4.1. Therapeutic indications

Nuvaxovid JN.1 is indicated for active immunisation to prevent COVID-19 caused by SARS-CoV-2 in individuals 12 years of age and older.

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

4.2. Posology and method of administration

Posology

Nuvaxovid JN.1 is administered intramuscularly as a single dose (0.5 mL) for individuals 12 years of age and older regardless of previous vaccination status.

For individuals who have previously been vaccinated with a COVID-19 vaccine, Nuvaxovid JN.1 should be administered at least 3 months after the most recent dose of a COVID-19 vaccine.

Immunocompromised individuals

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

Paediatric population

The safety and efficacy of Nuvaxovid JN.1 in children aged less than 12 years have not yet been established. No data are available.

Elderly population

No dose adjustment is required in elderly individuals ≥ 65 years of age.

Method of administration

Nuvaxovid JN.1 is for intramuscular injection only, preferably into 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 on handling and disposal of the vaccine, see section 6.6.

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 with Nuvaxovid. 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. An additional dose of the vaccine should not be given to those who have experienced anaphylaxis to a prior dose of Nuvaxovid.

Myocarditis and pericarditis

There is an increased risk of myocarditis and pericarditis following vaccination with Nuvaxovid. These conditions can develop within just a few days after vaccination and have primarily occurred within 14 days, 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.

Anxiety-related reactions

Anxiety-related reactions, including vasovagal reactions (syncope), hyperventilation, or stress‐related reactions may occur in association with vaccination as a psychogenic response to the needle injection. It is important that precautions are in place to avoid injury from fainting.

Concurrent illness

Vaccination should be postponed in individuals suffering from an 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

The efficacy, safety, and immunogenicity of the vaccine has been assessed in a limited number of immunocompromised individuals. The efficacy of Nuvaxovid JN.1 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

Individuals may not be fully protected until 7 days after their vaccination. As with all vaccines, vaccination with Nuvaxovid JN.1 may not protect all vaccine recipients.

Excipients

Sodium

This vaccine contains less than 1 mmol sodium (23 mg) per dose, that is to say, essentially 'sodium-free'.

Potassium

This vaccine contains potassium, less than 1 mmol (39 mg) per dose, that is to say, essentially 'potassium-free'.

Polysorbate 80

This medicine contains 0.05 mg of polysorbate 80 per dose. Polysorbates may cause allergic reactions.

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

Co-administration of Nuvaxovid (Original, Wuhan strain) with inactivated influenza vaccines has been evaluated in a limited number of participants in an exploratory clinical trial sub-study, see section 4.8 and section 5.1.

The binding antibody response to SARS-CoV-2 was lower when Nuvaxovid was given concomitantly with inactivated influenza vaccine. The clinical significance of this is unknown.

Concomitant administration of Nuvaxovid JN.1 with other vaccines has not been studied.

4.6. Fertility, pregnancy and lactation

Pregnancy

There is limited experience with use of Nuvaxovid in pregnant women.

Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryo/fetal development, parturition, or post-natal development, see section 5.3.

Administration of Nuvaxovid JN.1 in pregnancy should only be considered when the potential benefits outweigh any potential risks for the mother and fetus.

Breast-feeding

It is unknown whether Nuvaxovid JN.1 is excreted in human milk.

Fertility

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

4.7. Effects on ability to drive and use machines

Nuvaxovid JN.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

Nuvaxovid (Original, Wuhan strain)

Summary of the safety profile after primary series

Participants 18 years of age and older

The safety of Nuvaxovid was evaluated from an interim analysis of pooled data from 5 ongoing clinical trials conducted in Australia, South Africa, the United Kingdom, the United States and Mexico. At the time of the analysis, a total of 49,950 participants aged 18 years and older received at least one dose of the two-dose primary series of Nuvaxovid (n=30,058) or placebo (n=19,892). At the time of vaccination, the median age was 48 years (range 18 to 95 years). The median duration of follow-up was 70 days post-Dose 2, with 32,993 (66%) participants completing more than 2 months follow-up post-Dose 2.

Of the pooled reactogenicity data, which includes participants aged 18 years and older enrolled in the two phase 3 studies who received any dose of Nuvaxovid (n=20,055) or placebo (n=10,561), the most frequent adverse reactions were injection site tenderness (75%), injection site pain (62%), fatigue (53%), myalgia (51%), headache (50%), malaise (41%), arthralgia (24%), and nausea or vomiting (15%). Adverse reactions were usually mild to moderate in severity with a median duration of less than or equal to 2 days for local events and less than or equal to 1 day for systemic events following vaccination.

Overall, there was a higher incidence of adverse reactions in younger age groups: the incidence of injection site tenderness, injection site pain, fatigue, myalgia, headache, malaise, arthralgia, and nausea or vomiting was higher in adults aged 18 to less than 65 years than in those aged 65 years and above.

Local and systemic adverse reactions were more frequently reported after Dose 2 than after Dose 1.

Licensed inactivated seasonal influenza vaccines were co-administered to participants on the same day as Dose 1 of Nuvaxovid (n=217) or placebo (n=214) in the opposite deltoid muscle of the arm in 431 participants enrolled in an exploratory Phase 3 (2019nCoV-302) sub-study. The frequency of local and systemic adverse reactions in the influenza sub-study population was higher than in the main study population following Dose 1 in both Nuvaxovid and placebo recipients.

Adolescents 12 through 17 years of age

The safety of Nuvaxovid in adolescents was evaluated in an interim analysis of the paediatric expansion portion of an ongoing Phase 3 multicentre, randomised, observer-blinded, placebo-controlled study (Study 2019nCoV-301). Safety data were collected in 2,232 participants 12 through 17 years of age, with and without evidence of prior SARS-CoV-2 infection, in United States who received at least one dose of Nuvaxovid (n=1,487) or placebo (n=745). Demographic characteristics were similar among participants who received Nuvaxovid and those who received placebo.

The most frequent adverse reactions were injection site tenderness (71%), injection site pain (67%), headache (63%), myalgia (57%), fatigue (54%), malaise (43%), nausea or vomiting (23%), arthralgia (19%) and pyrexia (17%). Fever was observed more frequently in adolescents aged 12 through to 17 years compared to adults, with the frequency being very common after the second dose in adolescents. Adverse reactions were usually mild to moderate in severity with a median duration of less than or equal to 2 days for local events and less than or equal to 1 day for systemic events following vaccination.

Summary of the safety profile after booster dose

Participants 18 years of age and older

In an independent study (CoV-BOOST study, EudraCT 2021-002175-19) evaluating the use of a Nuvaxovid booster dose in individuals who had completed primary vaccination with an authorised mRNA COVID-19 vaccine or adenoviral vector COVID-19 vaccine, no new safety concerns were identified.

The safety and immunogenicity of a booster dose of Nuvaxovid was evaluated in an ongoing Phase 3, multicenter, randomized, observer-blinded, placebo-controlled study (Study 2019nCoV-301). Overall, 12,777 participants received a booster dose of the vaccine at least 6 months after the two-dose primary series (median of 11 months between completion of primary series and booster dose). Of the 12,777 participants who received a booster dose, 39 participants did not receive Nuvaxovid for all three doses. The safety analyses included evaluation of solicited local and systemic adverse reactions within 7 days after a booster dose for participants who completed the electronic diary (n=10,137).

The most frequent solicited adverse reactions were injection site tenderness (73%), injection site pain (61%), fatigue (52%), muscle pain (51%), headache (45%), malaise (40%), and joint pain (26%).

Adolescents 12 through 17 years of age

The safety of a booster dose of Nuvaxovid was evaluated in an interim analysis of an ongoing Phase 3 study (Study 2019nCoV-301). A total of 1,499 participants received a booster dose approximately 9 months after receiving Dose 2 of the primary series. A subset of 220 participants who received the booster dose were evaluated for solicited adverse reactions within 7 days after the booster dose (Ad Hoc Booster Safety Analysis Set), of whom 190 completed the electronic diary.

Solicited adverse reactions occurred at higher frequencies and with higher grade in adolescents compared to adults. The most frequent solicited adverse reactions were injection site tenderness (72%), headache (68%), fatigue (66%), injection site pain (64%), muscle pain (62%), malaise (47%), and nausea/vomiting (26%) with a median duration of 1 to 2 days following vaccination. No new safety concerns from the time of the booster dose administration through 28 days after administration were noted among participants.

Nuvaxovid JN.1 (Omicron-adapted Nuvaxovid)

The safety of Nuvaxovid JN.1 is inferred from the safety data of the Nuvaxovid (Original, Wuhan strain) vaccine and the safety data from the adapted Omicron BA.5 vaccine.

A booster dose of the Nuvaxovid monovalent Omicron BA.5 and bivalent Original/Omicron BA.5 vaccines were evaluated in an ongoing Phase 3 study in participants 18 years of age and older (2019nCoV-311 Part 2). In this study, 251 participants received a Nuvaxovid (Original, Wuhan strain) booster dose, 254 received a monovalent Omicron BA.5 booster dose, and 259 participants received a Nuvaxovid bivalent Original/Omicron BA.5 booster dose. Median follow-up time since the initial booster vaccination was 48 days through the data cutoff date of 31 May 2023.

The overall safety profile for the Nuvaxovid monovalent Omicron BA.5 booster doses was similar to that seen after the Nuvaxovid (Original, Wuhan strain) booster dose. The most frequent adverse reactions were injection site tenderness (> 50%), injection site pain (> 30%), fatigue (> 30%), headache (> 20%), myalgia (> 20%), and malaise (> 10%). No new adverse reactions were identified for the Nuvaxovid monovalent Omicron BA.5 booster doses. In 2019nCoV-311 Part 2 the frequency of local as well as systemic reactogenicity events was greater in women than in men, for all the vaccine constructs that were tested.

Tabulated list of adverse reactions

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).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 1: Adverse reactions from Nuvaxovid clinical trials and post authorisation experience in individuals 12 years of age and older

MedDRA 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)

Not known (cannot be estimated from the available data)

Blood and lymphatic system disorders

Lymphadenopathy

Immune system disorders

Anaphylaxis

Nervous system disorders

Headache

Paraesthesia

Hypoaesthesia

Cardiac disorders

Myocarditis

Pericarditis

Vascular disorders

Hypertensiond

Gastrointestinal disorders

Nausea or vomitinga

Skin and subcutaneous tissue disorders

Rash

Erythema

Pruritus

Urticaria

Musculoskeletal and connective tissue disorders

Myalgiaa

Arthralgiaa

General disorders and administration site conditions

Injection site tendernessa

Injection site paina

Fatiguea

Malaisea,b

Injection site rednessa,c

Injection site swellinga

Pyrexiae

Pain in extremity

Injection site pruritus

Chills

Injection site warmth

a Higher frequencies of these events were observed after the second dose.

b This term also included events reported as influenza-like illness.

c This term includes both injection site redness and injection site erythema (common).

d Hypertension was not reported in adolescents aged 12 through 17 years in the clinical study.

e Pyrexia was observed more frequently in adolescents aged 12 through 17 years compared to adults, with the frequency being very common after the second dose in adolescents.

Description of selected adverse reactions

Throughout the clinical trials, an increased incidence of hypertension following vaccination with Nuvaxovid (n=46, 1.0%) as compared to placebo (n=22, 0.6%) was observed in older adults during the 3 days following vaccination.

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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

No case of overdose has been reported. In the event of an overdose, monitoring of vital functions and possible symptomatic treatment is recommended.