COVID-19 mRNA vaccine (BNT162) Clinical Particulars - Form to be diluted 30 µg/dose for adults and ≥12 years (purple cap)

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4.1 Therapeutic indications

Comirnaty 30 micrograms/dose concentrate for dispersion for injection is indicated for active immunisation to prevent COVID-19 caused by SARS-CoV-2 virus, in individuals 12 years of age and older.

The use of this vaccine should be in accordance with official recommendations.

4.2 Posology and method of administration

Posology

Primary vaccination course

Individuals 12 years of age and older
Comirnaty is administered intramuscularly after dilution as a primary course of 2 doses (0.3 mL each). It is recommended to administer the second dose 3 weeks after the first dose (see sections 4.4 and 5.1).

Severely immunocompromised aged 12 years and older
A third primary course dose may be administered intramuscularly at least 28 days after the second dose to individuals who are severely immunocompromised (see section 4.4).

Interchangeability 
The interchangeability of Comirnaty with COVID-19 vaccines from other manufacturers to complete the primary course has not been established. Individuals who have received a dose of Comirnaty should continue to receive Comirnaty to complete the primary course. 

Doses of Comirnaty 30 micrograms/dose concentrate for dispersion for injection after dilution (supplied in a vial with a purple cap) and Comirnaty 30 micrograms/dose dispersion for injection (supplied in a vial with a grey cap) are considered interchangeable.

Booster dose

A booster dose of Comirnaty should be administered intramuscularly as early as 3 months after the primary course with Comirnaty in individuals 12 years of age and older.

Comirnaty may also be given as a booster dose in individuals 18 years of age and older who have received a primary course comprised of another mRNA vaccine or adenoviral vector vaccine. 

Paediatric population

There is a paediatric formulation available for children 5 to 11 years of age (i.e. 5 to less than 12 years of age). For details, please refer to the Summary of Product Characteristics for Comirnaty 10 micrograms/dose concentrate for dispersion for injection.

The safety and efficacy of Comirnaty in children aged less than 5 years have not yet been established.

Elderly population

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

Method of administration

Comirnaty 30 micrograms/dose concentrate for dispersion for injection should be administered intramuscularly after dilution (see section 6.6).

After dilution, vials of Comirnaty contain 6 doses of 0.3 mL of vaccine. In order to extract 6 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 is the deltoid muscle of the upper arm.

Do not inject the vaccine intravascularly, subcutaneously or intradermally. 

The vaccine should not be mixed in the same syringe with any other vaccines or medicinal products.

For precautions to be taken before administering the vaccine, see section 4.4.

For instructions regarding thawing, handling and disposal of the vaccine, see section 6.6.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

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 clearly recorded.

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 the vaccine. 

Close observation for at least 15 minutes is recommended following vaccination. No further dose of the vaccine should be given to those who have experienced anaphylaxis after a prior dose of Comirnaty.

Myocarditis and pericarditis

There is an increased risk of myocarditis and pericarditis following vaccination with Comirnaty. These conditions can develop within just a few days after vaccination, and have primarily occurred within 14 days. They have been observed more often after the second vaccination, and more often in younger males (see section 4.8). 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 (including parents or caregivers) 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.

The risk of myocarditis after a third dose of Comirnaty has not yet been characterised.

Anxiety-related reactions

Anxiety-related reactions, including vasovagal reactions (syncope), hyperventilation or stress‐related reactions (e.g. dizziness, palpitations, increases in heart rate, alterations in blood pressure, paraesthesia, hypoaesthesia and sweating) may occur in association with the vaccination process itself. Stress-related reactions are temporary and resolve on their own. Individuals should be advised to bring symptoms to the attention of the vaccination provider for evaluation. It is important that precautions are 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, the vaccine 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 and safety of the vaccine has not been assessed in immunocompromised individuals, including those receiving immunosuppressant therapy. The efficacy of Comirnaty may be lower in immunocompromised individuals.

The recommendation to consider a third dose in severely immunocompromised individuals is based on limited serological evidence from a case-series in the literature from the clinical management of patients with iatrogenic immunocompromisation after solid organ transplantation (see section 4.2).

Duration of protection

The duration of protection afforded by the vaccine is unknown as it is still being determined by ongoing clinical trials.

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 vaccine.

Excipients

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’.

4.5 Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed.

Concomitant administration of Comirnaty with other vaccines has not been studied.

4.6 Fertility, pregnancy and lactation

Pregnancy

A large amount of observational data from pregnant women vaccinated with Comirnaty during the second and third trimester have not shown an increase in adverse pregnancy outcomes. While data on pregnancy outcomes following vaccination during the first trimester are presently limited, no increased risk for miscarriage has been seen. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryo/foetal development, parturition or post-natal development (see section 5.3). Comirnaty can be used during pregnancy.

Breast-feeding

No effects on the breast‑fed newborn/infant are anticipated since the systemic exposure of breast‑feeding woman to Comirnaty is negligible. Observational data from women who were breast‑feeding after vaccination have not shown a risk for adverse effects in breast‑fed newborns/infants. Comirnaty can be used during breast‑feeding.

Fertility

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3)

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 may temporarily affect the ability to drive or use machines.

4.8 Undesirable effects

Summary of safety profile

Participants 16 years of age and older – after 2 doses
In Study 2, 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 vaccine 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 2 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 of age 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 participants 16 years of age and older receiving Comirnaty, that were seropositive for SARS-CoV-2 at baseline, 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 2, 2,260 adolescents (1,131 Comirnaty and 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 2 is ongoing.

The overall safety profile of Comirnaty in adolescents 12 to 15 years of age was similar to that seen in participants 16 years of age and older. 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 16 years of age and older – after booster dose
A subset from Study 2 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 overall safety profile for the booster dose was similar to that seen after 2 doses. 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%).

In Study 4, a placebo-controlled booster study, participants 16 years of age and older recruited from Study 2 received a booster dose of Comirnaty (5,081 participants), or placebo (5,044 participants) at least 6 months after the second dose of Comirnaty. Overall, participants who received a booster dose, had a median follow-up time of 2.5 months after the booster dose to the cut-off date (5 October 2021). No new adverse reactions of Comirnaty were identified.

Booster dose following primary vaccination with another authorised COVID-19 vaccine 
In 5 independent studies on the use of a Comirnaty booster dose in individuals who had completed primary vaccination with another authorized COVID-19 vaccine (heterologous booster dose), no new safety issues were identified (see section 5.1).

Tabulated list of adverse reactions from clinical studies and post-authorisation experience in individuals 12 years of age and older

Adverse reactions observed during clinical studies are listed below 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).

Table 1: Adverse reactions from Comirnaty clinical trials and post-authorisation experience in individuals 12 years of age and older

System Organ Class

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)

Blood and lymphatic system disorders

 

 

Lymphadenopathya

 

 

 

Immune system disorders

 

 

Hypersensitivity reactions (e.g. rash, pruritus, urticariab, angioedemab)

 

 

Anaphylaxis
Metabolism and nutrition disorders  Decreased appetite   

Psychiatric disorders

 

 

Insomnia

 

 

 

Nervous system disorders

Headache

 

Lethargy

Acute peripheral facial paralysisc

 

 

Paraesthesiad; Hypoaesthesiad
Cardiac disorders    

Myocarditisd ;

Pericarditisd

 

Gastrointestinal disorders

Diarrhoead

Nausea; Vomiting d

 

 

 

 
Skin and subcutaneous tissue disorder  Hyperhidrosis;
Night sweats
  Erythema multiformed

Musculoskeletal and connective tissue disorders

Arthralgia; Myalgia

 

Pain in extremitye

 

 

 

General disorders and administration site conditions

Injection site pain; Fatigue; Chills; Pyrexiaf; Injection site swelling

Injection site redness

Asthenia; Malaise; Injection site pruritus

 

 

Extensive swelling of vaccinated limbd;

Facial swellingg

a.    A higher frequency of lymphadenopathy (2.8% vs. 0.4%) was observed in participants receiving a booster dose in Study 4 compared to participants receiving 2 doses.
b.    The frequency category for urticaria and angioedema was rare.
c.    Through the clinical trial safety follow-up period to 14 November 2020, acute peripheral facial paralysis (or palsy) was reported by four participants in the COVID-19 mRNA Vaccine group. Onset was Day 37 after Dose 1 (participant did not receive Dose 2) and Days 3, 9, and 48 after Dose 2. No cases of acute peripheral facial paralysis (or palsy) were reported in the placebo group.
d.    Adverse reaction determined postauthorisation.
e.    Refers to vaccinated arm.
f.     A higher frequency of pyrexia was observed after the second dose compared to the first dose.
g.    Facial swelling in vaccine recipients with a history of injection of dermatological fillers has been reported in the post-marketing phase.

Description of selected adverse reactions

Myocarditis
The increased risk of myocarditis after vaccination with Comirnaty is highest in younger males (see section 4.4).

Two large European pharmacoepidemiological studies have estimated the excess risk in younger males following the second dose of Comirnaty. One study showed that in a period of 7 days after the second dose there were about 0.265 (95% CI 0.255 - 0.275) extra cases of myocarditis in 12-29 year old males per 10,000 compared to unexposed persons. In another study, in a period of 28 days after the second dose there were 0.57 [95% CI 0.39 – 0.75] extra cases of myocarditis in 16-24 year old males per 10,000 compared to unexposed persons.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation 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 via the national reporting system listed in Appendix V and include batch/Lot number if available.

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 vaccine 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.