2.1 Dose and Schedule

Administer 2 doses (0.5-mL each) of BEXSERO at least 1 month apart.

2.2 Administration

Shake the syringe immediately before use to form a homogeneous suspension. Do not use the vaccine if it cannot be resuspended. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if particulate matter or discoloration is found.

Administer BEXSERO as a 0.5-mL intramuscular injection into the deltoid muscle of the upper arm.

2.3 Use of BEXSERO with Other Meningococcal Group B Vaccines

Sufficient data are not available on the safety and effectiveness of using BEXSERO and other meningococcal group B vaccines interchangeably to complete the vaccination series.

5.1 Preventing and Managing Allergic Reactions

Appropriate observation and medical treatment should always be readily available in case of an anaphylactic reaction following the administration of the vaccine.

5.2 Syncope

Syncope (fainting) can occur in association with administration of BEXSERO. Ensure procedures are in place to avoid injury from falling associated with syncope.

5.3 Latex

The tip caps of the prefilled syringes contain natural rubber latex which may cause allergic reactions.

5.4 Limitation of Vaccine Effectiveness

BEXSERO may not protect all vaccine recipients. BEXSERO may not provide protection against all meningococcal serogroup B strains [see Clinical Pharmacology (12.1)].

5.5 Altered Immunocompetence

Some individuals with altered immunocompetence may have reduced immune responses to BEXSERO.

Complement Deficiency

Persons with certain complement deficiencies and persons receiving treatment that inhibits terminal complement activation (for example, eculizumab) are at increased risk for invasive disease caused by N. meningitidis serogroup B even if they develop antibodies following vaccination with BEXSERO. [See Clinical Pharmacology (12.1).]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared with rates in the clinical trials of another vaccine and may not reflect the rates observed in practice.

In 4 clinical trials, 3,058 individuals aged 10 through 25 years received at least one dose of BEXSERO, 1,436 participants received only BEXSERO, 2,089 received only placebo or a control vaccine, and 1,622 participants received a mixed regimen (placebo or control vaccine and BEXSERO).

In a randomized controlled study1 conducted in U.S. and Poland, 120 participants aged 10 through 25 years received at least 1 dose of BEXSERO, including 112 participants who received 2 doses of BEXSERO 2 months apart; 97 participants received saline placebo followed by MENVEO [Meningococcal (Groups A, C, Y, and W-135) Oligosaccharide Diphtheria CRM197 Conjugate Vaccine]. Across groups, median age was 13 years, males comprised 49%, and 60% were white, 34% were Hispanic, 4% were black, <1% were Asian, and 2% were other.

In a second randomized controlled study2 conducted in Chile, all subjects (N = 1,622) aged 11 through 17 years received at least 1 dose of BEXSERO. This study included a subset of 810 subjects who received 2 doses of BEXSERO 1 or 2 months apart. A control group of 128 subjects received at least 1 dose of placebo containing aluminum hydroxide. A subgroup of 128 subjects received 2 doses of BEXSERO 6 months apart. In this study, median age was 14 years, males comprised 44%, and 99% were Hispanic.

In a third randomized controlled study3 conducted in the United Kingdom (U.K.), 974 university students aged 18 through 24 years received at least 1 dose of BEXSERO, including 932 subjects who received 2 doses of BEXSERO 1 month apart. Comparator groups received 1 dose of MENVEO followed by 1 dose of placebo containing aluminum hydroxide (n = 956) or 2 doses of IXIARO (Japanese Encephalitis Vaccine, Inactivated, Adsorbed) (n = 947). Across groups, median age was 20 years, males comprised 46%, and 88% were white, 5% were Asian, 2% were black, <1% were Hispanic, and 4% were other.

In an uncontrolled study4 conducted in Canada and Australia, 342 participants aged 11 through 17 years received at least 1 dose of BEXSERO, including 338 participants who received 2 doses of BEXSERO 1 month apart. The median age was 13 years, males comprised 55%, and 80% were white, 10% were Asian, 4% were Native American/Alaskan, and 4% were other.

Local and systemic reactogenicity data were solicited from all participants in the studies conducted in Chile, U.S./Poland, Canada/Australia, and in a subset of participants in the U.K. study. Reports of unsolicited adverse events occurring within the first 7 days after each vaccination were collected in all studies. In the U.S./Poland study, reports of unsolicited adverse events were collected up to 1 month after the second vaccination.

Reports of all serious adverse events, medically attended adverse events, and adverse events leading to premature withdrawal were collected throughout the study period for the studies conducted in Chile (12 months), U.K. (12 months), U.S./Poland (8 months), and Canada/Australia (2 months).

Solicited Adverse Reactions

The reported rates of local and systemic reactions among participants aged 10 through 25 years following each dose of BEXSERO administered 2 months apart or control in the U.S./Polish study1 are presented in Table 1.

Solicited adverse reaction rates were similar among participants aged 11 through 24 years who received BEXSERO in the other 3 clinical studies,2,3,4 except for severe myalgia which was reported by 3% to 7% of subjects. Severe pain was reported by 8% of university students in the U.K.3

6.2 Additional Pre-licensure Safety Experience

In response to outbreaks of serogroup B meningococcal disease at 2 universities in the U.S., BEXSERO was administered as a 2-dose series at least 1 month apart. Information on serious adverse events was collected for a period of 30 days after each dose from 15,351 individuals aged 16 through 65 years who received at least 1 dose. Overall, 50 individuals (0.3%) reported serious adverse events, including one reaction considered related to vaccination, a case of anaphylaxis within 30 minutes following vaccination.

6.3 Postmarketing Experience

The following adverse reactions have been identified during postapproval use of BEXSERO. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to the vaccine.

Blood and Lymphatic System Disorders

Lymphadenopathy.

General Disorders and Administration Site Conditions

Injection site reactions (including extensive swelling of the vaccinated limb, blisters at or around the injection site, and injection site nodule which may persist for more than 1 month).

Immune System Disorders

Allergic reactions (including anaphylactic reactions), rash, eye swelling.

Nervous System Disorders

Syncope, vasovagal responses to injection.

8.1 Pregnancy

8.2 Lactation

Risk Summary

It is not known whether the vaccine components of BEXSERO are excreted in human milk. Available data are not sufficient to assess the effects of BEXSERO on the breastfed infant or on milk production/excretion. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for BEXSERO and any potential adverse effects on the breastfed child from BEXSERO or from the underlying maternal condition. For preventive vaccines, the underlying maternal condition is susceptibility to disease prevented by the vaccine.

8.4 Pediatric Use

Safety and effectiveness of BEXSERO have not been established in children younger than 10 years.

8.5 Geriatric Use

Safety and effectiveness of BEXSERO have not been established in adults older than 65 years.

12.1 Mechanism of Action

Protection against invasive meningococcal disease is conferred mainly by complement-mediated antibody-dependent killing of N. meningitidis. The effectiveness of BEXSERO was assessed by measuring serum bactericidal activity using human complement (hSBA).

NHBA, NadA, fHbp, and PorA are proteins found on the surface of meningococci and contribute to the ability of the bacterium to cause disease. Vaccination with BEXSERO leads to the production of antibodies directed against NHBA, NadA, fHbp, and PorA P1.4 (present in OMV). The susceptibility of serogroup B meningococci to complement-mediated antibody-dependent killing following vaccination with BEXSERO is dependent on both the antigenic similarity of the bacterial and vaccine antigens, as well as the amount of antigen expressed on the surface of the invading meningococci.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

BEXSERO has not been evaluated for carcinogenic or mutagenic potential or impairment of male fertility in animals. Vaccination of female rabbits with BEXSERO had no effect on fertility. [See Use in Specific Populations (8.1).]

14.1 Immunogenicity

In a clinical trial conducted in Canada and Australia, adolescents aged 11 through 17 years received 2 doses of BEXSERO 1 month apart. The hSBA responses 1 month after the second dose are shown in Table 2.

In a randomized, controlled clinical trial conducted in the U.K. among university students aged 18 through 24 years, hSBA responses in a subset of participants who received BEXSERO were measured 1 month and 11 months after the second dose (Table 3).

16.1 How Supplied

BEXSERO is supplied as a 0.5-mL suspension in a glass prefilled syringe (packaged without needles). The tip caps of the prefilled syringes contain natural rubber latex; the plungers are not made with natural rubber latex.

16.2 Storage and Handling

Do not freeze. Discard if the vaccine has been frozen.

Store refrigerated, at 36°F to 46°F (2°C to 8°C).

Protect from light.

Do not use after the expiration date.