Comirnaty Dilute To Use Paediatric Vaccine 10 micrograms

COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE 10 micrograms/dose concentrate for dispersion for injection 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.

Posology
Children 5 to 11 years of age (i.e. 5 to less than 12 years of age) COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE 10 micrograms/dose is administered intramuscularly after dilution as a primary course of 2 doses (0,2 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 5 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 DILUTE TO USE PAEDIATRIC VACCINE with COVID-19 vaccines from other manufacturers to complete the vaccination course has not been established. Individuals who have received a dose of COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE should continue to receive COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE to complete the primary course.

COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE 10 micrograms/dose should be used only for children 5 to 11 years of age.

Paediatric population
The safety and efficacy of COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE in children aged less than 5 years have not yet been established.

Method of administration
COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE 10 micrograms/dose concentrate for dispersion for injection should be administered intramuscularly after dilution (see section 6.6). After dilution, vials of COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE contain 10 doses of 0,2 mL of vaccine. In order to extract 10 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 10 doses from a single vial. Irrespective of the type of syringe and needle:
u2022 Each dose must contain 0,2 mL of vaccine
u2022 If the amount of vaccine remaining in the vial cannot provide a full dose of 0,2 mL, discard the vial and any excess volume
u2022 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 medicines. 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.

Hypersensitivity to COVID-19 mRNA vaccine (nucleoside modified) or to any of the excipients listed in section 6.1.

Traceability
In order to improve the traceability of biological medicines, the name and the batch number of the administered medicine 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 DILUTE TO USE PAEDIATRIC VACCINE.

Myocarditis and pericarditis
There is an increased risk of myocarditis and pericarditis following vaccination with COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE. 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.
Medical practitioners 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. Medical practitioners should consult guidance and/or specialists to diagnose and treat this condition. The risk of myocarditis after a third dose of COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE 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
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 DILUTE TO USE PAEDIATRIC VACCINE 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
Vaccination with COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE may not protect all vaccine recipients. Individuals may not be fully protected until 7 days after their second dose of vaccine.

Excipients
COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE contains less than 1 mmol sodium (0,9 mg) per dose, that is to say essentially u2018sodium-freeu2019.

No interaction studies have been performed. Concomitant administration of COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE with other vaccines has not been studied.

Pregnancy
A large amount of observational data from pregnant women vaccinated with COMIRNATY DILUTE TO USE PAEDIATRIC 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). COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE can be used during pregnancy.

Breastfeeding
No effects on the breastfed newborn/infant are anticipated since the systemic exposure of breastfeeding woman to COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE is negligible. Observational data from women who were breastfeeding after vaccination have not shown a risk for adverse effects in breastfed newborns/infants. COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE can be used during breastfeeding.

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

COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE 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.

Summary of the safety profile
Children 5 to 11 years of age (i.e. 5 to less than 12 years of age) u2013 after 2 doses In Study 3, a total of 1,518 children 5 to 11 years of age received at least 1 dose of COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE 10 mcg and a total of 750 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 6 September 2021, 2,158 (95,1 %) (1,444 COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE 10 mcg and 714 placebo) children have been followed for at least 2 months after the second dose of COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE 10 mcg. An analysis of Study 3 Phase 2/3 adverse event data also included another 2,379 participants [1,591 COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE 10 mcg and 788 placebo], of whom 71,2 % had a follow-up period for at least 2 weeks after Dose 2 up to the cut-off date of 8 October 2021. The safety evaluation in Study 3 is ongoing. The overall safety profile of COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE in participants 5 to 15 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 were injection site pain (> 80 %), fatigue (> 50 %), headache (> 30 %), injection site redness and swelling (> 20 %), myalgia and chills (> 10 %).

Adolescents 12 to 15 years of age u2013 after 2 doses In an analysis of long-term safety follow-up in Study 2, 2,260 adolescents (1,131 COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE 30 mcg and 1,129 placebo) were 12 to 15 years of age. Of these, 1,559 adolescents (786 COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE and 773 placebo) have been followed for at least u2265 4 months after the second dose of COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE. The safety evaluation in Study 2 is ongoing. The overall safety profile of COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE 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 u2013 after 2 doses In Study 2, a total of 22,026 participants 16 years of age and older received at least 1 dose of COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE 30 mcg and a total of 22,021 participants 16 years of age and 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 and older received 2 doses of COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE. 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 participantsu2019 unblinding dates, a total of 25,651 (58,2 %) participants (13,031 COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE and 12,620 placebo) 16 years of age and older were followed up for u2265 4 months after the second dose. This included a total of 15,111 (7,704 COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE and 7,407 placebo) participants 16 to 55 years of age and a total of 10,540 (5,327 COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE 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 DILUTE TO USE PAEDIATRIC VACCINE, that were seropositive for SARS-CoV-2 at baseline, was similar to that seen in the general population.
Participants 16 years of age and older u2013 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 2-dose course, received a booster dose of COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE 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 DILUTE TO USE PAEDIATRIC VACCINE (5,081 participants), or placebo (5,044 participants) at least 6 months after the second dose of COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE. 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 DILUTE TO USE PAEDIATRIC VACCINE were identified.

Booster dose following primary vaccination with another authorised COVID-19 vaccine
In 5 independent studies on the use of a COMIRNATY DILUTE TO USE PAEDIATRIC VACCINE booster dose in individuals who had completed primary vaccination with another authorized COVID-19 vaccine (heterologous booster dose), no new safety issues were identified.

Tabulated list of adverse reactions from clinical studies and post-authorisation in individuals 5 years of age and older
Adverse reactions observed during clinical studies are listed below according to the following frequency categories: Very common (u2265 1/10), common (u2265 1/100 to < 1/10), uncommon (u2265 1/1,000 to < 1/100), rare (u2265 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data).

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 DILUTE TO USE PAEDIATRIC VACCINE. 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.