Pneumococcal Vaccine 13-Valent

Pneumococcal Vaccine 13-Valent
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alonso Alvarado, M.D. [2]

Disclaimer

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Overview

Pneumococcal Vaccine 13-Valent is a vaccine that is FDA approved for the prophylaxis of infecetions caused by S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F in children 6 weeks to 17 years-old and adults 50 years old and older. Common adverse reactions include erythema at injection site, injection site pain, swelling at injection site, tenderness, decrease in appetite, aggravated and new onset arthralgia, difficulty moving arm, aggravated and new onset myalgia, decreased sleep, headache, hypersomnia, irritability, fatigue..

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

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. 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

For intramuscular injection only.

Each 0.5 mL dose is to be injected intramuscularly using a sterile needle attached to the supplied prefilled syringe. The preferred sites for injection are the anterolateral aspect of the thigh in infants and the deltoid muscle of the upper arm in toddlers, children and adults. The vaccine should not be injected in the gluteal area or areas where there may be a major nerve trunk and/or blood vessel.

Vaccination Schedule for Adults 50 years of Age and Older

Prevnar 13 is administered as a single dose.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Pneumococcal Vaccine 13-Valent in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Pneumococcal Vaccine 13-Valent in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

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

For intramuscular injection only.

Each 0.5 mL dose is to be injected intramuscularly using a sterile needle attached to the supplied prefilled syringe. The preferred sites for injection are the anterolateral aspect of the thigh in infants and the deltoid muscle of the upper arm in toddlers, children and adults. The vaccine should not be injected in the gluteal area or areas where there may be a major nerve trunk and/or blood vessel.

Vaccination 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.

This image is provided by the National Library of Medicine.

Vaccination Schedule for Unvaccinated Children 7 Months Through 5 Years of Age

For children 7 months through 5 years of age who have not received Prevnar® or Prevnar 13, the catch-up schedule in Table 2 applies:

This image is provided by the National Library of Medicine.

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 12–15 months). In children 24 months through 5 years of age, lower antibody concentrations were observed for some serotypes, compared to antibody concentrations following 3 doses of Prevnar 13 (given at 2, 4, and 6 months).

Vaccination Schedule for Children Previously Vaccinated With Prevnar Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM197 Protein)

Children 15 months through 5 years of age who are considered completely immunized with Prevnar may receive one dose of Prevnar 13 to elicit immune responses to the six additional serotypes. This catch-up (supplemental) dose of Prevnar 13 should be administered with an interval of at least 8 weeks after the final dose of Prevnar. The immune responses induced by this Prevnar 13 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 12–15 months).

Vaccination Schedule for Children 6 Years Through 17 Years of Age

In children 6 years through 17 years of age, Prevnar 13 is administered as single dose. If Prevnar was previously administered, then at least 8 weeks should elapse before receiving Prevnar 13.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Pneumococcal Vaccine 13-Valent in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Pneumococcal Vaccine 13-Valent in pediatric patients.

Contraindications

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

Warnings

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.

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.

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.

Adverse Reactions

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 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 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) 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.

This image is provided by the National Library of Medicine.

This image is provided by the National Library of Medicine.

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 naïve children 7 months through 5 years of age are shown in Tables 5 and 6.

This image is provided by the National Library of Medicine.

This image is provided by the National Library of Medicine.

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.

This image is provided by the National Library of Medicine.

This image is provided by the National Library of Medicine.

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.

This image is provided by the National Library of Medicine.

This image is provided by the National Library of Medicine.

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).

This image is provided by the National Library of Medicine.

This image is provided by the National Library of Medicine.

This image is provided by the National Library of Medicine.

This image is provided by the National Library of Medicine.

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

Postmarketing Experience

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.

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.

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 (14.3) and Adverse Reactions (6.2)]. 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.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): B A developmental and reproductive toxicity study has been performed in female rabbits at a dose approximately 20 times the human dose (on mg/kg basis) and revealed no evidence of impaired female fertility or harm to the fetus due to Prevnar 13. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this vaccine should be used during pregnancy only if clearly needed.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Pneumococcal Vaccine 13-Valent in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Pneumococcal Vaccine 13-Valent during labor and delivery.

Nursing Mothers

It is not known whether this vaccine is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Prevnar 13 is administered to a nursing woman.

Pediatric Use

Safety and effectiveness of Prevnar 13 in children below the age of 6 weeks have not been established.

Geriatic Use

• Of the total number of Prevnar 13 recipients (N=5,667), 3,051/5,667 or 53.8% were 65 years and older and 1,266/5,667 or 22.3% were 75 years and older.
• Antibody responses to Prevnar 13 were lower in persons ≥ 65 years of age compared to antibody responses in persons 50 through 59 years of age.
• No overall differences in safety outcomes were observed in persons aged ≥ 65 years as compared to persons 50 through 59 years of age.

Gender

There is no FDA guidance on the use of Pneumococcal Vaccine 13-Valent with respect to specific gender populations.

Race

There is no FDA guidance on the use of Pneumococcal Vaccine 13-Valent with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Pneumococcal Vaccine 13-Valent in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Pneumococcal Vaccine 13-Valent in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Pneumococcal Vaccine 13-Valent in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Pneumococcal Vaccine 13-Valent in patients who are immunocompromised.

High Risk Populations

Individuals with the diseases or conditions listed below are at increased risk of pneumococcal disease. Immunogenicity and safety data in these populations are limited.

Infants Born Prematurely

Immune responses elicited by Prevnar 13 administered on a US schedule to preterm infants have not been studied. When preterm infants (< 37 weeks gestational age, N=100) were administered 4 doses of Prevnar 13 on a non-US schedule, the serotype-specific IgG antibody responses after the third and fourth dose were lower compared to responses among term infants (≥ 37 weeks gestational age, N=100) for some serotypes; the effectiveness of Prevnar 13 in preterm infants cannot be established from this study.

Children with Sickle Cell Disease

In an open-label, single-arm, descriptive study, 2 doses of Prevnar 13 were administered 6 months apart to children ≥ 6 to < 18 years of age with sickle cell disease who previously received PPSV23 at least 6 months prior to enrollment. Children with a prior history of pneumococcal conjugate vaccination were excluded. For all vaccine serotypes, anti-pneumococcal opsonophagocytic activity (OPA) geometric mean antibody titers (GMTs) were higher after the first dose compared to pre-vaccination (N=95–131); OPA GMTs following the first and second dose were comparable. The effectiveness of Prevnar 13 in this specific population has not been established.

Adults with HIV Infection

In an open-label, single-arm, descriptive study, 3 doses of Prevnar 13 were administered 6 months apart to HIV-infected adults ≥ 50 years of age (median age 55 years), with CD4 counts ≥ 200 cells/µL and serum HIV RNA titer < 50,000 copies/mL. All subjects had been vaccinated previously with PPSV23 at least 6 months prior to enrollment. For all vaccine serotypes anti-pneumococcal OPA GMTs were higher after the first dose compared to pre-vaccination (N=94–108); OPA GMTs following the first, second and third dose were generally comparable. The effectiveness of Prevnar 13 in this specific population has not been established.

Administration and Monitoring

Administration

(Oral/Intravenous/etc)

Monitoring

Condition 1

(Description regarding monitoring, from Warnings section)

Condition 2

(Description regarding monitoring, from Warnings section)

Condition 3

(Description regarding monitoring, from Warnings section)

IV Compatibility

Solution

Compatible

• Solution 1
• Solution 2
• Solution 3

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Pharmacology

Pneumococcal polysaccharide vaccine
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ATC code	J07AL02
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Legal status	[[Prescription drug|Template:Unicode-only]](US)
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Mechanism of Action

Prevnar 13, comprised of pneumococcal polysaccharides conjugated to a carrier protein (CRM197), elicits a T-cell dependent immune response. Protein carrier-specific T-cells provide the signals needed for maturation of the B-cell response.

Nonclinical and clinical data support opsonophagocytic activity, as measured by opsonophagocytic activity (OPA) antibody assay, as a contributor to protection against pneumococcal disease. The OPA antibody assay provides an in vitro measurement of the ability of serum antibodies to eliminate pneumococci by promoting complement-mediated phagocytosis and is believed to reflect relevant in vivo mechanisms of protection against pneumococcal disease. OPA antibody titers are expressed as the reciprocal of the highest serum dilution that reduces survival of the pneumococci by at least 50%.

In infants that have received Prevnar 13, opsonophagocytic activity correlates well with serotype specific anti-capsular polysaccharide IgG levels as measured by ELISA. A serum anti-capsular polysaccharide antibody concentration of 0.35 µg/mL as measured by ELISA one month after the third dose as a single antibody reference concentration was used to estimate the effectiveness of Prevnar 13 against invasive pneumococcal disease (IPD) in infants and children. The assay used for this determination is a standardized ELISA involving pre-absorption of the test sera with pneumococcal C-polysaccharide and serotype 22F polysaccharide to reduce non-specific background reactivity. The single antibody reference value was based on pooled efficacy estimates from three placebo-controlled IPD efficacy trials with either Prevnar or the investigational 9-valent CRM197 conjugate pneumococcal polysaccharide vaccine. This reference concentration is only applicable on a population basis and cannot be used to predict protection against IPD on an individual basis. Functional antibodies elicited by the vaccine (as measured by a dribble opsonophagocytic activity [dOPA] antibody assay) were also evaluated in infants.

In adults, an antipolysaccharide binding antibody IgG level to predict protection against invasive pneumococcal disease or non-bacteremic pneumonia has not been defined. Noninferiority trials for Prevnar 13 were designed to show that functional OPA antibody responses (as measured by a microcolony OPA [mcOPA] antibody assay) for the Prevnar 13 serotypes are non-inferior and for some serotypes superior to the common serotypes in the currently licensed pneumococcal polysaccharide vaccine (PPSV23). OPA antibody titers measured in the mcOPA antibody assay cannot be compared directly to titers measured in the dOPA antibody assay.

Structure

Prevnar 13, Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM197 Protein) is a sterile suspension of saccharides of the capsular antigens of Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F, individually linked to non-toxic diphtheria CRM197 protein. Each serotype is grown in soy peptone broth. The individual polysaccharides are purified through centrifugation, precipitation, ultrafiltration, and column chromatography. The polysaccharides are chemically activated to make saccharides, which are directly conjugated by reductive amination to the protein carrier CRM197, to form the glycoconjugate. CRM197 is a nontoxic variant of diphtheria toxin isolated from cultures of Corynebacterium diphtheriae strain C7 (β197) grown in a casamino acids and yeast extract-based medium. CRM197 is purified through ultrafiltration, ammonium sulfate precipitation, and ion-exchange chromatography. The individual glycoconjugates are purified by ultrafiltration and column chromatography and analyzed for saccharide to protein ratios, molecular size, free saccharide, and free protein.

The individual glycoconjugates are compounded to formulate Prevnar 13. Potency of the formulated vaccine is determined by quantification of each of the saccharide antigens and by the saccharide to protein ratios in the individual glycoconjugates. Each 0.5 mL dose of the vaccine is formulated to contain approximately 2.2 µg of each of Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F saccharides, 4.4 µg of 6B saccharides, 34 µg CRM197 carrier protein, 100 µg polysorbate 80, 295 µg succinate buffer and 125 µg aluminum as aluminum phosphate adjuvant.

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

Pharmacodynamics

There is limited information regarding Pneumococcal Vaccine 13-Valent Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Pneumococcal Vaccine 13-Valent Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Pneumococcal Vaccine 13-Valent Nonclinical Toxicology in the drug label.

Clinical Studies

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Storage

There is limited information regarding Pneumococcal Vaccine 13-Valent Storage in the drug label.

Images

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Precautions with Alcohol

Alcohol-Pneumococcal Vaccine 13-Valent interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Pneumococcal Vaccine 13-Valent Brand Names in the drug label.

Look-Alike Drug Names

• (Paired Confused Name 1a) — (Paired Confused Name 1b)
• (Paired Confused Name 2a) — (Paired Confused Name 2b)
• (Paired Confused Name 3a) — (Paired Confused Name 3b)

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References

The contents of this FDA label are provided by the National Library of Medicine.