pneumococcal 13-valent conjugate vaccine
Dosage Form: injection, suspension
FULL PRESCRIBING INFORMATION
Indications and Usage for Prevnar 13
Prevnar 13™ is a vaccine approved for use 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.
Prevnar 13 is also indicated for the prevention of otitis media caused by Streptococcus 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.
Prevnar 13 Dosage and Administration
For intramuscular injection only.
Preparation for Administration
Since this product is a suspension containing an adjuvant, shake vigorously immediately prior to use to obtain a homogenous, white suspension in the vaccine container. Do not use the vaccine, if it cannot be resuspended. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration [see Description (11)]. This product should not be used if particulate matter or discoloration is found.
Do not mix Prevnar 13 with other vaccines/products in the same syringe.
Administration Information
Do not inject intravenously, intradermally, or subcutaneously.
Each 0.5 mL dose is to be injected intramuscularly. The preferred sites for injection are the anterolateral aspect of the thigh in infants or the deltoid muscle of the upper arm in toddlers and young children. The vaccine should not be injected in the gluteal area or areas where there may be a major nerve trunk and/or blood vessel.
Vaccine Schedule for Infants and Toddlers
Prevnar 13 is to be administered as a four-dose series at 2, 4, 6, and 12-15 months of age.
Vaccine Schedule for Unvaccinated Children ≥7 Months of Age
For children who are beyond the age of the routine infant schedule and have not received Prevnar or Prevnar 13, the following catch-up schedule applies:
The immune responses induced by this catch-up schedule may result in lower antibody concentrations for some serotypes, compared to antibody concentrations following 4 doses of Prevnar 13 (given at 2, 4, 6, and 12 to 15 months). In children 24 months through 5 years of age, the catch-up schedule may result in lower antibody concentrations for some serotypes, compared to antibody concentrations following 3 doses of Prevnar 13 (given at 2, 4, and 6 months). The clinical relevance of these lower antibody responses is not known.
Prevnar 13 Vaccine Schedule for Children Previously Vaccinated With Prevnar (Streptococcus pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F)
Children who have received one or more doses of Prevnar may complete the 4-dose immunization series with Prevnar 13. Children 15 months through 5 years of age who have received 4 doses of Prevnar may receive one dose of Prevnar 13 to elicit immune responses to the six additional serotypes. This catch-up dose of Prevnar 13 should be administered with an interval of at least 8 weeks after the fourth dose of Prevnar. The immune responses induced by this Prevnar 13 transition schedule may result in lower antibody concentrations for the 6 additional serotypes (types 1, 3, 5, 6A, 7F, and 19A), compared to antibody concentrations following 4 doses of Prevnar 13 (given at 2, 4, 6, and 12 to 15 months). The clinical relevance of these lower antibody responses is not known.
Dosage Forms and Strengths
Prevnar 13 is a suspension for intramuscular injection available in 0.5 mL single-dose pre-filled syringes.
Contraindications
Severe allergic reaction (e.g., anaphylaxis) to any component of Prevnar 13, Prevnar or any diphtheria toxoid-containing vaccine.
Warnings and Precautions
Management of Allergic Reactions or Other Adverse Reactions
Before administration of any dose, all precautions should be taken to prevent allergic or any other adverse reactions. This includes a review of the patient’s immunization history for possible sensitivity to the vaccine or similar vaccines and for previous vaccination-related adverse reactions in order to determine the existence of any contraindication to immunization with Prevnar 13 and to allow an assessment of risks and benefits. Epinephrine and other appropriate agents used for the control of immediate allergic reactions must be immediately available should an acute anaphylactic reaction occur following the administration of the vaccine.
Limitations of Vaccine Effectiveness
Prevnar 13 may not protect all individuals receiving the vaccine. Prevnar 13 will not protect against Streptococcus pneumoniae serotypes that are not in the vaccine or serotypes unrelated to those in the vaccine. It will also not protect against other microorganisms. This vaccine does not treat active infection.
Protection against otitis media is expected to be substantially lower than protection against invasive disease. In addition, because otitis media is caused by many organisms other than the 7 serotypes of Streptococcus pneumoniae included in the indication, protection against all causes of otitis media is expected to be lower than for pneumococcal otitis media caused by these 7 vaccine serotypes [see Clinical Studies (14.2)].
The duration of protection from immunization is not known.
Altered Immunocompetence
Data on the safety and effectiveness of Prevnar 13 when administered to children in specific groups at higher risk for invasive pneumococcal disease (e.g., children with congenital or acquired splenic dysfunction, HIV infection, malignancy, nephrotic syndrome) are not available.
Children in these groups may have reduced antibody response to active immunization due to impaired immune responsiveness. Vaccination in high-risk groups should be considered on an individual basis [see Drug Interactions (7.2)].
The use of pneumococcal conjugate vaccine does not replace the use of 23-valent pneumococcal polysaccharide vaccine (PPV23) in children ≥24 months of age with sickle cell disease, asplenia, HIV infection, chronic illness or who are otherwise immunocompromised.
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.
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. 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
The safety of Prevnar 13 was evaluated in 13 clinical trials in which 4,729 infants and toddlers 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 U.S. evaluated the safety of Prevnar 13 when administered concomitantly with routine U.S. 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 U.S. 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 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 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 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.
There was 1 hypotonic-hyporesponsive episode adverse reaction reported (0.015%).
Solicited Adverse Reactions in the Three U.S. 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 U.S. studies. 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 U.S. infants and toddlers are shown in Tables 3 and 4.
Unsolicited Adverse Reactions in the Three U.S. 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 a catch-up study conducted in Poland, 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.
A U.S. study evaluated the use of Prevnar 13 in children previously immunized with Prevnar. In this open label trial, 284 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 (75.0%), 15.8% were Black or African-American, and 1.6% were Asian; 86.6% of subjects were non-Hispanic and non-Latino and 13.4% were Hispanic or Latino. Overall, 54.0% of subjects were male infants.
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.
Clinical Trials Experience With Prevnar®
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 include:
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
The following adverse reactions have been reported through passive surveillance since market introduction of Prevnar and therefore, are considered adverse reactions for Prevnar 13 as well. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate its frequency or establish a causal relationship to the vaccine.
Administrative site conditions: Injection-site dermatitis, inject
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