PREVNAR 20 (Pneumococcal 20-valent Conjugate Vaccine [Diphtheria CRM197 Protein])

4.1 Dosing Considerations

• Individuals at higher risk of pneumococcal infection, including patients with sickle cell disease or human immunodeficiency virus (HIV) infection, and those previously vaccinated with one or more doses of the 23-valent pneumococcal polysaccharide vaccine (PPSV23), are recommended to receive at least one dose of PREVNAR 20 (see 7 WARNINGS AND PRECAUTIONS, Immune and 14 CLINICAL TRIALS, PREVNAR 13 Immune Responses in Special Populations).
• In individuals with a hematopoietic stem cell transplant (HSCT), the recommended immunization series with PREVNAR 20 consists of four doses of 0.5 mL. The primary series consists of three doses, with the first dose given 3 to 6 months after HSCT and with an interval of at least 1 month between doses. A booster dose is recommended 6 months after the third dose (see 7 WARNINGS AND PRECAUTIONS, Immune and 14 CLINICAL TRIALS, PREVNAR 13 Immune Responses in Special Populations).
• If the sequential use of PPSV23 is considered appropriate, PREVNAR 20 should be given first.

4.2 Recommended Dose and Dosage Adjustment

Adults 18 years of age and older

PREVNAR 20 is administered intramuscularly as a single 0.5 mL dose.

Pediatric population

The safety and immunogenicity of PREVNAR 20 in individuals younger than 18 years of age have not been established.

4.4 Administration

Do not mix PREVNAR 20 with any other vaccines or products in the same syringe.

Preparation for administration

Step 1. Resuspend drug product Hold the pre-filled syringe horizontally between the thumb and the forefinger and shake vigorously until the contents of the syringe are a homogeneous white suspension. Do not use the vaccine if it cannot be re‑suspended.
Step 2. Visual inspection Parenteral drug products should be inspected visually for large particulate matter and discoloration prior to administration. This product should not be used if large particulate matter or discoloration is found. If the suspension does not appear to be a homogeneous white suspension, repeat Steps 1 and 2.
Step 3. Remove syringe cap Remove the syringe cap from the Luer lock adapter by slowly turning the cap counter‑clockwise while holding the Luer lock adapter.   Note: Care should be taken to ensure that the extended plunger rod is not depressed while removing the syringe cap.
Step 4. Attach a sterile needle Attach a needle appropriate for intramuscular administration to the pre-filled syringe by holding the Luer lock adapter and turning the needle clockwise.

Administration

For intramuscular use only.

Each 0.5 mL dose is to be injected intramuscularly, preferably in the deltoid muscle, with care to avoid injection into or near nerves and blood vessels. The vaccine should not be injected in the gluteal area.

Do not administer PREVNAR 20 intravascularly.

PREVNAR 20 is a homogeneous white suspension for intramuscular injection supplied in a single-dose pre-filled syringe. Each 0.5 mL dose of the vaccine is formulated to contain approximately 2.2 mcg of each of S. pneumoniae serotypes 1, 3, 4, 5, 6A, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F and 33F saccharides, 4.4 mcg of 6B saccharide, 51 mcg CRM₁₉₇ carrier protein, 100 mcg polysorbate 80, 295 mcg succinic acid, 4.4 mg sodium chloride, and 125 mcg aluminum as aluminum phosphate adjuvant.

PREVNAR 20 is supplied in cartons of 1 and 10 single-dose pre-filled syringes, without needles.

The tip cap and plunger stopper of the pre‑filled syringe are not made with natural rubber latex.

To help ensure the traceability of vaccines for patient immunization record-keeping as well as safety monitoring, health professionals should record the time and date of administration, quantity of administered dose (if applicable), anatomical site and route of administration, brand name and generic name of the vaccine, the product lot number and expiry date.

8.1 Adverse Reaction Overview

The safety profile is based on the analysis of three Phase 3 clinical trials (see 14 CLINICAL TRIALS). There were 4,263 adult participants who received PREVNAR 20, which included 3,639 adults that were naïve to pneumococcal vaccines, 253 that had previously received the 23-valent pneumococcal polysaccharide vaccine, (Pneumovax® 23 [PPSV23]) only, 246 that had previously received PREVNAR 13 only, and 125 that had previously received both PPSV23 and PREVNAR 13. The most commonly reported solicited adverse reactions (>10%) were vaccination-site pain/tenderness, muscle pain, fatigue, headache and joint pain. Overall, the serious adverse events (SAEs) reported were consistent with diseases and conditions observed in adults of different age groups, and none were considered to be related to the study vaccine. In all three Phase 3 trials, PREVNAR 20 demonstrated a tolerability and safety profile similar to that of PREVNAR 13.

8.2 Clinical Trial Adverse Reactions

Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials, therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use.

Solicited Adverse Reactions

The frequency of solicited adverse reactions in adults <65 years of age naïve to pneumococcal vaccination and in adults ≥65 years of age by prior pneumococcal vaccination status are shown in Table 2 and Table 3, respectively. Local adverse reactions (redness, swelling, and pain at the injection site) were prompted daily for 10 consecutive days after vaccination. Systemic adverse events (fever, fatigue, headache, muscle pain, and joint pain) were prompted daily for 7 days after vaccination.

In general, the median onset day for local reactions was between Day 1 (day of vaccination) to Day 2.5, and they resolved with a median duration of 1 to 2 days. The median onset day for most systemic events was generally between Day 1 to Day 3.5, and they resolved with a median duration of 1 to 2 days.

Additional Information in Immunocompromised Patients in Studies with PREVNAR 13

Adults 18 years and older with HIV infection who received PREVNAR 13 had similar frequencies of adverse reactions as adults 50 years of age and older who received PREVNAR 13, except that fever and vomiting had a frequency category of Very Common (≥1/10) and nausea had a frequency category of Common (≥1/100 to <1/10).

Adults 18 years and older with a hematopoietic stem cell transplant who received PREVNAR 13 had similar frequencies of adverse reactions as adults 18 years and older who received PREVNAR 13, except that fever and vomiting had a frequency category of Very Common (≥1/10).

8.3 Less Common Clinical Trial Adverse Reactions

Listed below are the less common adverse reactions reported in clinical trials with PREVNAR 20 (Uncommon frequency ≥1/1,000 to < 1/100).

Immune system disorders: Hypersensitivity reaction, including face edema, dyspnea, bronchospasm

Gastrointestinal disorders: Diarrhea, nausea, vomiting

Skin and subcutaneous tissue disorders: Rash, angioedema

General disorders and administration site conditions: Vaccination-site pruritus, lymphadenopathy, vaccination-site urticaria, chills

8.5 Post-Market Adverse Reactions

Post-marketing Experience with PREVNAR 13

The following adverse reactions have been reported since market introduction of PREVNAR 13, and are 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. Although these adverse reactions reported in the post-marketing experience of PREVNAR 13 were not observed in the PREVNAR 20 clinical trials, they are considered possible adverse reactions for PREVNAR 20 as the components of PREVNAR 13 are also contained in PREVNAR 20.

10.1 Mechanism of Action

S. pneumoniae (pneumococcus) is a gram-positive diplococcus that can cause invasive disease including meningitis, sepsis, and pneumonia with bacteremia and non-invasive disease such as pneumonia without bacteremia. Non-bacteremic pneumococcal pneumonia accounts for the majority of pneumococcal disease cases among the adult population. Over 90 different serotypes of pneumococcus have been identified. The serotypes included in PREVNAR 20 were selected based on their relevance in causing global disease and have been associated with higher case fatality rates and mortality, antibiotic resistance, meningitis and outbreaks.

PREVNAR 20 contains 20 pneumococcal capsular polysaccharides all conjugated to a CRM₁₉₇ carrier protein, which modifies the immune response to the polysaccharide from a T cell independent response to a T cell dependent response. The T-cell dependent response leads to both an enhanced antibody response and generation of memory B cells, allowing for an anamnestic (booster) response on re-exposure to bacterial polysaccharide. In the absence of T-cell help, plain polysaccharide (PS) stimulated B-cells predominantly produce IgM antibodies; there is generally no affinity maturation of the antibodies, and no memory B-cells are generated. As vaccines, PSs are associated with poor or absent immunogenicity in infants less than 24 months of age and failure to induce immunological memory at any age.

Vaccination with PREVNAR 20 induces serum antibody production and immunologic memory against the serotypes contained within the vaccine. In adults, the levels of circulating antibodies that correlate with protection against pneumococcal disease have not been clearly defined.