Meningococcal Group B Vaccine

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Suspension Prefilled Syringe, Intramuscular:

Bexsero: (0.5 mL)

Suspension Prefilled Syringe, Intramuscular [preservative free]:

Trumenba: (0.5 mL) [contains polysorbate 80]

Pharmacology

Mechanism of Action

Bexsero: Induces immunity against meningococcal disease caused by serogroup B Neisseria meningitidis (MenB) via the formation of antibodies directed toward the recombinant protein antigens combined together with outer membrane vesicles (OMV) from a group B strain.

Trumenba: Protection against invasive meningococcal disease is conferred mainly by complement-mediated antibody-dependent killing of N. meningitidis.

Efficacy:

Bexsero: Composite hSBA titer response one month after the second dose: 63% to 88%

Trumenba: 84% of adolescents had a ≥4-fold rise in hSBA titer and composite response after the third dose.

Use: Labeled Indications

Meningococcal group B disease prevention:

US labeling: Active immunization of children, adolescents, and adults aged 10 to 25 years against invasive meningococcal disease caused by N. meningitidis serogroup B.

The Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination of certain groups of persons ≥10 years of age (ACIP [Folaranmi 2015]):

- Persons with persistent complement component deficiencies (including patients who are taking eculizumab)

- Persons with anatomic or functional asplenia (including sickle cell disease)

- Microbiologists routinely exposed to isolates of Neisseria meningitidis

- Persons identified to be at increased risk due to a serogroup B meningococcal disease outbreak

The ACIP states that a meningococcal group B vaccination series may be administered at clinical discretion to adolescents and young adults aged 16 to 23 years to provide short term protection against most strains of serogroup B meningococcal disease. The preferred age for vaccination is 16 to 18 years (ACIP [MacNeil 2015]).

Canadian labeling: Bexsero: Indicated for infants ≥2 months of age, children, adolescents, and adults through 25 years of age

The Canadian National Advisory Committee on Immunization (NACI) recommends use in patients ≥2 months of age at high risk for serogroup B meningococcal disease (including disease outbreaks) and may be considered on an individual basis in healthy patients 2 months to 24 years of age (NACI/CATMAT 2015).

Contraindications

Severe hypersensitivity to the meningococcal group B vaccine or any component of the formulation

Canadian labeling: Additional contraindications (not in the US labeling): Trumenba: Severe allergic reactions (eg, anaphylaxis) after a previous dose of this vaccine

Dosage and Administration

Dosing: Adult

Meningococcal group B disease prevention:

ACIP recommendations (ACIP [Folaranmi 2015; MacNeil 2015; Patton 2017]): Note: Vaccines are approved in adults ≤25 years of age; however, ACIP only recommends routine vaccination of persons aged ≥10 years who are at increased risk for serogroup B meningococcal disease (ACIP [Folaranmi 2015; Patton 2017]). Consider risk of exposure and patient's susceptibility to the disease when choosing a schedule.

Patients at increased risk for serogroup B meningococcal disease or during serogroup B meningococcal disease outbreak:

Bexsero: IM: 0.5 mL per dose given as 2 doses ≥1 month apart

Trumenba: IM: 0.5 mL per dose given as 3-dose series at 0, 1 to 2 months, and 6 months. If the interval between the first and second dose is ≥6 months, then the third dose is not needed.

Patients 16 to 23 years of age (preferred 16 to 18 years) who are not at increased risk for meningococcal disease (per clinical discretion): Note: To provide short-term protection against most strains of serogroup B meningococcal disease:

Bexsero: IM: 0.5 mL per dose given as 2 doses ≥1 month apart

Trumenba: IM: 0.5 mL per dose given as 2 doses 6 months apart. If the second dose is given earlier than 6 months, a third dose should be administered ≥4 months after the second dose.

NACI recommendations (NACI/CATMAT 2015): Note: Current guidelines do not address the Trumenba product. Vaccine is approved in adults ≤25 years of age; however, NACI recommends consideration for vaccination of any adults who are at high risk for serogroup B meningococcal disease. Consider risk of exposure and patient's susceptibility to the disease when choosing a schedule.

Bexsero:

Patients at high risk for serogroup B meningococcal disease or healthy patients ≤24 years of age who are not at high risk for meningococcal disease (per clinical discretion): IM: 0.5 mL per dose given as a 2-dose series ≥4 weeks apart

Close contacts and outbreak control of meningococcal serogroup B disease:

Unvaccinated: IM: 0.5 mL immediately after exposure; revaccinate with a single dose ≥4 weeks after first dose

Previously vaccinated: IM: 0.5 mL immediately after exposure

Trumenba (Canadian labeling):

Routine schedule: IM: 0.5 mL per dose given as a 2-dose series according to a 0- and 6-month schedule

Patients at increased risk for meningococcal serogroup B disease: IM: 0.5 mL per dose given as a 3-dose series with dose 1 and 2 separated by ≥1 month, followed by a third dose administered ≥4 months after the second dose

Dosing: Pediatric

Meningococcal group B disease prevention: Note: Products (Bexsero/Trumenba) are not interchangeable; the same product should be used for all doses in the series. Consult CDC/ACIP annual immunization schedules or National Advisory Committee on Immunization (NACI) guidelines (Canada) for additional information including specific detailed recommendations for catch-up scenarios and/or care of patients with high-risk conditions. According to ACIP, doses administered ≤4 days before minimum interval or age are considered valid; however, local or state mandates may supersede this timeframe (ACIP [Kroger 2017]).

ACIP Recommendations (ACIP/CDC [Robinson 2018], ACIP [Folaranmi 2015; MacNeil 2015; Patton 2017]): Although FDA-approved in children and adolescents ≥10 years, use in patients 10 to 15 years of age who are not at risk for infection is not recommended. In patients ≥16 years of age who are not at risk, use is per clinical discretion. For children ≥10 years and adolescents, ACIP recommends routine vaccination if any of the following high-risk situations: Persistent complement component deficiencies (inherited or chronic) or patients who are taking eculizumab, anatomic or functional asplenia, or persons identified to be at increased risk due to a serogroup B meningococcal disease during an outbreak.

Patients at increased risk:

Children ≥10 years and Adolescents: Note: Consider risk of exposure and patient's susceptibility to the disease when choosing a schedule; refer to ACIP recommendations for additional information.

Bexsero: IM: 0.5 mL per dose for a total of two doses administered at least 1 month apart

Trumenba:

2-dose schedule: IM: 0.5 mL per dose for a total of 2 doses administered as follows: Initial dose followed by a second dose 6 months later; Note: If the interval between the first and second dose is inadvertently <6 months, administer a third dose ≥4 months after the second dose (manufacturer labeling).

3-dose schedule: IM: 0.5 mL per dose for a total of 3 doses administered as follows: Initial dose followed by a second and third dose 1 to 2 months and 6 months after the first dose, respectively. If the interval between the first and second dose is ≥6 months, then the third dose is not needed.

Patients not at increased risk (per clinical discretion): Note: To provide short-term protection against most strains of serogroup B meningococcal disease: Adolescents ≥16 years: IM: 0.5 mL per dose. Administer 2-dose series of either Bexsero (separate doses by 1 month) or Trumenba (separate doses by 6 months; if the second dose is given earlier than 6 months, a third dose should be administered 4 months after the second dose)

NACI recommendations and Canadian labeling:

Bexsero:

Patients at high risk for serogroup B meningococcal disease or healthy patients who are not at high risk for meningococcal disease (per clinical discretion) (NACI/CATMAT 2015): Consider risk of exposure and patient's susceptibility to the disease when choosing a schedule.

Infants 2 to 5 months: IM: Total of 4 doses (0.5 mL each); a primary infant series is administered at 2, 4, and 6 months of age followed by a booster dose between 12 to 23 months of age; alternatively, may give first 3 doses at 2, 3, and 4 months of age, however, the immune response to 1 component (NHBA) of the vaccine is reduced with this regimen

Infants 6 months to <12 months (unvaccinated): IM: Total of 3 doses (0.5 mL each) with first and second dose administered at least 2 months apart; third dose is administered during second year of life at least 2 months after the second dose. The necessity of a booster dose has not been determined.

Children ≥1 year to <2 years of age (unvaccinated): IM: Total of 2 doses (0.5 mL each) administered at least 2 months apart. The necessity of a booster dose has not been determined.

Children ≥2 to <11 years of age: IM: Total of 2 doses (0.5 mL each) administered at least 2 months apart. The necessity for subsequent dosing has not been determined.

Children ≥11 years to Adolescents: IM: Total of 2 doses (0.5 mL each) administered at least 1 month apart. The necessity for subsequent dosing has not been determined.

Close contacts and outbreak control of meningococcal serogroup B disease (NACI/CATMAT 2015): Consider risk of exposure and patient's susceptibility to the disease when choosing a schedule.

Infants 2 months to <6 months:

Unvaccinated: IM: 0.5 mL immediately after exposure; revaccinate with 2 additional doses with ≥4 week interval between doses

Previously vaccinated: IM: 0.5 mL immediately after exposure

Infants 6 months to Children <11 years:

Unvaccinated: IM: 0.5 mL immediately after exposure; revaccinate with a single dose ≥8 weeks after first dose

Previously vaccinated: IM: 0.5 mL immediately after exposure

Children ≥11 years and Adolescents:

Unvaccinated: IM: 0.5 mL immediately after exposure; revaccinate with a single dose ≥4 weeks after first dose

Previously vaccinated: IM: 0.5 mL immediately after exposure

Trumenba: Note: Current guidelines (NACI/CATMAT 2015) do not address the Trumenba product. Children ≥10 years and Adolescents:

Routine schedule: IM: 0.5 mL per dose given as a 2-dose series administered 6 months apart (eg, a 0- and 6-month schedule)

Patients at increased risk for meningococcal serogroup B disease: IM: 0.5 mL per dose given as a 3-dose series with dose 1 and 2 separated by ≥1 month, followed by a third dose administered ≥4 months after the second dose

Reconstitution

Shake vigorously to ensure that a homogenous white suspension is obtained. Do not use the vaccine if it cannot be resuspended.

Administration

IM: For IM administration only, preferably into the upper deltoid region. Do not administer via IV, SubQ, or intradermal route. Do not mix with other vaccines or injections; separate needles and syringes should be used for each injection. To prevent syncope related injuries, patients should be vaccinated while seated or lying down (ACIP [Kroger 2017]). US law requires that the date of administration, the vaccine manufacturer, lot number of vaccine, and the administering person's name, title, and address be entered into the patient's permanent medical record.

For patients at risk of hemorrhage, the vaccine should be administered IM if, in the opinion of a health care provider familiar with the patient's bleeding risk, the vaccine can be administered by this route with reasonable safety. If the patient receives antihemophilia or other similar therapy, IM vaccination can be scheduled shortly after such therapy is administered. A fine needle (23-gauge or smaller) can be used for the vaccination and firm pressure applied to the site (without rubbing) for at least 2 minutes. The patient or family should be instructed concerning the risk of hematoma from the injection. Patients on anticoagulant therapy should be considered to have the same bleeding risks and treated as those with clotting factor disorders (ACIP [Kroger 2017]).

Storage

Bexsero: Store between 2°C to 8°C (36°F to 46°F). Do not freeze; discard if frozen. Protect from light.

Trumenba: Store between 2°C to 8°C (36°F to 46°F). Do not freeze; discard if frozen. Store syringes in the refrigerator horizontally (lying flat on the shelf) to minimize the redispersion time.

Drug Interactions

Eculizumab: May diminish the therapeutic effect of Meningococcal Group B Vaccine. Meningococcal Group B Vaccine may diminish the therapeutic effect of Eculizumab. The meningococcal vaccine may result in increased complement activation, possibly worsening the symptoms of any underlying complement-mediated diseases, such as hemolysis and anemia. Consider therapy modification

Fingolimod: May diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting fingolimod. If vaccinated during fingolimod therapy, revaccinate 2 to 3 months after fingolimod discontinuation. Consider therapy modification

Immunosuppressants: May diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Exceptions: Cytarabine (Liposomal). Consider therapy modification

Siponimod: May diminish the therapeutic effect of Vaccines (Inactivated). Management: Avoid administration of vaccines (inactivated) during treatment with siponimod and for 1 month after discontinuation due to potential decreased vaccine efficacy. Consider therapy modification

Venetoclax: May diminish the therapeutic effect of Vaccines (Inactivated). Monitor therapy

Adverse Reactions

Frequencies reported may include concomitant administration with routine pediatric vaccines or other vaccines.

>10%:

Central nervous system: Irritability (infants and children: 43% to 79%), drowsiness (infants and children: 53% to 72%; children: 30% to 51%), excessive crying (infants and children: 56% to 69%; children: 27% to 33%), fatigue (children, adolescents, and adults: 35% to 62%), headache (10% to 55%), malaise (children and adolescents: 50% to 56%; adults: 14%), chills (children and adolescents: 16% to 29%)

Gastrointestinal: Change in appetite (infants and children: 21% to 51%), diarrhea (children: 2% to 37%; infants and children: 18% to 24%; children and adolescents: years 9% to 15%), nausea (children, adolescents, and adults: 16% to 19%), vomiting (infants, children, and adolescents: ≤13%)

Local: Pain at injection site (children, adolescents, and adults: 82% to 98%), erythema at injection site (children: 60% to 98%; infants and children: 60% to 64%; children, adolescents, and adults: 45% to 54%), tenderness at injection site (children: 81% to 89%; infants and children: 65% to 66%), swelling at injection site (children: 26% to 63%; children and adolescents: 18% to 39%; infants and children: 26% to 31%), induration at injection site (infants and children: 33% to 56%; children, adolescents, and adults: 28% to 40%)

Neuromuscular & skeletal: Myalgia (children, adolescents, and adults: 31% to 57%), arthralgia (children, adolescents, and adults: 13% to 33%)

Miscellaneous: Fever (infants and children: 69% to 79%, ≥40°C [104°F] ≤1%; children: 10% to 28%, ≥40°C [104°F] ≤3%; children, adolescents, and adults: 1% to 8%)

1% to 10%:

Dermatologic: Skin rash (children: ≤9%), urticaria (infants and children: 5% to 6%)

Respiratory: Upper respiratory tract infection (infants: 10%; mostly considered unrelated to vaccination), nasopharyngitis (children, adolescents, and adults: ≥2%)

<1% (postmarketing, and/or case reports): Eczema, febrile seizures, hypersensitivity reaction (includes anaphylaxis), injection site blister formation, injection site nodule, Kawasaki syndrome, pallor, seizure, swelling of eye, syncope, vasodepressor syncope

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactoid/hypersensitivity reactions: Immediate treatment (including epinephrine 1 mg/mL) for anaphylactoid and/or hypersensitivity reactions should be available during vaccine use (ACIP [Kroger 2017]).
• Apnea: Post immunization apnea may occur in premature infants, particularly if history of respiratory immaturity.
• Syncope: Syncope has been reported with use of injectable vaccines and may result in serious secondary injury (eg, skull fracture, cerebral hemorrhage); typically reported in adolescents and young adults and within 15 minutes after vaccination. Procedures should be in place to avoid injuries from falling and to restore cerebral perfusion if syncope occurs (ACIP [Kroger 2017]).

Disease-related concerns:

• Acute illness: The decision to administer or delay vaccination because of current or recent febrile illness depends on the severity of symptoms and the etiology of the disease. Defer administration in patients with moderate or severe acute illness (with or without fever); vaccination should not be delayed for patients with mild acute illness (with or without fever) (ACIP [Kroger 2017]).
• Bleeding disorders: Use with caution in patients with bleeding disorders (including thrombocytopenia); bleeding/hematoma may occur from IM administration; if the patient receives antihemophilia or other similar therapy, IM injection can be scheduled shortly after such therapy is administered (ACIP [Kroger 2017]).
• Meningococcal infections: Not to be used to treat meningococcal infections or to provide immunity against N. meningitidis serogroups A, C, W-135, or Y. In addition, vaccine does not provide protection against all circulating meningococcal group B strains.

Concurrent drug therapy issues:

• Anticoagulant therapy: Use with caution in patients receiving anticoagulant therapy; bleeding/hematoma may occur from IM administration (ACIP [Kroger 2017]).
• Vaccines: In order to maximize vaccination rates, the ACIP recommends simultaneous administration (ie, >1 vaccine on the same day at different anatomic sites) of all age-appropriate vaccines (live or inactivated) for which a person is eligible at a single clinic visit, unless contraindications exist. Because of differences in components and dosing regimen, meningococcal group B vaccines are not interchangeable (ACIP [Kroger 2017]).

Special populations:

• Altered immunocompetence: Patients with certain complement deficiencies and patients receiving treatment that inhibits terminal complement activation (eg, eculizumab) are at an increased risk for invasive meningococcal infection, including post-vaccination. Consider deferring immunization during periods of severe immunosuppression (eg, patients receiving chemo/radiation therapy or other immunosuppressive therapy [including high-dose corticosteroids]); may have a reduced response to vaccination. In general, household and close contacts of persons with altered immunocompetence may receive all age appropriate vaccines. Inactivated vaccines should be administered ≥2 weeks prior to planned immunosuppression when feasible; inactivated vaccines administered during chemotherapy should be readministered after immune competence is regained (ACIP [Kroger 2017]; IDSA [Rubin 2014]).
• Pediatric: Apnea has occurred following intramuscular vaccine administration in premature infants; consider clinical status implications. In general, preterm infants should be vaccinated at the same chronological age as full-term infants (ACIP [Kroger 2017]).

Dosage form specific issues:

• Kanamycin: May contain kanamycin.
• Latex: The packaging (needle cover of prefilled syringe) may contain latex.
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Other warnings/precautions:

• Antipyretics: Antipyretics have not been shown to prevent febrile seizures; antipyretics may be used to treat fever or discomfort following vaccination (ACIP [Kroger 2017]). One study reported that routine prophylactic administration of acetaminophen to prevent fever prior to vaccination decreased the immune response of some vaccines; the clinical significance of this reduction in immune response has not been established (Prymula 2009).
• Appropriate use: Use of this vaccine for specific medical and/or other indications (eg, immunocompromising conditions, hepatic or kidney disease, diabetes) is also addressed in the annual ACIP Recommended Immunization Schedules (refer to CDC schedule for detailed information).
• Effective immunity: Vaccination may not result in effective immunity in all patients. Response depends on multiple factors (eg, type of vaccine, age of patient) and may be improved by administering the vaccine at the recommended dose, route, and interval. Vaccines may not be effective if administered during periods of altered immune competence (ACIP [Kroger 2017]).

Monitoring Parameters

Respiratory function for 48 to 72 hours following vaccination in premature infants (particularly if born ≤28 weeks gestation or if prior history of respiratory immaturity). Monitor for syncope for 15 minutes following administration (ACIP [Kroger 2017]). If seizure-like activity associated with syncope occurs, maintain patient in supine or Trendelenburg position to reestablish adequate cerebral perfusion.

Pregnancy

Pregnancy Considerations

Inactivated vaccines have not been shown to cause increased risks to the fetus (ACIP [Kroger 2017]). However, the Advisory Committee on Immunization Practices (ACIP) recommends deferring meningococcal group B vaccination in pregnant women unless the woman is at increased risk for meningococcal disease and vaccination benefits outweigh the potential risks (ACIP [Patton 2017]).

Patient Education

What is this drug used for?

• It is used to prevent meningococcal disease.

Frequently reported side effects of this drug

• Injection site pain, redness, or swelling
• Loss of strength and energy
• Headache
• Muscle pain
• Joint pain
• Chills
• Diarrhea
• Nausea

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Severe dizziness
• Passing out
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.