Pharmaceutical Name

Trade (marketing or proprietary) name: Beyfortus, Synagis®

Generic (nonproprietary or active ingredient) name: Respiratory syncytial virus monoclonal antibody (Nirsevimab), Palivizumab injection

Indication and Usage

Reason the product has been approved for sale on the market.

Beyfortus is a respiratory syncytial virus (RSV) F protein-directed fusion inhibitor indicated for the prevention of RSV lower respiratory tract disease in:

• Neonates and infants born during or entering their first RSV season.
• Children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season.

Synagis® is a respiratory syncytial virus (RSV) F protein inhibitor monoclonal antibody indicated for the prevention of serious lower respiratory tract disease caused by RSV in children at high risk of RSV disease.

• Safety and efficacy were established in children with bronchopulmonary dysplasia (BPD), infants with a history of premature birth (less than or equal to 35 weeks gestational age), and children with hemodynamically significant congenital heart disease (CHD).
• The safety and efficacy of Synagis have not been established for treatment of RSV disease.

Manufacturer Insert

Ingredients

Also known as “excipients” for vaccines.

Beyfortus: Nirsevimab-alip, a respiratory syncytial virus F protein-directed fusion inhibitor, is a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody produced in Chinese hamster ovary (CHO) cells by recombinant DNA technology.

BEYFORTUS (nirsevimab-alip) injection is a sterile, preservative-free, clear to opalescent, colorless to yellow solution for intramuscular injection. It is supplied in a single-dose siliconized Luer lock Type I glass pre-filled syringe with a FluroTec coated plunger stopper.

Each 0.5 mL contains 50 mg nirsevimab-alip, arginine hydrochloride (8 mg), histidine (1.1 mg), L-histidine hydrochloride monohydrate (1.6 mg), polysorbate 80 (0.1 mg), sucrose (21 mg), and water for injection (USP). The pH is 6.0.

Each 1 mL contains 100 mg nirsevimab-alip, arginine hydrochloride (17 mg), histidine (2.2 mg), L-histidine hydrochloride monohydrate (3.3 mg), polysorbate 80 (0.2 mg), sucrose (41 mg), and water for injection (USP). The pH is 6.0.

Synagis®

Palivizumab is a humanized monoclonal antibody (IgG1к) produced by recombinant DNA technology, directed to an epitope in the A antigenic site of the F protein of RSV. Palivizumab is a composite of human (95%) and murine (5%) antibody sequences. The human heavy chain sequence was derived from the constant domains of human IgG1 and the variable framework regions of the VH genes Cor and Cess. The human light chain sequence was derived from the constant domain of Cк and the variable framework regions of the VL gene K104 with Jк -4. The murine sequences were derived from a murine monoclonal antibody, Mab 1129, in a process that involved the grafting of the murine complementarity determining regions into the human antibody frameworks. Palivizumab is composed of two heavy chains and two light chains and has a molecular weight of approximately 148,000 Daltons. Synagis is supplied as a sterile, preservative-free liquid solution at 100 mg per mL to be administered by intramuscular injection. Thimerosal or other mercury-containing salts are not used in the production of Synagis. The solution has a pH of 6.0 and should appear clear or slightly opalescent.

Each 100 mg single-dose vial of Synagis liquid solution contains 100 mg of palivizumab and also contains chloride (0.5 mg), glycine (0.1 mg), and histidine (3.9 mg), in a volume of 1 mL.

Each 50 mg single-dose vial of Synagis liquid solution contains 50 mg of palivizumab and also contains chloride (0.2 mg), glycine (0.06 mg), and histidine (1.9 mg), in a volume of 0.5 mL.

Contraindications

Per the FDA, contraindications are conditions in a recipient that increases the risk for a serious adverse reaction. Product should not be administered when a patient has a listed contraindication.

Beyfortus is contraindicated in infants and children with a history of serious hypersensitivity reactions, including anaphylaxis, to nirsevimab-alip or to any of the excipients.

Synagis® is contraindicated in children who have had a previous significant hypersensitivity reaction to Synagis.

Warnings and Precautions

Per the FDA, warnings are clinically significant adverse reactions or risks. According to the CDC, a precaution is a condition in a recipient that might increase the risk for a serious adverse reaction, might cause diagnostic confusion, or might compromise the effectiveness of the product. In general, a product should be deferred when a precaution is present.

Beyfortus

Hypersensitivity Including Anaphylaxis: Serious hypersensitivity reactions, including anaphylaxis, have been observed with other human immunoglobulin G1 (IgG1) monoclonal antibodies. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, initiate appropriate medications and/or supportive therapy.

Use in Individuals with Clinically Significant Bleeding Disorders: As with any other IM injections, BEYFORTUS should be given with caution to infants and children with thrombocytopenia, any coagulation disorder, or to individuals on anticoagulation therapy.

Synagis®

Hypersensitivity Reactions: Cases of anaphylaxis and anaphylactic shock, including fatal cases, have been reported following initial exposure or re-exposure to Synagis. Other acute hypersensitivity reactions, which may be severe, have also been reported on initial exposure or re-exposure to Synagis. Signs and symptoms may include urticaria, pruritus, angioedema, dyspnea, respiratory failure, cyanosis, hypotonia, hypotension, and unresponsiveness. The relationship between these reactions and the development of antibodies to Synagis is unknown. If a significant hypersensitivity reaction occurs with Synagis, its use should be permanently discontinued. If anaphylaxis or other significant hypersensitivity reaction occurs, administer appropriate medications (e.g., epinephrine) and provide supportive care as required. If a mild hypersensitivity reaction occurs, clinical judgment should be used regarding cautious readministration of Synagis.

Coagulation Disorders: Synagis is for intramuscular use only. As with any intramuscular injection, Synagis should be given with caution to children with thrombocytopenia or any coagulation disorder.

RSV Diagnostic Test Interference: Palivizumab may interfere with immunological-based RSV diagnostic tests such as some antigen detection-based assays. In addition, palivizumab inhibits virus replication in cell culture, and therefore may also interfere with viral culture assays. Palivizumab does not interfere with reverse transcriptasepolymerase chain reaction based assays. Assay interference could lead to false-negative RSV diagnostic test results. Therefore, diagnostic test results, when obtained, should be used in conjunction with clinical findings to guide medical decisions.

Treatment of RSV Disease: The safety and efficacy of Synagis have not been established for treatment of RSV disease.

Proper Administration: The single-dose vial of Synagis does not contain a preservative. Administration of Synagis should occur immediately after dose withdrawal from the vial. The vial should not be re-entered. Discard any unused portion.

Manufacturer-Listed Adverse Reactions

Per the CDC, adverse reactions are an undesirable medical condition that has been demonstrated to be caused by a vaccine. Evidence for the causal relation is usually obtained through randomized clinical trials, controlled epidemiologic studies, isolation of the vaccine strain from the pathogenic site, or recurrence of the condition with repeated vaccination (i.e., rechallenge); synonyms include side effect and adverse effect.

Beyfortus: Injection site reactions (swelling/hardness), rash, and pain. The insert does not have a post-marketing adverse reaction section. Per the CDC, “Adverse reactions might occur after the coadministration of nirsevimab with a vaccine; these reactions should be reported to the Vaccine Adverse Event Reporting System (VAERS), and reports should specify that the patient received nirsevimab on the VAERS form in Section 9: “Prescriptions, over-the-counter medications, dietary supplements, or herbal remedies being taken at the time of vaccination.”

According to the NIH, “Doctors and nurses cannot know for sure when or if side effects will occur or how serious they will be. So, it is important to know which signs to look for and what to do if you start to have problems. Like most types of immunotherapy, monoclonal antibodies can cause skin reactions at the needle site and flu-like symptoms.”

Synagis® can cause: Anaphylaxis and anaphylactic shock, including fatal cases, Urticaria (Hives), Pruritus (Chronic itchy skin), Angioedema (Swelling), Dyspnea (Shortness of breath), Respiratory failure, Cyanosis (blue/purple skin), Hypotonia (Floppy infant syndrome), Hypotension (Low blood pressure), Unresponsiveness, Severe thrombocytopenia (platelet count less than 50,000 per microliter), and Injection site reactions.

Specific Populations

Pregnancy

BEYFORTUS is not indicated for use in females of reproductive potential.

Pregnancy Category C: Synagis is not indicated for adult usage. It is not known whether Synagis can cause fetal harm or could affect reproductive capacity when administered to a pregnant woman.

Breastfeeding

BEYFORTUS is not indicated for use in females of reproductive potential.

Fertility

Carcinogenesis, mutagenesis and reproductive toxicity studies have not been performed with BEYFORTUS/Synagis®.

Pediatric

The safety and effectiveness of BEYFORTUS have not been established in children older than 24 months of age.

The safety and effectiveness of Synagis in children greater than 24 months of age at the start of dosing have not been established.

Mechanism of Action

This is the specific biochemical interaction through which a drug or vaccine substance produces its pharmacological effect. This section also includes the minimum protective level designated for a certain disease.

Beyfortus is a monoclonal antibody with anti-RSV activity. There is limited experience with co-administration of BEYFORTUS with vaccines. In clinical trials, when BEYFORTUS was given concomitantly with routine childhood vaccines, the safety and reactogenicity profile of the coadministered regimen was similar to the childhood vaccines given alone.

Synagis®: Palivizumab is a recombinant humanized monoclonal antibody with anti-RSV activity.

Analytical Deep Dive

Covers maternal vaccine (abrysvo) and monoclonal antibody (nirsevimab):

Covers Synagis®:

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