Pharmaceutical Name

Trade (marketing or proprietary) name: Menactra®, MENVEO®

Generic (nonproprietary or active ingredient) name: Meningococcal (Groups A, C, Y and W-135) Polysaccharide Diphtheria Toxoid Conjugate Vaccine Solution for Intramuscular Injection, Meningococcal (Groups A, C, Y and W-135) Oligosaccharide Diphtheria CRM197 Conjugate Vaccine Solution for intramuscular injection

Indication and Usage

Reason the product has been approved for sale on the market.

Menactra is indicated for active immunization to prevent invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135. Menactra is approved for use in individuals 9 months through 55 years of age. Menactra does not prevent N meningitidis serogroup B disease.

MENVEO is a vaccine indicated for active immunization to prevent invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135. MENVEO is approved for use in persons 2 months through 55 years of age. MENVEO does not prevent N. meningitidis serogroup B infections.

Manufacturer Insert

Ingredients

Also known as “excipients” for vaccines.

Menactra is a sterile, intramuscularly administered vaccine that contains N meningitidis serogroup 8 A, C, Y and W-135 capsular polysaccharide antigens individually conjugated to diphtheria toxoid 9 protein. N meningitidis A, C, Y and W-135 strains are cultured on Mueller Hinton agar and 10 grown in Watson Scherp media containing casamino acid. Each 0.5 mL dose may contain residual 20 amounts of formaldehyde of less than 2.66 mcg (0.000532%), by calculation.

MENVEO is a vaccine indicated for active immunization to prevent invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135. MENVEO is approved for use in persons 2 months through 55 years of age. MENVEO does not prevent N. meningitidis serogroup B infections.

Contraindications

Per the FDA, contraindications are conditions in a recipient that increases the risk for a serious adverse reaction. Product should not be administered when a patient has a listed contraindication.

Menactra®

Severe allergic reaction (eg, anaphylaxis) after a previous dose of a meningococcal capsular polysaccharide-, diphtheria toxoid- or CRM197-containing vaccine, or to any component of Menactra.

MENVEO®

Severe allergic reaction (e.g., anaphylaxis) after a previous dose of MENVEO, any component of this vaccine, or any other CRM197, diphtheria toxoid or meningococcal containing vaccine is a contraindication to administration of MENVEO.

Warnings and Precautions

Per the FDA, warnings are clinically significant adverse reactions or risks. According to the CDC, a precaution is a condition in a recipient that might increase the risk for a serious adverse reaction, might cause diagnostic confusion, or might compromise the effectiveness of the product. In general, a product should be deferred when a precaution is present.

Menactra®

Guillain-Barré Syndrome: Persons previously diagnosed with Guillain-Barré syndrome (GBS) may be at increased risk of GBS following receipt of Menactra. The decision to give Menactra should take into account the potential benefits and risks. GBS has been reported in temporal relationship following administration of Menactra. The risk of GBS following Menactra vaccination was evaluated in a post-marketing retrospective cohort study.

Preventing and Managing Allergic Vaccine Reactions: Prior to administration, the healthcare provider should review the immunization history for possible vaccine sensitivity and previous vaccination-related adverse reactions to allow an assessment of benefits and risks. Epinephrine and other appropriate agents used for the control of immediate allergic reactions must be immediately available should an acute anaphylactic reaction occur.

Altered Immunocompetence:

• Reduced Immune Response – 14 Some individuals with altered immunocompetence, including some individuals receiving 15 immunosuppressant therapy, may have reduced immune responses to Menactra.
• 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, including invasive disease caused by serogroups A, C, Y and W-135, even if they develop antibodies following vaccination with Menactra.

Limitations of Vaccine Effectiveness: Menactra may not protect all recipients.

Syncope: Syncope (fainting) has been reported following vaccination with Menactra. Procedures should be in place to prevent falling injury and manage syncopal reactions.

Immunosuppressive Therapies: Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs, and corticosteroids (used in greater than physiologic doses) may reduce the immune response to vaccines.

MENVEO®

Management of Acute Allergic Reactions: Appropriate medical treatment must be available should an acute allergic reaction, including an anaphylactic reaction, occur following administration of MENVEO.

Syncope: Syncope, sometimes resulting in falling injury associated with seizure-like movements has been reported following vaccination with MENVEO. Vaccinees should be observed for at least 15 minutes after vaccine administration to prevent and manage syncopal reactions.

Altered Immunocompetence: Safety and effectiveness of MENVEO have not been evaluated in immunocompromised persons. If MENVEO is administered to immunocompromised persons, including those receiving immunosuppressive therapy, the expected immune response may not be obtained.

Guillain-Barré Syndrome: Guillain-Barré syndrome (GBS) has been reported in temporal relationship following administration of another U.S.-licensed meningococcal quadrivalent polysaccharide conjugate vaccine. The decision to administer MENVEO to subjects with a known history of Guillain-Barré Syndrome should take into account the potential benefits and risks.

Apnea in Premature Infants: Apnea following intramuscular vaccination has been observed in some infants born prematurely. The decision about when to administer an intramuscular vaccine, including MENVEO, to an infant born prematurely should be based on consideration of the individual infant’s medical status, and the potential benefits and possible risks of vaccination.

Immunosuppressive Treatments: Immunosuppressive therapies, such as irradiation, antimetabolite medications, alkylating agents, cytotoxic drugs, and corticosteroids (when used in greater than physiologic doses) may reduce the immune response to MENVEO. The immunogenicity of MENVEO has not been evaluated in persons receiving such therapies.

Manufacturer-Listed Adverse Reactions

Per the CDC, adverse reactions are an undesirable medical condition that has been demonstrated to be caused by a vaccine. Evidence for the causal relation is usually obtained through randomized clinical trials, controlled epidemiologic studies, isolation of the vaccine strain from the pathogenic site, or recurrence of the condition with repeated vaccination (i.e., rechallenge); synonyms include side effect and adverse effect.

Menactra can cause: Lymphadenopathy, Anaphylaxis/anaphylactic reaction, Wheezing, Difficulty breathing, Upper airway swelling, Urticaria (Hives), Erythema, Pruritus, Hypotension, Guillain-Barré syndrome, Paraesthesia, Vasovagal syncope, Dizziness, Convulsion, Facial palsy, Acute disseminated encephalomyelitis, Transverse myelitis, Myalgia, Large injection site reactions, extensive swelling of the injected limb (may be associated with erythema, warmth, tenderness or pain at the injection site).

Menveo can cause: Local lymphadenopathy, Hearing impaired, Ear pain, Vertigo, Vestibular disorder, Eyelid ptosis, Injection site pruritus, Pain, Erythema, Inflammation/swelling, including extensive swelling of the vaccinated limb, Fatigue, Tonic convulsion, Headache, Facial paresis, Balance disorder, Malaise (Discomfort), Pyrexia, Hypersensitivity reactions, Anaphylaxis, Vaccination site cellulitis, Fall, head injury, Alanine aminotransferase increased, Body temperature increased, Arthralgia, Bone pain, Dizziness, Syncope, Oropharyngeal pain, Skin exfoliation, Bell’s palsy.

Limitations of Effectiveness

Menactra may not protect all recipients.

Specific Populations

Pregnancy

There are no adequate and well-controlled studies of Menactra administration in pregnant women in the US.

Pregnancy Category B
Reproduction studies have been performed in female rabbits at a dose of approximately 20 times the human dose (on a mg/kg basis) and have revealed no evidence of impaired fertility or harm to the fetus due to MENVEO. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, MENVEO should be given to a pregnant woman only if clearly needed.

Breastfeeding

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Menactra and any potential adverse effects on the breastfed child from Menactra. Data are not available to assess the effects of Menactra on the breastfed infant or on milk production/excretion.

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when MENVEO is administered to a nursing woman. No studies have been conducted to assess the impact of MENVEO on milk production, its presence in breast milk or its effects on the breastfed child.

Fertility

Menactra has not been evaluated for carcinogenic or mutagenic potential, or for impairment of male fertility. A developmental animal toxicity study showed that Menactra had no effects on female fertility in mice.

MENVEO has not been evaluated for carcinogenic or mutagenic potential, or for impairment of male fertility.

Pediatric

Menactra is not approved for use in infants under 9 months of age.

Safety and effectiveness of MENVEO in children under 2 months of age have not been established.

Mechanism of Action

This is the specific biochemical interaction through which a drug or vaccine substance produces its pharmacological effect. This section also includes the minimum protective level designated for a certain disease.

Menactra®

The presence of bactericidal anti-capsular meningococcal antibodies has been associated with protection from invasive meningococcal disease (6) (7). Menactra induces the production of bactericidal antibodies specific to the capsular polysaccharides of serogroups A, C, Y and W-135.

MENVEO®

Neisseria meningitidis is a gram-negative diplococcus that causes life-threatening invasive disease such as meningitis and sepsis. Globally, 5 serogroups, A, B, C, Y and W-135 cause almost all invasive meningococcal infections. The presence of serum bactericidal antibodies protects against invasive meningococcal disease. Vaccination with MENVEO leads to the production of bactericidal antibodies directed against the capsular polysaccharides of serogroups A, C, Y and W-135.

Analytical Deep Dive

What is informed consent?