Vaccine Information: PREVNAR 13 (Page 3 of 8)

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

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

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

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

Cardiac disorders: Cyanosis

Immune system disorders: Anaphylactic/anaphylactoid reaction including shock

Nervous system disorders: Hypotonia

Skin and subcutaneous tissue disorders: Angioneurotic edema, erythema multiforme

Respiratory: Apnea

Vascular disorders: Pallor

7 DRUG INTERACTIONS

7.1 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 (14.2) and Adverse Reactions (6.1)].

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 inactivated influenza vaccines, trivalent and quadrivalent (Studies 10, 11 and 13)[see Clinical Studies (14.4) 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.

7.2 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.

7.3 Antipyretics

A post-marketing clinical study conducted in Poland using a non-US vaccination schedule (2, 3, 4, and 12 months of age) evaluated the impact of prophylactic oral acetaminophen on antibody responses to Prevnar 13. The data show that 3 doses of acetaminophen (the first dose administered at the time of each vaccination and the subsequent doses at 6 to 8 hour intervals) reduced the antibody response to some serotypes following the third dose of Prevnar 13, compared with responses among infants who received antipyretics only as needed for treatment. Reduced antibody responses were not observed after the fourth dose of Prevnar 13 when acetaminophen was administered prophylactically.

7.4 Prior Vaccination with PPSV23

Prior receipt of PPSV23 within 1 year results in diminished immune responses to Prevnar 13 compared to PPSV23 naïve individuals [see Clinical Studies (14.3)].

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Available data on Prevnar 13 administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy.

A developmental toxicity study has been performed in female rabbits administered Prevnar 13 prior to mating and during gestation. Each dose was approximately 20 times the human dose. This study revealed no evidence of harm to the fetus due to Prevnar 13 (see 8.1 Data).

Data

Animal

In a developmental toxicity study, female rabbits were administered Prevnar 13 by intramuscular injection twice prior to mating (17 days and 3 days prior to mating) and twice during gestation (gestation days 10 and 24), 0.5 mL/rabbit/occasion (each dose approximately 20 times the human dose). No adverse effects on pre-weaning development were observed. There were no vaccine-related fetal malformations or variations.

8.2 Lactation

Risk Summary

Data are not available to assess the effects of Prevnar 13 on the breastfed infant or on milk production/excretion. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Prevnar 13 and any potential adverse effects on the breastfed child from Prevnar 13 or from the underlying maternal condition. For preventive vaccines, the underlying maternal condition is susceptibility to disease prevented by the vaccine.

8.4 Pediatric Use

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

8.5 Geriatric Use

Of the total number of Prevnar 13 recipients aged 50 years and older in clinical studies (N=47,907), 94.5% (45,291 of 47,907 ) were 65 years and older and 30.3 % (14,498 of 47,907) were 75 years and older [see Clinical Studies (14.1) and (14.3)].

8.6 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.

Individuals with Hematopoietic Stem Cell Transplant

In an open-label, single-arm, descriptive study, 4 doses of Prevnar 13 were administered to subjects ≥2 years of age (range 2 to 71 years) who had received an allogeneic hematopoietic stem cell transplant 3 to 6 months prior to enrollment. All subjects had a history of stable engraftment (absolute neutrophil count>1000/µL, platelet count >50,000/µL), and did not have uncontrolled graft versus host disease. The first three doses of Prevnar 13 were administered one month apart, followed by a fourth dose of Prevnar 13 six months after the third dose. Sera were obtained approximately one month after each vaccination. Immune responses (IgG GMCs) after the first dose of Prevnar 13 were numerically higher for all serotypes compared with baseline. In addition, after each subsequent dose of Prevnar 13, IgG GMCs for all serotypes were numerically higher than responses after the previous dose. A post hoc analysis of the immune responses as measured by OPA antibody assay showed the pattern of functional antibody responses to be consistent with IgG responses for each serotype. The effectiveness of Prevnar 13 in this specific population has not been established.

Individuals 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 ≥18 years of age (median age 48 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 numerically higher after the first dose compared to pre-vaccination (N=227–253); 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.

In an open-label, single-arm, descriptive study, 3 doses of Prevnar 13 were administered 1 month apart to HIV-infected subjects ≥6 years of age with CD4 counts ≥200 cells/µL, and serum HIV RNA titer <50,000 copies/mL. Subjects had not previously been vaccinated with a pneumococcal vaccine. For all vaccine serotypes anti-pneumococcal OPA GMTs were numerically higher after the first dose compared to pre-vaccination (N=197–257); 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.

11 DESCRIPTION

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 or in a chemically-defined 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.

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