Source: European Medicines Agency (EU) Revision Year: 2021 Publisher: BioNTech Manufacturing GmbH, An der Goldgrube 12, 55131 Mainz, Germany Phone: +49 6131 9084-0 Fax: +49 6131 9084-2121 service@biontech.de
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
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 Comirnaty.
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, 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.
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.
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.
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).
The duration of protection afforded by the vaccine is unknown as it is still being determined by ongoing clinical trials.
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.
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’.
No interaction studies have been performed.
Concomitant administration of Comirnaty with other vaccines has not been studied.
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/foetal development, parturition or post-natal development (see section 5.3). Administration of Comirnaty in pregnancy should only be considered when the potential benefits outweigh any potential risks for the mother and foetus.
It is unknown whether Comirnaty is excreted in human milk.
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).
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.
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.
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.
Additionally, 306 existing Phase 3 participants 18 to 55 years of age received a booster dose (third dose) of Comirnaty approximately 6 months after the second dose. The overall safety profile for the booster dose (third dose) was similar to that seen 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.
In an analysis of Study 2, based on data up to the cut-off date of 13 March 2021, 2,260 adolescents (1,131 Comirnaty and 1,129 placebo) were 12 to 15 years of age. Of these, 1,308 adolescents (660 Comirnaty and 648 placebo) have been followed for at least 2 months after the second dose of Comirnaty. The safety evaluation in Study 2 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%).
A subset from Study 2 Phase ⅔ participants of 306 adults 18 to 55 years of age who completed the original Comirnaty 2-dose course, received a booster dose (third 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%).
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 | |||
| Cardiac disorders | Myocarditisd; Pericarditisd | |||||
| Gastrointestinal disorders | Diarrhoead | Nausea; Vomitingd | ||||
| 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 (5.2% vs 0.4%) was observed in participants receiving a booster dose (third dose) 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 post-authorisation.
e Refers to vaccinated arm.
f A higher frequency of pyrexia was observed after the second dose compare to the first dose.
g Facial swelling in vaccine recipients with a history of injection of dermatological fillers has been reported in the postmarketing phase.
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 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.
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.
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