Clinical Trial 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 practice.
Children 9 Through 12 Months of Age:
The safety of Menactra vaccine was evaluated in four clinical studies that enrolled 3,721 participants who received Menactra vaccine at 9 and 12 months of age. At 12 months of age, these children also received one or more other vaccines [Measles, Mumps, Rubella and Varicella Virus Vaccine Live (MMRV) or Measles, Mumps, and Rubella Virus Vaccine (MMR) and Varicella Virus Vaccine Live (V); Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM197
Protein) (PCV7); Hepatitis A Vaccine (HepA)]. A control group of 997 children was enrolled at 12 months of age and received two or more childhood vaccines [MMRV (or MMR + V), PCV7, HepA] at 12 months of age (see Pharmacology: Clinical Studies: Concomitant Vaccine Administration under Actions). Three percent of individuals received MMR and V, instead of MMRV, at 12 months of age.
The primary safety study was a controlled trial that enrolled 1256 children who received Menactra vaccine at 9 and 12 months of age. At 12 months of age, these children received MMRV (or MMR+V), PCV7, and HepA. A control group of 522 children received MMRV, PCV7, and HepA. Of the 1,778 children, 78% of participants (Menactra vaccine, N=1,056; control group, N=322) were enrolled at United States (US) sites and 22% at a Chilean site (Menactra vaccine, N=200; control group, N=200).
Individuals 2 Through 55 Years of Age:
The safety of Menactra vaccine was evaluated in eight clinical studies that enrolled 10,057 participants aged 2-55 years who received Menactra vaccine and 5,266 participants who received Menomune-A/C/Y/W-135, Meningococcal Polysaccharide Vaccine, Groups A, C, Y and W-135 Combined. There were no substantive differences in demographic characteristics between the vaccine groups. Among Menactra vaccine recipients 2-55 years of age 24.0%, 16.2%, 40.4% and 19.4% were in the 2-10, 11-14, 15-25 and 26-55-year age groups, respectively. Among Menomune-A/C/Y/W-135 vaccine recipients 2-55 years of age 42.3%, 9.3%, 30.0% and 18.5% were in the 2-10, 11-14, 15-25 and 26-55-year age groups, respectively. The three primary safety studies were randomized, active-controlled trials that enrolled participants 2-10 years of age (Menactra vaccine, N=1,713; Menomune-A/C/Y/W-135 vaccine, N=1,519), 11-18 years of age (Menactra vaccine, N=2,270; Menomune-A/C/Y/W-135 vaccine, N=972), and 18-55 years of age (Menactra vaccine, N=1,384; Menomune-A/C/Y/W-135 vaccine, N=1,170), respectively. Of the 3,232 children 2-10 years of age, 68% of participants (Menactra vaccine, N=1,164; Menomune-A/C/Y/W-135 vaccine, N=1,031) were enrolled at US sites and 32% (Menactra vaccine, N=549; Menomune-A/C/Y/W-135 vaccine, N=488) of participants at a Chilean site. The median ages in the Chilean and US subpopulations were 5 and 6 years, respectively. All adolescents and adults were enrolled at US sites. As the route of administration differed for the two vaccines (Menactra vaccine given intramuscularly, Menomune-A/C/Y/W-135 vaccine given subcutaneously), study personnel collecting the safety data differed from personnel administering the vaccine.
Booster Vaccination Study:
In an open-label trial conducted in the US, 834 individuals were enrolled to receive a single dose of Menactra vaccine 4-6 years after a prior dose. The median age of participants was 17.1 years at the time of the booster dose.
Participants were monitored after each vaccination for 20 or 30 minutes for immediate reactions, depending on the study. Solicited injection site and systemic reactions were recorded in a diary card for 7 consecutive days after each vaccination. Participants were monitored for 28 days (30 days for infants and toddlers) for unsolicited adverse events and for 6 months post-vaccination for visits to an emergency room, unexpected visits to an office physician, and serious adverse events (SAEs). Unsolicited adverse event information was obtained either by telephone interview or at an interim clinic visit. Information regarding adverse events that occurred in the 6-month post-vaccination time period was obtained via a scripted telephone interview.
Serious Adverse Events in All Safety Studies:
Serious adverse events were reported during a 6-month time period following vaccinations in individuals 9 months through 55 years of age. In children who received Menactra vaccine at 9 months and at 12 months of age, SAEs occurred at a rate of 2.0%-2.5%. In participants who received one or more childhood vaccine(s) (without co-administration of Menactra vaccine) at 12 months of age, SAEs occurred at a rate of 1.6%-3.6%, depending on the number and type of vaccines received. In children 2-10 years of age, SAEs occurred at a rate of 0.6% following Menactra vaccine and at a rate of 0.7% following Menomune-A/C/Y/W-135 vaccine. In adolescents 11 through 18 years of age and adults 18 through 55 years of age, SAEs occurred at a rate of 1.0% following Menactra vaccine and at a rate of 1.3% following Menomune-A/C/Y/W-135 vaccine. In adolescents and adults, SAEs occurred at a rate of 1.3% following booster vaccination with Menactra vaccine.
Solicited Adverse Events in the Primary Safety Studies:
The most frequently reported solicited injection site and systemic adverse reactions within 7 days following vaccination in children 9 months and 12 months of age were injection site tenderness and irritability.
The most frequently reported solicited local and systemic adverse reactions in US children aged 2-10 years were injection site pain and irritability. Diarrhea, drowsiness, and anorexia were also common. The most commonly reported solicited injection site and systemic adverse reactions in adolescents, ages 11-18 years, and adults, ages 18-55 years, after a single dose were injection site pain, headache, and fatigue. Except for redness in adults, injection site reactions were more frequently reported after Menactra vaccination than after Menomune-A/C/Y/W-135 vaccination.
Solicited Adverse Events in a Booster Vaccination Study:
For a description of the study design and number of participants. The most common solicited injection site and systemic reactions within 7 days of vaccination were pain (60.2%) and myalgia (42.8%), respectively. Overall rates of solicited injection site reactions and solicited systemic reactions were similar to those observed in adolescents and adults after a single Menactra dose. The majority of solicited reactions were Grade 1 or 2 and resolved within 3 days.
Adverse Events in Concomitant Vaccine Studies: Solicited Injection Site and Systemic Reactions When Given With Other Pediatric Vaccines:
For a description of the study design and number of participants (see Pharmacology: Clinical Trials: Concomitant Vaccine Administration under Actions). In the primary safety study, 1,378 US children were enrolled to receive Menactra vaccine alone at 9 months of age and Menactra vaccine plus one or more other routinely administered vaccines (MMRV, PCV7, and HepA) at 12 months of age (N=961). Another group of children received two or more routinely administered vaccines (MMRV, PCV7, and HepA vaccines) (control group, N=321) at 12 months of age. Participants who received Menactra vaccine and the concomitant vaccines at 12 months of age described above reported similar frequencies of tenderness, redness, and swelling at the Menactra vaccine injection site and at the concomitant vaccine injection sites. Tenderness was the most frequent injection site reaction (48%, 39%, 46%, and 43% at the Menactra vaccine, MMRV, PCV7, and HepA sites, respectively). Irritability was the most frequent systemic reaction, reported in 62% of recipients of Menactra vaccine plus concomitant vaccines, and 65% of the control group (see Pharmacodynamics: Clinical Studies: Concomitant Vaccine Administration under Actions).
Solicited Injection Site and Systemic Reactions When Given With Tetanus and Diphtheria Toxoid Adsorbed Vaccine (Td):
Injection site pain was reported more frequently after Td vaccination than after Menactra vaccination (71% versus 53%). The overall rate of systemic adverse events was higher when Menactra and Td vaccines were given concomitantly than when Menactra vaccine was administered 28 days after Td (59% versus 36%). In both groups, the most common reactions were headache (Menactra vaccine + Td, 36%; Td + Placebo, 34%; Menactra vaccine alone, 22%) and fatigue (Menactra vaccine + Td, 32%; Td + Placebo, 29%; Menactra vaccine alone, 17%). Fever ≥40.0°C occurred at ≤0.5% in all groups.
Solicited Injection Site and Systemic Reactions When Given With Typhoid Vi Polysaccharide Vaccine:
More participants experienced pain after Typhoid vaccination than after Menactra vaccination (Typhoid + Placebo, 76% versus Menactra vaccine + Typhoid, 47%). The majority (70%-77%) of injection site solicited reactions for both groups at either injection site were reported as Grade 1 and resolved within 3 days post-vaccination. In both groups, the most common systemic reaction was headache (Menactra vaccine + Typhoid, 41%; Typhoid + Placebo, 42%; Menactra vaccine alone, 33%) and fatigue (Menactra vaccine + Typhoid, 38%; Typhoid + Placebo, 35%; Menactra vaccine alone, 27%). Fever ≥40.0°C and seizures were not reported in either group.
In addition to reports in clinical trials, worldwide voluntary adverse events reports received since market introduction of Menactra vaccine are listed below. This list includes serious events and/or events which were included based on severity, frequency of reporting or a plausible causal connection to Menactra vaccine. Because these events were reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to vaccination.
Immune System Disorders:
Hypersensitivity reactions such as anaphylaxis/anaphylactic reaction, wheezing, difficulty breathing, upper airway swelling, urticaria, erythema, pruritus, hypotension.
Nervous System Disorders:
Guillain-Barré syndrome, paraesthesia, vasovagal syncope, dizziness, convulsion, facial palsy, acute disseminated encephalomyelitis, transverse myelitis.
Musculoskeletal and Connective Tissue Disorders:
Post-Marketing Safety Study:
The risk of GBS following receipt of Menactra vaccine was evaluated in a US retrospective cohort study using healthcare claims data from 9,578,688 individuals 11 through 18 years of age, of whom 1,431,906 (15%) received Menactra vaccine. Of 72 medical chart-confirmed GBS cases, none had received Menactra vaccine within 42 days prior to symptom onset. An additional 129 potential cases of GBS could not be confirmed or excluded due to absent or insufficient medical chart information. In an analysis that took into account the missing data, estimates of the attributable risk of GBS ranged from 0 to 5 additional cases of GBS per 1,000,000 vaccinees within the 6 week period following vaccination.