FDA Label for Pneumovax 23

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 Dosage And Administration

For intramuscular or subcutaneous injection only.

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.

Other

Single-Dose Vial

Administer a single 0.5-mL dose of PNEUMOVAX 23 using a sterile needle and syringe. Discard vial after use.

Single-Dose, Prefilled Syringe

Administer the entire contents of the single-dose, prefilled syringe per standard protocol using a sterile needle. Discard syringe after use.

Risk Summary

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Available human data from clinical trials of PNEUMOVAX 23 in pregnancy have not established the presence or absence of a vaccine-associated risk.

Developmental toxicity studies have not been conducted with PNEUMOVAX 23 in animals.

Risk Summary

It is not known whether PNEUMOVAX 23 is excreted in human milk. Data are not available to assess the effects of PNEUMOVAX 23 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 PNEUMOVAX 23 and any potential adverse effects on the breastfed child from PNEUMOVAX 23 or from the underlying maternal condition. For preventive vaccines, the underlying maternal condition is susceptibility to the disease prevented by the vaccine.

Manuf. and Dist. by: Merck Sharp & Dohme Corp., a subsidiary of
MERCK & CO., INC., Whitehouse Station, NJ 08889, USA

For patent information: www.merck.com/product/patent/home.html

Copyright © 2011-2019 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
All rights reserved.

Revised: 12/2019

usppi-v110-i-1912r040

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.

3 Dosage Forms And Strengths

PNEUMOVAX 23 is a clear, sterile solution supplied in a (0.5-mL dose) single-dose vial and a single-dose, prefilled syringe. [See Description (11) and How Supplied/Storage and Handling (16).]

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 Adverse Reactions

The most common adverse reactions, reported in >10% of subjects vaccinated with PNEUMOVAX 23 for the first time in a clinical trial, were: injection-site pain/soreness/tenderness (60.0%), injection-site swelling/induration (20.3%), headache (17.6%), injection-site erythema (16.4%), asthenia/fatigue (13.2%), and myalgia (11.9%). [See Adverse Reactions (6.1).]

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.

Primary Vaccination and Revaccination with PNEUMOVAX 23 in Adults 50 Years of Age or Older

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
  Injection-site necrosis

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.

8.4 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.

11 Description

PNEUMOVAX 23 (Pneumococcal Vaccine Polyvalent) is a sterile, liquid vaccine consisting of a mixture of purified capsular polysaccharides from Streptococcus pneumoniae types (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 a clear, colorless solution. Each 0.5-mL dose of vaccine contains 25 micrograms of each polysaccharide type in isotonic saline solution containing 0.25% phenol as a preservative. The vaccine is used directly as supplied. No dilution or reconstitution is necessary.

The vial stoppers, syringe plunger stopper and syringe tip cap are not made with natural rubber latex.

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.

Sequential Administration of Prevnar 13 and PNEUMOVAX 23

In a randomized, double-blind, placebo-controlled, multicenter study, healthy adults, 50 years of age and older, received Prevnar 13 followed by PNEUMOVAX 23 either 8 weeks later (Group 1) or 26 weeks later (Group 2). Four hundred subjects were randomized 1:1 into Group 1 or Group 2, all of whom were initially vaccinated with Prevnar 13; of these, 188 subjects received PNEUMOVAX 23 (Group 1) and 185 subjects received placebo (Group 2) at Week 8, and 172 subjects received placebo (Group 1) and 164 subjects received PNEUMOVAX 23 (Group 2) at Week 26.

Opsonophagocytic activity (OPA) titers were measured at prevaccination, at Week 12 and at Week 30 for the 12 shared serotypes contained in both PNEUMOVAX 23 and Prevnar 13 (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F), 2 of the 11 serotypes unique to PNEUMOVAX 23 (22F and 33F), and 1 serotype unique to Prevnar 13 (6A). OPA testing was performed on evaluable serum samples from all subjects at baseline (Day 1) and Week 12, and on sera from a random subset of subjects (approximately 50% of subjects) at Week 30. Estimated GMTs, GMT ratio, and 95% confidence intervals were obtained from a constrained Longitudinal Data Analysis model {1}.

For each of the shared serotypes, Week 12 OPA geometric mean titers (GMTs) in Group 1 were noninferior to those of Group 2, as the lower bounds of the 95% CIs for the OPA GMT ratios were >0.5 for all 12 shared serotypes. For serotypes 22F and 33F, OPA GMTs in Group 1 at Week 12 were superior to those of Group 2 at Week 12, as the lower bounds of the 95% CIs for the OPA GMT ratios were >2.0 for both serotypes.

The OPA GMTs to the 12 shared serotypes and 2 unique serotypes (22F and 33F) when measured 4 weeks after dosing with PNEUMOVAX 23 were generally similar between Group 1 (Week 12) and Group 2 (Week 30 subset).

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.

15 References

• Liang KY, Zeger S. Longitudinal data analysis of continuous and discrete responses for pre-post designs. Sankhyā: The Indian Journal of Statistics (Series B) 2000; 62: 134-148.

16 How Supplied/Storage And Handling

PNEUMOVAX 23 is supplied as follows:

NDC 0006-4943-00 — a box of 10 single-dose vials, color coded with a purple cap and stripe on the vial labels and cartons.

NDC 0006-4837-03 — a box of 10 single-dose, pre-filled Luer-Lok™ syringes with tip caps, color coded with a violet plunger rod and purple stripe on the syringe labels and cartons.

Storage And Handling

Storage and Handling

• Store at 2-8°C (36-46°F).
• All vaccine must be discarded after the expiration date.

The vial stoppers, syringe plunger stopper and syringe tip cap are not made with natural rubber latex.

17 Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Patient Information).

• Inform the patient, parent or guardian of the benefits and risks associated with vaccination.
• Tell the patient, parent or guardian that vaccination with PNEUMOVAX 23 may not offer 100% protection from pneumococcal infection.
• Provide the patient, parent or guardian with the vaccine information statements required by the National Childhood Vaccine Injury Act of 1986, with each immunization.
• Instruct the patient, parent or guardian to report any serious adverse reactions to their health care provider who in turn should report such events to the vaccine manufacturer or the U.S. Department of Health and Human Services through the Vaccine Adverse Event Reporting System (VAERS), 1-800-822-7967, or report online at www.vaers.hhs.gov.

Principal Display Panel - 5 Dose Vial Carton

NDC 0006-4739-00

One 5-Dose Vial
(0.5 mL/dose)

Pneumococcal
Vaccine
Polyvalent
PNEUMOVAX^® 23

Do not use in children less
than 2 years of age.

Each 0.5-mL dose contains
25 mcg of polysaccharide from
each pneumococcal capsular type.

Contains phenol 0.25% added
as preservative.

FOR SYRINGE USE ONLY

Rx only

PRINCIPAL DISPLAY PANEL - 5 Dose Vial Carton - pneumovax 01

Principal Display Panel - 10 Dose Vial Carton

NDC 0006-4943-00
10 Single-Dose 0.5-mL Vials

Pneumococcal Vaccine Polyvalent
PNEUMOVAX^®23

Do not use in children less than 2 years of age.

Each 0.5-mL dose contains 25 mcg of polysaccharide from each pneumococcal capsular type.
Contains phenol 0.25% added as preservative.

Rx only
FOR SYRINGE USE ONLY

PRINCIPAL DISPLAY PANEL - 10 Dose Vial Carton - pneumovax 02

Principal Display Panel - 0.5-Ml Syringes Carton

NDC 0006-4837-03

10 Single-dose 0.5-mL Syringes

Pneumococcal
Vaccine Polyvalent
PNEUMOVAX^®23

Do not use in children less than 2 years of age.
Each prefilled syringe contains 25 mcg of polysaccharide
from each pneumococcal capsular type.
Contains phenol 0.25% added as preservative.

Rx only

PRINCIPAL DISPLAY PANEL - 0.5-mL Syringes - pneumovax 03