Recommended Topic Related To:

Prevnar 13

"During the past several months, we at CDC have been working hard to take steps to increase HPV vaccination coverage among 11-12 year olds, including actively communicating with clinicians and parents about the benefits and safety of this cance"...

Prevnar 13

Side Effects
Interactions

SIDE EFFECTS

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. As with any vaccine, there is the possibility that broad use of Prevnar 13 could reveal adverse reactions not observed in clinical trials.

Clinical Trials Experience With Prevnar 13 In Children 6Weeks 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) 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 events 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 bleed approximately 1 month after the infant series; 2) 3.6% and 2.7% from the bleed after the infant series to the toddler dose; 3) 0.9% and 0.8% from the toddler dose to the bleed 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). 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 Agea

Graded Local Reaction Dose 1 Dose 2 Dose 3 Dose 4
Prevnar 13
(Nb=1375- 1612) %
Prevnar
(Nb=516- 606) %
Prevnar 13
(Nb=1069- 1331) %
Prevnar
(Nb=405- 510) %
Prevnar 13
(Nb=998- 1206) %
Prevnar
(Nb=348- 446) %
Prevnar 13
(Nb=874- 1060) %
Prevnar
(Nb=283- 379) %
Rednessc
  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 13.4d
  Severe 0 0 0 0 0 0 0 0
Swellingc
  Any 20.1 20.7 25.2 22.5 26.8 28.4 31.6 36.0d
  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 11.2d
  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
a Data are from three primary US safety studies (the US phase II 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.
b Number of subjects reporting Yes for at least 1 day or No for all days.
c 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).
d Statistically significant difference p < 0.05. No adjustments for multiplicity.

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 a,b

Graded Systemic Events Dose 1 Dose 2 Dose 3 Dose 4
Prevnar 13
(Na=1360 -1707) %
Prevnar
(Na=497- 640) %
Prevnar 13
(Na=1084- 1469) %
Prevnar
(Na=409- 555) %
Prevnar 13
(Na=997- 1361) %
Prevnar
(Na=354- 521) %
Prevnar 13
(Na=850- 1227) %
Prevnar
(Na=278- 436) %
Feverc
  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
a Number of subjects reporting Yes for at least 1 day or No for all days.
b Data are from three primary US safety studies (the US phase II 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.
c Fever gradings: Mild ( ≥ 38oC but ≤ 39oC), Moderate ( > 39oC but ≤ 40oC), and Severe ( > 40oC). 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.

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 study 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 na´ve 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 Vaccinationa

Graded Local Reaction 7 through 11 months 12 through 23 months 24 months through 5 years
Dose 1
Nb=86 %
Dose 2
Nb=86-87 %
Dose 3
Nb=78-82 %
Dose 1
Nb=108-110 %
Dose 2
Nb=98-106 %
Dose 1
Nb=147-149 %
Rednessc
  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
Swellingc
  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
a Study conducted in Poland (NCT00452452) Study 4.
b Number of subjects reporting Yes for at least 1 day or No for all days.
c 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).

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 Vaccinationa

Systemic Reaction 7 through 11 months 12 through 23 months 24 months through 5 years
Dose 1
Nb=86-87 %
Dose 2
Nb=86-87 %
Dose 3
Nb=78-81 %
Dose 1
Nb=108 %
Dose 2
Nb=98-100 %
Dose 1
Nb=147-148 %
Feverc
  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 Study conducted in Poland (NCT00452452) Study 4.
b Number of subjects reporting Yes for at least 1 day or No for all days.
c 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.

A US study (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 8.12

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 Vaccinationa

Graded Local Reaction 15 months through 23 monthsb 24 months through 59 monthsc
1 dose Prevnar 13 3 prior Prevnar doses
Nd=67-72 %
1 dose Prevnar 13 4 prior Prevnar doses
Nd=154-184 %
1 dose Prevnar 13 3 or 4 prior Prevnar doses
Nd=209-238 %
Rednesse
  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
Swellinge
  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
a Study conducted in US NCT00761631 (Study 5).
b Dose 2 data not shown.
c 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.
d Number of subjects reporting Yes for at least 1 day or No for all days.
e 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).

Table 8: Percentage of Subjects 15 Months Through 59 Months of Age, Previously Vaccinated With 3 or 4 Prio Infant Prevnar Doses, Reporting Solicited Systemic Adverse Reactions Within 7 Days After One Supplementa Prevnar 13 Vaccinationa

Systemic Reaction 15 through 23 monthsb 24 months through 59 monthsc
1 dose Prevnar 13 3 prior Prevnar doses
Nd=66-75 %
1 dose Prevnar 13 4 prior Prevnar doses
Nd=154-189 %
1 dose Prevnar 13 3 or 4 prior Prevnar doses
Nd=209-236 %
Fevere  
  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
a Study conducted in US NCT00761631 (Study 5).
b Dose 2 data not shown.
c 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.
dNumber of subjects reporting Yes for at least 1 day or No for all days.
e 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.

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

In a US study (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 10.14

Table 9: Percentage of Subjects 5 Through 17 Years of Age, Reporting Solicited Local Reactions Within 7 Days After Prevnar 13 Vaccinationa

Local Reaction Vaccine Group (as Administered)
Prevnar 13
(5 Through 9 Years)
Prevnar 13
(10 Through 17 Years)
Nb nc % Nb nc %
Redness
  Any 233 100 42.9 232 70 30.2
  Mildd 226 63 27.9 226 48 21.2
  Moderated 218 48 22.0 221 31 14.0
  Severed 212 7 3.3 213 4 1.9
Swelling
  Any 226 85 37.6 233 86 36.9
  Mildd 220 48 21.8 221 50 22.6
  Moderated 219 48 21.9 226 48 21.2
  Severed 211 7 3.3 214 4 1.9
Tenderness
  Any 265 230 86.8 283 252 89.0
  Significante 221 43 19.5 242 106 43.8
a Study conducted in US NCT00761631 (Study 5).
bN = number of subjects reporting Yes for at least 1 day or No for all days.
c n = Number of subjects reporting the specific characteristic.
dMild, 0.5 – 2.0 cm; moderate, 2.5 – 7.0 cm; severe, > 7.0 cm.
e Significant = present and interfered with limb movement.

Table 10: Percentage of Subjects 5 Through 17 Years of Age, Reporting Solicited Systemic Adverse Reactions Within 7 Days After Prevnar 13 Vaccinationa

Systemic Event Vaccine Group (as Administered)
Prevnar 13
(5 Through 9 Years)
Prevnar 13
(10 Through 17 Years)
Nb nc % Nb nc %
Any fever ≥ 38°C 214 13 6.1 214 12 5.6
Mildd 212 9 4.2 214 11 5.1
Moderated 212 5 2.4 212 1 0.5
Severed 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
a Study conducted in US NCT00761631 (Study 5).
b N = number of subjects reporting Yes for at least 1 day or No for all days.
c n = Number of subjects reporting the event.
d 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.

Clinical Trials Experience With Prevnar 13 In Adults ≥ 50 Years Of Age

The safety of Prevnar 13 was assessed in 6 clinical studies conducted in the US and Europe which included 6,198 adults (5,667 received Prevnar 13) ranging in age from 50 through 95 years.

The 5,667 Prevnar 13 recipients included 2,616 adults who were aged 50 through 64 years and 3,051 adults aged 65 years and older. Of the 5,667 Prevnar 13 recipients, 3,751 adults had not previously received PPSV23 (“PPSV23 unvaccinated”) and 1,916 adults were previously vaccinated (“PPSV23 previously vaccinated”) with PPSV23 at least 3 years prior to enrollment.

Two of the 6 clinical studies supporting safety were randomized comparing the safety and immunogenicity of Prevnar 13 with PPSV23 as a single dose in PPSV23 unvaccinated adults aged 50 through 64 years (Study 6) and in adults ≥ 70 years PPSV23 previously vaccinated ( ≥ 5 years prior to enrollment) (Study 7). One study was randomized comparing the safety and immunogenicity of a single dose of Prevnar 13 compared to a single dose of PPSV23 in PPSV23 unvaccinated adults aged 60 through 64 years (Study 8). One clinical safety study (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 US (Study 10) in adults age 50 through 59 years and the other in Europe (Study 11) in adults aged ≥ 65 years, evaluated the concomitant administration of Prevnar 13 with trivalent inactivated influenza vaccine (Fluarix®, A/H1N1, A/H3N2, and B, Fall 2007/Spring 2008: TIV) in these two age groups in PPSV23 unvaccinated adults.

The total safety population in the 6 studies was 6,198. In 5 of the 6 studies, more females than males were enrolled (50.2% - 61.8%). Across the 6 studies the racial distribution included: > 91% White; 0.2%-7.5% 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 6; in the 5 other studies 0.6%-4.8% were Hispanic or Latino.

In five studies, persons 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.

Persons 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 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.

Serious Adverse Events in Adult Clinical Studies

Across the 6 studies, serious adverse events within 1 month of vaccination were reported after an initial study dose in 0.2%-1.4% of 5055 persons vaccinated with Prevnar 13 and in 0.4%-1.7% of 1124 persons 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 1.2%-5.8% of persons vaccinated during the studies with Prevnar 13 and in 2.4%-5.5% of persons 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 TIV 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).

Solicited Adverse Reactions in Adult Clinical Studies

The incidence and severity of solicited adverse reactions that occurred within 14 days following each dose of Prevnar 13 or PPSV23 administered to adults in 4 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 Soicited Local Reactions Within 14 Days After Vaccination With Prevnar 13 or PPSV 23 in PPSV23 Unvaccinated Adultsa

Age in Years Study 6 Study 8
50-59 60-64 60-64
Local Reaction Prevnar 13b
Nc=152-322
%
Prevnar 13
Nc=193-331
%
PPSV23
Nc=190-301
%
Prevnar 13
Nc=270-370
%
PPSV23
Nc=134-175
%
Rednessd
Any 15.8 20.2 14.2 12.2 11.2
Mild 15.2 15.9 11.2 8.3 9.7
Moderate 5.0 8.6 4.9 6.4 3.9
Severe 0.7 1.7 0.0 1.2 0.8
Swellingd
Any 21.7 19.3 13.1 10.0 10.4
Mild 20.6 15.6 10.1 8.2 6.1
Moderate 4.3 8.2 4.4 3.8 7.6
Severe 0.0 0.6 1.1 0.0 0.0
Paine
Any 88.8 80.1 73.4 69.2g 58.3
Mild 85.9 78.6g 68.6 66.1g 52.9
Moderate 39.5 23.3 30.0 20.1 21.7
Severe 3.6 1.7 8.6g 2.3 0.8
Limitation of arm movementf
Any 40.7 28.5 30.8 23.5 28.2
Mild 38.6 26.9 29.3 22.7 26.1
Moderate 2.9 2.2 3.8 1.2 3.1
Severe 2.9 1.7 4.3 1.1 2.3
a Studies conducted in US NCT00427895 (Study 6) and NCT00574548 (Study 8).
b Open label administration of Prevnar 13.
c Number of subjects with known values.
d 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.
e Mild = awareness of symptom but easily tolerated, Moderate = discomfort enough to cause interference with usual activity, Severe = incapacitating with inability to do usual activity.
f 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.
g Statistically significant difference p < 0.05. No adjustments for multiplicity.

Table 12 - Percentage of Subjects With Solicited Local Reactions Within 14 Days After Vaccination With Prevnar 13 or PPSV23 in PPSV23 Previously Vaccinated Adultsa

Age in Years Study 7 Study 9
≥ 70 ≥ 68
Local Reaction Prevnar 13
Nc=306-362
%
PPSV23
Nc=324-383
%
Prevnar 13b
Nc=664-777
%
Rednessd
  Any 10.8 22.2g 14.3
  Mild 9.5 13.5 12.6
  Moderate 4.7 11.5s 6.5
  Severe 1.7 4.8g 1.1
Swellingd
  Any 10.4 23.1s 12.8
  Mild 8.9 14.0s 10.9
  Moderate 4.0 13.6s 5.5
  Severe 0.0 4.8s 0.6
Paine
  Any 51.7 58.5 51.0
  Mild 50.1 54.1 49.4
  Moderate 7.5 23.6s 9.0
  Severe 1.3 2.3 0.2
Limitation of armmovement f
  Any 10.5 27.6s 16.2
  Mild 10.3 25.2s 14.8
  Moderate 0.3 2.6s 1.6
  Severe 0.7 3.0s 1.6
a Study conducted in US and Sweden NCT00546572 (Study 7). Study conducted in US, Sweden and Germany NCT00500266 (Study 9).
b Open label administration of Prevnar 13.
c Number of subjects with known values.
d 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.
e Mild = awareness of symptom but easily tolerated, Moderate = discomfort enough to cause interference with usual activity, Severe = incapacitating with inability to do usual activity.
f 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.
g Statistically significant difference p < 0.05. No adjustments for multiplicity.

Table 13 : Percentage of Subjects With Solicited Systemic Events Within 14 Days After Vaccination With Prevnar 13 or PPSV23 in PPSV23 Unvaccinated Adultsa

Age in Years Study 6 Study 8
50-59 60-64 60-64
Prevnar 13b
Nc=137-248
%
Prevnar 13
Nc=174-277
%
PPSV23
Nc=176-273
%
Prevnar 13
Nc=261-328
%
PPSV23
Nc=127-173
%
Systemic Event
Fever
   ≥ 38.0°C 1.5 4.0 1.1 4.2 1.6
  38.0°C to 38.4°C 1.5 4.0 1.1 3.8 0.8
  38.4°C to 38.9°C 0.0 0.6 0.0 0.8 0.0
  38.9°C to 40.0°C 0.0 0.0 0.0 0.4 0.8
   > 40.0°C 0.0 0.0 0.0 0.0 0.0
Fatigue 63.3 63.2 61.5 50.5 49.1
Headache 65.9 54.0 54.4 49.7 46.1
Chills 19.6 23.5 24.1 19.9 26.9
Rash 14.2 16.5 13.0 8.6 13.4
Vomiting 6.9 3.9 5.4 3.1 3.1
Decreased appetite 25.3 21.3 21.7 14.7 23.0d
Generalized new muscle pain 61.8 56.2 57.8 46.9 51.5
Generalized aggravated muscle pain 39.9 32.6 37.3 22.0 32.5d
Generalized new joint pain 31.5 24.4 30.1 15.5 23.8d
Generalized aggravated joint pain 25.6 24.9 21.4 14.0 21.1
a Studies conducted in US NCT00427892 (Study 6) and NCT00574548 (Study 8).
b Open label administration of Prevnar 13.
c Number of subjects with known values.
d Statistically significant difference p < 0.05. No adjustments for multiplicity.

Table 14 : Percentage of Subjects With Systemic Events Within 14 Days After Vaccination With Prevnar 13 or PPSV23 in PPSV23 Previously Vaccinated Adultsa

Age in Years Study 7 Study 9
≥ 70 ≥ 68
Prevnar 13
Nc=299-350
%
PPSV23
Nc=303-367
%
Prevnar 13b
Nc=635-733
%
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
  38.4°C to 38.9°C 0.0 0.0 0.0
  38.9°C to 40.0°C 0.0 0.3 0.3
   > 40.0°C 0.0 0.0 0.0
Fatigue 34.0 43.3d 34.4
Headache 23.7 26.0 26.1
Chills 7.9 11.2 7.5
Rash 7.3 16.4d 8.4
Vomiting 1.7 1.3 0.9
Decreased appetite 10.4 11.5 11.2
Generalized new muscle pain 36.8 44.7d 25.3
Generalized aggravated muscle pain 20.6 27.5d 12.3
Generalized new joint pain 12.6 14.9 12.8
Generalized aggravated joint pain 11.6 16.5 9.7
a Study conducted in US and Sweden NCT00546572 (Study 7). Study conducted in US, Sweden and Germany NCT00500266 (Study 9).
b Open label administration of Prevnar 13.
c Number of subjects with known values.
d Statistically significant difference p < 0.05. No adjustments for multiplicity.

Solicited Adverse Reactions in Adult Clinical Studies of Concomitant Administration of Prevnar 13 and TIV (Fluarix)

The safety of concomitant administration of Prevnar 13 with TIV was assessed in 2 studies in PPSV23 unvaccinated adults aged 50 through 59 years (Study 10) and aged ≥ 65 years (Study 11).

Frequencies of local reactions within 14 days postvaccination in adults aged 50 through 59 years and in adults aged ≥ 65 years were similar after Prevnar 13 was administered with TIV compared to Prevnar 13 administered alone, with the exception of mild redness at the injection site, which was increased when Prevnar 13 was administered concomitantly with TIV and mild limitation of arm movement, which was increased when Prevnar 13 was administered alone.

An increase in some solicited systemic reactions within 14 days postvaccination was noted when Prevnar 13 was administered concomitantly with TIV compared with TIV given alone (headache, chills, rash, decreased appetite, muscle and joint pain) or with Prevnar 13 given alone (fatigue, headache, chills, decreased appetite, and joint pain).

Clinical Trials Experience With Prevnar In Infants And Toddlers

The safety experience with Prevnar is relevant to Prevnar 13 because the two vaccines share common components.

Generally, the adverse reactions reported in clinical trials with Prevnar 13 were also reported in clinical trials with Prevnar.

Overall, the safety of Prevnar was evaluated in a total of five clinical studies in the U.S. in which 18,168 infants and children received a total of 58,699 doses of vaccine at 2, 4, 6, and 12-15 months of age.

Adverse events reported in clinical trials with Prevnar that occurred within 3 days of vaccination in infants and toddlers and resulted in emergency room visits or hospitalizations, but were not presented in Section 6.1 as adverse reactions for Prevnar 13 are listed below:

Bronchiolitis, UTI, acute gastroenteritis, asthma, aspiration, breath holding, influenza, inguinal hernia repair, viral syndrome, URI, croup, thrush, wheezing, choking, conjunctivitis, pharyngitis, colic, colitis, congestive heart failure, roseola, sepsis.

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

Post-marketing Experience With Prevnar In Infants And Toddlers

There are no adverse reactions reported for Prevnar through passive post-marketing surveillance that were not already reported for Prevnar 13.

The safety of Prevnar given concomitantly with other vaccines as part of routine care was assessed in a three-year observational study performed at Northern California Kaiser Permanente (NCKP) in which 65,927 children received three doses of Prevnar in the first year of life. Primary safety outcomes analyses included an evaluation of pre-defined adverse events occurring in temporal relationship to immunization. Rates of adverse events occurring within various time periods post-vaccination (e.g., 0-2, 0-7, 0-14, and 0-30 days) were compared to the rates of those events occurring within a control time window (i.e., 31-60 days). Secondary safety outcomes analyses included comparisons to a historical control population of infants (1995-1996, N=40,223) prior to the introduction of Prevnar. In addition, the study included extended follow-up of subjects originally enrolled in the NCKP efficacy trial (N=37,866).

The primary safety outcomes analyses did not demonstrate a consistently elevated risk of healthcare utilization for croup, gastroenteritis, allergic reactions, seizures, wheezing diagnoses, or breath-holding across doses, healthcare settings, or multiple time windows. As in prelicensure trials, fever was associated with Prevnar administration. In analyses of secondary safety outcomes, the adjusted relative risk of hospitalization for reactive airways disease was 1.23 (95% CI: 1.11, 1.35). Potential confounders, such as differences in concomitantly administered vaccines, yearly variation in respiratory infections, or secular trends in reactive airways disease incidence, could not be controlled. Extended follow-up of subjects originally enrolled in the NCKP efficacy trial revealed no increased risk of reactive airways disease among Prevnar recipients. In general, the study results support the previously described safety profile of Prevnar.

Read the Prevnar 13 (pneumococcal 13-valent conjugate vaccine [diphtheria crm197 protein] suspension for intramuscular injection) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

Concomitant Immunizations

In clinical trials with infants and toddlers, Prevnar 13 was administered concomitantly with the following US licensed vaccines: Pediarix [Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Hepatitis B (Recombinant) and Inactivated Poliovirus Vaccine Combined] (DTaP-HBV-IPV) and ActHIB [Haemophilus b Conjugate Vaccine (Tetanus Toxoid Conjugate)] (PRP-T) for the first three doses and with PedvaxHIB [Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate)] (PRP-OMP), M-M-R II [Measles, Mumps, Rubella Virus Vaccine Live] (MMR) and Varivax [Varicella Virus Vaccine Live], or ProQuad [Measles, Mumps, Rubella and Varicella Virus Vaccine Live] (MMRV) and VAQTA [Hepatitis A vaccine, Inactivated] (HepA) for dose 4 [see Clinical Studies and ADVERSE REACTIONS].

In children and adolescents, data are insufficient to assess the concomitant administration of Prevnar 13 with Human Papillomavirus Vaccine (HPV), Meningococcal Conjugate Vaccine (MCV4) and Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine, Adsorbed (Tdap).

In adults, Prevnar 13 was administered concomitantly with US licensed Fluarix (TIV) for the 2007/2008 influenza season [see Clinical Studies and ADVERSE REACTIONS]. There are no data on the concomitant administration of Prevnar 13 with diphtheria toxoid-containing vaccines and other vaccines licensed for use in adults 50 years of age and older.

When Prevnar 13 is administered at the same time as another injectable vaccine(s), the vaccines should always be administered with different syringes and given at different injection sites.

Do not mix Prevnar 13 with other vaccines/products in the same syringe.

Immunosuppressive Therapies

Individuals with impaired immune responsiveness due to the use of immunosuppressive therapy (including irradiation, corticosteroids, antimetabolites, alkylating agents, and cytotoxic agents) may not respond optimally to active immunization.

Last reviewed on RxList: 9/19/2014
This monograph has been modified to include the generic and brand name in many instances.

Side Effects
Interactions
A A A

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


Women's Health

Find out what women really need.