Vaccine Information: Menveo (Page 2 of 6)

6.2 Postmarketing Experience

In addition to reports in clinical trials, worldwide voluntary reports of adverse events received for MENVEO in persons 11 through 55 years of age since market introduction of this vaccine are listed below. This list includes serious events or events which have plausible causal connection to MENVEO. Because these events are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to the vaccine.

Ear and Labyrinth Disorders

Hearing impaired, ear pain, vertigo, vestibular disorder.

Eye Disorders

Eyelid ptosis.

General Disorders and Administration Site Conditions

Injection site pruritus; pain; erythema; inflammation; and swelling, including extensive swelling of the vaccinated limb; fatigue; malaise; pyrexia.

Immune System Disorders

Hypersensitivity reactions, including anaphylaxis.

Infections and Infestations

Vaccination site cellulitis.

Injury, Poisoning and Procedural Complications

Fall, head injury.

Investigation

Alanine aminotransferase increased, body temperature increased.

Musculoskeletal and Connective Tissue Disorders

Arthralgia, bone pain.

Nervous System Disorders

Dizziness, syncope, tonic convulsion, headache, facial paresis, balance disorder.

Respiratory, Thoracic and Mediastinal Disorders

Oropharyngeal pain.

Skin and Subcutaneous Tissue Disorders

Skin exfoliation.

Postmarketing Observational Safety Study

In a postmarketing observational safety study conducted in a United States health maintenance organization, data from electronic health records of 48,899 persons 11 through 21 years of age were used to evaluate pre-specified events of interest following vaccination with MENVEO. Using a self-controlled case series method, Bell’s palsy showed a statistically significant increased risk in the period 1 to 84 days post vaccination compared with the control period, with an overall adjusted relative incidence of 2.9 (95% CI: 1.1-7.5). Among the 8 reported cases of Bell’s palsy, 6 cases occurred in persons who received MENVEO concomitantly with one or more of the following vaccines: Tdap, HPV, and Influenza vaccine. All reported Bell’s palsy cases resolved.

7 DRUG INTERACTIONS

7.1 Concomitant Administration with Other Vaccines

Do not mix MENVEO or any of its components with any other vaccine or diluent in the same syringe or vial.

In 2 clinical trials of infants initiating vaccination at 2 months of age,1,3 MENVEO was given concomitantly at 2, 4, and 6 months with routine infant vaccines: diphtheria toxoid; acellular pertussis; tetanus toxoid; inactivated polio types 1, 2, and 3; hepatitis B; Haemophilus influenzae type b (Hib) antigens; pentavalent rotavirus; and 7-valent pneumococcal conjugate vaccine. For Dose 4 given at 12 months of age, MENVEO was given concomitantly with the following vaccines: 7-valent pneumococcal conjugate, MMRV, or MMR+V, and inactivated hepatitis A. In a clinical trial of older infants (≥7 months of age) and toddlers,5 MENVEO was administered concomitantly with MMRV or MMR+V vaccine(s) at 12 months of age. No immune interference was observed for the concomitantly administered vaccines, including most pneumococcal vaccine serotypes (post Dose 3); no immune interference was observed post Dose 4 for any pneumococcal vaccine serotypes.1,3 [See Clinical Studies (14.5).]

For children 2 years through 10 years of age, no data are available to evaluate safety and immunogenicity of other childhood vaccines when administered concomitantly with MENVEO.

In a clinical trial in adolescents,14 MENVEO was given concomitantly with the following: Tdap and HPV; no interference was observed in meningococcal immune responses when compared with MENVEO given alone. Lower geometric mean antibody concentrations (GMCs) for antibodies to the pertussis antigens filamentous hemagglutinin (FHA) and pertactin were observed when MENVEO was administered concomitantly with Tdap and HPV as compared with Tdap alone. [See Clinical Studies (14.5).]

7.2 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 [see Warnings and Precautions (5.3)]. The immunogenicity of MENVEO has not been evaluated in persons receiving such therapies.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

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.

Nonclinical Studies

The effect of MENVEO on embryo-fetal and post-natal development was evaluated in pregnant rabbits. Animals were administered MENVEO 3 times prior to gestation, during the period of organogenesis (gestation Day 7) and later in pregnancy (gestation Day 20), 0.5 mL/rabbit/occasion (approximately 20-fold excess relative to the projected human dose on a body weight basis) by intramuscular injections. There were no adverse effects attributable to the vaccine on mating, female fertility, pregnancy, or embryo-fetal development. There were no vaccine-related fetal malformations or other evidence of teratogenesis noted in this study.

Clinical Studies

To date, no clinical trials have been specifically designed to evaluate the use of MENVEO in pregnant or lactating women.

Among the 5,065 women in the adolescent and adult populations enrolled in the studies, 43 women were found to be pregnant during the 6-month follow-up period after vaccination. Of these, 37 pregnancies occurred among 3,952 recipients of MENVEO (7 spontaneous abortions, no congenital anomalies). Six pregnancies occurred among 1,113 MENACTRA recipients (no spontaneous abortions, 1 congenital anomaly [hydrocephalus]).

Among the 7 subjects with adverse pregnancy outcomes who had received MENVEO, the estimated dates of conception were 5 days prior to vaccination (1 subject), 6 to 17 weeks post vaccination (5 subjects), and 6 months post vaccination (1 subject). In the subject who had received MENACTRA, the estimated date of conception was approximately 15 weeks post immunization.

Safety and effectiveness of MENVEO have not been established in pregnant women.

Pregnancy Registry for MENVEO

GlaxoSmithKline maintains a surveillance registry to collect data on pregnancy outcomes and newborn health status outcomes following exposure to MENVEO during pregnancy. Women who receive MENVEO during pregnancy should be encouraged to contact GlaxoSmithKline directly or their healthcare provider should contact GlaxoSmithKline by calling 1-877-413-4759.

8.3 Nursing Mothers

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.

8.4 Pediatric Populations

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

8.5 Geriatric Populations

Safety and effectiveness of MENVEO in adults 65 years of age and older have not been established.

11 DESCRIPTION

MENVEO [Meningococcal (Groups A, C, Y, and W-135) Oligosaccharide Diphtheria CRM197 Conjugate Vaccine] is a sterile liquid vaccine administered by intramuscular injection that contains N. meningitidis serogroup A, C, Y, and W-135 oligosaccharides conjugated individually to Corynebacterium diphtheriae CRM197 protein. The polysaccharides are produced by bacterial fermentation of N. meningitidis (serogroups A, C, Y, or W-135). N. meningitidis strains A, C, Y, and W-135 are each cultured and grown on Franz Complete medium and treated with formaldehyde. MenA, MenW-135, and MenY polysaccharides are purified by several extraction and precipitation steps. MenC polysaccharide is purified by a combination of chromatography and precipitation steps.

The protein carrier (CRM197 ) is produced by bacterial fermentation and is purified by a series of chromatography and ultrafiltration steps. C. diphtheriae is cultured and grown on CY medium containing yeast extracts and amino acids.

The oligosaccharides are prepared for conjugation from purified polysaccharides by hydrolysis, sizing, and reductive amination. After activation, each oligosaccharide is covalently linked to the CRM197 protein. The resulting glycoconjugates are purified to yield the 4 drug substances, which compose the final vaccine. The vaccine contains no preservative or adjuvant. Each dose of vaccine contains 10 mcg MenA oligosaccharide; 5 mcg of each of MenC, MenY, and MenW-135 oligosaccharides; and 32.7 to 64.1 mcg CRM197 protein. Residual formaldehyde per dose is estimated to be not more than 0.30 mcg.

The vials in which the vaccine components are contained are composed of Type I glass, USP.

The container closures (synthetic rubber stoppers) are not made with natural rubber latex.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

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.16 Vaccination with MENVEO leads to the production of bactericidal antibodies directed against the capsular polysaccharides of serogroups A, C, Y, and W-135.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

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

14 CLINICAL STUDIES

For all age groups, effectiveness has been inferred from the measurement of serogroup-specific anticapsular antibodies with bactericidal activity using pooled human serum that lacked bactericidal activity as the source of exogenous complement (hSBA). In the absence of a licensed comparator vaccine for use in infants, the pre-specified endpoint for effectiveness of MENVEO in U.S. infants receiving a 4- dose series at 2, 4, 6, and 12 months of age was the proportion of subjects achieving an hSBA ≥1:8, with the lower limit of the 2-sided 95% CI for the point estimate being ≥80% of vaccinees for serogroup A, and ≥85% of vaccinees for serogroups C, W-135, and Y 1 month following the final dose.

The effectiveness of MENVEO in subjects 2 years through 55 years of age was assessed by comparing the hSBA responses to immunization with MENVEO to those following immunization with the licensed meningococcal quadrivalent conjugate vaccine MENACTRA.

The primary effectiveness endpoint was hSBA seroresponse to each serogroup 28 days after vaccination. Seroresponse was defined as: a) post-vaccination hSBA ≥1:8 for subjects with a baseline hSBA <1:4; or, b) at least 4-fold higher than baseline titers for subjects with a pre-vaccination hSBA ≥1:4. Secondary endpoints included the proportion of subjects with post-vaccination hSBA ≥1:8 and the hSBA Geometric Mean Titer (GMT) for each serogroup. In a separate group of children 2 years through 5 years of age randomized to receive 2 doses of MENVEO administered 2 months apart, seroresponse rate, proportion with post-vaccination hSBA ≥1:8 and GMT were determined for each serogroup.

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