4.1. Therapeutic indications

Comirnaty LP.8.1 10 micrograms/dose dispersion for injection, single dose vial is indicated for active immunisation to prevent COVID-19 caused by SARS-CoV-2, in children aged 5 to 11 years.

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

4.2. Posology and method of administration

Posology

Children 5 to 11 years of age (i.e. 5 to less than 12 years of age)

Comirnaty LP.8.1 10 micrograms/dose dispersion for injection, single dose vial is administered intramuscularly as a single dose of 0.3 mL for children 5 to 11 years of age regardless of prior COVID-19 vaccination status (see sections 4.4 and 5.1).

For individuals who have previously been vaccinated with a COVID-19 vaccine, Comirnaty LP.8.1 should be administered at least 3 months after the most recent dose of a COVID-19 vaccine.

Severely immunocompromised individuals

Additional doses may be administered to individuals who are severely immunocompromised in accordance with national recommendations (see section 4.4).

Paediatric population

There are paediatric formulations available for infants and children aged 6 months to 4 years. For details, please refer to the Summary of Product Characteristics for other formulations.

The safety and efficacy of the vaccine in infants aged less than 6 months have not yet been established.

Method of administration

Comirnaty LP.8.1 10 micrograms/dose dispersion for injection, single dose vial should be administered intramuscularly (see section 6.6). Do not dilute prior to use.

The preferred site is the deltoid muscle of the upper arm.

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.

Single dose vials

Single dose vials of Comirnaty LP.8.1 contain 1 dose of 0.3 mL of vaccine.

• Withdraw a single 0.3 mL dose of Comirnaty LP.8.1.

• Discard vial and any excess volume.

• Do not pool excess vaccine from multiple vials.

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 indicate that most cases recover. Some cases required intensive care support and fatal cases have been observed.

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.

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

Safety and immunogenicity have been assessed in a limited number of immunocompromised individuals, including those receiving immunosuppressant therapy (see sections 4.8 and 5.1). The efficacy of Comirnaty LP.8.1 may be lower in immunocompromised individuals.

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 LP.8.1 may not protect all vaccine recipients. Individuals may not be fully protected until 7 days after their vaccination.

4.5. Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed.

Concomitant administration of Comirnaty LP.8.1 10 micrograms/dose dispersion for injection, single dose vial with other vaccines has not been studied.

4.6. Fertility, pregnancy and lactation

Pregnancy

No data are available yet regarding the use of Comirnaty LP.8.1 during pregnancy.

However, there are limited clinical study data (less than 300 pregnancy outcomes) from the use of Comirnaty in pregnant participants. A large amount of observational data from pregnant women vaccinated with the initially approved Comirnaty vaccine 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). Based on data available with other vaccine variants, Comirnaty LP.8.1 can be used during pregnancy.

Breast-feeding

No data are available yet regarding the use of Comirnaty LP.8.1 during breast‑feeding.

However, no effects on the breastfed newborn/infant are anticipated since the systemic exposure of breast‑feeding woman to the vaccine is negligible. Observational data from women who were breast‑feeding after vaccination with the initially approved Comirnaty vaccine have not shown a risk for adverse effects in breastfed newborns/infants. Comirnaty LP.8.1 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 LP.8.1 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

The safety of Comirnaty LP.8.1 is inferred from safety data of the prior Comirnaty vaccines.

Initially approved Comirnaty vaccine

Children 5 to 11 years of age (i.e. 5 to less than 12 years of age) – after 2 doses

In Study 3, a total of 3 109 children 5 to 11 years of age received at least 1 dose of the initially approved Comirnaty vaccine 10 mcg and a total of 1 538 children 5 to 11 years of age received placebo. At the time of the analysis of Study 3 Phase 2/3 with data up to the cut-off date of 20 May 2022, 2 206 (1 481 Comirnaty 10 mcg and 725 placebo) children have been followed for ≥ 4 months after the second dose in the placebo‑controlled blinded follow-up period. The safety evaluation in Study 3 is ongoing.

The overall safety profile of Comirnaty in participants 5 to 11 years of age was similar to that seen in participants 16 years of age and older. The most frequent adverse reactions in children 5 to 11 years of age that received 2 doses were injection site pain (> 80%), fatigue (> 50%), headache (> 30%), injection site redness and swelling (≥ 20%), myalgia, chills, and diarrhoea (> 10%).

Children 5 to 11 years of age (i.e. 5 to less than 12 years of age) – after booster dose

In a subset from Study 3, a total of 2 408 children 5 to 11 years of age received a booster dose of Comirnaty 10 mcg at least 5 months (range of 5.3 to 19.4 months) after completing the primary series. The analysis of the Study 3 Phase 2/3 subset is based on data up to the cut-off date of 28 February 2023 (median follow-up time of 6.4 months).

The overall safety profile for the booster dose was similar to that seen after the primary course. The most frequent adverse reactions in children 5 to 11 years of age after the booster dose were injection site pain (> 60%), fatigue (> 30%), headache (> 20%), myalgia, chills, injection site redness and swelling (> 10%).

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.

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 2 doses

In Study 2, a total of 22 026 participants 16 years of age or older received at least 1 dose of initially approved Comirnaty vaccine 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.

Participants 12 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. Overall, participants who received a booster dose, had a median follow-up time of 8.3 months (range 1.1 to 8.5 months) and 301 participants had been followed for ≥ 6 months after the booster dose to the cut-off date (22 November 2021).

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 2.8 months (range 0.3 to 7.5 months) after the booster dose in the blinded placebo‑controlled follow-up period to the cut-off date (8 February 2022). Of these, 1 281 participants (895 Comirnaty and 386 placebo) have been followed for ≥ 4 months after the booster dose of Comirnaty. No new adverse reactions of Comirnaty were identified.

A subset from Study 2 Phase 2/3 participants of 825 adolescents 12 to 15 years of age who completed the original Comirnaty 2-dose course, received a booster dose of Comirnaty approximately 11.2 months (range of 6.3 to 20.1 months) after receiving Dose 2. Overall, participants who received a booster dose, had a median follow-up time of 9.5 months (range 1.5 to 10.7 months) based on data up to the cut-off date (3 November 2022). No new adverse reactions of Comirnaty were identified.

Participants 12 years of age and older – after subsequent booster doses

The safety of a booster dose of Comirnaty in participants 12 years of age and older is inferred from safety data from studies of a booster dose of Comirnaty in participants 18 years of age and older.

A subset of 325 adults 18 to ≤ 55 years of age who had completed 3 doses of Comirnaty, received a booster (fourth dose) of Comirnaty 90 to 180 days after receiving Dose 3. Participants who received a booster (fourth dose) of Comirnaty had a median follow-up time of 1.4 months up to a data cut-off date of 11 March 2022. The most frequent adverse reactions in these participants were injection site pain (> 70%), fatigue (> 60%), headache (> 40%), myalgia and chills (> 20%), and arthralgia (> 10%).

In a subset from Study 4 (Phase 3), 305 adults > 55 years of age who had completed 3 doses of Comirnaty, received a booster (fourth dose) of Comirnaty 5 to 12 months after receiving Dose 3. Participants who received a booster (fourth dose) of Comirnaty had a median follow-up time of at least 1.7 months up to a data cut-off date of 16 May 2022. The overall safety profile for the Comirnaty booster (fourth dose) was similar to that seen after the Comirnaty booster (third dose). The most frequent adverse reactions in participants > 55 years of age were injection site pain (> 60%), fatigue (> 40%), headache (> 20%), myalgia and chills (> 10%).

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 authorised COVID-19 vaccine (heterologous booster dose), no new safety issues were identified.

Omicron-adapted Comirnaty

Children 5 to 11 years of age (i.e. 5 to less than 12 years of age) – after the booster (fourth dose)

In a subset from Study 6 (Phase 3), 113 participants 5 to 11 years of age who had completed 3 doses of Comirnaty, received a booster (fourth dose) of Comirnaty Original/Omicron BA.4-5 (5/5 mcg) 2.6 to 8.5 months after receiving Dose 3. Participants who received a booster (fourth dose) of Comirnaty Original/Omicron BA.4-5 had a median follow-up time of 6.3 months.

The overall safety profile for the Comirnaty Original/Omicron BA.4-5 booster (fourth dose) was similar to that seen after 3 doses. The most frequent adverse reactions in participants 5 to 11 years of age were injection site pain (> 60%), fatigue (> 40%), headache (> 20%), and myalgia (> 10%).

Participants 12 years of age and older – after a booster dose of Comirnaty Original/Omicron BA.4-5 (fourth dose)

In a subset from Study 5 (Phase 2/3), 107 participants 12 to 17 years of age, 313 participants 18 to 55 years of age and 306 participants 56 years of age and older who had completed 3 doses of Comirnaty, received a booster (fourth dose) of Comirnaty Original/Omicron BA.4-5 (15/15 mcg) 5.4 to 16.9 months after receiving Dose 3. Participants who received a booster (fourth dose) of Comirnaty Original/Omicron BA.4-5 had a median follow-up time of at least 1.5 months.

The overall safety profile for the Comirnaty Original/Omicron BA.4-5 booster (fourth dose) was similar to that seen after 3 doses. The most frequent adverse reactions in participants 12 years of age and older were injection site pain (> 60%), fatigue (> 50%), headache (> 40%), myalgia (> 20%), chills (> 10%), and arthralgia (> 10%).

Participants 12 years of age and older – after a booster dose of Comirnaty Omicron XBB.1.5 (fourth dose or more)

In a subset from Study 13 (Phase 2/3), 412 participants 12 years of age and older, who had received at least 3 doses of an authorised mRNA COVID-19 vaccine, received a booster (fourth dose or more) of Comirnaty Omicron XBB.1.5 2.0 to 24.1 months after receiving Dose 3. Participants who received a booster (fourth dose or more) of Comirnaty XBB.1.5 had a median follow-up time of 6.3 months.

The safety profile of Comirnaty Omicron XBB.1.5 was similar to the overall Comirnaty safety profile.

Participants 12 years of age and older – after a single dose of Comirnaty Omicron XBB.1.5

In a subset from Study 13 (Phase 2/3), 311 participants 12 years of age and older who were considered to be baseline SARS-CoV-2 positive and COVID-19 vaccine-naïve, received 1 dose of Comirnaty Omicron XBB.1.5. Participants had a median follow-up time of 6.4 months.

The safety profile of Comirnaty Omicron XBB.1.5 was similar to the overall Comirnaty safety profile. The most frequent adverse reactions in participants were injection site pain (> 50%), fatigue (> 30%), headache (> 20%), myalgia, diarrhoea, arthralgia, chills and injection site swelling (> 10%).

Participants 12 years of age and older – after a single dose of Comirnaty Omicron JN.1

In a subset from Study 13 (Phase 2/3), 216 participants 12 years of age and older received 1 dose of Comirnaty Omicron JN.1 and had a median follow-up time of 6.3 months.

The safety profile of Comirnaty Omicron JN.1 was similar to the overall Comirnaty safety profile. The most frequent adverse reactions in participants were injection site pain (> 60%), fatigue (>30%), headache (>20%), myalgia, chills and injection site swelling (>10%).

Participants 18 years of age and older – after a single dose of Comirnaty Omicron KP.2

In a subset from Study 13 (Phase 2/3), 102 participants 18 years of age and older received 1 dose of Comirnaty Omicron KP.2 and had a median follow-up time of 6.3 months.

The safety profile of Comirnaty Omicron KP.2 was similar to the overall Comirnaty safety profile. The most frequent adverse reactions in participants were injection site pain (> 50%), fatigue (>40%), headache and myalgia (>20%).

Tabulated list of adverse reactions from clinical studies of Comirnaty and Comirnaty Original/Omicron BA.4-5 and post‑authorisation experience of Comirnaty in individuals 5 years of age and older

Adverse reactions observed during clinical studies and post-authorisation experience 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 2. Adverse reactions from Comirnaty and Comirnaty Original/Omicron BA.4-5 clinical trials and Comirnaty post‑authorisation experience in individuals 5 years of age and older

System Organ Class

Frequency

Adverse reactions

Blood and lymphatic system disorders

Common

Lymphadenopathya

Immune system disorders

Uncommon

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

Not known

Anaphylaxis

Metabolism and nutrition disorders

Uncommon

Decreased appetite

Psychiatric disorders

Uncommon

Insomnia

Nervous system disorders

Very common

Headache

Uncommon

Dizzinessd; lethargy

Rare

Acute peripheral facial paralysisc

Not known

Paraesthesiad; hypoaesthesiad

Cardiac disorders

Very rare

Myocarditisd; pericarditisd

Gastrointestinal disorders

Very common

Diarrhoead

Common

Nausea; vomitingd,j

Skin and subcutaneous tissue disorder

Uncommon

Hyperhidrosis; night sweats

Not known

Erythema multiformed

Musculoskeletal and connective tissue disorders

Very common

Arthralgia; myalgia

Uncommon

Pain in extremitye

Reproductive system and breast disorders

Not known

Heavy menstrual bleedingi

General disorders and administration site conditions

Very common

Injection site pain; fatigue; chills; pyrexiaf; injection site swelling

Common

Injection site rednessh

Uncommon

Asthenia; malaise; injection site pruritus

Not known

Extensive swelling of vaccinated limbd; facial swellingg

a. In participants 5 years of age and older, a higher frequency of lymphadenopathy was reported after a booster (≤ 2.8%) dose than after primary (≤ 0.9%) doses of the vaccine.

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 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.

h. Injection site redness occurred at a higher frequency (very common) in children 5 to 11 years of age and in immunocompromised participants 5 years of age and older.

i. Most cases appeared to be non-serious and temporary in nature.

j. The frequency category for vomiting was very common in pregnant women 18 years of age and older and in immunocompromised participants 5 to 18 years of age.

Special populations

Infants born to pregnant participants – after 2 doses of Comirnaty

Study C4591015 (Study 9), a Phase 2/3, placebo-controlled study, evaluated a total of 346 pregnant participants who received Comirnaty (n = 173) or placebo (n = 173). Infants (Comirnaty n = 167 or placebo n = 168) were evaluated up to 6 months. No safety concerns were identified that were attributable to maternal vaccination with Comirnaty.

Immunocompromised participants (adults and children)

In study C4591024 (Study 10), a total of 124 immunocompromised participants 2 years of age and older received Comirnaty (see section 5.1).

Safety with concomitant vaccine administration

Concomitant administration with seasonal influenza vaccine

In Study 8, a Phase 3 study, participants 18 through 64 years of age who received Comirnaty coadministered with seasonal inactivated influenza vaccine (SIIV), quadrivalent followed 1 month later by placebo, were compared to participants who received an inactivated influenza vaccine with placebo followed 1 month later by Comirnaty alone (n = 553 to 564 participants in each group).

Concomitant administration with pneumococcal conjugate vaccine

In Study 11 (B7471026), a Phase 3 study, participants 65 years of age and older who received a booster dose of Comirnaty coadministered with 20-valent pneumococcal conjugate vaccine (20vPNC) (n = 187) were compared to participants who received Comirnaty alone (n = 185).

Concomitant administration with an unadjuvanted recombinant protein RSV vaccine or with an unadjuvanted recombinant protein RSV vaccine and a high dose influenza vaccine

In Study 12 (C5481001), a Phase 1/2 study, participants 65 years of age and older who received Comirnaty Original/Omicron BA.4-5 and RSV vaccine coadministered in one arm plus high dose quadrivalent influenza vaccine (QIV) (n = 158) or placebo (n = 157) in the opposite arm were compared to participants who received the individual vaccines given with placebo.

Description of selected adverse reactions

Myocarditis and pericarditis

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 0.56 (95% CI: 0.37 - 0.74) extra cases of myocarditis in 16-24 year old males per 10 000 compared to unexposed persons.

Limited data indicate that the risk of myocarditis and pericarditis after vaccination with Comirnaty in children aged 5 to 11 years seems lower than in ages 12 to 17 years.

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 a Yellow card. Reporting forms and information can be found at https://coronavirus-yellowcard.mhra.gov.uk/ or search for MHRA Yellow Card in the Google Play or Apple App Store.

Alternatively, adverse events of concern in association with Comirnaty can be reported to Pfizer Medical Information on 01304 616161 or via www.pfizersafetyreporting.com.

Please do not report the same adverse event(s) to both systems as all reports will be shared between Pfizer and MHRA (in an anonymized form) and dual reporting will create unnecessary duplicates.

4.9. Overdose

There have been reports of higher than recommended doses of Comirnaty in clinical trials and post-authorisation experience. In general, adverse events reported with overdoses have been similar to the known adverse reaction profile of Comirnaty.

In the event of overdose, monitoring of vital functions and possible symptomatic treatment is recommended.