1.1 Indications and Use

PNEUMOVAX® 23 is a vaccine indicated for active immunization for the prevention of pneumococcal disease caused by the 23 serotypes contained in the vaccine (1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, and 33F). PNEUMOVAX 23 is approved for use in persons 50 years of age or older and persons aged ≥2 years who are at increased risk for pneumococcal disease.

1.2 Limitations of Use

PNEUMOVAX 23 will not prevent disease caused by capsular types of pneumococcus other than those contained in the vaccine.

2.1 Preparation

• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. If either of these two conditions exists, the vaccine should not be administered.
• Do not mix PNEUMOVAX 23 with other vaccines in the same syringe or vial.
• Use a separate sterile syringe and needle for each individual patient to prevent transmission of infectious agents from one person to another.
  Single-Dose Vial
  Withdraw 0.5 mL from the vial using a sterile needle and syringe free of preservatives, antiseptics, and detergents.
  Single-Dose, Prefilled Syringe
  The package does not contain a needle. Attach a sterile needle to the prefilled syringe by twisting in a clockwise direction until the needle fits securely on the syringe.

2.2 Administration

Administer PNEUMOVAX 23 intramuscularly or subcutaneously into the deltoid muscle or lateral mid-thigh. Do not inject intravascularly or intradermally.

2.3 Revaccination

The Advisory Committee on Immunization Practices (ACIP) has recommendations for revaccination against pneumococcal disease for persons at high risk who were previously vaccinated with PNEUMOVAX 23. Routine revaccination of immunocompetent persons previously vaccinated with a 23-valent vaccine, is not recommended.

4.1 Hypersensitivity

Do not administer PNEUMOVAX 23 to individuals with a history of anaphylactic/anaphylactoid or severe allergic reaction to any component of the vaccine. [See Description (11).]

5.1 Persons with Moderate or Severe Acute Illness

Defer vaccination with PNEUMOVAX 23 in persons with moderate or severe acute illness.

5.2 Persons with Severely Compromised Cardiovascular or Pulmonary Function

Caution and appropriate care should be exercised in administering PNEUMOVAX 23 to individuals with severely compromised cardiovascular and/or pulmonary function in whom a systemic reaction would pose a significant risk.

5.3 Use of Antibiotic Prophylaxis

This vaccine does not replace the need for penicillin (or other antibiotic) prophylaxis against pneumococcal infection. In patients who require penicillin (or other antibiotic) prophylaxis against pneumococcal infection, such prophylaxis should not be discontinued after vaccination with PNEUMOVAX 23.

5.4 Persons with Altered Immunocompetence

Persons who are immunocompromised, including persons receiving immunosuppressive therapy, may have a diminished immune response to PNEUMOVAX 23. [See Use in Specific Populations (8.6).]

5.5 Persons with Chronic Cerebrospinal Fluid Leakage

PNEUMOVAX 23 may not be effective in preventing pneumococcal meningitis in patients who have chronic cerebrospinal fluid (CSF) leakage resulting from congenital lesions, skull fractures, or neurosurgical procedures.

6.1 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.

In a randomized, double-blind, placebo-controlled crossover clinical trial, subjects were enrolled in four different cohorts defined by age (50-64 years of age and ≥65 years of age) and vaccination status (no pneumococcal vaccination or receipt of a pneumococcal polysaccharide vaccine 3-5 years prior to the study). Subjects in each cohort were randomized to receive intramuscular injections of PNEUMOVAX 23 followed by placebo (saline containing 0.25% phenol), or placebo followed by PNEUMOVAX 23, at 30-day (±7 days) intervals. The safety of an initial vaccination (first dose) was compared to revaccination (second dose) with PNEUMOVAX 23 for 14 days following each vaccination.

All 1008 subjects (average age, 67 years; 49% male and 51% female; 91% Caucasian, 4.7% African-American, 3.5% Hispanic, and 0.8% Other) received placebo injections.

Initial vaccination was evaluated in a total of 444 subjects (average age 65 years; 32% male and 68% female; 93% Caucasian, 3.2% African-American, 3.4% Hispanic, and 1.1% Other).

Revaccination was evaluated in 564 subjects (average age 69 years; 53% male and 47% female; 90% Caucasian, 3.5% Hispanic, 6.0% African-American, and 0.5% Other).

6.2 Post-Marketing Experience

The following list of adverse reactions includes those identified during post approval use of PNEUMOVAX 23. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or their causal relationship to product exposure.

General disorders and administration site conditions
  Cellulitis
  Malaise
  Fever (>102°F)
  Warmth at the injection site
  Decreased limb mobility
  Peripheral edema in the injected extremity

Digestive System
  Nausea
  Vomiting

Hematologic/Lymphatic
  Lymphadenitis
  Lymphadenopathy
  Thrombocytopenia in patients with stabilized idiopathic thrombocytopenic purpura
  Hemolytic anemia in patients who have had other hematologic disorders
  Leukocytosis

Hypersensitivity reactions including
  Anaphylactoid reactions
  Serum Sickness
  Angioneurotic edema

Musculoskeletal System
  Arthralgia
  Arthritis

Nervous System
  Paresthesia
  Radiculoneuropathy
  Guillain-Barré syndrome
  Febrile convulsion

Skin
  Rash
  Urticaria
  Cellulitis-like reactions
  Erythema multiforme

Investigations
  Increased serum C-reactive protein

7.1 Concomitant Administration with Other Vaccines

In a randomized clinical study, a reduced immune response to ZOSTAVAX® as measured by gpELISA was observed in individuals who received concurrent administration of PNEUMOVAX 23 and ZOSTAVAX compared with individuals who received these vaccines 4 weeks apart. Consider administration of the two vaccines separated by at least 4 weeks. [See Clinical Studies (14.3).]

Limited safety and immunogenicity data from clinical trials are available on the concurrent administration of PNEUMOVAX 23 and vaccines other than ZOSTAVAX.

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

PNEUMOVAX 23 is not approved for use in children less than 2 years of age. Children in this age group do not develop an effective immune response to the capsular types contained in this polysaccharide vaccine.

The ACIP has recommendations for use of PNEUMOVAX 23 in children 2 years of age or older, who have previously received pneumococcal vaccines, and who are at increased risk for pneumococcal disease.

8.5 Geriatric Use

In one clinical trial of PNEUMOVAX 23, conducted post-licensure, a total of 629 subjects who were aged ≥65 years and 201 subjects who were aged ≥75 years were enrolled.

In this trial, the safety of PNEUMOVAX 23 in adults 65 years of age and older (N=629) was compared to the safety of PNEUMOVAX 23 in adults 50 to 64 years of age (N=379). The subjects in this study had underlying chronic illness but were in stable condition; at least 1 medical condition at enrollment was reported by 86.3% of subjects who were 50 to 64 years old, and by 96.7% of subjects who were 65 to 91 years old. The rate of vaccine-related systemic adverse experiences was higher following revaccination (33.1%) than following primary vaccination (21.7%) in subjects ≥65 years of age, and was similar following revaccination (37.5%) and primary vaccination (35.5%) in subjects 50 to 64 years of age.

Since elderly individuals may not tolerate medical interventions as well as younger individuals, a higher frequency and/or a greater severity of reactions in some older individuals cannot be ruled out.

Post-marketing reports have been received in which some elderly individuals had severe adverse experiences and a complicated clinical course following vaccination. Some individuals with underlying medical conditions of varying severity experienced local reactions and fever associated with clinical deterioration requiring hospital care.

8.6 Immunocompromised Individuals

Persons who are immunocompromised, including persons receiving immunosuppressive therapy, may have a diminished immune response to PNEUMOVAX 23.

12.1 Mechanism of Action

PNEUMOVAX 23 induces type-specific antibodies that enhance opsonization, phagocytosis, and killing of pneumococci by leukocytes and other phagocytic cells. The levels of antibodies that correlate with protection against pneumococcal disease have not been clearly defined.

14.1 Effectiveness

The protective efficacy of pneumococcal vaccines containing six (types 1, 2, 4, 8, 12F, and 25) or twelve (types 1, 2, 3, 4, 6A, 8, 9N, 12F, 25, 7F, 18C, and 46) capsular polysaccharides was investigated in two controlled studies in South Africa in male novice gold miners ranging in age from 16 to 58 years, in whom there was a high attack rate for pneumococcal pneumonia and bacteremia. In both studies, participants in the control groups received either meningococcal polysaccharide serogroup A vaccine or saline placebo. In both studies, attack rates for vaccine type pneumococcal pneumonia were observed for the period from 2 weeks through about 1 year after vaccination. Protective efficacy was 76% and 92%, respectively, for the 6- and 12-valent vaccines, for the capsular types represented.

Three similar studies in South African young adult male novice gold miners were carried out by Dr. R. Austrian and associates using similar pneumococcal vaccines prepared for the National Institute of Allergy and Infectious Diseases, with pneumococcal vaccines containing a 6-valent formulation (types 1, 3, 4, 7, 8, and 12) or a 13-valent formulation (types 1, 2, 3, 4, 6, 7, 8, 9, 12, 14, 18, 19, and 25) capsular polysaccharides. The reduction in pneumococcal pneumonia caused by the capsular types contained in the vaccines was 79%. Reduction in type-specific pneumococcal bacteremia was 82%.

A prospective study in France found a pneumococcal vaccine containing fourteen (types 1, 2, 3, 4, 6A, 7F, 8, 9N, 12F, 14, 18C, 19F, 23F, and 25) capsular polysaccharides to be 77% (95%CI: 51% to 89%) effective in reducing the incidence of pneumonia among male and female nursing home residents with a mean age of 74 (standard deviation of 4 years).

In a study using a pneumococcal vaccine containing eight (types 1, 3, 6, 7, 14, 18, 19, and 23) capsular polysaccharides, vaccinated children and young adults aged 2 to 25 years who had sickle cell disease, congenital asplenia, or undergone a splenectomy experienced significantly less bacteremic pneumococcal disease than patients who were not vaccinated.

In the United States, one post-licensure randomized controlled trial, in the elderly or patients with chronic medical conditions who received a 14-valent pneumococcal polysaccharide vaccine (types 1, 2, 3, 4, 6A, 8, 9N, 12F, 14, 19F, 23F, 25, 7F, and 18C), did not support the efficacy of the vaccine for nonbacteremic pneumonia.

A retrospective cohort analysis study based on the U.S. Centers for Disease Control and Prevention (CDC) pneumococcal surveillance system, showed 57% (95%CI: 45% to 66%) overall protective effectiveness against invasive infections caused by serotypes included in PNEUMOVAX 23 in persons ≥6 years of age, 65 to 84% effectiveness among specific patient groups (e.g., persons with diabetes mellitus, coronary vascular disease, congestive heart failure, chronic pulmonary disease, and anatomic asplenia) and 75% (95%CI: 57% to 85%) effectiveness in immunocompetent persons aged ≥65 years of age. Vaccine effectiveness could not be confirmed for certain groups of immunocompromised patients.

14.2 Immunogenicity

The levels of antibodies that correlate with protection against pneumococcal disease have not been clearly defined.

Antibody responses to most pneumococcal capsular types are generally low or inconsistent in children less than 2 years of age.

14.3 Concomitant Administration with Other Vaccines

In a double-blind, controlled clinical trial, 473 adults, 60 years of age or older, were randomized to receive ZOSTAVAX and PNEUMOVAX 23 concomitantly (N=237), or PNEUMOVAX 23 alone followed 4 weeks later by ZOSTAVAX alone (N=236). At four weeks postvaccination, the varicella-zoster virus (VZV) antibody levels following concomitant use were significantly lower than the VZV antibody levels following nonconcomitant administration (GMTs of 338 vs. 484 gpELISA units/mL, respectively; GMT ratio = 0.70 (95% CI: [0.61, 0.80]).

Limited safety and immunogenicity data from clinical trials are available on the concurrent administration of PNEUMOVAX 23 and vaccines other than ZOSTAVAX.