Menovac

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Menovac uses


1 INDICATIONS AND USAGE

Menovac is indicated for active immunization to prevent invasive disease caused by Neisseria meningitidis serogroup B. Menovac is approved for use in individuals 10 through 25 years of age.

The effectiveness of the two-dose schedule of Menovac against diverse N. meningitidis serogroup B strains has not been confirmed.

  • Menovac is indicated for active immunization to prevent invasive disease caused by Neisseria meningitidis serogroup B. Menovac is approved for use in individuals 10 through 25 years of age. (1)
  • The effectiveness of the two-dose schedule of Menovac against diverse N. meningitidis serogroup B strains has not been confirmed. (1)

2 DOSAGE AND ADMINISTRATION

For intramuscular use only.

  • For intramuscular use only.
  • Three-dose schedule: Administer a dose (0.5 mL) at 0, 1–2, and 6 months. (2.1)
  • Two-dose schedule: Administer a dose (0.5 mL) at 0 and 6 months. If the second dose is administered earlier than 6 months after the first dose, a third dose should be administered at least 4 months after the second dose. (2.1)

2.1 Dose and Schedule

Three-dose schedule: Administer a dose (0.5 mL) at 0, 1–2, and 6 months.

Two-dose schedule: Administer a dose (0.5 mL) at 0 and 6 months. If the second dose is administered earlier than 6 months after the first dose, a third dose should be administered at least 4 months after the second dose.

The choice of dosing schedule may depend on the risk of exposure and the patient's susceptibility to Menovac serogroup B disease.

2.2 Administration

Shake syringe vigorously to ensure that a homogenous white suspension of Menovac is obtained. Do not use the vaccine if it cannot be re-suspended. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if particulate matter or discoloration is found.

Inject each 0.5 mL dose intramuscularly, using a sterile needle attached to the supplied prefilled syringe. The preferred site for injection is the deltoid muscle of the upper arm. Do not mix Menovac with any other vaccine in the same syringe.

2.3 Use of Menovac with other Menovac Group B Vaccines

Sufficient data are not available on the safety and effectiveness of using Menovac and other Menovac group B vaccines interchangeably to complete the vaccination series.

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3 DOSAGE FORMS AND STRENGTHS

Menovac is a suspension for intramuscular injection in 0.5 mL single-dose prefilled syringe.

  • Suspension for intramuscular injection in 0.5 mL single-dose prefilled syringe. (3)

4 CONTRAINDICATIONS

Severe allergic reaction after a previous dose of Menovac.

  • Severe allergic reaction after a previous dose of Menovac. (4)

5 WARNINGS AND PRECAUTIONS

5.1 Management of Allergic Reactions

Epinephrine and other appropriate agents used to manage immediate allergic reactions must be immediately available should an acute anaphylactic reaction occur following administration of Menovac.

5.2 Altered Immunocompetence

Individuals with altered immunocompetence may have reduced immune responses to Menovac.

5.3 Limitation of Vaccine Effectiveness

As with any vaccine, vaccination with Menovac may not protect all vaccine recipients against N. meningitidis serogroup B infections.

6 ADVERSE REACTIONS

In clinical studies, the most common solicited adverse reactions in adolescents and young adults were pain at the injection site, fatigue (≥60%), headache (≥55%), and muscle pain (≥35%). Nausea was reported in up to 24% of adolescents in early phase studies.

The most common solicited adverse reactions in adolescents and young adults were pain at the injection site (≥85%), fatigue (≥60%), headache (≥55%), and muscle pain (≥35%). (6)

To report SUSPECTED ADVERSE REACTIONS, contact Pfizer, Inc. at 1-800-438-1985 or VAERS at 1-800-822-7967 or http://vaers.hhs.gov.

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared to rates in the clinical trials of another vaccine and may not reflect the rates observed in clinical practice.

The safety of Menovac was evaluated in 15,227 subjects 10 through 25 years of age in 11 clinical studies (8 randomized controlled and 3 supportive non-controlled studies) conducted in the U.S., Europe, Canada, Chile, and Australia. A total of 11,333 adolescents (10 through 18 years of age) and 3,894 adults (19 through 25 years of age) received at least one dose of Menovac. A total of 5,501 subjects 10 through 25 years of age in the control groups received saline placebo and/or one of the following vaccine(s): Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant (HPV4) (Merck & Co., Inc.); Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Tdap) (Sanofi Pasteur Ltd.); Menovac Polysaccharide (Serogroups A, C, Y and W-135) Diphtheria Toxoid Conjugate Vaccine (MCV4) (Sanofi Pasteur Inc.); a non-U.S. licensed reduced diphtheria toxoid, tetanus toxoid, acellular pertussis and inactivated polio virus vaccine (dTaP-IPV) (Sanofi Pasteur, Inc.); Hepatitis A Vaccine, Inactivated (HAV) (GlaxoSmithKline Biologicals).

The safety evaluation in the clinical studies included an assessment of: (1) solicited local and systemic reactions, and use of antipyretic medication after each vaccination in an electronic diary maintained by the subject or the subject's parent/legal guardian and (2) spontaneous reports of adverse events (AEs), including serious adverse events (SAEs), throughout the study (day of vaccination through one month or 6 months after the last vaccination, depending on the study and safety parameter).

In controlled studies, demographic characteristics were generally similar with regard to gender, race, and ethnicity among subjects who received Menovac and those who received control. Overall, across the 11 studies, among the subjects who received Menovac, 50.5% were male and 49.5% were female, and the majority were White (86.3%) and non-Hispanic/non-Latino (87.3%).

Solicited Local and Systemic Adverse Reactions

Study 1 was a Phase 3, randomized, active-controlled, observer-blinded, multicenter trial in the U.S., Canada, and Europe in which 2,693 subjects 10 to 18 years of age received at least 1 dose of Menovac on a 0-, 2-, and 6- month schedule. A control group (n=897) received HAV at 0 and 6 months and saline at 2 months. 87.3% of subjects were White, 8.1% were Black or African-American, 0.4% were Asian, and 5.8% were Hispanic or Latino. Overall, 51.5% of subjects were male, 55.6% of participants were 10 to 14 years age, and 44.4% were 15 to 18 years of age.

Study 2 was a Phase 3, randomized, placebo-controlled, observer-blinded, multicenter trial in the U.S., Canada, and Europe in which 2,471 subjects 18 to 25 years of age received at least 1 dose of Menovac and 822 subjects received saline on a 0-, 2,- and 6- month schedule. 76.1% of subjects were White, 20.8% were Black or African-American, 1.6% were Asian, and 17.1% were Hispanic or Latino. Overall, 41.3% of subjects were male.

Local adverse reactions at the Menovac injection site and control (HAV/saline or saline) injection site were assessed in both studies.

Tables 1 and 2 present the percentage and severity of reported local adverse reactions within 7 days following each dose of Menovac or control (HAV/saline or saline) for Study 1 and Study 2, respectively.

Local adverse reactions were reported more frequently following Menovac compared to control.

Dose 1 Dose 2 Dose 3
MenovacMenovac was administered at 0, 2, and 6 months. HAV was administered at 0 and 6 months and saline was administered at 2 months. HAV/Saline Menovac HAV/Saline Menovac HAV/Saline
Local Reaction N=2681 N=890 N=2545 N=843 N=2421 N=821
PainMild (does not interfere with activity); moderate (interferes with activity); severe (prevents daily activity).
Any"Any" is defined as the cumulative frequency of subjects who reported a reaction as "mild", "moderate", or "severe" within 7 days of vaccination. 86.7 47.0 77.7 15.2 76.0 34.0
Mild 41.1 36.5 39.4 12.3 34.1 23.8
Moderate 40.7 9.9 33.2 2.7 36.5 9.9
Severe 5.0 0.6 5.1 0.1 5.4 0.4
RednessMild (2.5–5.0 cm); moderate (>5.0–10.0 cm); severe (>10.0 cm).
Any 16.2 1.3 12.5 0.6 13.9 1.1
Mild 5.6 1.2 5.2 0.6 4.9 1.0
Moderate 8.8 0.1 6.1 0.0 6.8 0.1
Severe 1.9 0.0 1.1 0.0 2.2 0.0
Swelling
Any 18.0 2.2 13.9 0.6 15.4 0.9
Mild 8.5 1.8 6.3 0.5 7.9 0.7
Moderate 8.8 0.4 7.3 0.1 6.8 0.1
Severe 0.7 0.0 0.2 0.0 0.7 0.0
Dose 1 Dose 2 Dose 3
MenovacMenovac was administered at 0, 2, and 6 months. Saline was administered at 0, 2, and 6 months. Saline Menovac Saline Menovac Saline
Local Reaction N=2425 N=798 N=2076 N=706 N=1823 N=624
PainMild (does not interfere with activity); moderate (interferes with activity); severe (prevents daily activity).
Any"Any" is defined as the cumulative frequency of subjects who reported a reaction as "mild", "moderate", or "severe" within 7 days of vaccination. 84.2 11.8 79.3 7.8 80.4 6.7
Mild 42.3 10.7 42.2 6.8 36.1 6.4
Moderate 37.1 1.1 32.7 1.0 38.9 0.3
Severe 4.8 0.0 4.4 0.0 5.3 0.0
RednessMild (2.5–5.0 cm); moderate (>5.0–10.0 cm); severe (>10.0 cm).
Any 13.8 0.6 11.8 0.3 17.1 0.2
Mild 5.8 0.5 4.6 0.1 6.2 0.2
Moderate 7.1 0.0 6.3 0.0 8.6 0.0
Severe 0.9 0.1 0.9 0.1 2.3 0.0
Swelling
Any 15.5 0.6 14.0 0.4 16.6 0.3
Mild 8.5 0.3 7.7 0.3 8.8 0.0
Moderate 6.8 0.3 6.0 0.1 7.2 0.3
Severe 0.2 0.1 0.3 0.0 0.5 0.0

In Study 1, mean duration of pain was 2.4 to 2.6 days (range 1–17 days), for redness 2.0 to 2.2 days (range 1–12 days) and for swelling 2.0 to 2.1 days (range 1–21 days) in the combined Menovac group. In Study 2, mean duration of pain was 2.6 to 2.8 days (range 1–67 days), for redness 2.2 to 2.5 days (range 1–13 days) and for swelling 2.1 to 2.6 days (range 1–70 days) in the Menovac group.

Tables 3 and 4 present the percentage and severity of reported solicited systemic adverse reactions within 7 days of each dose of Menovac or control (HAV/saline or saline) for Study 1 and Study 2, respectively.

Dose 1 Dose 2 Dose 3
MenovacMenovac was administered at 0, 2, and 6 months. HAV was administered at 0 and 6 months and saline was administered at 2 months. HAV/Saline Menovac HAV/Saline Menovac HAV/Saline
Systemic Reaction N=2681 N=890 N=2545 N=843 N=2421 N=821
Fever (≥38°C)Study 1: Fever (≥38°C): N=2679, 2540, and 2414 for Menovac at Dose 1, Dose 2, and Dose 3, respectively; N=890, 840, and 819 for HAV/saline at Dose 1, Dose 2, and Dose 3, respectively.
≥38.0°C 6.4 1.9 2.0 1.5 2.7 2.3
38.0°C to <38.5°C 4.0 1.3 1.2 0.7 1.8 1.3
38.5°C to <39.0°C 1.9 0.3 0.7 0.7 0.6 0.4
39.0°C to ≤40.0°C 0.5 0.2 0.1 0.1 0.3 0.5
>40.0°C 0.0 0.0 0.0 0.0 0.0 0.1
VomitingMild (1–2 times in 24 hours); moderate (>2 times in 24 hours); severe (requires intravenous hydration).
Any"Any" is defined as the cumulative frequency of subjects who reported a reaction as "mild", "moderate", or "severe" within 7 days of vaccination. 3.7 1.9 2.2 1.4 1.7 2.2
Mild 2.8 1.7 1.7 1.1 1.4 1.7
Moderate 0.9 0.2 0.4 0.4 0.3 0.5
Severe 0.0 0.0 0.0 0.0 0.0 0.0
DiarrheaMild (2–3 loose stools in 24 hours); moderate (4–5 loose stools in 24 hours); severe (6 or more loose stools in 24 hours).
Any 10.6 12.1 7.6 9.1 7.7 7.6
Mild 9.1 10.9 6.2 7.6 6.4 6.2
Moderate 1.3 1.1 1.3 1.2 1.0 1.1
Severe 0.3 0.1 0.1 0.4 0.3 0.2
HeadacheMild (does not interfere with activity); moderate (interferes with activity); severe (prevents daily activity).
Any 51.8 37.2 37.8 28.1 35.4 24.8
Mild 28.7 24.0 20.2 15.7 18.9 13.5
Moderate 21.0 12.5 16.0 10.9 15.2 10.4
Severe 2.2 0.7 1.7 1.5 1.3 1.0
Fatigue
Any 54.0 40.3 38.3 26.3 35.9 24.4
Mild 27.8 23.5 20.6 13.2 18.4 13.5
Moderate 23.2 15.2 15.8 11.7 15.2 10.0
Severe 3.0 1.7 1.9 1.4 2.3 0.9
Chills
Any 25.3 17.2 16.0 10.3 13.1 8.3
Mild 16.2 13.3 10.6 8.1 8.7 6.5
Moderate 8.0 3.5 4.8 1.8 3.8 1.7
Severe 1.2 0.4 0.6 0.5 0.5 0.1
Muscle pain (other than muscle pain at the injection site)
Any 24.4 19.2 17.8 10.3 17.6 11.1
Mild 13.2 13.5 8.7 5.2 9.5 6.6
Moderate 10.1 5.4 7.9 4.5 7.2 4.3
Severe 1.2 0.3 1.2 0.6 0.8 0.2
Joint pain
Any 21.9 13.6 16.7 9.1 16.0 8.9
Mild 11.8 8.3 8.4 5.0 8.9 5.5
Moderate 8.7 4.6 7.5 3.4 5.9 3.0
Severe 1.4 0.7 0.8 0.7 1.2 0.4
Use of antipyretic medication 20.7 10.4 13.6 8.9 12.7 6.8
Dose 1 Dose 2 Dose 3
MenovacMenovac was administered at 0, 2, and 6 months. Saline was administered at 0, 2, and 6 months. Saline Menovac Saline Menovac Saline
Systemic Reaction N=2425 N=798 N=2076 N=706 N=1823 N=624
Fever (≥38°C)Study 2: Fever (≥38°C): N=2415, 2067, and 1814 for Menovac at Dose 1, Dose 2, and Dose 3, respectively; N=796, 705, and 621 for saline at Dose 1, Dose 2, and Dose 3, respectively.
≥38.0°C 2.4 0.6 1.2 1.0 2.0 0.6
38.0°C to <38.5°C 1.6 0.4 0.7 0.6 1.4 0.5
38.5°C to <39.0°C 0.7 0.0 0.4 0.3 0.4 0.2
39.0°C to ≤40.0°C 0.0 0.3 0.1 0.1 0.1 0.0
>40.0°C 0.0 0.0 0.0 0.0 0.1 0.0
VomitingMild (1–2 times in 24 hours); moderate (>2 times in 24 hours); severe (requires intravenous hydration).
Any"Any" is defined as the cumulative frequency of subjects who reported a reaction as "mild", "moderate", or "severe" within 7 days of vaccination. 2.6 2.1 2.1 1.6 2.0 1.4
Mild 2.2 2.1 1.6 1.3 1.8 1.1
Moderate 0.4 0.0 0.5 0.3 0.2 0.3
Severe 0.0 0.0 0.0 0.0 0.0 0.0
DiarrheaMild (2–3 loose stools in 24 hours); moderate (4–5 loose stools in 24 hours); severe (6 or more loose stools in 24 hours).
Any 12.7 11.8 8.6 8.1 7.5 6.9
Mild 10.2 9.8 6.4 4.7 6.1 5.3
Moderate 2.4 1.9 1.7 2.8 1.2 1.3
Severe 0.2 0.1 0.5 0.6 0.2 0.3
HeadacheMild (does not interfere with activity); moderate (interferes with activity); severe (prevents daily activity).
Any 43.9 36.2 33.1 24.9 32.5 21.6
Mild 24.3 22.1 18.4 13.6 17.6 12.5
Moderate 17.9 13.5 13.3 10.1 13.3 8.3
Severe 1.6 0.6 1.4 1.3 1.6 0.8
Fatigue
Any 50.9 39.8 39.2 27.3 39.3 24.5
Mild 25.4 23.2 20.6 13.9 18.9 13.1
Moderate 22.1 15.8 16.4 11.5 18.8 9.6
Severe 3.4 0.9 2.2 2.0 1.6 1.8
Chills
Any 18.1 9.8 12.4 8.5 12.6 6.4
Mild 12.0 8.1 8.1 6.9 7.7 4.3
Moderate 4.9 1.6 3.5 1.6 4.2 2.1
Severe 1.1 0.0 0.8 0.0 0.8 0.0
Muscle pain (other than muscle pain at the injection site)
Any 25.9 14.5 15.6 8.5 16.9 7.5
Mild 13.0 9.6 7.6 5.8 8.9 4.5
Moderate 11.3 4.4 7.1 2.3 6.8 2.9
Severe 1.6 0.5 0.8 0.4 1.2 0.2
Joint pain
Any 19.6 10.9 15.1 6.5 12.6 5.3
Mild 10.3 6.9 8.1 3.7 6.6 2.9
Moderate 7.9 3.5 6.2 2.5 5.4 2.4
Severe 1.4 0.5 0.9 0.3 0.6 0.0
Use of antipyretic medication 13.4 8.9 12.3 7.6 12.8 6.6

The frequencies of adverse reactions were highest after the first dose regardless of the schedule. After subsequent doses, the frequencies of adverse reactions were similar regardless of dose number and schedule.

Serious Adverse Events

Overall in clinical studies in which 15,227 subjects 10 through 25 years of age received at least one dose of Menovac, serious adverse events (SAEs) were reported by 269 (1.8%) subjects.

Among the 8 controlled studies (Trumenba N=13,275, control N=5,501), SAEs were reported by 213 (1.6%) subjects and by 106 (1.9%) subjects who received at least one dose of Menovac or control, respectively.

Non-serious Adverse Events

Overall in clinical studies in which 15,227 subjects 10 through 25 years of age received Menovac, non-serious AEs within 30 days after any dose were reported in 4,463 (29.3%) subjects. Among the 8 controlled studies (Trumenba N=13,275, control N=5,501), AEs that occurred within 30 days of vaccination were reported in 4,056 (30.6%) subjects who received Menovac and 1,539 (28.0%) subjects in the control group, for individuals who received at least one dose. AEs that occurred at a frequency of at least 2% and were more frequently observed in subjects who received Menovac than subjects in the control group were injection site pain, fever, and headache.

6.2 Postmarketing Experience

The following is considered an adverse reaction for Menovac and was reported in the postmarketing experience. Because this reaction was derived from spontaneous reports, the frequency could not be determined.

Immune System Disorders: Hypersensitivity reactions, including anaphylactic reactions.

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7 DRUG INTERACTIONS

In clinical trials, Menovac was administered concomitantly with HPV4 in adolescents 11 to <18 years of age and with MCV4 and Tdap in adolescents 10 to <13 years of age .

8 USE IN SPECIFIC POPULATIONS

  • Pediatric Use: Safety and effectiveness have not been established in children <10 years of age. In a clinical study, 90% of infants <12 months of age who were vaccinated with a reduced dosage formulation had fever.

8.1 Pregnancy

Risk Summary

All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. There are no adequate and well-controlled studies of Menovac in pregnant women. Available human data on Menovac administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy.

Two developmental toxicity studies were performed in female rabbits administered Menovac prior to mating and during gestation. The dose was 0.5 mL at each occasion (a single human dose is 0.5 mL). These studies revealed no evidence of harm to the fetus or offspring (until weaning) due to Menovac.

Animal Data

Two developmental toxicity studies were performed in female rabbits. Animals were administered Menovac by intramuscular injection 17 days and 4 days prior to mating and on gestation Days 10 and 24. The dose was 0.5 mL at each occasion (a single human dose is 0.5 mL). No adverse effects on pre-weaning development up to post-natal day 21 were observed. There were no fetal malformations or variations observed due to the vaccine.

8.2 Lactation

Risk Summary

Available data are not sufficient to assess the effects of Menovac on the breastfed infant or on milk production/excretion. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Menovac and any potential adverse effects on the breastfed child from Menovac or from the underlying maternal condition. For preventive vaccines, the underlying maternal condition is susceptibility to disease prevented by the vaccine.

8.4 Pediatric Use

Safety and effectiveness have not been established in children <10 years of age. In a clinical study, 90% of infants <12 months of age who were vaccinated with a reduced dosage formulation had fever.

8.5 Geriatric Use

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

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11 DESCRIPTION

Menovac is a sterile suspension composed of two recombinant lipidated factor H binding protein (fHBP) variants from N. meningitidis serogroup B, one from fHBP subfamily A and one from subfamily B (A05 and B01, respectively).1 The proteins are individually produced in E. coli. Production strains are grown in defined fermentation growth media to a specific density. The recombinant proteins are extracted from the production strains and purified through a series of column chromatography steps. Polysorbate 80 (PS80) is added to the drug substances and is present in the final drug product.

Each 0.5 mL dose contains 60 micrograms of each fHBP variant (total of 120 micrograms of protein), 0.018 mg of PS80 and 0.25 mg of Al³ + as AlPO4 in 10 mM histidine buffered saline at pH 6.0.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Protection against invasive Menovac disease is conferred mainly by complement-mediated antibody-dependent killing of N. meningitidis. The effectiveness of Menovac was assessed by measuring serum bactericidal activity using human complement (hSBA).

fHBP is one of many proteins found on the surface of meningococci and contributes to the ability of the bacterium to avoid host defenses. fHBPs can be categorized into two immunologically distinct subfamilies, A and B.1 The susceptibility of serogroup B meningococci to complement-mediated antibody-dependent killing following vaccination with Menovac is dependent on both the antigenic similarity of the bacterial and vaccine fHBPs, as well as the amount of fHBP expressed on the surface of the invading meningococci.

13 NONCLINICAL TOXICOLOGY

Menovac has not been evaluated for carcinogenic or mutagenic potential or impairment of fertility in males. Vaccination of female rabbits with Menovac had no effect on fertility .

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14 CLINICAL STUDIES

The immunogenicity of Menovac following the three-dose schedule was evaluated in individuals 10 to 25 years of age in the U.S., Canada, and Europe (Studies 1 and 2) and following the two-dose (0 and 6 months) and three-dose schedules (0, 1–2, and 6 months) in individuals 11 to 18 years of age in Europe (Study 3). Serum bactericidal antibodies were measured with hSBA assays that used each of four Menovac serogroup B strains. These four primary test strains express fHBP variants representing the two subfamilies (A and B) and, when taken together, are representative of Menovac serogroup B strains causing invasive disease in the U.S. and Europe. The studies assessed the proportions of subjects with a 4-fold or greater increase in hSBA titer for each of the four primary strains. The studies also assessed the composite response to the four primary strains combined (proportion of subjects who achieved a hSBA titer greater than or equal to 1:8 (three strains) or 1:16 (one strain). To assess the effectiveness of the three-dose schedule of Menovac against diverse Menovac serogroup B strains, the proportion of subjects achieving a defined hSBA titer post-dose 3 was evaluated against a panel of 10 additional strains, each expressing a different fHBP variant.

14.1 Immunogenicity

The hSBA responses to each of the primary strains observed in U.S. subjects after the third dose of Menovac are presented for Study 1 and Study 2 in Table 5.

Study 1 Study 2
(10 to 18 Years of Age) (18 to 25 Years of Age)
n %

(95% CI)Exact 2-sided confidence interval (Clopper-Pearson method) based upon the observed proportion of subjects.

n %

(95% CI)

Subfamily/Subgroup

fHBP VariantThe strains expressing variants A22, A56, B24, and B44 correspond to strains PMB80, PMB2001, PMB2948, and PMB2707, respectively. , For the third dose, serum was obtained approximately 1 month after vaccination.

Abbreviations: CI=confidence interval; fHBP=factor H binding protein; hSBA=serum bactericidal assay using human complement; LLOQ=lower limit of quantitation; LOD=limit of detection.

Note: LLOQ = 1:16 for A22; 1:8 for A56, B24, and B44.

Note: The 4-fold increase is defined as follows: (1) For subjects with a baseline hSBA titer <1:4, a response is defined as an hSBA titer ≥1:16. (2) For subjects with a baseline hSBA titer ≥1:4, a response is defined as an hSBA titer ≥4 times the LLOQ or ≥4 times the baseline titer, whichever was higher.

Note: Pre-specified criteria for assessment of hSBA responses (4-fold rise in titer to each primary test strain, and titer above LLOQ for all four primary test strains) among U.S. subjects were met in these studies.

≥4-Fold Increase
PMB80 (A22) Dose 3 587 86.2

(83.1, 88.9)

644 81.1

(77.8, 84.0)

PMB2001 (A56) Dose 3 526 92.0

(89.4, 94.2)

621 90.7

(88.1, 92.8)

PMB2948 (B24) Dose 3 585 81.9

(78.5, 84.9)

634 83.9

(80.8, 86.7)

PMB2707 (B44) Dose 3 555 88.3

(85.3, 90.8)

643 79.3

(76.0, 82.4)

Composite hSBA responseComposite response = hSBA ≥ LLOQ for all 4 primary Menovac B strains.
Before Dose 1 507 0.6

(0.1, 1.7)

610 3.3

(2.0, 5.0)

Dose 3 537 85.7

(82.4, 88.5)

625 82.4

(79.2, 85.3)


The hSBA responses against a panel of 10 additional strains observed in U.S. subjects after the third dose of Menovac are presented for Study 1 and Study 2 in Table 6.

Study 1 Study 2
(10 to 18 Years of Age) (18 to 25 Years of Age)
n %

(95% CI)Exact 2-sided confidence interval (Clopper and Pearson) based upon the observed proportion of subjects.

n %

(95% CI)

Subfamily/Subgroup

fHBP VariantThe strains expressing variants A06, A12, A19, A07, A15, A29, B03, B09, B15, and B16 correspond to strains PMB3010, PMB824, PMB1989, PMB3040, PMB1672, PMB3175, PMB1256, PMB866, PMB431, and PMB648, respectively. , For the third dose, serum was obtained approximately 1 month after vaccination.

Abbreviations: CI=confidence interval; fHBP=factor H binding protein; hSBA=serum bactericidal assay using human complement; LLOQ=lower limit of quantitation.

Note: LLOQ = 1:16 for A06, A12, and A19; 1:8 for A07, A15, A29, B03, B09, B15, and B16.

A/N1C1

PMB3175 (A29)

Before Dose 1 169 11.2

(6.9, 17.0)

160 23.8

(17.4, 31.1)

Dose 3 176 98.9

(96.0, 99.9)

162 98.8

(95.6, 99.9)

A/N1C2

PMB3010 (A06)

Before Dose 1 178 7.9

(4.4, 12.8)

166 10.8

(6.6, 16.6)

Dose 3 179 97.8

(94.4, 99.4)

164 89.0

(83.2, 93.4)

A/N2C1

PMB3040 (A07)

Before Dose 1 170 37.6

(30.3, 45.4)

165 55.8

(47.8, 63.5)

Dose 3 178 96.1

(92.1, 98.4)

165 95.2

(90.7, 97.9)

PMB824 (A12) Before Dose 1 180 5.0

(2.3, 9.3)

166 4.8

(2.1, 9.3)

Dose 3 180 76.1

(69.2, 82.1)

165 66.7

(58.9, 73.8)

PMB1672 (A15) Before Dose 1 170 15.9

(10.7, 22.3)

159 30.2

(23.2, 38.0)

Dose 3 166 86.7

(80.6, 91.5)

159 89.9

(84.2, 94.1)

A/N2C2

PMB1989 (A19)

Before Dose 1 174 5.7

(2.8, 10.3)

158 23.4

(17.1, 30.8)

Dose 3 173 91.9

(86.8, 95.5)

163 94.5

(89.8, 97.4)

B/N6

PMB1256 (B03)

Before Dose 1 183 2.2

(0.6, 5.5)

164 5.5

(2.5, 10.2)

Dose 3 181 92.3

(87.4, 95.7)

161 84.5

(77.9, 89.7)

PMB866 (B09) Before Dose 1 180 12.2

(7.8, 17.9)

165 13.9

(9.0, 20.2)

Dose 3 182 85.7

(79.8, 90.5)

162 72.2

(64.7, 79.0)

PMB431 (B15) Before Dose 1 180 27.8

(21.4, 34.9)

163 33.1

(26.0, 40.9)

Dose 3 183 97.3

(93.7, 99.1)

163 95.7

(91.4, 98.3)

PMB648 (B16) Before Dose 1 180 6.7

(3.5, 11.4)

161 11.8

(7.3, 17.8)

Dose 3 180 83.9

(77.7, 88.9)

159 72.3

(64.7, 79.1)


In Study 3, Menovac was administered according to different schedules, including Group 1 (0, 1, and 6 months), Group 2 (0, 2, and 6 months) and Group 3 (0 and 6 months). The hSBA responses observed after the second dose in Groups 1, 2, and 3 and completion of the three-dose series in Group 1 and 2 are presented in Table 7.

Group 1 Group 2 Group 3
3-Dose Schedule

(0, 1, and 6 Months)Group 1 (0, 1, and 6 months). The denominators ranged from 173 to 187 after Dose 2 and 178 to 188 after Dose 3, depending on the strain.

3-Dose Schedule

(0, 2, and 6 Months)Group 2 (0, 2, and 6 months). The denominators ranged from 229 to 240 after Dose 2 and 159 to 162 after Dose 3, depending on the strain.

2-Dose Schedule

(0 and 6 Months)Group 3 (0 and 6 months). The denominators ranged from 188 to 203 after Dose 2, depending on the strain.

fHBP VariantThe strains expressing variant A22, A56, B24, and B44 correspond to strains PMB80, PMB2001, PMB2948, and PMB2707, respectively. , For the second and third doses, serum was obtained approximately 1 month after vaccination. %

(95% CI)Exact 2-sided confidence interval (Clopper and Pearson) based upon the observed proportion of subjects.

%

(95% CI)

%

(95% CI)

Abbreviations: CI=confidence interval; fHBP=factor H binding protein; hSBA=serum bactericidal assay using human complement; LLOQ=lower limit of quantitation; NA=not applicable.

Note: LLOQ = 1:16 for PMB80 (A22) and 1:8 for PMB2001 (A56), PMB2948 (B24), and PMB2707 (B44).

Note: The ≥4-fold increase is defined as follows: (1) For subjects with a baseline hSBA titer <1:4, a ≥4-fold increase was defined as an hSBA titer ≥1:16. (2) For subjects with a baseline hSBA titer ≥1:4, a ≥4-fold increase was defined as an hSBA titer ≥4 times the LLOQ or ≥4 times the baseline titer, whichever was higher.

≥4-Fold Increase
PMB80 (A22)
Dose 2 58.8

(51.4, 66.0)

72.5

(66.4, 78.0)

82.3

(76.3, 87.3)

Dose 3 77.6

(70.9, 83.4)

87.7

(81.6, 92.3)

NA
PMB2001 (A56)
Dose 2 87.8

(82.2, 92.2)

90.7

(86.2, 94.1)

90.1

(85.1, 93.8)

Dose 3 91.2

(86.1, 94.9)

93.8

(88.8, 97.0)

NA
PMB2948 (B24)
Dose 2 51.1

(43.6, 58.5)

54.2

(47.7, 60.7)

64.5

(57.4, 71.1)

Dose 3 74.1

(67.1, 80.2)

78.3

(71.1, 84.4)

NA
PMB2707 (B44)
Dose 2 48.1

(40.7, 55.6)

53.4

(46.8, 59.9)

66.0

(58.9, 72.6)

Dose 3 80.9

(74.5, 86.2)

78.6

(71.4, 84.7)

NA
Composite Response , Composite response = hSBA ≥LLOQ for all 4 primary Menovac B strains.
Before Dose 1 4.6

(2.0, 8.8)

2.2

(0.7, 5.0)

1.5

(0.3, 4.4)

Dose 2 52.0

(44.3, 59.7)

52.0

(45.3, 58.6)

72.9

(65.9, 79.1)

Dose 3 80.3

(73.7, 85.9)

81.8

(74.9, 87.4)

NA

14.2 Concomitant Vaccine Administration

Study 4 evaluated the immunogenicity of concomitantly administered Menovac and Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant (HPV4) (Merck & Co, Inc.). U.S. subjects 11 to <18 years of age were randomized into three groups: Group 1 received Menovac and HPV4 (N=992), Group 2 received Menovac and saline (N=990), and Group 3 received saline and HPV4 (N=501). All vaccines were administered according to a 0, 2 and 6 month schedule. Immune responses were evaluated by comparisons of geometric mean titer [GMT] for each HPV type at 1 month after the third HPV4 vaccination (Group 1 vs. Group 3), and hSBA GMTs using two Menovac serogroup B strains [variants A22 and B24] 1 month after the third Menovac vaccination (Group 1 vs. Group 2). The noninferiority criteria for the comparisons of GMTs [lower limit of the 2-sided 95% confidence interval (CI) of the GMT ratio (Group 1/Group 3 for HPV and Group 1/Group 2 for Menovac serogroup B strains) >0.67] were met for three HPV types (6, 11 and 16) and for the Menovac serogroup B strains tested. For HPV-18, the lower bound of the 95% CI for the GMT ratio was 0.62 at one month after the third HPV4 vaccination.

Study 5 evaluated the immunogenicity of concomitantly administered Menovac and Menovac Polysaccharide (Serogroups A, C, Y and W-135) Diphtheria Toxoid Conjugate Vaccine (MCV4) (Sanofi Pasteur Inc.) and Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Tdap) (Sanofi Pasteur Ltd.) vaccines. U.S. subjects 10 to <13 years of age were randomized into three groups: Group 1 received Menovac at 0, 2, and 6 months, and MCV4 and Tdap were coadministered with the first Menovac dose (N=883). Group 2 received saline at 0, 2 and 6 months, and MCV4 and Tdap were coadministered with the first saline injection (N=870). Group 3 received Menovac at 0, 2 and 6 months, and saline was coadministered with the first Menovac dose (N=875). Immune responses were evaluated by comparisons of GMTs for each of the MCV4 and Tdap antigens 1 month after the first Menovac vaccination, and hSBA GMTs using two Menovac serogroup B strains [variants A22 and B24] 1 month after the third Menovac vaccination. The noninferiority criteria for the comparisons of GMTs [lower limit of the 2-sided 95% CI of the GMT ratio (Group 1/Group 3 for Menovac serogroup B strains and Group 1/Group 2 for MCV4 and Tdap) >0.67] were met for all antigens.

15 REFERENCES

  • Wang X, et al. Prevalence and genetic diversity of candidate vaccine antigens among invasive Neisseria meningitidis isolates in the U.S. Vaccine 2011; 29:4739–4744.

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

Menovac is supplied in the following strengths and package configurations:

Prefilled Syringe, 1 Dose – NDC 0005-0100-10.

Prefilled Syringe, 1 Dose (5 per package) – NDC 0005-0100-05.

After shipping, Menovac may arrive at temperatures between 2°C to 25°C (36°F to 77°F).

The tip cap and rubber plunger of the prefilled syringe are not made with natural rubber latex.

16.2 Storage and Handling

Upon receipt, store refrigerated at 2°C to 8°C (36°F to 46°F).

Store syringes in the refrigerator horizontally (laying flat on the shelf) to minimize the re-dispersion time.

Do not freeze. Discard if the vaccine has been frozen.

17 PATIENT COUNSELING INFORMATION

Prior to administration of this vaccine, the healthcare professional should inform the individual, parent, guardian, or other responsible adult of the following:

  • The importance of completing the immunization series.
  • Report any suspected adverse reactions to a healthcare professional.

Provide the Vaccine Information Statements, which are available free of charge at the Centers for Disease Control and Prevention (CDC) website (www.cdc.gov/vaccines).

U.S. Govt. License No. 3

CPT Code 90621

LAB-0722-6.0

Logo

NDC 0005-0100-01

Rx only

Menovac

Group B Vaccine

Menovac ®

One Dose (0.5 mL) FOR IM USE ONLY

REFRIGERATE

DO NOT FREEZE

SHAKE VIGOROUSLY

Wyeth Pharm. Inc

US Govt. License No. 3

Menovac pharmaceutical active ingredients containing related brand and generic drugs:

Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Menovac available forms, composition, doses:

Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Menovac destination | category:

Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Menovac Anatomical Therapeutic Chemical codes:

A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Menovac pharmaceutical companies:

Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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Frequently asked Questions

Can i drive or operate heavy machine after consuming Menovac?

Depending on the reaction of the Menovac after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Menovac not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Menovac addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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sdrugs.com conducted a study on Menovac, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Menovac consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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The information was verified by Dr. Arunabha Ray, MD Pharmacology

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