Meningococcal (Groups A / C / Y and W-135) Diphtheria Conjugate Vaccine

Dosage Forms

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

Injection, solution [preservative free]:

Menactra: 4 mcg each of polysaccharide antigen groups A, C, Y, and W-135 [bound to diphtheria toxoid 48 mcg] per 0.5 mL [MCV4 or MenACWY-D] [contains formaldehyde]

Menveo: MenA oligosaccharide 10 mcg, MenC oligosaccharide 5 mcg, MenY oligosaccharide 5 mcg, and MenW-135 oligosaccharide 5 mcg [bound to CRM₁₉₇ protein 32.7-64.1 mcg] per 0.5 mL (0.5 mL) [MenACWY-CRM; supplied in two vials, one containing MenA powder and one containing MenCYW-135 liquid]

Pharmacology

Mechanism of Action

Induces immunity against meningococcal disease via the formation of bactericidal antibodies directed toward the polysaccharide capsular components of Neisseria meningitidis serogroups A, C, Y and W-135.

Use: Labeled Indications

Meningococcal disease prevention: Active immunization of infants and children (≥2 months of age [Menveo]; ≥9 months of age [Menactra]) and persons ≤55 years of age against invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y, and W-135.

The Advisory Committee on Immunization Practices (ACIP) (CDC/ACIP [Cohn 2013]; CDC/ACIP [MacNeil 2014]; CDC/ACIP [MacNeil 2016]):

ACIP recommends routine vaccination of the following:

- Children and adolescents 11 to 18 years of age

- Persons ≥2 months of age who are at increased risk of meningococcal disease

- Persons (in all recommended age groups) at increased risk who are part of outbreaks caused by vaccine preventable serogroups

Those at increased risk of meningococcal disease include the following:

- Persons ≥2 months of age with medical conditions such as anatomic or functional asplenia (including sickle cell disease), HIV, or persistent complement component deficiencies (eg, C₅-C₉, properdin, factor H, or factor D, persons receiving eculizumab)

- Persons ≥2 months of age who travel to or reside in countries where meningococcal disease is hyperendemic or epidemic, especially if contact with the local population will be prolonged

- Unvaccinated or incompletely vaccinated first year college students living in residence halls (CDC/ACIP [Bilukha 2005])

- Military recruits

- Microbiologists with occupational exposure

The Canadian National Advisory Committee on Immunization (NACI): NACI recommends a routine vaccination at ~12 years of age but no booster unless at a continued high risk of exposure. Either quadrivalent vaccine may be used; NACI does not have a preference. NACI recommends use of Menveo (off-label use) for high risk persons 2 months to 2 years of age if vaccination with a quadrivalent vaccine is needed; may also be considered for use in persons ≥56 years of age (NACI 39[1] 2013). Additional recommendations may be found at http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/13vol39/acs-dcc-1/index-eng.php

Contraindications

Severe hypersensitivity (eg, anaphylaxis) to other meningococcal-containing vaccines or any component of the formulation including diphtheria toxoid or CRM₁₉₇ (a diphtheria toxin carrier protein)

Dosage and Administration

Dosing: Adult

Meningococcal disease, prevention:

ACIP recommendations (CDC/ACIP [Bilukha 2005]; CDC/ACIP [Cohn 2013]; CDC/ACIP [MacNeil 2016]): Use of the abbreviation, MenACWY, refers to either meningococcal quadrivalent conjugate vaccine. MenACWY-CRM refers specifically to Menveo; MenACWY-D refers specifically to Menactra.

Primary vaccination: IM:

Adults 19 to 21 years: Not routinely recommended; may receive one 0.5 mL dose as a catch-up vaccination if no dose was received after the sixteenth birthday.

Adults ≥22 years of age: Not routinely recommended; see dosing for persons at increased risk

Primary vaccination: Persons at increased risk for meningococcal disease:

Note: If using MenACWY-D (Menactra), administer ≥4 weeks after completion of all pneumococcal conjugate vaccine doses.

Adults not previously vaccinated and who have persistent complement deficiencies (including eculizumab use), functional or anatomic asplenia, or who have HIV infection: MenACWY-CRM (Menveo) or MenACWY-D (Menactra): IM: Two 0.5 mL doses, given ≥2 months apart.

Other adults not previously vaccinated and who are first-year college students living in residential housing; traveling to or residing in areas where meningococcal disease is endemic/hyperendemic; at risk during a community outbreak; military recruits; or microbiologists routinely exposed to Neisseria meningitidis: MenACWY-CRM (Menveo) or MenACWY-D (Menactra): IM: One 0.5 mL dose. College students should have documentation of a vaccination not more than 5 years before enrollment (preferably a dose on or after their sixteenth birthday).

Booster dose: Persons NOT at increased risk for meningococcal disease (routine immunization): Adults ≤21 years of age: MenACWY-CRM (Menveo) or MenACWY-D (Menactra): IM: One 0.5 mL dose if the first dose was given prior to the sixteenth birthday. A booster dose is not needed if the primary dose was given after the sixteenth birthday unless the person becomes at increased risk for meningococcal disease.

Booster vaccination: Persons at increased risk for meningococcal disease: Repeat dose every 5 years if the person remains at increased risk.

Dosing: Pediatric

Note: Use of the abbreviation, MenACWY, refers to either meningococcal quadrivalent conjugate vaccine. MenACWY-CRM refers specifically to Menveo; MenACWY-D refers specifically to Menactra. Consult CDC/ACIP annual immunization schedules 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]).

Primary immunization:

Note: Although FDA-approved in <11 years of age, use is only recommended in patients at increased risk; routine use not recommended (CDC/ACIP [Cohn 2013]; CDC/ACIP [MacNeil 2014]; CDC/ACIP [MacNeil 2016])

CDC (ACIP) recommendations (ACIP [Robinson 2018]; CDC/ACIP [Cohn 2013]; CDC/ACIP [MacNeil 2014]; CDC/ACIP [MacNeil 2016]):

Primary vaccination for patients NOT at increased risk for meningococcal disease:

Infants and Children <11 years: Not routinely recommended; see dosing for persons at increased risk

Children 11 to 12 years: MenACWY-CRM (Menveo) or MenACWY-D (Menactra): IM: 0.5 mL as a single dose. Children not at increased risk for meningococcal disease who may have been previously vaccinated with Hib-MenCY-TT (Menhibrix) or MenACWY (Menactra or Menveo) prior to their 10th birthday should receive the routinely recommended dose of MenACWY at 11 to 12 years.

Adolescents: IM: 0.5 mL as a single dose if not previously vaccinated

Primary vaccination for patients at increased risk for meningococcal disease: Note: If MenACWY-D (Menactra) product is used, administer it before or concomitantly with DTaP, and administer ≥4 weeks after completion of all PCV doses as age appropriate.

Infants ≥2 months and Children <2 years:

Anatomic or functional asplenia (including sickle cell disease): Dosing based on age at initial dose:

Infants 8 weeks to 6 months: MenACWY-CRM (Menveo): IM: 0.5 mL per dose for a total of 4 doses administered at 2, 4, 6, and 12 months of age

Children 7 to 23 months (incomplete vaccination): MenACWY-CRM (Menveo): IM: 0.5 mL per dose for a total of 2 doses administered at least 12 weeks apart; the second dose should be administered at least 12 weeks after the first dose.

Persistent complement component deficiency (including eculizumab use) or HIV-exposed/-infected: Dosing based on age at first dose:

Infants 8 weeks to 6 months: MenACWY-CRM (Menveo): IM: 0.5 mL per dose for a total of 4 doses administered at 2, 4, 6, and 12 months of age

Infants and Children 7 to 23 months:

MenACWY-CRM (Menveo): Infants and Children 7 to 23 months: IM: 0.5 mL per dose for a total of 2 doses; the second dose should be given at age ≥12 months and at least 12 weeks after the first dose

MenACWY-D (Menactra): Infants and Children 9 to 23 months: IM: 0.5 mL per dose for a total of 2 doses; the second dose should be given at least 12 weeks after the first dose. May be given as early as 8 weeks apart if needed prior to travel. Note: Administer before or concomitantly with DTaP and administer ≥4 weeks after completion of all PCV doses.

Community outbreak (due to vaccine serogroup): Infants ≥2 months to Children 23 months: Initiate or complete an age appropriate series of MenACWY-CRM (Menveo) or MenACWY-D (Menactra); see previous Primary immunization for dosing.

Travel to or residence in countries with hyperendemic or epidemic meningococcal disease: Infants 2 months to Children 23 months: Initiate or complete an age appropriate series of MenACWY-CRM (Menveo) or MenACWY-D (Menactra); see previous Primary immunization for dosing.

Children ≥2 years and Adolescents, not previously vaccinated and who have persistent complement deficiencies (including eculizumab use), functional or anatomic asplenia, or who have HIV infection: MenACWY-CRM (Menveo) or MenACWY-D (Menactra): IM: 0.5 mL per dose for a total of 2 doses administered at least 8 weeks apart.

Other children ≥2 years and Adolescents at increased risk not previously vaccinated and who are either: First year college students ≤21 years of age living in residential housing, traveling to or residents of areas where meningococcal disease is endemic/hyperendemic, at risk during a community outbreak, or microbiologists routinely exposed to Neisseria meningitidis: MenACWY-CRM (Menveo) or MenACWY-D (Menactra): IM: 0.5 mL as a single dose. College students ≤21 years should have documentation of a vaccination not more than 5 years before enrollment (preferably a dose on their 16th birthday).

Booster dose: (CDC/ACIP [Cohn 2013]):

Booster vaccination for patients NOT at increased risk for meningococcal disease: IM: 0.5 mL as a single dose. If primary vaccination was at 11 to 12 years, the booster dose should be given at age 16. If the primary vaccination was given at 13 to 15 years, the booster dose should be given at age 16 to 18. Minimum interval between MenACWY (Menveo or Menactra) doses is 8 weeks. A booster dose is not needed if the primary dose was given after the 16th birthday unless the person becomes at increased risk for meningococcal disease.

Booster vaccination for patients at increased risk for meningococcal disease:

If first dose received at 2 months to 6 years of age: Repeat dose 3 years after primary vaccination and every 5 years thereafter if the person remains at increased risk.

If first dose received at ≥7 years of age: Repeat dose 5 years after primary vaccination and every 5 years thereafter if the person remains at increased risk.

Reconstitution

Menveo: Prior to use, remove entire contents from vial of MenCYW-135 and inject into vial containing MenA powder. Invert and shake well until dissolved. The resulting solution should be clear, colorless, and particle free. A small amount of liquid will remain in the vial after withdrawing the 0.5 mL dose.

Administration

IM: Administer by IM route, preferably into the central 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 intramuscularly if, in the opinion of a physician 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, intramuscular 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]).

For IM administration only. Based on limited data, inadvertent SubQ administration provides a lower serologic response; however, the response is still considered to be protective. If inadvertently administered by the SubQ route, revaccination is not necessary.

Storage

Menactra: Store between 2°C to 8°C (35°F to 46°F); do not freeze. Discard product exposed to freezing.

Menveo: Prior to reconstitution, store between 2°C to 8°C (36°F to 46°F); do not freeze. Protect from light. Use immediately after reconstitution but may be stored at 2°C to 25°C (36°F to 77°F) for up to 8 hours; do not freeze. Discard product exposed to freezing.

Drug Interactions

Diphtheria and Tetanus Toxoids, and Acellular Pertussis Vaccine: May diminish the therapeutic effect of Meningococcal (Groups A / C / Y and W-135) Diphtheria Conjugate Vaccine. More specifically, prior administration of the diphtheria and tetanus toxoids, and acellular pertussis vaccine may diminish antibody response to the meningococcal (groups A / C / Y / and W-135) diphtheria conjugate vaccine in some patients. Management: Administer the meningococcal (groups A / C / Y and W-135) diphtheria conjugate vaccine (Menactra brand) before or concurrently with the diphtheria and tetanus toxoids, and acellular pertussis vaccine (Daptacel brand) in children 4 to 6 years of age. Monitor therapy

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

Pneumococcal Conjugate Vaccine (13-Valent): Meningococcal (Groups A / C / Y and W-135) Diphtheria Conjugate Vaccine may diminish the therapeutic effect of Pneumococcal Conjugate Vaccine (13-Valent). Management: It is recommended to administer PCV13 at least 4 weeks prior to the administration of MenACYW-D (Menactra brand) vaccine in persons with anatomic asplenia or functional asplenia. This interaction does not apply to the MenACYW-CRM (Menveo brand) vaccine. 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

Actual percentages may vary by product and age group. Adverse reactions occur with children, adolescents, and adults unless otherwise specified.

>10%:

Central nervous system: Pain (60%), irritability (infants: 27% to 57%; children: 12% to 22%), drowsiness (infants: 17% to 50%; children: 11% to 18%), headache (adolescents & adults: 22% to 41%; children: 5% to 18%), excessive crying (infants: 12% to 41%), fatigue (adolescents & adults: 17% to 35%), malaise (adolescents & adults: 10% to 24%; children: 11% to 14%)

Gastrointestinal: Anorexia (8% to 12%; infants: 30%), change in appetite (infants: 12% to 23%; children: 9% to 10%), diarrhea (infants, children, adolescents, & adults: 7% to 16%), nausea (5% to 12%), vomiting (2% to 3%; infants: 5% to 14%)

Local: Pain at injection site (adolescents & adults: 38% to 59%; children: 33% to 45%), tenderness at injection site (infants: 10% to 37%), erythema at injection site (infants & children: 11% to 30%; adolescents & adults: 11% to 16%), induration at injection site (11% to 19%; infants: 7% to 8%), swelling at injection site (infants, children, adolescents, & adults: 11% to 17%)

Neuromuscular & skeletal: Myalgia (10% to 43%), arthralgia (adolescents & adults: 6% to 20%; children: 3% to 7%)

Miscellaneous: Crying (abnormal; infants: 33%), fever (infants, children, & adolescents: ≤12%; adults: 1% to 2%)

1% to 10%:

Central nervous system: Chills (4% to 10%)

Dermatologic: Skin rash (infants, children, & adolescents: 2% to 6%; adults: 1% to 2%)

<1%, postmarketing, and/or case reports: Accidental injury, acute disseminated encephalomyelitis, anaphylaxis, angioedema, apnea (premature infants), appendicitis, attempted suicide, auditory impairment, Bell palsy, blepharoptosis, cellulitis at injection site, gastrointestinal disease (Vitello-intestinal duct remnant), Cushing syndrome, dehydration, dizziness, dyspnea, equilibrium disturbance, erythema, exfoliation of skin, facial nerve paralysis, falling, febrile seizures, gastroenteritis, Guillain-Barre syndrome, herniated disc, herpes zoster infection, hypersensitivity reaction, hypotension, increased serum alanine aminotransferase, inflammation inguinal hernia, injection site pruritus, Kawasaki syndrome, lymphadenopathy, oropharyngeal pain, ostealgia, otalgia, paresthesia, pelvic inflammatory disease, pneumonia, pruritus, seizure, sepsis, staphylococcal infection, suicidal tendencies, swelling, swelling of injected limb, syncope, transverse myelitis, upper airway swelling, urticaria, vasopressor syncope, vertigo, vestibular disturbance, viral hepatitis, wheezing

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]).
• 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 a history of 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 serogroup B or diphtheria.

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. The ACIP prefers each dose of a specific vaccine in a series come from the same manufacturer when possible; however, vaccination should not be deferred because a specific brand name is unavailable (ACIP [Kroger 2017]).

Administration of Menactra (MenACWY-D) one month after Daptacel (DTaP) has been shown to have reduced meningococcal antibody responses in children; for children ages 2 through 6 years, these vaccines should be administered simultaneously or Menactra should be administered prior to or 6 months after Daptacel. This interaction does not apply to Menveo (MenACWY-CRM) (CDC/ACIP [Cohn 2013]).

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 been reported following IM 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]). Children with functional or anatomic asplenia should delay receiving Menactra (MenACWY-D) until 2 years of age to avoid immune interference with the 13-valent pneumococcal conjugate vaccine (PCV13); Menactra should be given at least 4 weeks after completion of the PCV13 series; if meningococcal immunity is required in pediatric patients 2 to 23 months of age, the alternative is administration of Menveo (MenACWY-CRM) (CDC/ACIP [MacNeil 2014]).

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). Specific recommendations for use of this vaccine in immunocompromised patients with asplenia, cancer, HIV infection, cerebrospinal fluid leaks, cochlear implants, hematopoietic stem cell transplant (prior to or after), sickle cell disease, solid organ transplant (prior to or after), or those receiving immunosuppressive therapy for chronic conditions are available from the IDSA (Rubin 2014).
• Effective immunity: Vaccination may not result in effective immunity in all patients. Response depends upon 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

Monitor for syncope for at least 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

Based on available data, an increased risk of adverse pregnancy outcomes has not been observed following maternal vaccination with a meningococcal (Groups A / C / Y and W-135) diphtheria conjugate vaccine (Myers 2017; Zheteyeva 2013).

Inactivated bacterial vaccines have not been shown to cause increased risks to the fetus (ACIP [Kroger 2017]). Pregnancy should not preclude vaccination if otherwise indicated (CDC/ACIP [Cohn 2013]).

Data collection to monitor pregnancy and infant outcomes following exposure to Menactra is ongoing. Health care providers are encouraged to enroll females exposed to Menactra during pregnancy in the Sanofi Pasteur Inc vaccine registry (1-800-822-2463).

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, swelling, or irritation
• Headache
• Loss of strength and energy
• Muscle pain
• Joint pain
• Lack of appetite
• Diarrhea
• Irritability (children)
• Fatigue (children)
• Abnormal crying (children)
• Chills (children)
• Vomiting (children)

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

• Severe dizziness
• Passing out
• Abnormal movements
• Facial paralysis
• Muscle weakness
• 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.