Tozinameran Other names: BNT162b2

The efficacy and safety of the vaccine has not been assessed in immunocompromised individuals, including those receiving immunosuppressant therapy. The efficacy of tozinameran 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.

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. A second dose of the vaccine should not be given to those who have experienced anaphylaxis to the first dose of tozinameran.

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.

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.

Anxiety-related reactions, including vasovagal reactions (syncope), hyperventilation or stress‐related reactions (e.g. dizziness, palpitations, increases in heart rate, alterations in blood pressure, tingling sensations 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.

There is an increased risk of myocarditis and pericarditis following vaccination with tozinameran. 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. 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 tozinameran has not yet been characterised.

There is limited experience with use of COVID-19 mRNA vaccine (nucleoside modified) in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryo/foetal development, parturition or post-natal development. Administration in pregnancy should only be considered when the potential benefits outweigh any potential risks for the mother and foetus.

For women of childbearing age, pregnancy should be excluded before vaccination. In addition, women of childbearing age should be advised to avoid pregnancy for at least 2 months after their second dose.

All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Available data on COVID-19 mRNA vaccine (nucleoside modified) administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy.

It is unknown whether mRNA vaccine is excreted in human milk. A risk to the newborns/infants cannot be excluded. COVID-19 mRNA vaccine (nucleoside modified) should not be used during breast-feeding.

Fertility

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.

COVID-19 mRNA vaccine (nucleoside modified) has no or negligible influence on the ability to drive and use machines. However, some of the adverse reactions may temporarily affect the ability to drive or use machines.

Summary of safety profile

The safety of the mRNA vaccine (nucleoside modified) was evaluated in participants 16 years of age and older in 2 clinical studies that included 21,744 participants that have received at least one dose of the vaccine.

In Study 2, a total of 21,720 participants 16 years of age or older received at least 1 dose of mRNA vaccine (nucleoside modified) and a total of 21,728 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 the vaccine.

At the time of the analysis of Study 2, a total of 19,067 (9,531 mRNA vaccine and 9,536 placebo) participants 16 years of age or older were evaluated for safety for at least 2 months after the second dose of the mRNA vaccine (nucleoside modified). This included a total of 10,727 (5,350 mRNA vaccine and 5,377 placebo) participants 16 to 55 years of age and a total of 8,340 (4,181 mRNA vaccine and 4,159 placebo) participants 56 years and older.

The most frequent adverse reactions in participants 16 years of age and older were injection site pain (>80%), fatigue (>60%), headache (>50%), myalgia and 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.

List of adverse reactions from clinical studies

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).

Adverse reactions from mRNA vaccine (nucleoside modified) clinical trials and post-authorisation experience:

Blood and lymphatic system disorders

Uncommon: Lymphadenopathy

Immune system disorders

Uncommon: Hypersensitivity reactions (e.g. rash, pruritus, urticaria^a, angioedema^a)

Not known: Anaphylaxis

Psychiatric disorders

Uncommon: Insomnia

Nervous system disorders

Very common: Headache

Rare: Acute peripheral facial paralysis^b

Gastrointestinal disorders

Very common: Diarrhoea^c

Common: Nausea; Vomiting^c

Musculoskeletal and connective tissue disorders

Very common: Arthralgia; Myalgia

Uncommon: Pain in extremity^d

General disorders and administration site conditions

Very common: Injection site pain; Fatigue; Chills; Pyrexia^e; Injection site swelling

Common: Injection site redness

Uncommon: Malaise; Injection site pruritus

^a The frequency category for urticaria and angioedema was Rare.
^b 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.
^c Adverse reaction determined post-authorisation.
^d Refers to vaccinated arm.
^e A higher frequency of pyrexia was observed after the second dose.

The safety profile in 545 subjects receiving mRNA vaccine (nucleoside modified), that were seropositive for SARS-CoV-2 at baseline, was similar to that seen in the general population.