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Vaccines

Vaccines
Vaccines for prevention of prevalent infectious diseases.

Vaccines Medications

Please select a product from the list to view its approved indications as well as the link to its full prescribing information. The list is not an all-inclusive list of Pfizer medications in a therapeutic area and inclusion of a product within this list should not suggest it is approved for a broad therapeutic area. Please refer to each medication’s individual prescribing information for specific details.

PREVNAR® 13 (pneumococcal 13-valent conjugate vaccine - diphtheria CRM197 protein)

These highlights do not include all the information needed to use PREVNAR 13 safety and effectively. See full prescribing information for PREVNAR 13.

4 CONTRAINDICATIONS

Severe allergic reaction (e.g., anaphylaxis) to any component of Prevnar 13 or any diphtheria toxoid-containing vaccine [see Description (11)].

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 Prevnar 13.

5.2 Altered Immunocompetence

Individuals with altered immunocompetence, including those at higher risk for invasive pneumococcal disease (e.g., individuals with congenital or acquired splenic dysfunction, HIV infection, malignancy, hematopoietic stem cell transplant, nephrotic syndrome), may have reduced antibody responses to immunization with Prevnar 13 [see Use in Specific Populations (8.6)].

5.3 Apnea in Premature Infants

Apnea following intramuscular vaccination has been observed in some infants born prematurely. Decisions about when to administer an intramuscular vaccine, including Prevnar 13, to infants born prematurely should be based on consideration of the individual infant's medical status and the potential benefits and possible risks of vaccination.

6 ADVERSE REACTIONS

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.

6.1 Clinical Trials Experience With Prevnar 13 in Children 6 Weeks Through 17 Years of Age

The safety of Prevnar 13 was evaluated in 13 clinical trials in which 4,729 infants (6 weeks through 11 months of age) and toddlers (12 months through 15 months of age) received at least one dose of Prevnar 13 and 2,760 infants and toddlers received at least one dose of Prevnar active control. Safety data for the first three doses are available for all 13 infant studies; dose 4 data are available for 10 studies; and data for the 6-month follow-up are available for 7 studies. The vaccination schedule and concomitant vaccinations used in these infant trials were consistent with country-specific recommendations and local clinical practice. There were no substantive differences in demographic characteristics between the vaccine groups. By race, 84.0% of subjects were White, 6.0% were Black or African-American, 5.8% were Asian and 3.8% were of 'Other' race (most of these being biracial). Overall, 52.3% of subjects were male infants.

Three studies in the US (Studies 1, 2 and 3)1,2,3 evaluated the safety of Prevnar 13 when administered concomitantly with routine US pediatric vaccinations at 2, 4, 6, and 12–15 months of age. Solicited local and systemic adverse reactions were recorded daily by parents/guardians using an electronic diary for 7 consecutive days following each vaccination. For unsolicited adverse events, study subjects were monitored from administration of the first dose until one month after the infant series, and for one month after the administration of the toddler dose. Information regarding unsolicited and serious adverse events, newly diagnosed chronic medical conditions, and hospitalizations since the last visit were collected during the clinic visit for the fourth-study dose and during a scripted telephone interview 6 months after the fourth-study dose. Serious adverse events were also collected throughout the study period. Overall, the safety data show a similar proportion of Prevnar 13 and Prevnar subjects reporting serious adverse events. Among US study subjects, a similar proportion of Prevnar 13 and Prevnar recipients reported solicited local and systemic adverse reactions as well as unsolicited adverse events.

Serious Adverse Events in All Infant and Toddler Clinical Studies

Serious adverse events were collected throughout the study period for all 13 clinical trials. This reporting period is longer than the 30-day post-vaccination period used in some vaccine trials. The longer reporting period may have resulted in serious adverse events being reported in a higher percentage of subjects than for other vaccines. Serious adverse events reported following vaccination in infants and toddlers occurred in 8.2% among Prevnar 13 recipients and 7.2% among Prevnar recipients. Serious adverse events observed during different study periods for Prevnar 13 and Prevnar respectively were: 1) 3.7% and 3.5% from dose 1 to the blood draw approximately 1 month after the infant series; 2) 3.6% and 2.7% from the blood draw after the infant series to the toddler dose; 3) 0.9% and 0.8% from the toddler dose to the blood draw approximately 1 month after the toddler dose and 4) 2.5% and 2.8% during the 6 month follow-up period after the last dose.

The most commonly reported serious adverse events were in the 'Infections and infestations' system organ class including bronchiolitis (0.9%, 1.1%), gastroenteritis, (0.9%, 0.9%), and pneumonia (0.9%, 0.5%) for Prevnar 13 and Prevnar respectively.

There were 3 (0.063%) deaths among Prevnar 13 recipients, and 1 (0.036%) death in Prevnar recipients, all as a result of sudden infant death syndrome (SIDS). These SIDS rates are consistent with published age specific background rates of SIDS from the year 2000.

Among 6,839 subjects who received at least 1 dose of Prevnar 13 in clinical trials conducted globally, there was 1 hypotonic-hyporesponsive episode adverse reaction reported (0.015%). Among 4,204 subjects who received at least 1 dose of Prevnar in clinical trials conducted globally, there were 3 hypotonic-hyporesponsive episode adverse reactions reported (0.071%). All 4 events occurred in a single clinical trial in Brazil in which subjects received whole cell pertussis vaccine at the same time as Prevnar 13 or Prevnar.

Solicited Adverse Reactions in the Three US Infant and Toddler Studies

A total of 1,907 subjects received at least 1 dose of Prevnar 13 and 701 subjects received at least 1 dose of Prevnar in the three US studies (Studies 1, 2 and 3)1,2,3. Most subjects were White (77.3%), 14.2% were Black or African-American, and 1.7% were Asian; 79.1% of subjects were non-Hispanic and non-Latino and 14.6% were Hispanic or Latino. Overall, 53.6% of subjects were male infants.

The incidence and severity of solicited adverse reactions that occurred within 7 days following each dose of Prevnar 13 or Prevnar administered to US infants and toddlers are shown in Tables 3 and 4.

Table 3: Percentage of US Infant and Toddler Subjects Reporting Solicited Local Reactions at the Prevnar 13 or Prevnar Injection Sites Within 7 Days After Each Vaccination at 2, 4, 6, and 12–15 Months of Age*
Dose 1 Dose 2 Dose 3 Dose 4
Graded Local Reaction Prevnar 13
(N=1375–1612)
%
Prevnar
(N=516–606)
%
Prevnar 13
(N=1069–1331)
%
Prevnar
(N=405–510)
%
Prevnar 13
(N=998–1206)
%
Prevnar
(N=348–446)
%
Prevnar 13
(N=874–1060)
%
Prevnar
(N=283–379)
%
*
Data are from three primary US safety studies (the US Phase 2 infant study [National Clinical Trial (NCT) number NCT00205803] Study 1, the US noninferiority study [NCT00373958] Study 2, and the US lot consistency study [NCT00444457] Study 3). All infants received concomitant routine infant immunizations. Concomitant vaccines and pneumococcal conjugate vaccines were administered in different limbs.
Number of subjects reporting Yes for at least 1 day or No for all days.
Diameters were measured in caliper units of whole numbers from 1 to 14 or 14+. One caliper unit = 0.5 cm. Measurements were rounded up to the nearest whole number. Intensity of induration and erythema were then characterized as Mild (0.5–2.0 cm), Moderate (2.5–7.0 cm), or Severe (>7.0 cm).
§
Statistically significant difference p <0.05. No adjustments for multiplicity.
Redness
  Any 24.3 26.0 33.3 29.7 37.1 36.6 42.3 45.5
  Mild 23.1 25.2 31.9 28.7 35.3 35.3 39.5 42.7
  Moderate 2.2 1.5 2.7 2.2 4.6 5.1 9.6 13.4§
  Severe 0 0 0 0 0 0 0 0
Swelling
  Any 20.1 20.7 25.2 22.5 26.8 28.4 31.6 36.0§
  Mild 17.2 18.7 23.8 20.5 25.2 27.5 29.4 33.8
  Moderate 4.9 3.9 3.7 4.9 3.8 5.8 8.3 11.2§
  Severe 0 0 0.1 0 0 0 0 0
Tenderness
  Any 62.5 64.5 64.7 62.9 59.2 60.8 57.8 62.5
  Interferes with limb movement 10.4 9.6 9.0 10.5 8.4 9.0 6.9 5.7
Table 4: Percentage of US Infant and Toddler Subjects Reporting Solicited Systemic Adverse Reactions Within 7 Days After Each Vaccination at 2, 4, 6, and 12–15 Months of Age*,
Dose 1 Dose 2 Dose 3 Dose 4
Graded Systemic Events Prevnar 13
(N*=1360 – 1707)
%
Prevnar
(N*=497–640)
%
Prevnar 13
(N*=1084–1469)
%
Prevnar
(N*=409–555)
%
Prevnar 13
(N*=997–1361)
%
Prevnar
(N*=354–521)
%
Prevnar 13
(N*=850–1227)
%
Prevnar
(N*=278–436)
%
*
Number of subjects reporting Yes for at least 1 day or No for all days.
Data are from three primary US safety studies (the US Phase 2 infant study [NCT00205803] Study 1, the US noninferiority study [NCT00373958] Study 2, and the US lot consistency study [NCT00444457] Study 3). All infants received concomitant routine infant immunizations. Concomitant vaccines and pneumococcal conjugate vaccines were administered in different limbs.
Fever gradings: Mild (≥38°C but ≤39°C), Moderate (>39°C but ≤40°C), and Severe (>40°C). No other systemic event other than fever was graded. Parents reported the use of antipyretic medication to treat or prevent symptoms in 62 to 75% of subjects after any of the 4 doses. There were no statistical differences in frequencies of adverse reactions reported between the Prevnar 13 and Prevnar groups.
Fever
  Any 24.3 22.1 36.5 32.8 30.3 31.6 31.9 30.6
  Mild 23.6 21.7 34.9 31.6 29.1 30.2 30.3 30.0
  Moderate 1.1 0.6 3.4 2.8 4.2 3.3 4.4 4.6
  Severe 0.1 0.2 0.1 0.3 0.1 0.7 1.0 0
Decreased appetite 48.3 43.6 47.8 43.6 47.6 47.6 51.0 49.4
Irritability 85.6 83.6 84.8 80.4 79.8 80.8 80.4 77.8
Increased sleep 71.5 71.5 66.6 63.4 57.7 55.2 48.7 55.1
Decreased sleep 42.5 40.6 45.6 43.7 46.5 47.7 45.3 40.3

The incidence rates of any fever (≥38.0°C) were similar on days 1 and 2 following each dose of Prevnar 13 compared to after each dose of Prevnar administered to US infants and toddlers (day 1 = day of vaccination). After dose 1, fever was reported in 11.0–12.7% on day 1 and 6.4–6.8% on day 2. After dose 2, fever was reported in 12.3–13.1% on day 1 and 12.5–12.8% on day 2. After dose 3, fever was reported in 8.0–9.6% on day 1 and 9.1–10.5% on day 2. And after dose 4, fever was reported in 6.3–6.4% on day 1 and 7.3–9.7% on day 2.

Unsolicited Adverse Reactions in the Three US Infant and Toddler Safety Studies

The following were determined to be adverse drug reactions based on experience with Prevnar 13 in clinical trials.

Reactions occurring in greater than 1% of infants and toddlers: diarrhea, vomiting, and rash.

Reactions occurring in less than 1% of infants and toddlers: crying, hypersensitivity reaction (including face edema, dyspnea, and bronchospasm), seizures (including febrile seizures), and urticaria or urticaria-like rash.

Safety Assessments in the Catch-Up Studies in Infants and Children Through 5 Years of Age

In a catch-up study4 conducted in Poland (Study 4), 354 children (7 months through 5 years of age) receiving at least one dose of Prevnar 13 were also monitored for safety. All subjects in this study were White and non-Hispanic. Overall, 49.6% of subjects were male infants. The incidence and severity of solicited adverse reactions that occurred within 4 days following each dose of Prevnar 13 administered to pneumococcal-vaccine naïve children 7 months through 5 years of age are shown in Tables 5 and 6.

Table 5: Percentage of Subjects 7 Months Through 5 Years of Age Reporting Solicited Local Reactions Within 4 Days After Each Catch-Up Prevnar 13 Vaccination*
7 through 11 months 12 through 23 months 24 months through 5 years
Graded Local Reaction Dose 1
N=86
%
Dose 2
N=86–87
%
Dose 3
N=78–82
%
Dose 1
N=108–110
%
Dose 2
N=98–106
%
Dose 1
N=147–149
%
*
Study conducted in Poland (NCT00452452) Study 4.
Number of subjects reporting Yes for at least 1 day or No for all days.
Diameters were measured in caliper units of whole numbers from 1 to 14 or 14+. One caliper unit = 0.5 cm. Measurements were rounded up to the nearest whole number. Intensity of redness and swelling were then characterized as Mild (0.5–2.0 cm), Moderate (2.5–7.0 cm), or Severe (>7.0 cm).
Redness
  Any 48.8 46.0 37.8 70.0 54.7 50.0
  Mild 41.9 40.2 31.3 55.5 44.7 37.4
  Moderate 16.3 9.3 12.5 38.2 25.5 25.7
  Severe 0.0 0.0 0.0 0.0 0.0 0.0
Swelling
  Any 36.0 32.2 25.0 44.5 41.0 36.9
  Mild 32.6 28.7 20.5 36.7 36.2 28.2
  Moderate 11.6 14.0 11.3 24.8 12.1 20.3
  Severe 0.0 0.0 0.0 0.0 0.0 0.0
Tenderness
  Any 15.1 15.1 15.2 33.3 43.7 42.3
  Interferes with limb movement 1.2 3.5 6.4 0.0 4.1 4.1
Table 6: Percentage of Subjects 7 Months Through 5 Years of Age Reporting Solicited Systemic Adverse Reactions Within 4 Days After Each Catch-Up Prevnar 13 Vaccination*
7 through 11 months 12 through 23 months 24 months through 5 years
Systemic Reaction Dose 1
N=86–87
%
Dose 2
N=86–87
%
Dose 3
N=78–81
%
Dose 1
N=108
%
Dose 2
N=98–100
%
Dose 1
N=147–148
%
*
Study conducted in Poland (NCT00452452) Study 4.
Number of subjects reporting Yes for at least 1 day or No for all days.
Fever gradings: Mild (≥38°C but ≤39°C), Moderate (>39°C but ≤40°C), and Severe (>40°C). No other systemic event other than fever was graded.
Fever
  Mild 3.4 8.1 5.1 3.7 5.1 0.7
  Moderate 1.2 2.3 1.3 0.9 0.0 0.7
  Severe 0.0 0.0 0.0 0.0 0.0 0.0
Decreased appetite 19.5 17.2 17.5 22.2 25.5 16.3
Irritability 24.1 34.5 24.7 30.6 34.0 14.3
Increased sleep 9.2 9.3 2.6 13.0 10.1 11.6
Decreased sleep 24.1 18.4 15.0 19.4 20.4 6.8

A US study5 (Study 5) evaluated the use of Prevnar 13 in children previously immunized with Prevnar. In this open label trial, 596 healthy children 15 through 59 months of age previously vaccinated with at least 3 doses of Prevnar, received 1 or 2 doses of Prevnar 13. Children 15 months through 23 months of age (group 1) received 2 doses, and children 24 months through 59 months of age (group 2) received one dose. Most subjects were White (74.3%), 14.9% were Black or African-American, and 1.2% were Asian; 89.3% of subjects were non-Hispanic and non-Latino and 10.7% were Hispanic or Latino. Overall, 52.2% of subjects were male.

The incidence and severity of solicited adverse reactions that occurred within 7 days following one dose of Prevnar 13 administered to children 15 months through 59 months of age are shown in Tables 7 and 8.

Table 7: Percentage of Subjects 15 Months Through 59 Months of Age, Previously Vaccinated With 3 or 4 Prior Infant Doses of Prevnar, Reporting Solicited Local Reactions Within 7 Days After One Supplemental Prevnar 13 Vaccination*
15 months through 23 months 24 months through 59 months
Graded Local Reaction 1 dose Prevnar 13
3 prior Prevnar doses
N§=67–72
%
1 dose Prevnar 13
4 prior Prevnar doses
N§=154–184
%
1 dose Prevnar 13
3 or 4 prior Prevnar doses
N§=209–238
%
*
Study conducted in US NCT00761631 (Study 5).
Dose 2 data not shown.
The data for this age group are only represented as a single result as 95% of children received 4 doses of Prevnar prior to enrollment.
§
Number of subjects reporting Yes for at least 1 day or No for all days.
Diameters were measured in caliper units of whole numbers from 1 to 14 or 14+. One caliper unit = 0.5 cm. Measurements were rounded up to the nearest whole number. Intensity of redness and swelling were then characterized as Mild (0.5–2.0 cm), Moderate (2.5–7.0 cm), or Severe (>7.0 cm).
Redness
  Any 26.4 28.2 35.4
  Mild 18.8 24.3 31.1
  Moderate 11.4 7.5 12.1
  Severe 1.5 0.0 0.0
Swelling
  Any 23.9 19.6 20.7
  Mild 18.6 16.4 17.2
  Moderate 8.8 8.1 7.5
  Severe 0.0 0.0 0.0
Tenderness
  Any 48.6 47.3 62.6
  Interferes with limb movement 5.9 6.4 10.7
Table 8: Percentage of Subjects 15 Months Through 59 Months of Age, Previously Vaccinated With 3 or 4 Prior Infant Prevnar Doses, Reporting Solicited Systemic Adverse Reactions Within 7 Days After One Supplemental Prevnar 13 Vaccination*
15 through 23 months 24 months through 59 months
Systemic Reaction 1 dose Prevnar 13
3 prior Prevnar doses
N§=66–75
%
1 dose Prevnar 13
4 prior Prevnar doses
N§=154–189
%
1 dose Prevnar 13
3 or 4 prior Prevnar doses
N§=209–236
%
*
Study conducted in US NCT00761631 (Study 5).
Dose 2 data not shown.
The data for this age group are only represented as a single result as 95% of children received 4 doses of Prevnar prior to enrollment.
§
Number of subjects reporting Yes for at least 1 day or No for all days.
Fever gradings: Mild (≥38°C but ≤39°C), Moderate (>39°C but ≤40°C), and Severe (>40°C). No other systemic event other than fever was graded.
Fever
  Any 19.1 19.9 8.1
  Mild 16.2 17.4 7.6
  Moderate 6.1 3.9 1.9
  Severe 0.0 0.0 0.5
Decreased appetite 44.4 39.3 28.1
Irritability 73.3 65.1 45.8
Increased sleep 35.2 35.3 18.8
Decreased sleep 25.0 29.7 14.8

Clinical Trials Experience With Prevnar 13 in Children 5 Through 17 Years of Age

In a US study5 (Study 5), the safety of Prevnar 13 was evaluated in children 5 through 9 years of age previously immunized with at least one dose of Prevnar, and in children 10 through 17 years of age with no prior pneumococcal vaccination. In this open label trial, 592 children, including those with asthma, received a single dose of Prevnar 13. The percentage of children 5 through 9 years of age who received 3 and 4 prior doses of Prevnar was 29.1% and 54.5% respectively.

Most subjects were White (72.8%), 21.8% were Black or African-American, and 1.5% were Asian; 91.4% of subjects were non-Hispanic and non-Latino and 8.6% were Hispanic or Latino. Overall, 51.2% of subjects were male.

The incidence and severity of solicited adverse reactions that occurred within 7 days following one dose of Prevnar 13 administered to children 5 through 17 years of age are shown in Tables 9 and 10.

Table 9: Percentage of Subjects 5 Through 17 Years of Age, Reporting Solicited Local Reactions Within 7 Days After Prevnar 13 Vaccination *
Vaccine Group (as Administered)
Prevnar 13
(5 Through 9 Years)
Prevnar 13
(10 Through 17 Years)
Local Reaction N n % N n %
*
Study conducted in US NCT00761631 (Study 5).
N = number of subjects reporting Yes for at least 1 day or No for all days.
n = Number of subjects reporting the specific characteristic.
§
Mild, 0.5 – 2.0 cm; moderate, 2.5 – 7.0 cm; severe, >7.0 cm.
Significant = present and interfered with limb movement.
Redness
  Any 233 100 42.9 232 70 30.2
  Mild§ 226 63 27.9 226 48 21.2
  Moderate§ 218 48 22.0 221 31 14.0
  Severe§ 212 7 3.3 213 4 1.9
Swelling
  Any 226 85 37.6 233 86 36.9
  Mild§ 220 48 21.8 221 50 22.6
  Moderate§ 219 48 21.9 226 48 21.2
  Severe§ 211 7 3.3 214 4 1.9
Tenderness
  Any 265 230 86.8 283 252 89.0
  Significant 221 43 19.5 242 106 43.8
Table 10: Percentage of Subjects 5 Through 17 Years of Age, Reporting Solicited Systemic Adverse Reactions Within 7 Days After Prevnar 13 Vaccination*
Vaccine Group (as Administered)
Prevnar 13
(5 Through 9 Years)
Prevnar 13
(10 Through 17 Years)
Systemic Event N n % N n %
*
Study conducted in US NCT00761631 (Study 5).
N = number of subjects reporting Yes for at least 1 day or No for all days.
n = Number of subjects reporting the event.
§
Fever gradings: Mild (≥38°C but ≤39°C), Moderate (>39°C but ≤40°C), and Severe (>40°C). No other systemic event other than fever was graded. Parents reported the use of antipyretic medication to treat or prevent symptoms in 45.1% and 33.1% of subjects 5 through 9 years of age and 10 through 17 years of age, respectively.
Any fever ≥38°C 214 13 6.1 214 12 5.6
Mild§ 212 9 4.2 214 11 5.1
Moderate§ 212 5 2.4 212 1 0.5
Severe§ 210 1 0.5 212 1 0.5
Decreased appetite 227 52 22.9 223 51 22.9
Irritability 234 73 31.2 234 59 25.2
Increased sleep 226 48 21.2 229 61 26.6
Decreased sleep 212 12 5.7 224 42 18.8
Hives (urticaria) 213 4 1.9 214 3 1.4

6.2 Clinical Trials Experience With Prevnar 13 in Adults ≥18 Years of Age

The safety of Prevnar 13 was assessed in 7 clinical studies (Studies 6–12)6–12 conducted in the US and Europe which included 91,593 adults (48,806 received Prevnar 13) ranging in age from 18 through 101 years.

The 48,806 Prevnar 13 recipients included 899 adults who were aged 18 through 49 years, 2,616 adults who were aged 50 through 64 years, 45,291 adults aged 65 years and older. Of the 48,806 Prevnar 13 recipients, 46,890 adults had not previously received Pneumovax® 23 (pneumococcal polysaccharide vaccine [23-valent], PPSV23) ("PPSV23 unvaccinated") and 1,916 adults were previously vaccinated ("PPSV23 previously vaccinated") with PPSV23 at least 3 years prior to enrollment.

Safety and Immunogenicity Studies

Safety and immunogenicity of Prevnar 13 is supported by 6 clinical studies. Study 66 evaluated the safety and immunogenicity of Prevnar 13 in adults 18 through 64 years of age who had not received a previous dose of pneumococcal vaccine. Adults 18 through 59 years of age received a single dose of Prevnar 13, and adults 60 through 64 years of age received a single dose of Prevnar 13 or PPSV23.

Study 7 was randomized and compared the safety and immunogenicity of Prevnar 13 with PPSV23 as a single dose in adults ≥70 years vaccinated with PPSV23 (≥5 years prior to enrollment).7 Study 8 was randomized and evaluated the safety and immunogenicity of Prevnar 13 and PPSV23 in different sequential order in PPSV23 naive adults aged 60 through 64 years8.

One clinical safety study9 (Study 9) of Prevnar 13, conducted in PPSV23 previously vaccinated (≥3 years prior to enrollment) adults aged ≥68 years was a single arm study. Two studies, one in the US10 (Study 10) in adults aged 50 through 59 years and the other in Europe11 (Study 11) in adults aged ≥65 years, evaluated the concomitant administration of Prevnar 13 with inactivated influenza vaccine, trivalent (Fluarix®, A/H1N1, A/H3N2, and B, Fall 2007/Spring 2008: IIV3) in these two age groups in PPSV23 unvaccinated adults.

The total safety population in the 6 safety and immunogenicity studies was 7,097. In 5 of the 6 safety and immunogenicity studies, more females than males were enrolled (50.2% – 61.8%). Across the 6 studies the racial distribution included: >85% White; 0.2%–10.7% Black or African American; 0%–1.7% Asian; <1% Native Hawaiian or other Pacific Islander; ≤1%, American Indian or Alaskan Native. Ethnicity data were not collected in Study 11; in the 5 other studies 0.6%–4.8% were Hispanic or Latino.

In five studies,6–8,10,11 subjects with pre-existing underlying diseases were enrolled if the medical condition was stable (did not require a change in therapy or hospitalization for worsening disease for 12 weeks before receipt of study vaccine) except in Study 9 where subjects were enrolled if the medical condition was stable for 6 or more weeks before receipt of study vaccine.

In the 6 safety and immunogenicity studies,6–11 subjects were excluded from study participation due to prior receipt of diphtheria toxoid-containing vaccines within 6 months of study vaccine. However, the time of prior receipt of a diphtheria toxoid-containing vaccine was not recorded.

Solicited adverse reactions for Prevnar 13 in the safety and immunogenicity studies were monitored by subjects recording local adverse reactions and systemic reactions daily using an electronic diary for 14 consecutive days following vaccination. Unsolicited serious and non-serious adverse events were collected for one month after each vaccination. In addition, serious adverse events were collected for an additional 5 months after each vaccination (at the 6-month follow-up phone contact) in all studies except Study 11.

Following licensure of Prevnar 13 in adults ≥50 years of age, a randomized, double-blind, placebo-controlled US study (Study 13) was conducted to evaluate concomitant administration of Prevnar 13 with inactivated influenza vaccine, quadrivalent (Fluzone® Quadrivalent, A/H1N1, A/H3N2, B/Brisbane, and B/Massachusetts, Fall 2014/Spring 2015: IIV4) in PPSV23 previously vaccinated adults ≥50 years of age. Unsolicited serious and non-serious adverse events were collected as described above for Studies 6–10.

Efficacy Study

Study 1212 was a randomized double-blind placebo-controlled study conducted in the Netherlands in community-dwelling adults aged 65 years and older with no prior pneumococcal vaccination history. A total of 84,496 subjects received either a single dose of Prevnar 13 (42,240) or placebo (42,256) in a 1:1 randomization. Among the 84,496 subjects, 58,072 (68.7%) were ≥65 to <75 years of age, 23,481 (27.8%) were ≥75 and <85 years of age, and 2,943 (3.5%) were ≥85 years of age. In the total safety population, more males (55.9%) were enrolled than females. The racial distribution was 98.5% White, 0.3% Black, 0.7% Asian, 0.5% Other, with <0.1% having missing data.

Adults with immunocompromising conditions or receiving immunosuppressive therapy and adults residing in a long-term care facility or requiring semiskilled nursing care were excluded. Adults with pre-existing medical conditions, as well as subjects with a history of smoking were eligible for enrollment. In the safety population, 42.3% of subjects had pre-existing medical conditions including heart disease (25.4%), lung disease or asthma (15.1%) and type 1 and type 2 diabetes mellitus (12.5%). Smoking was reported at baseline by 12.3% of the subjects.

For a subset of 2,011 subjects (1,006 Prevnar 13 recipients and 1,005 placebo recipients), solicited adverse reactions were monitored by recording local and systemic events using electronic diaries for 7 days after vaccination; unsolicited adverse events were collected for 28 days after vaccination, and serious adverse events were collected for 6 months after vaccination. For the remaining 41,231 Prevnar 13 and 41,250 placebo vaccinated subjects, serious adverse events were collected for 28 days after vaccination.

Serious Adverse Events in Adult Clinical Studies

Safety and Immunogenicity Studies

Across the 6 safety and immunogenicity studies,6–11 serious adverse events within 1 month of vaccination were reported after an initial study dose in 0.2%–1.4% of 5,057 subjects vaccinated with Prevnar 13, and in 0.4%–1.7% of 1,124 subjects vaccinated after an initial study dose of PPSV23. From 1 month to 6 months after an initial study dose, serious adverse events were reported in 0.2%–5.8% of subjects vaccinated during the studies with Prevnar 13 and in 2.4%–5.5% of subjects vaccinated with PPSV23. One case of erythema multiforme occurred 34 days after receipt of a second dose of Prevnar 13.

Twelve of 5,667 (0.21%) Prevnar 13 recipients and 4 of 1,391 (0.29 %) PPSV23 recipients died. Deaths occurred between Day 3 and Day 309 after study vaccination with Prevnar 13 or PPSV23. Two of 12 deaths occurred within 30 days of vaccination and both deaths were in subjects >65 years of age. One death due to cardiac failure occurred 3 days after receiving placebo. This subject had received Prevnar 13 and IIV3 one month earlier. The other death was due to peritonitis 20 days after receiving Prevnar 13. The reported causes of the 10 remaining deaths occurring greater than 30 days after receiving Prevnar 13 were cardiac disorders (4), neoplasms (4), Mycobacterium avium complex pulmonary infection (1) and septic shock (1).

Efficacy Study

In Study 1212 (subjects 65 years and older), serious adverse events within 1 month of vaccination were reported in 327 of 42,237 (0.8%) Prevnar 13 recipients (352 events) and in 314 of 42,225 (0.7%) placebo recipients (337 events). In the subset of subjects where serious adverse events were monitored for 6 months, 70 of 1,006 (7%) Prevnar 13 vaccinated subjects (90 events) and 60 of 1,005 (6%) placebo vaccinated subjects (69 events) reported serious adverse events.

During the follow-up period (average of 4 years) for case accumulation there were 3,006 deaths (7.1%) in the Prevnar 13 group and 3,005 deaths (7.1%) in the placebo group. There were 10 deaths (<0.1%) in the Prevnar 13 group and 10 deaths (<0.1%) in the placebo group within 28 days of vaccination. There were 161 deaths (0.4%) in the Prevnar 13 group and 144 deaths (0.3%) in the placebo group within 29 days – 6 months following vaccination. These data do not provide evidence for a causal relationship between deaths and vaccination with Prevnar 13.

Solicited Adverse Reactions in Adult Clinical Studies

The incidence and severity of solicited adverse reactions that occurred within 7 or 14 days following each dose of Prevnar 13, PPSV23, or placebo administered to adults in 5 studies are shown in Tables 11, 12, 13, and 14.

The commonly reported local adverse reactions after Prevnar 13 vaccination in PPSV23 unvaccinated and PPSV23 previously vaccinated adults were redness, swelling and pain at the injection site, or limitation of arm movement (Tables 11 and 12). The commonly reported systemic adverse reactions in PPSV23 unvaccinated and PPSV23 previously vaccinated adults were fatigue, headache, chills, rash, decreased appetite, or muscle pain and joint pain (Tables 13 and 14).

Table 11 - Percentage of Subjects With Solicited Local Adverse Reactions Within 7 or 14 Days in PPSV23 Unvaccinated Adults*
Study 6 Study 8 Study 12
Age in Years 18–49 50–59 60–64 60–64 ≥65
Local Reaction Prevnar 13
N=266–787
%
Prevnar 13
N=152–322
%
Prevnar 13
N=193–331
%
PPSV23
N=190–301
%
Prevnar 13
N=270–370
%
PPSV23
N=134–175
%
Prevnar 13
N=886–914
%
Placebo
N=859–865
%
*
Studies conducted in US NCT00427895 (Study 6) and NCT00574548 (Study 8) reported local reactions within 14 days. Study conducted in the Netherlands NCT00744263 (Study 12) reported local reactions within 7 days.
Open label administration of Prevnar 13.
Number of subjects with known values (number of subjects reporting yes for at least one day or no for all days).
§
Diameters were measured in caliper units of whole numbers from 1 to 21 or 21+. One caliper unit = 0.5 cm. Measurements were rounded up to the nearest whole number. Intensity of redness and swelling were then characterized as Mild = 2.5 to 5.0 cm, Moderate = 5.1 to 10.0 cm, and Severe is >10.0 cm.
Statistically significant difference p <0.05. No adjustments for multiplicity.
#
Mild = awareness of symptom but easily tolerated, Moderate = discomfort enough to cause interference with usual activity, Severe = incapacitating with inability to do usual activity.
Þ
Mild = some limitation of arm movement, Moderate = unable to move arm above head but able to move arm above shoulder, and Severe = unable to move arm above shoulder.
Redness§
  Any 30.5 15.8 20.2 14.2 12.2 11.2 4.9 1.2
  Mild 26.4 15.2 15.9 11.2 8.3 9.7 3.7 0.8
  Moderate 11.9 5.0 8.6 4.9 6.4 3.9 1.7 0.3
  Severe 2.8 0.7 1.7 0.0 1.2 0.8 0.5 0.1
Swelling§
  Any 39.4 21.7 19.3 13.1 10.0 10.4 6.8 1.2
  Mild 37.2 20.6 15.6 10.1 8.2 6.1 5.5 0.7
  Moderate 15.1 4.3 8.2 4.4 3.8 7.6 2.6 0.6
  Severe 1.4 0.0 0.6 1.1 0.0 0.0 0.1 0.1
Pain#
  Any 96.7 88.8 80.1 73.4 69.2 58.3 36.1 6.1
  Mild 93.2 85.9 78.6 68.6 66.1 52.9 32.9 5.6
  Moderate 77.1 39.5 23.3 30.0 20.1 21.7 7.7 0.6
  Severe 16.0 3.6 1.7 8.6 2.3 0.8 0.3 0.1
Limitation of arm movementÞ
  Any 75.2 40.7 28.5 30.8 23.5 28.2 14.1 3.2
  Mild 71.5 38.6 26.9 29.3 22.7 26.1 12.4 2.5
  Moderate 18.5 2.9 2.2 3.8 1.2 3.1 1.7 0.5
  Severe 15.6 2.9 1.7 4.3 1.1 2.3 1.2 0.7
Table 12 - Percentage of Subjects With Solicited Local Adverse Reactions in PPSV23 Previously Vaccinated Adults*
Study 7 Study 9
Age in Years ≥70 ≥68
Local Reaction Prevnar 13
N=306–362
%
PPSV23
N=324–383
%
Prevnar 13
N=664–777
%
*
Study conducted in US and Sweden NCT00546572 (Study 7) reported local reactions within 14 days. Study conducted in US, Sweden and Germany NCT00500266 (Study 9) reported local reactions within 14 days.
Number of subjects with known values.
Open label administration of Prevnar 13.
§
Diameters were measured in caliper units of whole numbers from 1 to 21 or 21+. One caliper unit = 0.5 cm. Measurements were rounded up to the nearest whole number. Intensity of redness and swelling were then characterized as Mild = 2.5 to 5.0 cm, Moderate = 5.1 to 10.0 cm, and Severe is >10.0 cm.
Statistically significant difference p <0.05. No adjustments for multiplicity.
#
Mild = awareness of symptom but easily tolerated, Moderate = discomfort enough to cause interference with usual activity, Severe = incapacitating with inability to do usual activity.
Þ
Mild = some limitation of arm movement, Moderate = unable to move arm above head but able to move arm above shoulder, and Severe = unable to move arm above shoulder.
Redness§
  Any 10.8 22.2 14.3
  Mild 9.5 13.5 12.6
  Moderate 4.7 11.5 6.5
  Severe 1.7 4.8 1.1
Swelling§
  Any 10.4 23.1 12.8
  Mild 8.9 14.0 10.9
  Moderate 4.0 13.6 5.5
  Severe 0.0 4.8 0.6
Pain#
  Any 51.7 58.5 51.0
  Mild 50.1 54.1 49.4
  Moderate 7.5 23.6 9.0
  Severe 1.3 2.3 0.2
Limitation of arm movementÞ
  Any 10.5 27.6 16.2
  Mild 10.3 25.2 14.8
  Moderate 0.3 2.6 1.6
  Severe 0.7 3.0 1.6
Table 13 - Percentage of Subjects With Solicited Systemic Events in PPSV23 Unvaccinated Adults*
Study 6 Study 8 Study 12
Age in Years 18–49 50–59 60–64 60–64 ≥65
Prevnar 13
N=221–561
%
Prevnar 13
N=137–248
%
Prevnar 13
N=174–277
%
PPSV23
N=176–273
%
Prevnar 13
N=261–328
%
PPSV23
N=127–173
%
Prevnar 13
N=881–896
%
Placebo
N=860–878
%
*
Studies conducted in US NCT00427895 (Study 6) and NCT00574548 (Study 8) reported systemic events within 14 days. Study conducted in the Netherlands NCT00744263 (Study 12) reported systemic events within 7 days.
Open label administration of Prevnar 13.
Number of subjects with known values (number of subjects reporting yes for at least one day or no for all days).
§
Statistically significant difference p <0.05. No adjustments for multiplicity.
Fevers >40.0°C were confirmed to be data entry errors and remain in the table for the following: 1 case in the 18- to 49- year-old cohort (Study 6), and 7 cases in the Prevnar 13 group and 3 cases in placebo group (Study 12). For the other cohorts in Study 6 and for Study 8, data entry errors were removed.
Systemic Event
Fever
  ≥38.0°C 7.2 1.5 4.0 1.1 4.2 1.6 2.9§ 1.3
  38.0°C to 38.4°C 4.2 1.5 4.0 1.1 3.8 0.8 1.1 0.6
  38.5°C to 38.9°C 1.9 0.0 0.6 0.0 0.8 0.0 0.6 0.2
  39.0°C to 40.0°C 1.4 0.0 0.0 0.0 0.4 0.8 0.7 0.2
  >40.0°C 0.5 0.0 0.0 0.0 0.0 0.0 0.8 0.3
Fatigue 80.5 63.3 63.2 61.5 50.5 49.1 18.8§ 14.8
Headache 81.4 65.9 54.0 54.4 49.7 46.1 15.9 14.8
Chills 38.1 19.6 23.5 24.1 19.9 26.9 9.4 8.4
Rash 21.3 14.2 16.5 13.0 8.6 13.4 3.3§ 0.8
Vomiting 15.0 6.9 3.9 5.4 3.1 3.1 0.3 0.9
Decreased appetite 55.6 25.3 21.3 21.7 14.7 23.0§ 5.3 3.7
Generalized new muscle pain 82.0 61.8 56.2 57.8 46.9 51.5 18.4§ 8.4
Generalized aggravated muscle pain 55.9 39.9 32.6 37.3 22.0 32.5§ 9.1§ 4.4
Generalized new joint pain 41.7 31.5 24.4 30.1 15.5 23.8§ 7.4 5.4
Generalized aggravated joint pain 28.6 25.6 24.9 21.4 14.0 21.1 5.2 4.2
Table 14 - Percentage of Subjects With Systemic Events in PPSV23 Previously Vaccinated Adults*
Study 7 Study 9
Age in Years ≥70 ≥68
Prevnar 13
N=299–350
%
PPSV23
N=303–367
%
Prevnar 13
N=635–733
%
*
Study conducted in US and Sweden NCT00546572 (Study 7) reported systemic events within 14 days. Study conducted in US, Sweden and Germany NCT00500266 (Study 9) reported systemic events within 14 days.
Number of subjects with known values.
Open label administration of Prevnar 13.
§
Statistically significant difference p <0.05. No adjustments for multiplicity.
Systemic Event
Fever
  ≥38.0°C 1.0 2.3 1.1
  38.0°C to 38.4°C 1.0 2.0 0.8
  38.5°C to 38.9°C 0.0 0.0 0.0
  39.0°C to 40.0°C 0.0 0.3 0.3
  >40.0°C 0.0 0.0 0.0
Fatigue 34.0 43.3§ 34.4
Headache 23.7 26.0 26.1
Chills 7.9 11.2 7.5
Rash 7.3 16.4§ 8.4
Vomiting 1.7 1.3 0.9
Decreased appetite 10.4 11.5 11.2
Generalized new muscle pain 36.8 44.7§ 25.3
Generalized aggravated muscle pain 20.6 27.5§ 12.3
Generalized new joint pain 12.6 14.9 12.8
Generalized aggravated joint pain 11.6 16.5 9.7

Safety Results from Adult Clinical Study of Concomitant Administration of Prevnar 13 and IIV4 (Fluzone Quadrivalent) (Study 13)

The safety profile of Prevnar 13 when administered concomitantly with seasonal inactivated influenza vaccine, quadrivalent, to PPSV23 previously vaccinated adults ≥50 years of age was generally consistent with the known safety profile of Prevnar 13.

6.3 Post-marketing Experience With Prevnar 13 in Infants and Toddlers

The following adverse events have been reported through passive surveillance since market introduction of Prevnar 13. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to the vaccine. The following adverse events were included based on one or more of the following factors: severity, frequency of reporting, or strength of evidence for a causal relationship to Prevnar 13 vaccine.

Administration site conditions: Vaccination-site dermatitis, vaccination-site pruritus, vaccination-site urticaria

Blood and lymphatic system disorders: Lymphadenopathy localized to the region of the injection site

Cardiac disorders: Cyanosis

Immune system disorders: Anaphylactic/anaphylactoid reaction including shock

Nervous system disorders: Hypotonia

Skin and subcutaneous tissue disorders: Angioneurotic edema, erythema multiforme

Respiratory: Apnea

Vascular disorders: Pallor

1 INDICATIONS AND USAGE

1.1 Children 6 Weeks Through 5 Years of Age

In children 6 weeks through 5 years of age (prior to the 6th birthday), Prevnar 13® is indicated for:

  • active immunization for the prevention of invasive disease caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F.
  • active immunization for the prevention of otitis media caused by S. pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. No otitis media efficacy data are available for serotypes 1, 3, 5, 6A, 7F, and 19A.

1.2 Children 6 Years Through 17 Years of Age

In children 6 years through 17 years of age (prior to the 18th birthday), Prevnar 13 is indicated for:

  • active immunization for the prevention of invasive disease caused by S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F.

1.3 Adults 18 Years of Age and Older

In adults 18 years of age and older, Prevnar 13 is indicated for:

  • active immunization for the prevention of pneumonia and invasive disease caused by S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F.

1.4 Limitations of Prevnar 13 Use and Effectiveness

  • Prevnar 13 does not protect against disease caused by S. pneumoniae serotypes that are not in the vaccine.

TRUMENBA® (Meningococcal Group B Vaccine)

These highlights do not include all the information needed to use TRUMENBA safety and effectively. See full prescribing information for TRUMENBA.

4 CONTRAINDICATIONS

Severe allergic reaction after a previous dose of Trumenba.

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 Trumenba.

5.2 Altered Immunocompetence

Reduced Immune Response

Some individuals with altered immunocompetence may have reduced immune responses to Trumenba.

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 serogroup B even if they develop antibodies following vaccination with Trumenba [see Clinical Pharmacology (12.0)].

5.3 Limitation of Vaccine Effectiveness

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

5.4 Syncope

Syncope (fainting) can occur in association with administration of injectable vaccines, including Trumenba. Procedures should be in place to avoid injury from fainting.

6 ADVERSE REACTIONS

In clinical 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%). Nausea was reported in up to 24% of adolescents in early phase studies.

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 Trumenba 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 Trumenba. 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.); Meningococcal 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 Trumenba and those who received control. Overall, across the 11 studies, among the subjects who received Trumenba, 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 Trumenba 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 Trumenba 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 Trumenba 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 Trumenba or control (HAV/saline or saline) for Study 1 and Study 2, respectively.

Local adverse reactions were reported more frequently following Trumenba compared to control (see Tables 1 and 2).

Table 1: Percentages of Subjects 10 to 18 Years of Age (Study 1*) Reporting Local Adverse Reactions Within 7 Days After Each Vaccination
Dose 1 Dose 2 Dose 3
Trumenba HAV/Saline Trumenba HAV/Saline Trumenba HAV/Saline
Local Reaction N=2681 N=890 N=2545 N=843 N=2421 N=821
*
Study 1: National Clinical Trial (NCT) number NCT01830855.
Trumenba was administered at 0, 2, and 6 months. HAV was administered at 0 and 6 months and saline was administered at 2 months.
Mild (does not interfere with activity); moderate (interferes with activity); severe (prevents daily activity).
§
"Any" is defined as the cumulative frequency of subjects who reported a reaction as "mild", "moderate", or "severe" within 7 days of vaccination.
Mild (2.5–5.0 cm); moderate (>5.0–10.0 cm); severe (>10.0 cm).
Pain
  Any§ 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
Redness
  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
Table 2: Percentages of Subjects 18 to 25 Years of Age (Study 2*) Reporting Local Adverse Reactions Within 7 Days After Each Vaccination
Dose 1 Dose 2 Dose 3
Trumenba Saline Trumenba Saline Trumenba Saline
Local Reaction N=2425 N=798 N=2076 N=706 N=1823 N=624
*
Study 2: National Clinical Trial (NCT) number NCT01352845.
Trumenba was administered at 0, 2, and 6 months. Saline was administered at 0, 2, and 6 months.
Mild (does not interfere with activity); moderate (interferes with activity); severe (prevents daily activity).
§
"Any" is defined as the cumulative frequency of subjects who reported a reaction as "mild", "moderate", or "severe" within 7 days of vaccination.
Mild (2.5–5.0 cm); moderate (>5.0–10.0 cm); severe (>10.0 cm).
Pain
  Any§ 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
Redness
  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 Trumenba 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 Trumenba group.

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

Table 3: Percentages of Subjects 10 to 18 Years of Age (Study 1*) Reporting Systemic Adverse Reactions and Use of Antipyretic Medications Within 7 Days After Each Vaccination
Dose 1 Dose 2 Dose 3
Trumenba HAV/Saline Trumenba HAV/Saline Trumenba HAV/Saline
Systemic Reaction N=2681 N=890 N=2545 N=843 N=2421 N=821
*
Study 1: National Clinical Trial (NCT) number NCT01830855.
Trumenba was administered at 0, 2, and 6 months. HAV was administered at 0 and 6 months and saline was administered at 2 months.
Study 1: Fever (≥38°C): N=2679, 2540, and 2414 for Trumenba 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.
§
Mild (1–2 times in 24 hours); moderate (>2 times in 24 hours); severe (requires intravenous hydration).
"Any" is defined as the cumulative frequency of subjects who reported a reaction as "mild", "moderate", or "severe" within 7 days of vaccination.
#
Mild (2–3 loose stools in 24 hours); moderate (4–5 loose stools in 24 hours); severe (6 or more loose stools in 24 hours).
Þ
Mild (does not interfere with activity); moderate (interferes with activity); severe (prevents daily activity).
Fever (≥38°C)
  ≥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
Vomiting§
  Any 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
Diarrhea#
  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
HeadacheÞ
  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
FatigueÞ
  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
ChillsÞ
  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)Þ
  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 painÞ
  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
Table 4: Percentages of Subjects 18 to 25 Years of Age (Study 2*) Reporting Systemic Adverse Reactions and Use of Antipyretic Medications Within 7 Days After Each Vaccination
Dose 1 Dose 2 Dose 3
Trumenba Saline Trumenba Saline Trumenba Saline
Systemic Reaction N=2425 N=798 N=2076 N=706 N=1823 N=624
*
Study 2: National Clinical Trial (NCT) number NCT01352845.
Trumenba was administered at 0, 2, and 6 months. Saline was administered at 0, 2, and 6 months.
Study 2: Fever (≥38°C): N=2415, 2067, and 1814 for Trumenba 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.
§
Mild (1–2 times in 24 hours); moderate (>2 times in 24 hours); severe (requires intravenous hydration).
"Any" is defined as the cumulative frequency of subjects who reported a reaction as "mild", "moderate", or "severe" within 7 days of vaccination.
#
Mild (2–3 loose stools in 24 hours); moderate (4–5 loose stools in 24 hours); severe (6 or more loose stools in 24 hours).
Þ
Mild (does not interfere with activity); moderate (interferes with activity); severe (prevents daily activity).
Fever (≥38°C)
  ≥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
Vomiting§
  Any 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
Diarrhea#
  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
HeadacheÞ
  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
FatigueÞ
  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
ChillsÞ
  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)Þ
  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 painÞ
  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 Trumenba, 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 Trumenba or control, respectively.

Non-serious Adverse Events

Overall in clinical studies in which 15,227 subjects 10 through 25 years of age received Trumenba, 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 Trumenba 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 Trumenba than subjects in the control group were injection site pain, fever, and headache.

6.2 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Trumenba. Because these reactions are reported voluntarily froma population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to product exposure.

Immune System Disorders: Hypersensitivity reactions, including anaphylactic reactions.

Nervous system disorder: Syncope (fainting).

1 INDICATIONS AND USAGE

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

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

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