD, ≥ 15 days post-dose 2, N = 703), there were 4 cases of COVID-19 compared to 8 cases for control (N = 680), corresponding to a vaccine efficacy of 51.91% [95% CI: -59.98, 85.54]. A large proportion (89.6%) of older adults received their second dose < 6 weeks after their first. In older adults (≥ 65 years old) who had received SD as a first dose (≥ 22 days post-dose 1), there were 6 cases of COVID-19 for Vaxzevria (N = 945) compared to 13 for control (N = 896), with 0 vs 2 cases in the Vaxzevria and control groups, respectively, leading to hospitalisation (WHO severity grading ≥ 4).
Analysis of efficacy data from study D8110C00001. Vaxzevria has been evaluated based on an analysis (data lock: 5 March 2021) from a randomised, double blinded, placebo-controlled Phase III trial conducted in the United States, Peru and Chile. The trial randomised 32,451 healthy adults or those with medically-stable chronic diseases ≥ 18 years of age. The study excluded participants with severe and/or uncontrolled cardiovascular, gastrointestinal, liver, renal, endocrine/metabolic disease, and neurological illnesses; as well as those with severe immunosuppression. All participants are planned to be followed for up to 1 year for assessments of efficacy against COVID-19 disease.
In the updated primary efficacy analysis 26,212 participants received two doses of Vaxzevria (N = 17,662) or placebo (N = 8,550). Participants randomised to Vaxzevria received (5 x 1010 vp per dose) administered via IM injection on Day 1 and Day 29 (-3 to +7 days). The median dose interval was 29 days and the majority of participants received the second dose ≥ 26 to ≤ 36 days (95.7% and 95.3%, respectively) after dose 1.
Baseline demographics were balanced across the Vaxzevria and the placebo groups. Of the participants who received Vaxzevria, 79.1% were aged 18 to 64 years and 20.9% were ≥ 65 years of age; 43.8% of subjects were female. Of those randomised, 79.3% were White, 7.9% were Black, 4.2% were Asian, 4.2% were American Indian or Alaska Native, 0.3% were Native Hawaiian or Other Pacific Islander, and 2.4% were of multiple races (1.7% were unknown or not reported). A total of 10,376 (58.8%) participants who received Vaxzevria versus 5,105 (59.7%) who received placebo had at least one pre-existing comorbidity. At the time of analysis the median follow up time post-dose 2 was 61 days.
Comorbidity was defined as a chronic kidney disease, chronic obstructive pulmonary disease (COPD), lower immune health because of a solid organ transplant, history of obesity (BMI > 30), serious heart conditions, sickle cell disease, type 1 and 2 diabetes, asthma, dementia, cerebrovascular diseases, cystic fibrosis, high blood pressure, liver disease, scarring in the lungs (pulmonary fibrosis), thalassemia, history of smoking.
Final determination of COVID-19 cases was made by an adjudication committee. A total of 203 participants had SARS-CoV-2 virologically confirmed COVID-19 occurring ≥ 15 days post second dose and met either the Category A or Category B criteria, and had no prior evidence of a previous SARS-CoV-2 infection.
Category A: One or more of the following:
Pneumonia diagnosed by chest X-ray, or computed tomography scan.
Oxygen saturation of ≤ 94% on room air or requiring either new initiation or escalation in supplemental oxygen.
New or worsening dyspnoea/shortness of breath.
Category B: Two or more of the following:
Fever > 100°F (> 37.8°C) or feverishness;
New or worsening cough.
Myalgia/muscle pain.
Fatigue that interferes with activities of daily living.
Vomiting and/or diarrhoea (only one finding to be counted toward endpoint definition).
Anosmia and/or ageusia (only one finding to be counted toward endpoint definition).
Vaxzevria significantly decreased the incidence of COVID 19 compared to placebo (see Table 5).
In the pre-specified primary efficacy analysis, based on 190 adjudicated cases, there were 65 (0.4%) COVID-19 cases in participants receiving Vaxzevria (N = 17,817) and 125 (1.5%) COVID-19 cases in participants receiving placebo (N = 8,589), with a vaccine efficacy of 76.0%, [95% CI: 67.6, 82.2].

Efficacy in sub-groups.

Participants with one or more comorbidities who received the Vaxzevria ≥ 15 days post-dose 2 had an efficacy of 75.24% (95% CI: 64.18, 82.88) and participants without comorbidities had a vaccine efficacy of 71.81% (95% CI: 55.5, 82.14).
In participants ≥ 65 years old who had received Vaxzevria (≥ 15 days post-dose 2; N = 3,696), there were 5 (0.1%) cases of COVID-19 compared to 14 (0.8%) cases for placebo (N = 1,812), corresponding to a vaccine efficacy of 83.5% [95% CI: 54.17, 94.06].

Updated efficacy analyses.

In the 6-month follow-up analysis (data lock: 30 July 2021), updated efficacy analyses were performed with additional confirmed COVID-19 cases accrued during blinded placebo-controlled follow-up, with a median follow-up time post second dose of 78 days in participants who received Vaxzevria and 71 days in participants who received placebo. Overall vaccine efficacy against symptomatic COVID-19 illness in subjects without prior evidence of SARS-CoV-2 infection was 66.98% (95% CI: 58.87, 73.50) with 141 (0.80%) cases of COVID-19 reported in participants who had received two doses of Vaxzevria (N = 17,617) and 184 (2.16%) cases reported in participants who had received placebo (N = 8,528). In participants ≥ 65 years old there were 6 (0.16%) cases reported in the Vaxzevria group (N = 3,696) compared with 19 (1.05%) cases in the placebo group (N = 1,816), corresponding to a vaccine efficacy of 86.35% (95% CI: 65.79, 94.55).
In individuals with or without prior evidence of SARS-CoV-2 infection, vaccine efficacy against symptomatic COVID-19 illness was 66.96% (95% CI: 58.94, 73.41) with 144 (0.78%) versus 189 (2.11%) cases of COVID-19 in the Vaxzevria (N = 18,450) and placebo (N = 8,960) groups, respectively.
Against severe or critical symptomatic COVID-19 illness, vaccine efficacy was 95.69% (95% CI: 66.33, 99.45) with 1 (0.01%) case reported in the Vaxzevria group (N = 17,617) and 10 (0.12%) cases reported in the placebo group (N = 8,528). There were 2 (0.01%) versus 15 (0.18%) cases of COVID-19-related emergency department visits in the Vaxzevria (N = 17,617) and placebo (N = 8,528) groups, respectively, corresponding to a vaccine efficacy of 94.17% (95% CI: 74.49, 98.67).
The prevention of SARS-CoV-2 infection (symptomatic and asymptomatic) was evaluated by the occurrence of SARS-CoV-2 nucleocapsid antibodies ≥ 15 days post second dose. In the 6-month follow-up analysis, there were 295 (1.67%) SARS-CoV-2 infections in the Vaxzevria group (N = 17,617) and 323 (3.79%) infections in the placebo group (N = 8,528), corresponding to a vaccine efficacy of 61.01% (95% CI: 54.35; 66.70).

Immunogenicity data in individuals receiving 2 doses (primary analysis of pooled data from the pivotal Oxford clinical trials - 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 Vaxzevria, 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 6).
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 (97.3% [N = 149, 95% CI: 93.3; 99.3]) and the second SD (100.0% [N = 156, 95% CI: 97.7; not evaluable]). The majority of older adults had a dose interval of < 6 weeks. The increase in S-binding antibodies for older adults with a dose interval of < 6 weeks (28 days after second SD: GMT = 18,759.6 [N = 126, 95% CI: 15,764.8; 22,323.3] was comparable to all participants who received their second dose after an interval of < 6 weeks (see Table 6).
In participants with serological evidence of prior SARS-CoV-2 infection at baseline (GMT = 10,979.1 [N = 36; 95% CI: 6,452.7; 18,680.5]), S antibody titres peaked 28 days after dose 1 (GMT = 139,010.4 [N = 35; 95% CI: 95,429.0; 202,495.1]) but did not increase further after the second dose.
Spike-specific T cell responses as measured by IFN-γ enzyme-linked immunospot (ELISpot) assay are induced 14 days after a first dose of Vaxzevria. Geometric mean responses are generally similar across age strata and regardless of presence of comorbidity. These do not rise further after a second dose. Th1 cytokines are induced by Vaxzevria with cells expressing IFN-γ, IL-2, and/or TNFα which are generally similar between age categories.
Efficacy of a third dose of Vaxzevria. No data has been evaluated regarding the efficacy of a third dose of Vaxzevria in preventing clinically evident COVID-19 infection or severe COVID-19 illness.

Study D7220C00001, immunogenicity of a booster dose following primary vaccination with Vaxzevria or an mRNA COVID-19 vaccine.

D7220C00001 is a phase II/III partially double-blind, active-controlled study in which 367 participants ≥ 30 years old previously vaccinated with Vaxzevria and 322 participants ≥ 30 years old previously vaccinated with an mRNA vaccine received a single booster dose of Vaxzevria at least 90 days after receiving the second dose of their primary vaccination course.
Immunogenicity was assessed in 342 participants previously vaccinated with Vaxzevria and 294 participants previously vaccinated with an mRNA vaccine, all of whom were seronegative at baseline.
The effectiveness of Vaxzevria administered as a single booster dose in participants previously vaccinated with Vaxzevria was demonstrated by evaluating non-inferiority of the immune response of pseudoneutralising antibody titres against the ancestral strain compared to that elicited by a 2-dose primary vaccination course in a subset of matched participants in Study D8110C00001.
Non-inferiority for GMT ratio was demonstrated when comparing pseudoneutralising antibody titres 28 days after the booster dose to titres 28 days after the primary vaccination course (see Table 7).
Vaxzevria was also shown to be effective in eliciting antibody responses in participants who had previously received primary vaccination with an mRNA vaccine. In these participants, a single booster dose of Vaxzevria resulted in increased humoral responses, with geometric mean fold rise (GMFR) of 3.77 (95% CI: 3.26, 4.37) in pseudoneutralising antibody titres against the ancestral strain from pre-booster to 28 days after the booster dose.

COV001 immunogenicity of a third (booster) dose following primary vaccination with Vaxzevria.

COV001 included 90 participants aged 18-55 years who received a third (booster) dose with Vaxzevria. Antibody responses were assessed in 75 participants who had received their two doses of the primary vaccination course within an 8-16 week interval, followed by a third (booster) dose administered between 28-38 weeks after the second dose. There was a statistically significant increase in spike IgG antibody titres after the third dose from a median of 1792 EU [IQR 899-4634] at 28 days after the second dose to 3746 EU [IQR 2047-6420] 28 days after the third dose; pairwise comparison in 73 participants for whom samples were available using Wilcoxon signed rank test; p = 0.0043).
The relative efficacy of Vaxzevria as a third (booster) dose compared to other vaccines as boosters is not known. It is noted that the incremental increase in antibody concentrations is lower following a third (booster) dose with ChAdOx1-S than following mRNA vaccines in published studies. See Figure 1.
Efficacy in emerging SARS-CoV-2 variants. 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 Vaxzevria clinical development program by clinical and surveillance virology monitoring.

5.2 Pharmacokinetic Properties

Not applicable.

5.3 Preclinical Safety Data

Genotoxicity.

Vaxzevria is a vaccine, as such, genotoxicity (mutagenicity) studies have not been conducted.

Carcinogenicity.

Vaxzevria is a vaccine, as such, carcinogenicity studies have not been conducted.

6 Pharmaceutical Particulars

6.1 List of Excipients

Vaxzevria contains the excipients histidine, histidine hydrochloride monohydrate, sodium chloride, magnesium chloride hexahydrate, disodium edetate (EDTA), sucrose, ethanol absolute, polysorbate 80 and water for injections.
Vaxzevria 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.
The following information is intended to guide healthcare professionals only in case of an unforeseen temporary temperature excursion. It is not a recommended storage or shipping condition.
The shelf-life of unopened vials includes the following unforeseen excursions from refrigerated storage (2°C to 8°C) for a single period of: 12 hours up to 30°C; 72 hours down to -3°C.
Unopened vials must always be returned to refrigerated storage (2°C to 8°C) following an unforeseen temperature excursion.
The occurrence of an unforeseen temperature excursion for unopened vials does not impact how the vials should be stored after first opening (first vial puncture).

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

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

Vaxzevria 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