Consumer medicine information

Comirnaty COVID-19 Vaccine

Tozinameran

BRAND INFORMATION

Brand name

Comirnaty

Active ingredient

Tozinameran

Schedule

S4

 

Consumer medicine information (CMI) leaflet

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

SUMMARY CMI

COMIRNATY® COVID-19 VACCINE

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about receiving this vaccine, speak to your doctor or pharmacist.

 This vaccine is new or being used differently. Please report side effects. See the full CMI for further details.

1. Why am I being given COMIRNATY?

COMIRNATY is a vaccine given to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in adults and adolescents from 12 years of age and older. COMIRNATY contains the active ingredient tozinameran. For more information, see Section 1. Why am I being given COMIRNATY? in the full CMI.

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

You should not be given COMIRNATY if you have had an allergic reaction to any of the ingredients in COMIRNATY. See list at the end of the CMI. Check with your doctor if you have had: a severe allergic reaction or breathing problems after any other vaccine or after being given COMIRNATY in the past; fainted following any needle injection; a severe illness or infection with high fever; a weakened immune system or are on a medicine that affects your immune system; a bleeding disorder, bruise easily or are on a blood thinning medicine. As with any vaccine, COMIRNATY may not fully protect all those who receive it and it is not known how long you will be protected.

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

COMIRNATY should not be given to children under 12 years. For more information, see Section 2. What should I know before I am given COMIRNATY? in the full CMI.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription. Tell your doctor or pharmacist if you have recently received any other vaccine. For more information, see Section 3. What if I am taking other medicines? in the full CMI.

4. How will I be given COMIRNATY?

COMIRNATY will be given as an injection into the muscle of your upper arm by a doctor, nurse or pharmacist. You will be given one dose followed by a second dose at least 21 days later. It is very important that you receive your second dose. If you are immunocompromised, you may receive a third dose of Comirnaty at least 28 days after the second dose as part of the primary vaccination. A doctor, nurse or pharmacist will observe you for at least 15 minutes after being given COMIRNATY. You may receive a booster dose at least 6 months after the primary vaccination. For more information, see Section 4. How will I be given COMIRNATY? in the full CMI.

5. What should I know while being given COMIRNATY?

Things you should know
  • If you receive one dose of COMIRNATY, you should receive a second dose of the same vaccine 21 days later to complete the primary vaccination schedule. If you are immunocompromised, you may receive a third dose of Comirnaty at least 28 days after the second dose as part of the primary vaccination.
  • A booster dose of COMIRNATY may be given at least 6 months after the primary vaccination for people 12 years of age and older.
  • You may not be protected against COVID-19 disease until at least seven days after your second dose.
  • You may not be protected if you only receive one dose, so a second dose is important.
Driving or using machines
  • Be careful before you drive or use any machines or tools until you know how COMIRNATY affects you. Some of the side effects of COMIRNATY may temporarily affect your ability to drive or use machines.

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

6. Are there any side effects?

Very common side effects of COMIRNATY include pain/swelling at injection site, tiredness, headache, muscle pain, chills, joint pain and fever. 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 directly at www.tga.gov.au/reporting-problems.



FULL CMI

COMIRNATY® COVID-19 VACCINE

Active ingredient: tozinameran

This vaccine has provisional approval in Australia to prevent COVID-19 disease caused by SARS-CoV-2 virus in adults and adolescents from 12 years of age and older. This approval has been granted on the basis of short term safety and efficacy 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 using COMIRNATY. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about receiving COMIRNATY.

Where to find information in this leaflet:

1. Why am I being given COMIRNATY?
2. What should I know before I am given COMIRNATY?
3. What if I am taking other medicines?
4. How will I be given COMIRNATY?
5. What should I know while being given COMIRNATY?
6. Are there any side effects?
7. Product details

1. Why am I being given COMIRNATY?

COMIRNATY contains the active ingredient tozinameran. COMIRNATY is an mRNA (messenger ribonucleic acid) vaccine.

COMIRNATY is a vaccine given to prevent COVID-19 disease caused by SARS-CoV-2 virus in adults and adolescents from 12 years of age and older.

COMIRNATY works by triggering your immune system to produce antibodies and blood cells that work against the virus, to protect against COVID-19 disease.

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

Warnings

COMIRNATY should not be given:

  1. if you are allergic to tozinameran or any of the ingredients listed at the end of this leaflet.

Check with your doctor if you have:

  • had a severe allergic reaction or breathing problems after any other vaccine or after being given COMIRNATY in the past.
  • fainted following any needle injection.
  • a severe illness or infection with high fever. However, you can have your vaccination if you have a mild fever or upper airway infection like a cold.
  • a weakened immune system, such as due to HIV infection or are on a medicine that affects your immune system.
  • a bleeding disorder, bruise easily or are on a blood thinning medicine.

During treatment, 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?

Very rare cases of myocarditis (inflammation of the heart muscle) and pericarditis (inflammation of the lining outside the heart) have been reported after vaccination with COMIRNATY. The cases have mostly occurred within two weeks following vaccination, more often after the second vaccination, and more often occurred in younger men. Following vaccination, you should be alert to signs of myocarditis and pericarditis, such as breathlessness, palpitations and chest pain, and seek immediate medical attention should these occur.

You may develop a temporary, stress-related response associated with the process of receiving your injection. This may include dizziness, fainting, sweating, increased heart rate and/or anxiety. If you start to feel faint at any time during the process of receiving your injection, let your doctor, nurse or pharmacist know and take actions to avoid falling and injuring yourself, such as sitting or lying down.

As with any vaccine, COMIRNATY may not fully protect all those who receive it and it is not known how long you will be protected.

Pregnancy and breastfeeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before you receive this vaccine.

Children and adolescents

COMIRNATY should not be given to children under 12 years.

3. What if I am taking other medicines?

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

Tell your doctor or pharmacist if you have recently received any other vaccine.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect, or are affected by, COMIRNATY.

4. How will I be given COMIRNATY?

  • COMIRNATY will be given as an injection into the muscle of your upper arm by a doctor, nurse or pharmacist.
  • For primary vaccination, you will be given two doses. One dose followed by a second dose at least 21 days later. If you miss the second dose, ask your doctor for advice.
  • If you are immunocompromised, you may receive a third dose of Comirnaty at least 28 days after the second dose as part of the primary vaccination.
  • A doctor, nurse or pharmacist will observe you for at least 15 minutes after being given COMIRNATY.
  • A booster dose of COMIRNATY may be given at least 6 months after the primary vaccination for people 12 years of age and older.

5. What should I know while being given COMIRNATY?

Things you should know

  • If you receive one dose of COMIRNATY, you should receive a second dose of the same vaccine at least 21 days later to complete the primary vaccination schedule.
  • If you are immunocompromised, you may receive a third dose of Comirnaty at least 28 days after the second dose as part of the primary vaccination.
  • A booster dose of COMIRNATY may be given at least 6 months after the primary vaccination for people 12 years of age and older.
  • You may not be protected against COVID-19 disease until at least seven days after your second dose.
  • You may not be protected if you only receive one dose, so a second dose is important.

Driving or using machines

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

Some of the side effects of COMIRNATY may temporarily affect your ability to drive or use machines.

Storage of the vaccine

COMIRNATY is stored at -90°C to -60°C. It must be kept in the original package in order to protect from light.

A doctor, nurse or pharmacist will prepare the injection for you before you are given it.

Getting rid of any unwanted vaccine

A doctor, nurse or pharmacist will dispose of any unused vaccine.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

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

Very common side effects

Very common side effectsWhat to do
  • pain/swelling at injection site
  • tiredness
  • headache
  • muscle pain
  • chills
  • joint pain
  • fever
Speak to your doctor if you have any of these very common side effects and they worry you.

Common side effects

Common side effectsWhat to do
  • redness at injection site
  • nausea
Speak to your doctor if you have any of these common side effects and they worry you.

Uncommon side effects

Uncommon side effectsWhat to do
  • enlarged lymph nodes
  • feeling unwell
  • arm pain
  • insomnia
  • decreased appetite
  • excessive sweating
  • night sweats
  • physical weakness and/or lack of energy
Speak to your doctor if you have any of these side effects and they worry you.

Rare side effects

Rare side effectsWhat to do
  • temporary one-sided facial drooping
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice this side effect.

Other side effects (frequency unknown)

Other side effects (frequency unknown)What to do
  • severe allergic reaction
  • allergic reactions such as rash, itching, hives or swelling of the face
  • inflammation of the heart muscle (myocarditis) or inflammation of the lining outside the heart (pericarditis) which can result in chest pain, breathlessness and/or palpitations
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.
  • diarrhoea
  • vomiting
  • pain in arm
  • extensive swelling of vaccinated arm
  • swelling of face (people who have had facial dermal fillers)
  • unusual sensation (e.g. tingling or pricking, “pins-and-needles”)
  • numbness
  • skin lesions (bull's-eye-shaped)
Speak to your doctor if you have any of these side effects and they worry you.

Tell your doctor or pharmacist 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. By reporting side effects, you can help provide more information on the safety of this vaccine.

7. Product details

What COMIRNATY contains

Active ingredient
(main ingredient)
  • tozinameran
Other ingredients
(inactive ingredients)
  • ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) (ALC-0315)
  • 2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide (ALC-0159)
  • Distearoylphosphatidylcholine (DSPC)
  • Cholesterol
  • Potassium chloride
  • Monobasic potassium phosphate
  • Sodium chloride
  • Dibasic sodium phosphate dihydrate
  • Sucrose
  • Water for injections

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

What COMIRNATY looks like

COMIRNATY is a white to off-white suspension provided in a multidose clear glass vial.

After dilution, each vial contains 6 doses of vaccine.

AUST R 346290.

Who distributes COMIRNATY

Pfizer Australia Pty Ltd
Sydney NSW
Toll Free Number: 1800 675 229
www.pfizermedinfo.com.au

COMIRNATY® is a registered trademark of BioNTech SE. Used under license.

This leaflet was prepared in April 2022.

© Copyright

Published by MIMS May 2022

BRAND INFORMATION

Brand name

Comirnaty

Active ingredient

Tozinameran

Schedule

S4

 

1 Name of Medicine

Tozinameran.

2 Qualitative and Quantitative Composition

This is a multidose vial and must be diluted before use.
One vial (0.45 mL) contains 6 doses of 0.3 mL after dilution, see Section 4.2 Dose and Method of Administration.
1 dose (0.3 mL) contains 30 micrograms of tozinameran (embedded in lipid nanoparticles).
The active ingredient is a single-stranded, 5'-capped messenger RNA (mRNA) produced using a cell-free in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Concentrated suspension for injection (sterile concentrate).
Comirnaty is a white to off-white frozen suspension.

4 Clinical Particulars

4.1 Therapeutic Indications

Comirnaty (tozinameran) COVID-19 Vaccine has provisional approval for the indication below:
Active immunisation to prevent coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2, in individuals 12 years of age and older.
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 depends on the evidence of longer term efficacy and safety from ongoing clinical trials and post-market assessment.

4.2 Dose and Method of Administration

Dosage.

Individuals 12 years of age and older.

Comirnaty is administered intramuscularly after dilution as a primary course of 2 doses at least 21 days apart. See dosing instructions below.

Booster dose in individuals 12 years of age and older.

A booster dose of Comirnaty may be administered intramuscularly at least 6 months after the completion of a COVID-19 vaccine primary series in individuals 12 years of age and older.
The decision when and for whom to implement a booster dose of Comirnaty should be made based on available vaccine safety and effectiveness data (see Section 4.4 Special Warnings and Precautions for Use; Section 5.1 Pharmacodynamic Properties), in accordance with official recommendations.

Interchangeability.

There are limited data on the interchangeability of Comirnaty with other COVID-19 vaccines to complete the primary vaccination course or the booster dose. Individuals who have received 1 dose of Comirnaty should preferably receive a second dose of Comirnaty to complete the primary vaccination course and for any additional doses.

Severely immunocompromised aged 12 years and older.

In accordance with official recommendations, a third dose may be given, as part of the primary series, at least 28 days after the second dose to individuals who are severely immunocompromised (see Section 4.4 Special Warnings and Precautions for Use).

Elderly population.

No dosage adjustment is required in elderly individuals ≥ 65 years of age.

Method of administration.

Comirnaty should be administered intramuscularly after dilution (see Handling instructions).
After dilution, vials of Comirnaty contain six doses of 0.3 mL of vaccine. In order to extract six doses from a single vial, low dead-volume syringes and/or needles should be used. The low dead-volume syringe and needle combination should have a dead volume of no more than 35 microlitres. If standard syringes and needles are used, there may not be sufficient volume to extract a sixth dose from a single vial. Irrespective of the type of syringe and needle:
Each dose must contain 0.3 mL of vaccine.
If the amount of vaccine remaining in the vial cannot provide a full dose of 0.3 mL, discard the vial and any excess volume.
Do not pool excess vaccine from multiple vials.
The preferred site of administration is the deltoid muscle of the upper arm.
Do not inject Comirnaty intravascularly, subcutaneously or intradermally.
Comirnaty should not be mixed in the same syringe with any other vaccines or medicinal products.
For precautions to be taken before administering Comirnaty, see Section 4.4 Special Warnings and Precautions for Use.

Handling instructions.

Comirnaty should be prepared by a healthcare professional using aseptic technique to ensure the sterility of the prepared suspension.
Please refer to the manufacturer's product information for figures related to the following instructions.

Thawing prior to dilution.

The multidose vial is stored frozen and must be thawed prior to dilution. Frozen vials should be transferred to an environment of 2°C to 8°C to thaw; a 195 vial pack may take 3 hours to thaw. Alternatively, frozen vials may also be thawed for 30 minutes at temperatures up to 30°C for immediate use.
The unopened vial can be stored for up to 1 month at 2°C to 8°C. Within the 1-month shelf-life at 2°C to 8°C, up to 12 hours may be used for transportation.
Allow the thawed vial to come to room temperature and gently invert it 10 times prior to dilution. Do not shake.
Prior to dilution, the thawed suspension may contain white to off-white opaque amorphous particles.

Dilution.

The thawed vaccine must be diluted in its original vial with 1.8 mL sodium chloride 9 mg/mL (0.9%) solution for injection, using a 21 gauge or narrower needle and aseptic techniques. Do not use any other diluent.
Equalise vial pressure before removing the needle from the vial stopper by withdrawing 1.8 mL air into the empty diluent syringe.
Gently invert the diluted suspension 10 times. Do not shake.
The diluted vaccine should present as an off-white suspension with no particulates visible. Discard the diluted vaccine if particulates or discolouration are present.
The diluted vials should be marked with the date and time of dilution.
Do not freeze or shake the diluted suspension. If refrigerated, allow the diluted suspension to come to room temperature prior to use.

Preparation of individual 0.3 mL doses of Comirnaty.

After dilution, the vial contains 2.25 mL from which 6 doses of 0.3 mL can be extracted.
Using aseptic technique, cleanse the vial stopper with a single-use antiseptic swab.
Withdraw 0.3 mL of Comirnaty.
Low dead-volume syringes and/or needles should be used in order to extract 6 doses from a single vial. The low dead-volume syringe and needle combination should have a dead volume of no more than 35 microlitres.
If standard syringes and needles are used, there may not be sufficient volume to extract a sixth dose from a single vial.
Each dose must contain 0.3 mL of vaccine.
If the amount of vaccine remaining in the vial cannot provide a full dose of 0.3 mL, discard the vial and any excess volume.
Verify a final injection volume of 0.3 mL prior to administration.
Discard syringe and needle after administration to a single patient.
Use a new, sterile needle and syringe to draw up each new dose.
Discard any unused vaccine 6 hours after dilution.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in Section 6.1 List of Excipients.

4.4 Special Warnings and Precautions for Use

Traceability.

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be recorded in the Australian Immunisation Register.

General recommendations.

Hypersensitivity and anaphylaxis.

Events of anaphylaxis have been reported. Appropriate medical treatment and supervision should always be readily available in case of an anaphylactic reaction following the administration of Comirnaty.
The individual should be kept under close observation for at least 15 minutes following vaccination. A second dose of Comirnaty should not be given to those who have experienced anaphylaxis to the first dose of Comirnaty.

Myocarditis and pericarditis.

Very rare cases of myocarditis and pericarditis have been observed following vaccination with Comirnaty. Cases have occurred following first and second vaccinations and following booster doses. These cases have primarily occurred within 14 days following vaccination, more often after the second vaccination, and more often in younger males. Available data suggest that the course of myocarditis and pericarditis following vaccination is not different from myocarditis or pericarditis in general.
Healthcare professionals should be alert to the signs and symptoms of myocarditis and pericarditis. Vaccinees should be instructed to seek immediate medical attention if they develop symptoms indicative of myocarditis or pericarditis such as (acute and persisting) chest pain, shortness of breath, or palpitations following vaccination. Healthcare professionals should consult guidance and/or specialists to diagnose and treat this condition.
For further details, please refer to the relevant clinical guidelines developed by the Australian Technical Advisory Group on Immunisation.

Anxiety-related reactions.

Anxiety-related reactions, including vasovagal reactions (syncope), hyperventilation or stress-related reactions may occur in association with vaccination as a psychogenic response to the needle injection. It is important that precautions are in place to avoid injury from fainting.
Some individuals may have stress-related responses associated with the process of vaccination itself. Stress-related responses are temporary and resolve on their own. They may include dizziness, fainting, palpitations, increases in heart rate, alterations in blood pressure, feeling short of breath, tingling sensations, sweating and/or anxiety. Individuals should be advised to bring symptoms to the attention of the vaccination provider for evaluation and precautions should be in place to avoid injury from fainting.

Syncope.

Syncope (fainting) may occur in association with administration of injectable vaccines. Procedures should be in place to avoid injury from fainting.

Concurrent illness.

Vaccination should be postponed in individuals suffering from acute severe febrile illness or acute infection. The presence of a minor infection and/or low grade fever should not delay vaccination.

Thrombocytopenia and coagulation disorders.

As with other intramuscular injections, Comirnaty should be given with caution in individuals receiving anticoagulant therapy or those with thrombocytopenia or any coagulation disorder (such as haemophilia) because bleeding or bruising may occur following an intramuscular administration in these individuals.

Immunocompromised individuals.

The efficacy, safety and immunogenicity of Comirnaty has not been assessed in immunocompromised individuals, including those receiving immunosuppressant therapy. The efficacy of Comirnaty may be lower in immunosuppressed individuals.

Duration of protection.

The duration of protection afforded by Comirnaty is unknown as it is still being determined by ongoing clinical trials and observational studies.

Limitations of vaccine effectiveness.

As with any vaccine, vaccination with Comirnaty may not protect all vaccine recipients. Individuals may not be fully protected until 7 days after their second dose of Comirnaty.

Use in the elderly.

Clinical studies of Comirnaty include participants 65 years of age and older and their data contributes to the overall assessment of safety and efficacy. See Section 5.1 Pharmacodynamic Properties, Clinical trials, Efficacy against COVID-19. No dosage adjustment is required in elderly individuals ≥ 65 years of age.
The data for use in the frail elderly (> 85 years) is limited. The potential benefits of vaccination versus the potential risk and clinical impact of even relatively mild systemic adverse events in the frail elderly should be carefully assessed on a case-by-case basis.
The safety of a booster dose of Comirnaty in individuals 65 years of age and older is based on safety and immunogenicity data in adults 18 to 55 years of age.

Paediatric use.

The safety and efficacy of Comirnaty in children aged less than 12 years of age have not yet been established.
Limited safety and effectiveness data is available for booster dose in adolescents 12 to 15 years of age and no immunogenicity data is available for booster dose in this age group. The safety and effectiveness of a booster dose of Comirnaty in individuals 12 to 17 years of age is based on safety and effectiveness data in adults at least 18 to 55 years of age.
Real world evidence from the Ministry of Health of Israel and surveillance by CDC in USA on the administration of third doses of Comirnaty given after the primary course revealed no new safety concerns in adolescents 12 to 17 years of age.
Very rare cases of myocarditis and pericarditis have been observed following vaccination with Comirnaty in adolescents (see Section 4.4 Special Warnings and Precautions for Use, Myocarditis and pericarditis).

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No interaction studies have been performed.
Concomitant administration of Comirnaty with other vaccines has not been studied.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

In a combined fertility and developmental toxicity study, female rats were intramuscularly administered Comirnaty prior to mating and during gestation (4 full human doses of 30 microgram each, spanning between pre-mating day 21 and gestation day 20). SARS CoV-2 neutralising antibodies were present in maternal animals from prior to mating to the end of the study on postnatal day 21 as well as in fetuses and offspring. There were no vaccine related effects on female fertility and pregnancy rate.
(Category B1)
There is limited experience with use of Comirnaty in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryo/fetal development, parturition or post-natal development (see Section 4.6 Fertility, Pregnancy and Lactation, Effects on fertility). Administration of Comirnaty in pregnancy should only be considered when the potential benefits outweigh any potential risks for the mother and fetus.
It is unknown whether tozinameran is excreted in human milk. A combined fertility and developmental toxicity study in rats did not show harmful effects on offspring development before weaning (see Section 4.6 Fertility, Pregnancy and Lactation, Effects on fertility).

4.7 Effects on Ability to Drive and Use Machines

Comirnaty has no, or negligible, influence on the ability to drive and use machines. However, some of the effects 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)

Summary of safety profile.

The safety of Comirnaty was evaluated in participants 12 years of age and older in 2 clinical studies that included 23,205 participants (comprised of 22,074 participants 16 years of age and older and 1,131 adolescents 12 to 15 years of age) that have received at least one dose of Comirnaty.
Additionally, 306 existing Phase 3 participants 18 to 55 years of age received a booster dose of Comirnaty approximately 6 months after the second dose in the non-placebo-controlled booster dose portion of Study C4591001. The overall safety profile for the booster dose was similar to that seen after 2 doses.

Participants 16 years of age and older - after 2 doses.

In Study C4591001, a total of 22,026 participants 16 years of age or older received at least 1 dose of Comirnaty and a total of 22,021 participants 16 years of age or older received placebo (including 138 and 145 adolescents 16 and 17 years of age in the Comirnaty and placebo groups, respectively). A total of 20,519 participants 16 years of age or older received 2 doses of Comirnaty.
At the time of the analysis of Study C4591001 with a data cut-off of 13 March 2021 for the placebo-controlled blinded follow-up period up to the participants' unblinding dates, a total of 25,651 (58.2%) participants (13,031 Comirnaty and 12,620 placebo) 16 years of age and older were followed up for ≥ 4 months after the second dose. This included a total of 15,111 (7,704 Comirnaty and 7,407 placebo) participants 16 to 55 years of age and a total of 10,540 (5,327 Comirnaty and 5,213 placebo) participants 56 years and older.
The most frequent adverse reactions in participants 16 years of age and older that received 2 doses were injection site pain (> 80%), fatigue (> 60%), headache (> 50%), myalgia (> 40%), chills (> 30%), arthralgia (> 20%), pyrexia and injection site swelling (> 10%) and were usually mild or moderate in intensity and resolved within a few days after vaccination. A slightly lower frequency of reactogenicity events was associated with greater age.
The safety profile in 545 subjects receiving Comirnaty, that were seropositive for SARS-CoV-2 at baseline, was similar to that seen in the general population.
Study C4591001 also included 200 participants with confirmed stable human immunodeficiency virus (HIV) infection. The safety profile of the participants receiving Comirnaty (n = 100) in the individuals with stable HIV infection was similar to that seen in the general population.

Adolescents 12 to 15 years of age - after 2 doses.

In an analysis of long-term safety follow-up in Study C4591001, 2,260 adolescents (1,131 Comirnaty; 1,129 placebo) were 12 to 15 years of age. Of these, 1,559 adolescents (786 Comirnaty and 773 placebo) have been followed for ≥ 4 months after the second dose of Comirnaty. The safety evaluation in Study C4591001 is ongoing.
The most frequent adverse reactions in adolescents 12 to 15 years of age that received 2 doses were injection site pain (> 90%), fatigue and headache (> 70%), myalgia and chills (> 40%), arthralgia and pyrexia (> 20%).

Participants 18 years of age and older - after booster dose.

A subset from Study C4591001 Phase 2/3 participants of 306 adults 18 to 55 years of age who completed the original Comirnaty 2-dose course, received a booster dose of Comirnaty approximately 6 months (range of 4.8 to 8.0 months) after receiving Dose 2.
The most frequent adverse reactions in participants 18 to 55 years of age were injection site pain (> 80%), fatigue (> 60%), headache (> 40%), myalgia (> 30%), chills and arthralgia (> 20%).

Tabulated list of adverse reactions from clinical studies.

Adverse reactions observed during clinical studies are listed in Table 1 according to the following frequency categories:
Very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data).
The safety profile in 545 subjects receiving Comirnaty, that were seropositive for SARS-CoV-2 at baseline, was similar to that seen in the general population.

Post-marketing experience.

Although the events listed in Table 2 were not observed in the clinical trials, they are considered adverse drug reactions for Comirnaty as they were reported in the post-marketing experience. As these reactions were derived from spontaneous reports, the frequencies could not be determined and are thus considered as not known.

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

Overdose data is available from 52 study participants included in the clinical trial that due to an error in dilution received 58 micrograms of Comirnaty. The Comirnaty recipients did not report an increase in reactogenicity or adverse reactions.
In the event of overdose, monitoring of vital functions and possible symptomatic treatment is recommended.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: vaccines, other viral vaccines, ATC code: J07BX03.

Mechanism of action.

The nucleoside-modified messenger RNA in Comirnaty is formulated in lipid nanoparticles, which enable delivery of the non-replicating RNA into host cells to direct transient expression of the SARS-CoV-2 spike (S) antigen. The mRNA codes for membrane-anchored, full-length S with two point mutations within the central helix. Mutation of these two amino acids to proline locks S in an antigenically preferred prefusion conformation. Comirnaty elicits both neutralising antibody and cellular immune responses to the antigen, which may contribute to protection against COVID-19.

Clinical trials.

Efficacy.

Study C4591001 is a multicentre, multinational, Phase 1/2/3 randomised, placebo-controlled, observer-blind dose-finding, vaccine candidate selection and efficacy study in participants 12 years of age and older. Randomisation was stratified by age: 12 to 15 years of age, 16 to 55 years of age, or 56 years of age and older, with a minimum of 40% of participants in the ≥ 56-year stratum. The study excluded participants who were immunocompromised and those who had previous clinical or microbiological diagnosis of COVID-19. Participants with pre-existing stable disease, defined as disease not requiring significant change in therapy or hospitalisation for worsening disease during the 6 weeks before enrolment, were included as were participants with known stable infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV).

Efficacy in participants 16 years of age and older - after 2 doses.

In the Phase 2/3 portion of Study C4591001, based on data accrued through 14 November 2020, approximately 44,000 participants were randomised equally and were to receive 2 doses of Comirnaty or placebo. The efficacy analyses included participants that received their second vaccination within 19 to 42 days after their first vaccination. The majority (93.1%) of vaccine recipients received the second dose 19 days to 23 days after Dose 1. Participants are planned to be followed for up to 24 months after Dose 2, for assessments of safety and efficacy against COVID-19. In the clinical study, participants were required to observe a minimum interval of 14 days before and after administration of an influenza vaccine in order to receive either placebo or Comirnaty. In the clinical study, participants were required to observe a minimum interval of 60 days before or after receipt of blood/plasma products or immunoglobulins through to conclusion of the study in order to receive either placebo or Comirnaty.
The population for the analysis of the primary efficacy endpoint included, 36,621 participants 12 years of age and older (18,242 in the Comirnaty group and 18,379 in the placebo group) who did not have evidence of prior infection with SARS-CoV-2 through 7 days after the second dose. In addition, 134 participants were between the ages of 16 to 17 years of age (66 in the Comirnaty group and 68 in the placebo group) and 1616 participants 75 years of age and older (804 in the Comirnaty group and 812 in the placebo group).
At the time of the primary efficacy analysis, participants had been followed for symptomatic COVID-19 for in total 2,214 person-years for the Comirnaty group and in total 2,222 person-years for the placebo group.
There were no meaningful clinical differences in overall vaccine efficacy in participants who were at risk of severe COVID-19 including those with 1 or more comorbidities that increase the risk of severe COVID-19 (e.g. asthma, body mass index (BMI) ≥ 30 kg/m2, chronic pulmonary disease, diabetes mellitus, hypertension).
Comirnaty efficacy information is presented in Table 3.
In the second primary analysis, efficacy of Comirnaty in preventing first COVID-19 occurrence from 7 days after Dose 2 compared to placebo was 94.6% (95% credible interval of 89.9% to 97.3%) in participants 16 years of age and older with or without evidence of prior infection with SARS-CoV-2.
Additionally, subgroup analyses of the primary efficacy endpoint showed similar efficacy point estimates across genders, ethnic groups, and participants with medical comorbidities associated with high risk of severe COVID-19.
Updated efficacy analyses were performed with additional confirmed COVID-19 cases accrued during blinded placebo-controlled follow-up through 13 March 2021, representing up to 6 months of follow up after Dose 2 for participants in the efficacy population.
The updated vaccine efficacy information is presented in Table 4.

Efficacy against severe COVID-19 in participants 12 years of age or older - after 2 doses.

As of 13 March 2021, vaccine efficacy against severe COVID-19 is presented only for participants with or without prior SARS-CoV-2 infection (Table 5) as the COVID-19 case counts in participants without prior SARS-CoV-2 infection were the same as those in participants with or without prior SARS-CoV-2 infection in both the Comirnaty and placebo groups.

Efficacy and immunogenicity in adolescents 12 to 15 years of age - after 2 doses.

An analysis of Study C4591001 has been performed in adolescents 12 to 15 years of age up to a data cut-off date of 13 March 2021.
In an analysis of Study C4591001 in adolescents 12 to 15 years of age without evidence of prior infection, there were no cases in 1005 participants who received the vaccine and 16 cases out of 978 who received placebo. The point estimate for efficacy is 100% (95% confidence interval 75.3, 100.0). In participants with or without evidence of prior infection there were 0 cases in the 1119 who received vaccine and 18 cases in 1110 participants who received placebo. This also indicates the point estimate for efficacy is 100% (95% confidence interval 78.1, 100.0). No cases of severe disease occurred in adolescents.
In Study C4591001, an analysis of SARS-CoV-2 neutralising titres in a randomly selected subset of participants was performed to demonstrate non-inferior immune responses (within 1.5-fold) comparing adolescents 12 to 15 years of age to participants 16 to 25 years of age who had no serological or virological evidence of past SARS-CoV-2 infection. The immune response to Comirnaty in adolescents 12 to 15 years of age (n = 190) was non-inferior to the immune response in participants 16 to 25 years of age (n = 170), based on results for SARS-CoV-2 neutralising titres at 1 month after Dose 2. The geometric mean titres (GMT) ratio of the adolescents 12 to 15 years of age group to the participants 16 to 25 years of age group was 1.76, with a 2 sided 95% CI of 1.47 to 2.10, meeting the 1.5-fold non-inferiority criterion (the lower bound of the 2 sided 95% CI for the geometric mean ratio [GMR] > 0.67).
An updated efficacy analysis of Study C4591001 has been performed in approximately 2,260 adolescents 12 to 15 years of age evaluating confirmed COVID-19 cases accrued up to a data cut off date of 2 September 2021, representing up to 6 months of follow-up after Dose 2 for participants in the efficacy population. The dominant SARS-CoV-2 variant at the time of the efficacy study was B.1.1.7 (Alpha).
The updated vaccine efficacy information in adolescents 12 to 15 years of age is presented in Table 6.

Immunogenicity in participants 18 years of age and older - after booster dose.

Effectiveness of a booster dose of Comirnaty was based on an assessment of 50% neutralising titres (NT50) against SARS-CoV-2 (USA_WA1/2020). In Study C4591001, analyses of NT50 1 month after the booster dose compared to 1 month after the primary series in individuals 18 to 55 years of age, who had no serological or virological evidence of past SARS-CoV-2 infection up to 1 month after the booster vaccination, demonstrated noninferiority for both GMR and difference in seroresponse rates. Seroresponse for a participant was defined as achieving a ≥ 4-fold rise in NT50 from baseline (before Dose 1). These analyses are summarised in Table 7.

5.2 Pharmacokinetic Properties

Not applicable.

5.3 Preclinical Safety Data

Genotoxicity/carcinogenicity.

Neither genotoxicity nor carcinogenicity studies were performed. The components of Comirnaty (lipids and mRNA) are not expected to have genotoxic potential.

6 Pharmaceutical Particulars

6.1 List of Excipients

((4-hydroxybutyl) azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) (ALC-0315), 2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide (ALC-0159), distearoylphosphatidylcholine (DSPC), cholesterol, potassium chloride, monobasic potassium phosphate, sodium chloride, dibasic sodium phosphate dihydrate, sucrose, water for injections.
This vaccine contains less than 1 mmol potassium (39 mg) per dose, that is to say essentially 'potassium-free'.
This vaccine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially 'sodium‑free'.

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products except those mentioned in Section 4.2 Dose and Method of Administration.

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.

Unopened vial.

9 months at -90°C to -60°C.
Unopened vials may be stored and transported at -25°C to -15°C for a total of 2 weeks and can be returned to -90°C to -60°C.
Once removed from the freezer, the unopened vial can be stored for up to 1 month at 2°C to 8°C. Within the 1 month shelf-life at 2°C to 8°C, up to 12 hours may be used for transportation.
Prior to use, the unopened vial can be stored for up to 2 hours at temperatures up to 30°C.
Once thawed, Comirnaty should not be re-frozen.

Diluted medicinal product.

Chemical and physical in-use stability, including during transportation, has been demonstrated for 6 hours at 2°C to 30°C after dilution in sodium chloride 9 mg/mL (0.9%) solution for injection. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.

6.4 Special Precautions for Storage

Store in a freezer at -90°C to -60°C.
Store in the original package in order to protect from light.
During storage, minimise exposure to room light, and avoid exposure to direct sunlight and ultraviolet light.
Thawed vials can be handled in room light conditions.
When you are ready to thaw or use Comirnaty:

Transfers of frozen vials stored at ultra-low temperature (< -60°C).

Closed-lid vial trays containing 195 vials removed from ultra-low temperature frozen storage (< -60°C) may be at temperatures up to 25°C for up to 5 minutes for transfer between ultra-low-temperature environments.
Open-lid vial trays, or vial trays containing less than 195 vials removed from ultra-low temperature frozen storage (< -60°C) may be at temperatures up to 25°C for up to 3 minutes to remove vials or for transfer between ultra-low-temperature environments.
After vial trays are returned to ultra-low temperature frozen storage following temperature exposure up to 25°C, they must remain in ultra-low temperature frozen storage for at least 2 hours before they can be removed again.

Transfers of frozen vials stored at -25°C to -15°C.

Closed-lid vial trays containing 195 vials removed from frozen storage (-25°C to -15°C) may be at temperatures up to 25°C for up to 3 minutes.
Open-lid vial trays, or vial trays containing less than 195 vials, removed from frozen storage (-25°C to -15°C) may be at temperatures up to 25°C for up to 1 minute.
Once a vial is removed from the vial tray, it should be thawed for use.

Transportation.

If local redistribution of unopened vials is needed, and full trays containing vials cannot be transported at -90°C to -60°C, available data support physical and chemical stability during transportation of 1 or more thawed vials at 2°C to 8°C for up to 12 hours. Any hours used for transport of unopened vials at 2°C to 8°C count against the 1 month limit for storage at 2°C to 8°C.
If local redistribution of diluted medicinal product in vials or syringes is needed, available data support physical and chemical stability during transportation at 2°C to 30°C for up to 6 hours. Any hours used for transport of diluted medicinal product in vials or syringes at 2°C to 30°C count against the 6-hour limit for storage at 2°C to 30°C. Microbiological risks and package integrity, particularly for prepared dosing syringes, are the responsibility of the preparer during transportation of diluted medicinal product.
For storage conditions after thawing and dilution of the medicinal product, see Section 6.3 Shelf Life.
For additional advice on storing Comirnaty, contact Pfizer Australia on 1800 675 229.

6.5 Nature and Contents of Container

2 mL clear multidose vial (Type I glass) with a stopper (synthetic bromobutyl rubber) and a flip-off plastic cap with aluminium seal. Each vial contains 6 doses, see Section 4.2 Dose and Method of Administration.
Pack size: 195 vials.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

CAS number.

2417899-77-3.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes