Beyfortus Injection

BEYFORTUS is indicated for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants during their first RSV season. BEYFORTUS should be used in accordance with official recommendations.

Posology
The recommended dose is a single dose of 50 mg administered intramuscularly for infants with body weight < 5 kg and a single dose of 100 mg administered intramuscularly for infants with body weight u2265 5 kg. BEYFORTUS should be administered prior to commencement of the RSV season, or from birth for infants born during the RSV season. Dosing in infants with a body weight from 1,0 kg to < 1,6 kg is based on extrapolation, no clinical data are available. Exposure in infants < 1 kg is anticipated to yield higher exposures than in those weighing more. The benefits and risks of nirsevimab use in infants < 1 kg should be carefully considered. There are limited data available in extremely preterm infants (gestational age [GA] < 29 weeks) less than 8 weeks of age. No clinical data available in infants with a postmenstrual age (gestational age at birth plus chronological age) of less than 32 weeks (see section 5.1). For infants undergoing cardiac surgery with cardiopulmonary bypass, an additional dose may be administered as soon as the infant is stable after surgery to ensure adequate nirsevimab serum levels. If within 90 days after receiving the first dose of BEYFORTUS, the additional dose should be 50 mg or 100 mg according to body weight. If more than 90 days have elapsed since the first dose, the additional dose could be a single dose of 50 mg regardless of body weight, to cover the remainder of the RSV season. There are no safety and efficacy data available on repeat dosing.
Paediatric population
The safety and efficacy of nirsevimab in children aged 2 to 18 years have not been established. No data are available.
Method of administration
BEYFORTUS is for intramuscular injection only. It is administered intramuscularly, preferably in the anterolateral aspect of the thigh. The gluteal muscle should not be used routinely as an injection site because of the risk of damage to the sciatic nerve.
Instructions for administration
BEYFORTUS is available in a 50 mg and a 100 mg pre-filled syringe. Check the labels on the carton and pre-filled syringe to make sure you have selected the correct 50 mg or 100 mg presentation as required. There is no standard protocol on needle size across countries. Healthcare professionals should use a needle long enough to reach deep into the muscle to ensure that the product is deposited within the proper tissue layer, an appropriate length and gauge of needle must be selected. Healthcare professionals should review their local requirements for needle usage.

Hypersensitivity to the active substance or to any of its 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 product should be clearly recorded.
Hypersensitivity including anaphylaxis
Serious hypersensitivity reactions, including anaphylaxis, have been observed with monoclonal antibodies. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration and initiate appropriate medicines and/or supportive therapy.
Clinically significant bleeding disorders
As with any other intramuscular injections, BEYFORTUS should be given with caution to infants with thrombocytopenia or any coagulation disorder.

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.
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 BEYFORTUS was given with routine childhood vaccines, the safety and reactogenicity profile of the co-administered regimen was similar to the childhood vaccines given alone. BEYFORTUS can be given concomitantly with childhood vaccines. BEYFORTUS 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.

Pregnancy
No applicable.
Breastfeeding
Not applicable.
Fertility
Not applicable.

Not applicable.

a. 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.
b. Tabulated list of adverse reactions
Table 1 presents the adverse reactions reported in 2 966 term and preterm infants (GA u2265 29 weeks) who received nirsevimab in clinical trials. 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 are defined as: 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); frequency not known (cannot be estimated from available data).
Table 1: Adverse reactions
MedDRA SOC MedDRA Preferred Term Frequency
Skin and subcutaneous tissue disorders Rash a Uncommon
General disorders and administration site conditions Injection site reaction b Uncommon
Pyrexia Uncommon
a Rash was defined by the following grouped preferred terms: rash, rash maculo-papular, rash macular.
b 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
Safety was also 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 (614) or palivizumab (304). The safety profile was comparable to the palivizumab comparator and consistent with the safety profile in term and preterm infants GA u2265 29 weeks (D5290C00003 and MELODY).
Immunogenicity
As with all therapeutic proteins, there is potential for immunogenicity.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of BEYFORTUS is important. It allows continued monitoring of the benefit/risk balance of BEYFORTUS. Health care providers are asked to report any suspected adverse reactions to: u2022 The Pharmacovigilance Unit at Sanofi: [email protected] (email), https://ae.reporting.sanofi/ (web portal) or +27 11 256 3700 (tel), or u2022 SAHPRA via the u201c6.04 Adverse Drug Reaction Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8

There is no specific treatment for an overdose with nirsevimab. In the event of an overdose, the individual should be monitored for the occurrence of adverse reactions and provided with symptomatic treatment as appropriate.