Cominarty 30.0 _g Concentrate for dispersion for injection

COMIRNATY 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.

Posology

Individuals 12 years of age and older

COMIRNATY is administered intramuscularly after dilution as a 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). There are no data available on the interchangeability of COMIRNATY with other COVID-19 vaccines to complete the vaccination course. Individuals who have received 1 dose of COMIRNATY should receive a second dose of COMIRNATY to complete the vaccination course.

Special populations

Elderly

No dosage adjustment is required in elderly individuals u2265 65 years of age.

Paediatric population

The safety and efficacy of COMIRNATY in paediatric participants aged less than 12 years have not yet been established. Limited data are available.

Method of administration

COMIRNATY should be administered intramuscularly after dilution (see section 6.6). After dilution, vials of COMIRNATY contain six doses of 0,3 mL of vaccine. In order to extract six 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 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 [((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) (ALC- 0315); 2 [(polyethylene glycol)-2000]-N,N-ditetradecylacetamide (ALC-0159); 1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC); cholesterol; potassium chloride; potassium dihydrogen phosphate sodium chloride; disodium phosphate dihydrate; sucrose; water for injections].

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

Myocarditis and pericarditis

Very rare cases of myocarditis and pericarditis have been observed following vaccination with COMIRNATY. These cases have primarily occurred within 14 days following vaccination, more often after the second vaccination, and more often in younger men. 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 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.

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, 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.

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, safety and immunogenicity of the vaccine has not been assessed in immunocompromised individuals, including those receiving immunosuppressant therapy. The efficacy of COMIRNATY may be lower in immunosuppressed 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

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

COMIRNATY contains less than 1 mmol potassium (39 mg) per dose, that is to say essentially u2018potassium-freeu2019. COMIRNATY contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially u2018sodium-freeu2019. Refer to sections 4.3 or 6.1 for the full list of excipients.

No interaction studies have been performed. Concomitant administration of COMIRNATY with other vaccines has not been studied.

Pregnancy

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.

Breastfeeding

It is unknown whether COMIRNATY is excreted in human milk.

Fertility

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.

Summary of the safety profile

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.

Participants 16 years of age and older

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 participantsu2019 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 u2265 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 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 (> 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

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 were injection site pain (> 90 %), fatigue and headache (> 70 %), myalgia and chills (> 40 %), arthralgia and pyrexia (> 20 %).

Tabulated list of adverse reactions from clinical studies and post-authorisation 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 (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).

Table 1: Adverse reactions from COMIRNATY clinical trials in individuals 12 years of age and older

System organ class Frequency Adverse reaction

• Blood and lymphatic system disorders Uncommon Lymphadenopathy
• Immune system disorders Uncommon Hypersensitivity reactions (e.g. rash, pruritus, urticaria a , angioedema a ) Not known Anaphylaxis
• Metabolism and nutrition disorders Uncommon Decreased appetite
• Psychiatric disorders Uncommon Insomnia
• Nervous system disorders Very common Headache Uncommon Lethargy Rare Acute peripheral facial paralysis b
• Gastrointestinal disorders Common Nausea
• Skin and subcutaneous tissue disorders Uncommon Hyperhidrosis, night sweats
• Musculoskeletal and connective tissue disorders Very common Arthralgia, myalgia Uncommon Pain in extremity c
• General disorders and administration site conditions Very common Injection site pain, fatigue, chills, pyrexia d , injection site swelling Common Injection site redness
• Uncommon Asthenia, 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. Refers to vaccinated arm.

d. A higher frequency of pyrexia was observed after the second dose.

Post-marketing side effects

Cardiac disorders: Myocarditis, pericarditis

Gastrointestinal disorders: Diarrhoea, vomiting

General disorders and administration site conditions: Extensive swelling of vaccinated limb, facial swelling

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8.

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.