TRUMENBA

General Administration Information
For storage information, see the specific product information within the How Supplied section.
-Inform the patient, parent, guardian, or responsible adult of the benefits and risks of the vaccine. Provide the Vaccine Information Statements from the manufacturer to the patient, parent, or guardian before each immunization. The action is required by the National Childhood Vaccine Injury Act of 1986.
-Record in the patient's permanent record the manufacturer, lot number, administration date, and the name and address of the person administering the vaccine. These actions are required by the National Childhood Vaccine Injury Act of 1986.

Route-Specific Administration

Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. After vigorous shaking, the meningococcal group B vaccine (4 strain) is a homogenous white suspension. If discoloration or visible particulate matter are present, discard the syringe.
-Do not mix with any other vaccine or product in the same syringe.
Intramuscular Administration
-Prior to administration, clean skin over the injection site with a suitable cleansing agent.
-Vigorously shake the prefilled syringe prior to administration to ensure a homogenous white suspension; DO NOT administer if the vaccine cannot be re-suspended.
-The preferred injection site is the deltoid muscle of the upper arm; do NOT inject into the gluteal area or other areas where there may be a major nerve trunk.

The safety of the meningococcal group B vaccine (4 strain) was evaluated in 15,227 subjects in 11 clinical studies (8 randomized controlled and 3 supportive non-controlled studies) conducted in the U.S., Europe, Canada, Chile, and Australia. An injection site reaction within the first 7 days after a dose was the most frequently reported adverse event in young adult and pediatric patients (10 to 25 years old) receiving the meningococcal group B vaccine (4 strain). The reactions generally were of higher incidence with the first dose versus with repeat doses in the series. In clinical trials, recipients of the vaccine experienced pain/tenderness (76% to 86.7%), erythema or redness (11.8% to 17.1%), and induration or swelling at the injection site (13.9% to 18%).

Gastrointestinal adverse reactions were reported during clinical trials in patients immunized with meningococcal group B vaccine (4 strain). These adverse reactions included diarrhea (7.5% to 12.7%) and vomiting (1.7% to 3.7%). Severe diarrhea or vomiting occurred in less than 1%. During early phase studies, nausea was reported in up to 24% of adolescents.

Patients receiving meningococcal group B vaccine (4 strain) during clinical trials have experienced a variety of systemic adverse reactions. These reactions included arthralgia (12.6% to 21.9%), chills (12.4% to 18.1%), fatigue (27.3% to 54%), fever of 38 degrees C or more (1.2% to 6.4%), headache (32.5% to 51.8%), and myalgia (15.6% to 25.9%).

Allergic reactions, including anaphylactoid reactions (anaphylaxis), have been reported with the meningococcal group B vaccine (4 strain) in postmarketing surveillance. Epinephrine and other appropriate agents used to manage immediate allergic reactions must be immediately available should an acute anaphylactic reaction occur. Syncope and vasovagal responses to injection have also been reported postmarketing.

Prior to administration, inform the parent, guardian, or responsible adult of the benefits and risks of the vaccine, and provide the Vaccine Information Statement, accessible at the Centers for Disease Control and Prevention (CDC) website. These actions are required by the National Childhood Vaccine Injury Act of 1986. If a dose of a vaccine that immunizes against meningococcal disease has been previously given, question the parent or guardian about previous adverse reactions that may preclude further administration. Report all adverse reactions to the Vaccine Adverse Event Reporting System (VAERS), as well as the manufacturer. The toll-free number for VAERS is 1-800-822-7967. Educate the responsible adult(s) to promptly report any adverse reaction after vaccine administration to a health care provider.

Use of a meningococcal group B vaccine (4 strain) is contraindicated in patients with a previous allergic reaction to the vaccine. With any biologic product, the prescriber or health care professional should take precautions to prevent allergic reactions. The health care professional should have immediate availability of epinephrine 1mg/mL injection and other agents used in the treatment of severe anaphylaxis in the event of a serious allergic reaction to the vaccine.

Meningococcal group B vaccine (4 strain) is only indicated for intramuscular (IM) administration. This vaccine may not be appropriate for patients with increased risk of bleeding such as thrombocytopenia, bleeding disorders (e.g., hemophilia), coagulopathy, vitamin K deficiency, or for those receiving anticoagulant therapy; caution and appropriate precautions to minimize the risk of bleeding or hematoma formation are advised.

The decision to administer or to delay vaccination with meningococcal group B vaccine (4 strain) because of current or recent febrile illness depends on the severity of symptoms and on the etiology of the disease. The Advisory Committee on Immunization Practices has recommended that vaccinations be delayed during the course of a moderate or severe acute febrile illness. All vaccines can be administered to persons with minor illnesses such as diarrhea, mild upper-respiratory infection with or without low-grade fever, or other low-grade febrile illness. Persons with moderate or severe febrile illness should be vaccinated as soon as they have recovered from the acute phase of the illness.

Patients suffering from significant immunosuppression may not have an adequate antibody response to meningococcal group B vaccine (4 strain). Immunosuppressed persons may include patients with human immunodeficiency virus (HIV) infection; severe combined immunodeficiency (SCID); hypogammaglobulinemia; agammaglobulinemia; altered immune states due to diseases such as generalized neoplastic disease; or an immune system compromised by corticosteroid therapy with greater than physiologic doses, radiation therapy, or chemotherapy, including alkylating drugs and antimetabolites. Short-term (less than 2 weeks) corticosteroid therapy or intra-articular, bursal, or tendon injections with corticosteroids should not be immunosuppressive. Patients vaccinated with meningococcal vaccine within 2 weeks before starting immunosuppressive therapy or while receiving immunosuppressive therapy should be considered unvaccinated and should be revaccinated at least 3 months after therapy is discontinued if immune competence has been restored. According to the Advisory Committee on Immunization Practices (ACIP), individuals with functional/anatomical asplenia, sickle cell disease, or persistent complement deficiencies (i.e., C3, C5 to C9, properdin, factor D, factor H, or eculizumab use) require a 3-dose series with meningococcal group B vaccine (4 strain) administered at 0, 1 to 2, and 6 months. Patients with certain complement deficiencies and those receiving treatment that inhibits terminal complement activation (i.e. eculizumab) are at increased risk for invasive disease caused by N. meningitidis serogroup B even if they develop antibodies following vaccination.

Syncope or fainting may occur in association with administration of meningococcal group B vaccine (4 strain). Procedures should be in place to avoid injury from fainting.

Description: Meningococcal group B vaccines (Trumenba and Bexsero) are the first vaccines FDA-approved to prevent invasive disease caused by Neisseria meningitidis serogroup B. The vaccines are composed of antigenic meningococcal surface proteins. Trumenba is comprised of two recombinant factor H binding proteins (fHBP) from serogroup B, one from fHBP subfamily A (A01) and one from subfamily B (B01). Meningococcal group B vaccines were designated as a breakthrough therapy and received expedient review by the FDA because other available vaccines do not prevent infections from N. meningitidis serogroup B; serogroup B is responsible for approximately one-third of all invasive meningococcal disease cases (160 of the 500 reported U.S. meningococcal disease cases in 2012), and because of increased concern due to meningococcal group B outbreaks occurring at U.S. universities. The FDA approved the vaccines based on the results of multicenter, clinical trials involving pediatric and young adult patients (11 to 24 years of age) that demonstrated the immune response, as measured by bactericidal activity against the 3 (Bexsero) or 4 (Trumenba) serogroup B strains representative of the prevalent strains in the U.S. Meningococcal group B vaccines should be routinely administered to those 10 years and older who are considered high risk for meningococcal group B disease. People considered high risk are those with persistent complement component deficiencies or those receiving eculizumab, anatomic or functional asplenia, microbiologists who work with Neisseria meningitidis, and those living in an outbreak area. Additionally, the vaccine may be administered at the discretion of the treating clinician to adolescents and young adults aged 16 to 23 years to provide short-term protection against most strains of meningococcal group B disease; the preferred age for vaccination is 16 to 18 years. Meningococcal group B vaccines are FDA-approved for use in pediatric patients 10 years and older.

General Dosing Information
-The meningococcal group B vaccine (4 strain) vaccine should be routinely administered to people 10 years of age and older who are considered high risk for meningococcal group B disease. People considered high risk are those with persistent complement component deficiencies or those receiving a complement inhibitor (e.g., eculizumab, ravulizumab), anatomic or functional asplenia, microbiologists who work with Neisseria meningitidis, and those living in an outbreak area. Additionally, the vaccine may be administered at the discretion of the treating clinician to adolescents and young adults aged 16 to 23 years who are not at increased risk for meningococcal disease to provide short-term protection against most strains of meningococcal group B disease; the preferred age for vaccination is 16 to 18 years.
-The 2 meningococcal group B vaccines are not interchangeable; the same vaccine product must be used for all doses. Meningococcal group B vaccines may be administered concomitantly with other vaccines, but at a different anatomic site, if feasible.

For meningococcal infection prophylaxis due to Neisseria meningitidis serogroup B:
NOTE: The efficacy of meningococcal group B vaccine is based on the demonstration of immune response, as measured by bactericidal activity against the 4 serogroup B strains representative of prevalent strains in the U.S. Efficacy of meningococcal Group B vaccine against diverse serogroup B strains has not been established.
NOTE: The choice of dosing schedule (2 dose or 3 dose) depends on the patient's risk of exposure and susceptibility to meningococcal serogroup B disease.
Intramuscular dosage (2 dose schedule):
Children and Adolescents 10 to 17 years: 0.5 mL IM, preferably in the deltoid region. Give as a 2-dose series, with doses administered on a 0- and 6-month schedule. If the second dose is administered earlier than 6 months, administer a third dose at least 4 months after the second dose. The 2 dose schedule is preferred for vaccination of adolescents 16 years and older not at increased risk for meningococcal disease.
Intramuscular dosage (3 dose schedule):
Children and Adolescents 10 to 17 years: 0.5 mL IM, preferably in the deltoid region. Give as a 3-dose series, with doses administered on a 0-, 1- to 2-, and 6-month schedule. The 3 dose schedule is preferred for vaccination of patients at high risk for meningococcal disease.
-for booster dosing or revaccination of patients who remain at increased risk for meningococcal infection*:
Intramuscular dosage:
Children and Adolescents 10 to 17 years: 0.5 mL IM. For continued protection of persons at high risk for meningococcal disease, give booster dose 1 year after primary immunization and repeat every 2 to 3 years thereafter.

Maximum Dosage Limits:
-Neonates
Safety and efficacy not established.
-Infants
Safety and efficacy not established.
-Children
1 to 9 years: Safety and efficacy not established.
10 to 12 years: 0.5 mL/dose IM.
-Adolescents
0.5 ml/dose IM.

Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Meningococcal disease is a result of an invasive infection by Neisseria meningitis; the five main N. meningitis serogroups responsible for meningococcal disease are A, B, C, Y, and W. Vaccination with meningococcal group B vaccine (4 strain) provides protection against invasive meningococcal disease caused by serogroup B. Neisserial adhesin A (NadA), Neisserial Heparin Binding Antigen (NHBA), factor H binding protein (fHBP), and PorA P1.4 (present in outer membrane vesicles [OMV]) are meningococcal surface proteins which contribute to the ability of the bacterium to cause disease. There are 2 immunologically distinct fHBP subfamilies, A and B. The Meningococcal group B vaccine (4 strain) is composed of two recombinant factor H binding protein (fHBP) variants from serogroup B, one from fHBP subfamily A and one from subfamily B. Immunization with the vaccine induces complement-mediated antibody dependent killing of N. meningitides, providing bactericidal activity against serogroup B meningococci; however, vaccine efficacy depends on the antigenic similarity of the bacterial and vaccine antigens, as well as the amount of antigen expressed on the surface of the invading N. meningitides.

Pharmacokinetics: Meningococcal group B vaccine (4 strain) is administered intramuscularly. Vaccination does not ensure immunity. Distrubution, metabolism, and excretion of the vaccine have not been defined.

Efficacy of the 3-dose vaccination series was evaluated during a clinical trial involving pediatric patients, ages 11 to 17 years. These children and adolescents were administered the vaccine on a 0-, 2-, and 6-month schedule, with human complement (hSBA) titers, indicating serum bactericidal activity, measured one month after the 2nd and 3rd doses. The primary endpoints were the percentage of subjects with greater than or equal to 4-fold rise in hSBA titers for each of the four test strains, and the percentage of subjects who achieved titers greater than or equal to the lower limit of quantitation (LLOQ) for all four strains (composite response). At one month after the 3rd dose at least a 4-fold rise in hSBA titers were observed in 85.3% to 86.4% for strain A22, 95% to 95.3% for strain A56, 83.4% to 84.8% for strain B24, and 77% to 80.7% for strain B44; the percentage of vaccine recipients to achieve the composite response of titers greater than or equal to LLOQ for all 4 strains was 81% to 83.9%.