2.1 Dose and Schedule

Two-dose schedule: Administer a dose (0.5 mL) at 0 and 6 months. If the second dose is administered earlier than 6 months after the first dose, a third dose should be administered at least 4 months after the second dose.

Three-dose schedule: Administer a dose (0.5 mL) at 0, 1-2, and 6 months.

The choice of dosing schedule may depend on the risk of exposure and the individual’s susceptibility to meningococcal serogroup B disease.

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.

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 Management of Allergic Reactions

Appropriate medical treatment must be immediately available to manage potential anaphylactic reactions following administration of BEXSERO.

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 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)].

5.4 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

The safety of BEXSERO was evaluated in 5 clinical studies (Table 1) in which a total of 4,861 participants aged 10 through 25 years received at least 1 dose of BEXSERO. 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 Study 1, conducted in the United States (U.S.), Australia, Canada, Czech Republic, Estonia, Finland, and Turkey, 1,803 participants aged 10 through 25 years received at least 1 dose of BEXSERO either as a 0-, 2-, 6-month schedule (n = 897) or 0-, 6-month schedule (n = 906). A single dose of MENVEO [Meningococcal (Groups A, C, Y, and W-135) Oligosaccharide Diphtheria CRM197 Conjugate Vaccine] was administered 1 month after the third dose in the 0-, 2-, 6-month group and 2 months after the first dose of BEXSERO in the 0-, 6-month group (these participants received saline placebo at month 7). A separate group (n = 178) received a single dose of MENVEO followed 6 months later by 2 doses of BEXSERO administered 1 month apart (these participants received saline placebo at month 2). Approximately 30% of participants were from the U.S. In this trial, the median age was 16 years, males comprised 47%, and 89% of participants were White, 5% were Asian, 4% were Black, and 2% were of other racial groups. Among study participants, 5% were Hispanic.

In Study 2, an uncontrolled study 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 (unapproved dosing schedule). The median age was 13 years, males comprised 55%, and 80% of participants were White, 10% were Asian, 4% were Native American/Alaskan, and 4% were of other racial groups.

In Study 3, conducted in the United Kingdom (U.K.), 974 university students aged 18 through 24 years received at least 1 dose of BEXSERO, including 932 participants who received 2 doses of BEXSERO 1 month apart (unapproved dosing schedule). 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% of participants were White, 5% were Asian, 2% were Black, <1% were Hispanic, and 4% were of other racial groups.

In Study 4, conducted in Chile, 1,622 participants aged 11 through 17 years received at least 1 dose of BEXSERO according to approved and unapproved dosing schedules. A control group of 128 participants received at least 1 dose of placebo containing aluminum hydroxide. In this study, median age was 14 years, males comprised 44%, and 99% were Hispanic.

In Study 5, conducted in the 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 (unapproved dosing schedule); 97 participants received saline placebo followed by MENVEO. Across groups, the median age was 13 years, males comprised 49%, and 60% of participants were White, 34% were Hispanic, 4% were Black, <1% were Asian, and 2% were of other racial groups.

Local and systemic reactogenicity data were solicited from all participants in the trials with the exception of one trial (Study 3) where they were solicited in a subset of participants only. Reports of unsolicited adverse events occurring within the first 7 days after each vaccination were collected in all trials. Reports of unsolicited adverse events occurring within the 30 days after each vaccination were collected in 2 trials (Study 1, Study 5).

Reports of all serious adverse events, medically attended adverse events, and adverse events leading to premature withdrawal were collected throughout the study period of 2 months (Study 2), 8 months (Study 5), or 12 months (Study 1, Study 3, Study 4).

Solicited Adverse Reactions

The rates of local and systemic adverse reactions reported in Study 1 among participants aged 10 through 25 years following each dose of BEXSERO or a single dose of MENVEO are presented in Table 2.

Solicited adverse reactions were also collected in 4 additional clinical trials (Studies 2-5) in participants aged 10 through 25 years who received BEXSERO. Pain was the most common local adverse reaction reported (83% to 96%), with severe pain reported by 8% to 29% of participants, across trials. Among the systemic reactions collected, myalgia (37% to 75%), headache (21% to 47%), and fatigue/malaise (17% to 58%) were the most commonly reported systemic reactions across trials.

Unsolicited Adverse Events

In Study 1, unsolicited adverse events (non-serious and serious) that occurred within 7 days of any dose of study vaccination were reported by 14% of participants in the group receiving BEXSERO as a 0-, 6-month schedule (n = 900), 13% of participants in the group receiving BEXSERO as a 0-, 2-, 6-month schedule (n = 893), and 20% of participants in the MENVEO group (n = 178).

A non-serious event of arthritis with onset 10 days after receipt of BEXSERO in a 24-year-old male was assessed as vaccine-related by the study investigator. The participant, later found to be HLA-B27 positive, may be at increased risk for arthritis unrelated to vaccination.

In the other controlled trials (Study 3, Study 4, Study 5) (BEXSERO n = 2,221, control n = 2,204), non-serious unsolicited adverse events that occurred within 7 days of any dose were reported by 439 (20%) participants receiving BEXSERO and 197 (9%) control recipients. Unsolicited adverse reactions that were reported among at least 2% of participants and were more frequently reported in participants receiving BEXSERO than in control recipients were injection site pain, headache, injection site induration unresolved within 7 days, and nasopharyngitis.

Serious Adverse Events

In Study 1, serious adverse events that occurred within 30 days of any dose of study vaccination were reported by 1.2% of participants in the group receiving BEXSERO as a 0-, 6-month schedule (n = 900), 1.0% of participants in the group receiving BEXSERO as a 0-, 2-, 6-month schedule (n = 893), and 0% of participants in the MENVEO group (n = 178). None of these events were considered related to BEXSERO.

Overall, in Studies 2-5, among 3,058 participants aged 10 through 25 years who received at least 1 dose of BEXSERO, 66 (2.1%) participants reported serious adverse events at any time during the trial. In the 3 controlled trials (Study 3, Study 4, Study 5) (BEXSERO n = 2,716, control n = 2,078), serious adverse events within 30 days after any dose were reported in 23 (0.8%) participants receiving BEXSERO and 10 (0.5%) control recipients. In Study 4, among participants who received 3 doses of BEXSERO (n = 628), 15 (2.4%) participants reported serious adverse events at any time during the trial.

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 post-approval 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

Risk Summary

All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

There are no adequate and well-controlled studies of BEXSERO in pregnant women in the U.S. Available human data on BEXSERO administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy.

A developmental toxicity study was performed in female rabbits administered BEXSERO prior to mating and during gestation. The dose was 0.5 mL at each occasion (a single human dose is 0.5 mL). This study revealed no adverse effects on fetal or pre-weaning development due to BEXSERO (see Data).

Data

Animal Data: In a developmental toxicity study, female rabbits were administered BEXSERO by intramuscular injection on Days 29, 15, and 1 prior to mating and on Gestation Days 7 and 20. The total dose was 0.5 mL at each occasion (a single human dose is 0.5 mL). No adverse effects on pre-weaning development up to Postnatal Day 29 were observed. There were no fetal malformations or variations observed.

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.

NHBA, NadA, and fHbp are proteins found on the surface of meningococci and contribute to the ability of the bacteria to cause disease. OMV derived from the bacterial outer membrane contains PorA and other surface proteins. Vaccination with BEXSERO leads to the production of antibodies directed against NHBA, NadA, fHbp, and 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.

16.1 How Supplied

BEXSERO is available in 0.5-mL single-dose, disposable, prefilled TIP-LOK syringes (Luer Lock syringes) packaged without needles. TIP-LOK syringes are to be used with Luer Lock compatible needles.

The tip cap and rubber plunger stopper of the prefilled syringe 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.