BEYFORTUS Solution for injection Ref.[50357] Active ingredients: Nirsevimab

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.bocytopenia or any coagulation disorder.

Hypersensitivity including anaphylaxis

Serious hypersensitivity reactions have been reported following Beyfortus administration. Anaphylaxis has been observed with human immunoglobulin G1 (IgG1) monoclonal antibodies. If signs and symptoms of anaphylaxis or other clinically significant hypersensitivity reaction occur, immediately discontinue administration and initiate appropriate medicinal products and/or supportive therapy.

Clinically significant bleeding disorders

As with any other intramuscular injections, nirsevimab should be given with caution to individuals with thrombocytopenia or any coagulation disorder.

Immunocompromised children

In some immunocompromised children with protein-losing conditions, a high clearance of nirsevimab has been observed in clinical trials (see section 5.2), and nirsevimab may not provide the same level of protection in those individuals.

Polysorbate 80 (E433)

This medicine contains 0.1 mg of polysorbate 80 in each 50 mg (0.5 mL) dose and 0.2 mg in each 100 mg (1 mL) dose. Polysorbates may cause allergic reactions.

No interaction studies have been performed. Monoclonal antibodies do not typically have significant interaction potential, as they do not directly affect cytochrome P450 enzymes and are not substrates of hepatic or renal transporters. Indirect effects on cytochrome P450 enzymes are unlikely as the target of nirsevimab is an exogenous virus.

Nirsevimab does not interfere with reverse transcriptase polymerase chain reaction (RT-PCR) or rapid antigen detection RSV diagnostic assays that employ commercially available antibodies targeting antigenic site I, II, or IV on the RSV fusion (F) protein.

Concomitant administration with vaccines

Since nirsevimab is a monoclonal antibody, a passive immunisation specific for RSV, it is not expected to interfere with the active immune response to co-administered vaccines.

There is limited experience of co-administration with vaccines. In clinical trials, when nirsevimab was given with routine childhood vaccines, the safety and reactogenicity profile of the co-administered regimen was similar to the childhood vaccines given alone. Nirsevimab can be given concomitantly with childhood vaccines.

Nirsevimab should not be mixed with any vaccine in the same syringe or vial (see section 6.2). When administered concomitantly with injectable vaccines, they should be given with separate syringes and at different injection sites.

Not applicable.

Not applicable.

Summary of the safety profile

The most frequent adverse reaction was rash (0.7%) occurring within 14 days post dose. The majority of cases were mild to moderate in intensity. Additionally, pyrexia and injection site reactions were reported at a rate of 0.5% and 0.3% within 7 days post dose, respectively. Injection site reactions were non-serious.

Tabulated list of adverse reactions

Table 1 presents the adverse reactions reported in 2 966 term and preterm infants (GA ≥29 weeks) who received nirsevimab in clinical trials, and in post-marketing setting (see section 4.4).

Adverse reactions reported from controlled clinical trials are classified by MedDRA System Organ Class (SOC). Within each SOC, preferred terms are arranged by decreasing frequency and then by decreasing seriousness. Frequencies of occurrence of adverse reactions are defined as: 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) and not known (cannot be estimated from available data).

Table 1. Adverse reactions:

^a Adverse reaction from spontaneous reporting.
^b Rash was defined by the following grouped preferred terms: rash, rash maculo-papular, rash macular.
^c Injection site reaction was defined by the following grouped preferred terms: injection site reaction, injection site pain, injection site induration, injection site oedema, injection site swelling.

Infants at higher risk for severe RSV disease in their first season

Safety was evaluated in MEDLEY in 918 infants at higher risk for severe RSV disease, including 196 extremely preterm infants (GA <29 weeks) and 306 infants with chronic lung disease of prematurity, or haemodynamically significant congenital heart disease entering their first RSV season, who received nirsevimab (n=614) or palivizumab (n=304). The safety profile of nirsevimab in infants who received nirsevimab in their first RSV season was comparable to the palivizumab comparator and consistent with the safety profile of nirsevimab in term and preterm infants GA ≥29 weeks (D5290C00003 and MELODY).

Infants who remain vulnerable to severe RSV disease in their second season Safety was evaluated in MEDLEY in 220 children with chronic lung disease of prematurity or haemodynamically significant congenital heart disease who received nirsevimab or palivizumab in their first RSV season and went on to receive nirsevimab entering their second RSV season (180 subjects received nirsevimab in both Season 1 and 2, 40 received palivizumab in Season 1 and nirsevimab in Season 2). The safety profile of nirsevimab in children who received nirsevimab in their second RSV season was consistent with the safety profile of nirsevimab in term and preterm infants GA ≥29 weeks (D5290C00003 and MELODY).

Safety was also evaluated in MUSIC, an open label, uncontrolled, single dose trial in 100 immunocompromised infants and children ≤24 months, who received nirsevimab in their first or second RSV season. This included subjects with at least one of the following conditions: immunodeficiency (combined, antibody, or other etiology) (n=33); systemic high-dose corticosteroid therapy (n=29); organ or bone marrow transplantation (n=16); receiving immunosuppressive chemotherapy (n=20); other immunosuppressive therapy (n=15), and HIV infection (n=8). The safety profile of nirsevimab was consistent with that expected for a population of immunocompromised children and with the safety profile of nirsevimab in term and preterm infants GA ≥29 weeks (D5290C00003 and MELODY).

The safety profile of nirsevimab in children during their second RSV season was consistent with the safety profile of nirsevimab observed during their first RSV season.

Term and Preterm Infants entering their first RSV season

Safety of nirsevimab was also evaluated in HARMONIE, a randomised open-label multicentre trial in 8 034 term and preterm infants (GA ≥29 weeks) entering their first RSV season (not eligible for palivizumab), who received nirsevimab (n=4 016) or no intervention (n=4 018) for the prevention of RSV LRTI hospitalisation. The safety profile of nirsevimab administered in the first RSV season was consistent with the safety profile of nirsevimab in the placebo-controlled trials (D5290C00003 and MELODY).

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 the national reporting system listed in Appendix V.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.