PNEUMOVAX* 23 (Pneumococcal Vaccine Polyvalent), is a sterile, liquid vaccine for intramuscular or subcutaneous injection. It consists of a mixture of highly purified capsular polysaccharides from the 23 most prevalent or invasive pneumococcal types of Streptococcus pneumoniae, including the six serotypes that most frequently cause invasive drug- resistant pneumococcal infections among children and adults in the United States. ¹ (See Table 1.) The 23- valent vaccine accounts for at least 90% of pneumococcal blood isolates and at least 85% of all pneumococcal isolates from sites which are generally sterile as determined by ongoing surveillance of U. S. data. ²

PNEUMOVAX 23 is manufactured according to methods developed by the MERCK Research Laboratories. Each 0.5 mL dose of vaccine contains 25 µg of each polysaccharide type dissolved in isotonic saline solution containing 0.25% phenol as a preservative.

PNEUMOVAX 23 is indicated for vaccination against pneumococcal disease caused by those pneumococcal types included in the vaccine. Effectiveness of the vaccine in the prevention of pneumococcal pneumonia and pneumococcal bacteremia has been demonstrated in controlled trials in South Africa, France and in case-control studies.

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

If it is known that a person has not received any pneumococcal vaccine or if earlier pneumococcal vaccination status is unknown, then persons in the categories listed below should be administered pneumococcal vaccine; however, if a person has received a primary dose of pneumococcal vaccine, before administering an additional dose of vaccine, please refer to the Revaccination section.

Vaccination with PNEUMOVAX 23 is recommended for selected individuals as follows:

Immunocompetent persons:

• routine vaccination for persons 50 years of age or older ^†
• persons aged ³2 years with chronic cardiovascular disease (including congestive heart failure and cardiomyopathies), chronic pulmonary disease (including chronic obstructive pulmonary disease and emphysema), or diabetes mellitus¹
• persons aged ³2 years with alcoholism, chronic liver disease (including cirrhosis) or cerebrospinal fluid leaks¹
• persons aged ³2 years with functional or anatomic asplenia (including sickle cell disease and splenectomy) ¹
• persons aged ³2 years living in special environments or social settings (including Alaskan Natives and certain American Indian populations) ¹

Immunocompromised persons:

• persons aged ³2 years, including those with HIV infection, leukemia, lymphoma, Hodgkin†s disease, multiple myeloma, generalized malignancy, chronic renal failure or nephrotic syndrome; those receiving immunosuppressive chemotherapy (including corticosteroids); and those who have received an organ or bone marrow transplant. ¹

Timing of Vaccination

Pneumococcal vaccine should be given at least two weeks before elective splenectomy, if possible.

For planning cancer chemotherapy or other immunosuppressive therapy (e.g., for patients with Hodgkin†s disease or those who undergo organ or bone marrow transplantation), pneumococcal vaccination should be administered at least two weeks prior to the initiation of immunosuppressive therapy. Vaccination during chemotherapy or radiation therapy should be avoided. Based on literature reports, pneumococcal vaccine may be given as early as several months following completion of chemotherapy or radiation therapy for neoplastic disease.34,36 In Hodgkin†s disease, immune response to vaccination may be impaired for two years or longer after intensive chemotherapy (with or without radiation). During the two years following the completion of chemotherapy or other immunosuppressive therapy, antibody responses improve in some patients as the interval between the end of treatment and pneumococcal vaccination increases. ³⁴

Persons with asymptomatic or symptomatic HIV infection should be vaccinated as soon as possible after their diagnosis is confirmed.

Use With Other Vaccines

The ACIP states that pneumococcal vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine. ¹ In contrast to pneumococcal vaccine, influenza vaccine is recommended annually, for appropriate populations. ³¹

Revaccination

Early studies have indicated that local reactions (i. e., arthus-type reactions) among adults receiving the second dose of 14-valent vaccine within 2 years after the first dose are more severe than those occurring after initial vaccination. However, subsequent studies have suggested that revaccination after intervals of ³4 years is not associated with an increased incidence of adverse side effects.¹

Routine revaccination of immunocompetent persons previously vaccinated with 23-valent polysaccharide vaccine is not recommended.¹ However, revaccination once is recommended for persons ³2 years of age who are at highest risk of serious pneumococcal infection and those likely to have a rapid decline in pneumococcal antibody levels, provided that at least five years have passed since receipt of a first dose of pneumococcal vaccine. ¹

The highest risk group includes persons with functional or anatomic asplenia (e.g., sickle cell disease or splenectomy), HIV infection, leukemia, lymphoma, Hodgkin†s disease, multiple myeloma, generalized malignancy, chronic renal failure, nephrotic syndrome, or other conditions associated with immunosuppression (e.g., organ or bone marrow transplantation), and those receiving immunosuppressive chemotherapy (including long-term systemic corticosteroids).¹

For children £10 years of age at revaccination and at highest risk of severe pneumococcal infection (e.g., children with functional or anatomic asplenia, including sickle cell disease or splenectomy or conditions associated with rapid antibody decline after initial vaccination including nephrotic syndrome, renal failure or renal transplantation), the ACIP recommends that revaccination may be considered three years after the previous dose.¹

If prior vaccination status is unknown for patients in the high risk group, patients should be given pneumococcal vaccine.¹

All persons ³65 years of age who have not received vaccine within 5 years (and were < 65 years of age at the time of vaccination) should receive another dose of vaccine.¹

Because data are insufficient concerning the safety of pneumococcal vaccine when administered three or more times, revaccination following a second dose is not routinely recommended.¹

Do not inject intravenously or intradermally.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. PNEUMOVAX 23 is a clear, colorless solution. The vaccine is used directly as supplied. No dilution or reconstitution is necessary. Phenol 0.25% has been added as a preservative.

It is important to use a separate sterile syringe and needle for each individual patient to prevent transmission of infectious agents from one person to another.

Withdraw 0.5 mL from the vial using a sterile needle and syringe free of preservatives, antiseptics, and detergents.

Administer a single 0.5 mL dose of PNEUMOVAX 23 subcutaneously or intramuscularly (preferably in the deltoid muscle or lateral mid-thigh), with appropriate precautions to avoid intravascular administration.

Store unopened and opened vials at 2-8° C( 36-46° F). The vaccine is used directly as supplied. No dilution or reconstitution is necessary. Phenol 0.25% has been added as a preservative. All vaccine must be discarded after the expiration date.

Use With Other Vaccines

The ACIP states that pneumococcal vaccine may be administered at the same time as influenza vaccine (by separate injection in the other arm) without an increase in side effects or decreased antibody response to either vaccine.¹ In contrast to pneumococcal vaccine, influenza vaccine is recommended annually, for appropriate populations. ³

No. 4739 † PNEUMOVAX 23 is supplied as one 5-dose vial of liquid vaccine, color coded with a purple cap and stripe on the vial labels and cartons, NDC 0006-4739-00.

No. 4739 † PNEUMOVAX 23 is supplied as one 5-dose vial of liquid vaccine, in a box of 10 five-dose vials, color coded with a purple cap and stripe on the vial labels and cartons, NDC 0006-4739-50.

No. 4943 † PNEUMOVAX 23 is supplied as a single-dose vial of liquid vaccine, in a box of 10 singledose vials, color coded with a purple cap and stripe on the vial labels and cartons, NDC 0006-4943-00.

REFERENCES

1. Recommendation of the Advisory Committee on Immunization Practices † Prevention of Pneumococcal Disease, Morbidity and Mortality Weekly Report, 46(RR-8): 1-25, April 4, 1997.

2. Robbins, J. B.; Lee, C. J.; Schiffman, G.; Austrian, R.; Henrichsen, J.; Mγ¤kelγ¤, RH.; Broome, C. V.; Facklam, R. R.; Tiesjema, RH.; Rastogi, S. C.: Considerations for formulating the second-generation pneumococcal capsular polysaccharide vaccine with emphasis on the cross-reactive types within groups, J. Infect. Dis. 148: 1136-1159, 1983.

3. WHO: Vital statistics and causes of death, World Health Statistics Annual, 1, 1976.

4. Austrian, A.; Gold, J.: Pneumococcal bacteremia with especial reference to bacteremic pneumococcal pneumonia, Ann. Intern. Med. 60: 759-776, 1964.

5. Austrian, R.: Random gleanings from a life with the pneumococcus, J. Infect. Dis. 131: 474-484, 1975.

6. Austrian, R.: Vaccines of pneumococcal capsular polysaccharides and the prevention of pneumococcal pneumonia ; †The role of immunological factors in infectious, allergic and autoimmune processes†, R. F. Beers, Jr. and E. G. Bassett (eds.), New York, Raven Press: 79-89, 1976.

7. Mufson, M. A.; Kruss, D. M.; Wasil, R. E.; Metzger, WI.: Capsular types and outcome of bacteremic pneumococcal disease in the antibiotic era, Arch. Intern. Med. 134: 505-510, 1974.

8. Mufson, M. A.: Pneumococcal infections, J. A. M. A. 246 (17): 1942-1948, 1981.

9. Barrett-Connor, E.: Bacterial infection and sickle cell anemia: an analysis of 250 infections in 166 patients and a review of the literature, Medicine 50: 97-112, 1971.

10. Unpublished data; files of Merck Research Laboratories.

11. Borgono, J. M.; McLean, A. A.; Vella, RR; Woodhour, A. F.; Canepa, I.; Davidson, W. L.; Hilleman, M. R.: Vaccination and revaccination with polyvalent pneumococcal polysaccharide vaccines in adults and infants (40010), Proc. Soc. Exper. Biol. & Med. 157: 148- 154, 1978.

12. Hilleman, M. R.; McLean, A. A.; Vella, RR; Weibel, R. E.; Woodhour, A. F.: Polyvalent pneumococcal polysaccharide vaccines, Bull. World Health Organ. 56: 371-375, 1978.

13. Smit, P.; Oberholzer, D.; Hayden-Smith, S.; Koornhof, H. J.; HilIeman, M. R.: Protective efficacy of pneumococcal polysaccharide vaccines, J. A. M. A. 238: 2613-2616, 1977.

14. Weibel, R. E.; Vella, RR; McLean, A. A.; Woodhour, A. F.; Hilleman, M. R.: Studies in human subjects of polyvalent pneumococcal vaccines (39894), Proc. Soc. Exper. Biol. & Med. 156: 144- 150, 1977.

15. Austrian, R.; Douglas, R. M.; Schiffman, G.; Coetzee, A. M.; Koornhof, H. J.; Hayden-Smith, S.; Reid, R. D. W.: Prevention of pneumococcal pneumonia by vaccination, Trans. Assoc. Am. Physicians 89: 184-194, 1976.

16. Gaillat, J.; Zmirou, D.; Mallaret, M. R.: Essai clinique du vaccin antipneuomococcique chez des personnes agees vivant en institution, Rev. Epidemiol. Sante Publique. 33: 437-44, 1985.

17. Simberkoff, M. S.; Cross, A. R; Al-Ibrahim, M.: Efficacy of pneumococcal vaccine in high risk patients: results of a Veterans Administration cooperative study, New Engl. J. Med. 315: 1318- 27, 1986.

18. Broome, C. V.: Efficacy of pneumococcal polysaccharide vaccines, Rev. Infect. Dis. 3( suppl): S82- S96, 1981.

19. Spika, J. S.; Fedson, D. S.; Facklam, R. R.: Pneumococcal vaccination-controversies and opportunities, Infect. Dis. Clin. North Am. 4: 11-27, 1990.

20. Fine, M. J.; Smith, M. A.; Carson, C. A.; Meffe, F.; Sankey, S. S.; Weissfeld, L. A.; Detsky, A. S.; Kapoor, W. N.: Efficacy of pneumococcal vaccination in adults: a meta-analysis of randomized controlled trials, Arch. Intern. Med. 154: 2666- 77, 1994.

21. Fedson, D. S.; Shapiro, E. D.; LaForce, F. M.; Mufson, M. A.; Musher, D. M.; Spika, J. S.; Breiman, R. F.: Pneumococcal vaccine after 15 years of use: another view, Arch. Intern. Med. 154: 2531- 35, 1994.

22. Butler, J. C.; Brelman, R. F.; Campbell, J. F.; Lipman, H. B.; Broome, C. V.; Facklam, A .R.: Pneumococcal polysaccharide vaccine efficacy. An evaluation of current recommendations, J. A. M. A. 270: 1826- 31, 1993.

23. Shapiro, E. D.; Berg, A. T.; Austrian, R.; Schroeder, D.; Parcells, V.; Margolis, A.; Adair, R. K.; Clemens, J. D.: The protective efficacy of polyvalent pneumococcal polysaccharide vaccine, New Engl. J. Med. 325: 1453- 60, 1991.

24. Farr, B. M.; Johnston, B. L.; Cobb, O. K.; Fisch, M. J.; Germanson T. R; Adal, K. A.; Anglim, A. M.: Preventing pneumococcal bacteremia in patients at risk. Results of a matched case-control study, Arch. Intern. Med. 155: 2336- 2340, 1995.

25. Shapiro, E. D.; Clemens, J. D.: A controlled evaluation of the protective efficacy of pneumococcal vaccine for patients at high risk of serious pneumococcal infections, Ann. Intern. Med. 101: 325- 30, 1984.

26. Sims, R. V.; Steinmann, W. C.; McConviue, J. H.; King, LA.; Zwick, W. C.; Schwartz, J. S.: The clinical effectiveness of pneumococcal vaccine in the elderly, Ann. Intern. Med 108: 653- 7, 1988.

27. Forrester, H. L; Jahnigen, D. W.; LaForce, F. M.: Inefficacy of pneumococcal vaccine in a high-risk population, Am. J. Med. 83: 425-30, 1987.

28. Ammann, A. J.; Addiego, J.; Wara, D. W.; Lubin, B.; Smith, W. B.; Mentzer, W. C.: Polyvalent pneumococcal-polysaccharide immunization of patients with sickle-cell anemia and patients with splenectomy, New Engl. J. Med. 297: 897-900, 1977.

29. Musher, D. M.; Groover, J. E.; Rowland, J. M.; Watson, D. A.; Struewing, J. B.; Baughn, R. E.; Mufson, M. A.: Antibody to capsular polysaccharides of Streptococcus pneumoniae: prevalence, persistence, and response to revaccination, Clinical Infect. Dis. 17: 66-73, 1993.

30. Konradsen, H. B.: Quantity and avidity of pneumococcal antibodies before and up to five years after pneumococcal vaccination of elderly persons, Clinical Infect. Dis. 21: 616-20, 1995.

31. Carlson, A. J.; Davidson, W. L.; McLean, A. A.; Vella, PR; Weibel, R. E.; Woodhour, A. F.; Hilleman, M. R.: Pneumococcal vaccine dose, revaccination, and coadministration with influenza vaccine (40596), Proc. Soc. Exp. Biol. & Med. 161: 558-563, 1979.

32. Vaccine Adverse Event Reporting System-United States, Morbidity and Mortality Weekly Report 39( 41): 730-33, October 19, 1990.

33. Kelton, J. G.: Vaccination-associated relapse of immune thrombocytopenia, J. Am. Med. Assoc. 245( 4): 369-371, 1981.

34. Siber, G. R.; Weitzman, S. A.; Aisenberg, A. C.: Antibody response of patients with Hodgkin†s disease to protein and polysaccharide antigens, Rev. Infect. Dis. 3(Suppl): S144-S159, March-April 1981.

35. Siber, G. R.; Gorham, C.; Martin, P.; Corkery, J. C.; Schiffman, G.: Antibody response to pretreatment immunization and post-treatment boosting with bacterial polysaccharide vaccines in patients with Hodgkin†s disease, Ann Intern Med. 104: 467-475, 1986.

The following adverse experiences have been reported with PNEUMOVAX 23 in clinical trials and/or post-marketing experience:

Local reactions at injection site including soreness, warmth, erythema, swelling and induration.I Very rarely, cellulitis-like reactions were reported. These cellulitis-like reactions, reported in post-marketing experience, show short onset time from vaccine administration and were transient in nature.

Fever £102° F.

Other adverse experiences reported in clinical trials and in post-marketing experience include:

Body as a Whole

• Cellulitis
• Asthenia
• Malaise
• Fever(£102° F)

Digestive System

• Nausea
• Vomiting

Hematologic/Lymphatic

• Lymphadenitis
• Thrombocytopenia in patients with stabilized idiopathic thrombocytopenic purpura 33
• Hemolytic anemia in patients who have had other hematologic disorders

Hypersensitivity

• Anaphylactoid reactions
• Serum Sickness
• Angioneurotic edema

Musculoskeletal System

• Arthralgia
• Arthritis
• Myalgia

Nervous System

• Headache
• Paresthesia
• Radiculoneuropathy
• Guillain Barre Syndrome

Skin

• Rash
• Urticaria

No information provided.

For planning cancer chemotherapy or other immunosuppressive therapy (e.g., for patients with Hodgkin†s disease or those who undergo organ or bone marrow transplantation), the timing of the vaccination is critical. (See INDICATIONS, Timing of Vaccination.)

If the vaccine is used in persons receiving immunosuppressive therapy, the expected serum antibody response may not be obtained and potential impairment of future immune responses to pneumococcal antigens may occur. (See INDICATIONS, Timing of Vaccination.)

Intradermal administration may cause severe local reactions.

General

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.

Any febrile respiratory illness or other active infection is reason for delaying use of PNEUMOVAX 23, except when, in the opinion of the physician, withholding the agent entails even greater risk.

In patients who require penicillin (or other antibiotic) prophylaxis against pneumococcal infection, such prophylaxis should not be discontinued after vaccination with PNEUMOVAX 23.

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.

Routine revaccination of immunocompetent persons previously vaccinated with a 23-valent vaccine is not recommended. However, revaccination once is recommended for persons aged = 2 years who are at highest risk for serious pneumococcal infections and those likely to have a rapid decline in pneumococcal antibody levels. (See INDICATIONS, Revaccination.)

Instructions to Healthcare Provider

The healthcare provider should determine the current health status and previous vaccination history of the vaccinee. (See INDICATIONS, Revaccination.)

The healthcare provider should question the patient, parent or guardian about reactions to a previous dose of PNEUMOVAX 23 or other pneumococcal vaccine.

Information for Patients

See PATIENT INFORMATION section.

Pregnancy

Pregnancy Category C: Animal reproduction studies have not been conducted with PNEUMOVAX 23. It is also not known whether PNEUMOVAX 23 can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. PNEUMOVAX 23 should be given to a pregnant woman only if clearly needed.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when PNEUMOVAX 23 is administered to a nursing woman.

Pediatric Use

In general, children less than 2 years of age respond poorly to the capsular types of PNEUMOVAX 23 that are most often the cause of pneumococcal disease in this age group. (See CLINICAL PHARMACOLOGY, Immunogenicity.) Safety and effectiveness in children below the age of 2 years have not been established. Accordingly, PNEUMOVAX 23 is not recommended in this age group.

Geriatric Use

Persons 65 years of age or older were enrolled in several clinical studies of PNEUMOVAX 23 that were conducted pre- and post-licensure. In the largest of these studies, the safety of PNEUMOVAX 23 in adults 65 years of age and older was compared to the safety of PNEUMOVAX 23 in adults 50 to 64 years of age. Of 1007 subjects enrolled in this study, 433 subjects were 65 to 74 years of age, and 195 subjects were 75 years of age or older. No overall difference in safety was observed between these subjects and younger subjects. However, 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.

No information provided.

Hypersensitivity to any component of the vaccine. Epinephrine injection (1:1000) must be immediately available should an acute anaphylactoid reaction occur due to any component of the vaccine.

Pneumococcal infection is a leading cause of death throughout the world³ and a major cause of pneumonia, bacteremia, meningitis, and otitis media.

Strains of drug-resistant S. pneumoniae have become increasingly common in the United States and in other parts of the world. In some areas as many as 35% of pneumococcal isolates have been reported to be resistant to penicillin. Many penicillin resistant pneumococci are also resistant to other antimicrobial drugs (e.g., erythromycin, trimethoprim-sulfamethoxazole and extended-spectrum cephalosporins); therefore emphasizing the importance of vaccine prophylaxis against pneumococcal disease.

Epidemiology

Pneumococcal infection causes approximately 40,000 deaths annually in the United States.

At least 500,000 cases of pneumococcal pneumonia are estimated to occur annually in the United States; S. pneumoniae accounts for approximately 25-35% of cases of community acquired bacterial pneumonia in persons who require hospitalization. ¹

Pneumococcal disease accounts for an estimated 50,000 cases of pneumococcal bacteremia annually in the United States. Some studies suggest the overall annual incidence of bacteremia to be approximately 15 to 30 cases/100,000 population with 50 to 83 cases/100,000 for persons 65 years of age and older and 160 cases/100,000 for children less than two years of age.

The incidence of pneumococcal bacteremia is as high as 1% (940 cases/100,000 population) among persons with acquired immunodeficiency syndrome (AIDS).

In the United States, the risk of acquiring bacteremia is lower among whites than among persons in some other racial/ethnic groups (i.e., blacks, Alaskan Natives, and American Indians).

Despite appropriate antimicrobial therapy and intensive medical care, the overall case-fatality rate for pneumococcal bacteremia is 15-20% among adults4, and among elderly patients this rate is approximately 30-40%. An overall case-fatality rate of 36% was documented for adult inner-city residents who were hospitalized for pneumococcal bacteremia. ¹

In the United States, pneumococcal disease accounts for an estimated 3,000 cases of meningitis annually. The estimated overall annual incidence of pneumococcal meningitis is approximately 1 to 2 cases per 100,000 population. The incidence of pneumococcal meningitis is highest among children six to 24 months and persons aged 65 years; rates for blacks are twice as high as those for whites or Hispanics. Recurrent pneumococcal meningitis may occur in patients who have chronic cerebrospinal fluid leakage resulting from congenital lesions, skull fractures, or neurosurgical procedures. ¹

Invasive pneumococcal disease (e.g., bacteremia or meningitis) and pneumonia cause high morbidity and mortality in spite of effective antimicrobial control by antibiotics. ⁴ These effects of pneumococcal disease appear due to irreversible physiologic damage caused by the bacteria during the first 5 days following onset of illness, 5,6 and occur irrespective of antimicrobial therapy. ^5,7 Vaccination offers an effective means of further reducing the mortality and morbidity of this disease.

Risk Factors

In addition to the very young and persons 65 years of age or older, patients with certain chronic conditions are at increased risk of developing pneumococcal infection and severe pneumococcal illness.

Patients with chronic cardiovascular diseases (e.g., congestive heart failure or cardiomyopathy), chronic pulmonary diseases (e.g., chronic obstructive pulmonary disease or emphysema), or chronic liver diseases (e.g., cirrhosis), diabetes mellitus, alcoholism or asthma (when it occurs with chronic bronchitis, emphysema, or long-term use of systemic corticosteroids) have an increased risk of pneumococcal disease. In adults, this population is generally immunocompetent. ¹

Patients at high risk are those who have a decreased responsiveness to polysaccharide antigen or an increased rate of decline in serum antibody concentrations as a result of: immunosuppressive conditions (congenital immunodeficiency, human immunodeficiency virus [HIV] infection, leukemia, lymphoma, multiple myeloma, Hodgkin†s disease, or generalized malignancy); organ or bone marrow transplantation; therapy with alkylating agents, antimetabolites, or systemic corticosteroids; chronic renal failure or nephrotic syndrome. ^1,8

Patients at the highest risk of pneumococcal infection are those with functional or anatomic asplenia (e.g., sickle cell disease⁹ or splenectomy), because this condition leads to reduced clearance of encapsulated bacteria from the bloodstream. Children who have sickle cell disease or have had a splenectomy are at increased risk for fulminant pneumococcal sepsis associated with high mortality. ¹

Immunogenicity

It has been established that the purified pneumococcal capsular polysaccharides induce antibody production and that such antibody is effective in preventing pneumococcal disease. ^6,10 Clinical studies have demonstrated the immunogenicity of each of the 23 capsular types when tested in polyvalent vaccines.

Studies with 12-, 14-, and 23- valent pneumococcal vaccines in children two years of age and older and in adults of all ages showed immunogenic responses. ^1-14 Protective Capsular type-specific antibody levels generally develop by the third week following vaccination. ³

Bacterial capsular polysaccharides induce antibodies primarily by T-cell-independent mechanisms. Therefore, antibody response to most pneumococcal capsular types is generally poor or inconsistent in children aged <2 years whose immune systems are immature. ¹

Efficacy

The protective efficacy of pneumococcal vaccines containing 6 or 12 capsular polysaccharides was investigated in two controlled studies of young, healthy gold miners in South Africa, in whom there was a high attack rate for pneumococcal pneumonia and bacteremia. ³ Capsular type-specific attack rates for pneumococcal pneumonia were observed for the period from 2 weeks through about 1 year after vaccination. Protective efficacy was 76% and 92%, respectively, in the two studies for the capsular types represented.

In similar studies carried out by Dr. R. Austrian and associates, ¹⁵ using similar pneumococcal vaccines prepared for the National Institute of Allergy and Infectious Diseases, the reduction in 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 pneumococcal vaccine to be 77% effective in reducing the incidence of pneumonia among nursing home residents. ¹⁶

In the United States, two postlicensure randomized controlled trials, in the elderly or patients with chronic medical conditions, who received a multivalent polysaccharide vaccine, did not support the efficacy of the vaccine for nonbacteremic pneumonia. ^17,18 However, these studies may have lacked sufficient statistical power to detect a difference in the incidence of laboratory-confirmed, nonbacteremic pneumococcal pneumonia between the vaccinated and nonvaccinated study groups. ⁹

A meta-analysis of nine randomized controlled trials of pneumococcal vaccine concluded that pneumococcal vaccine is efficacious in reducing the frequency of nonbacteremic pneumococcal pneumonia among adults in low risk groups but not in high-risk groups. ²⁰ These studies may have been limited because of the lack of specific and sensitive diagnostic tests for nonbacteremic pneumococcal pneumonia. The pneumococcal polysaccharide vaccine is not effective for the prevention of common upper respiratory disease in children.¹

More recently, multiple, case-control studies have shown pneumococcal vaccine is effective in the prevention of serious pneumococcal disease, with point estimates of efficacy ranging from 56% to 81% in immunocompetent persons. ^{21- 26}

Only one case-control study did not document effectiveness against bacteremic disease possibly due to study limitations, including small sample size and incomplete ascertainment of vaccination status in patients. ²⁷ In addition, case-patients and persons who served as controls may not have been comparable regarding the severity of their underlying medical conditions, potentially creating a biased underestimate of vaccine effectiveness. ^1,19

A serotype prevalence study, based on the Centers for Disease Control pneumococcal surveillance system, demonstrated 57% overall protective effectiveness against invasive infections caused by serotypes included in the vaccine in persons ³6 years of age, 65-84% 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% effectiveness in immunocompetent persons aged ³65 years of age. Vaccine effectiveness could not be confirmed for certain groups of immunocompromised patients; however, the study could not recruit sufficient numbers of unvaccinated patients from each disease group.

In an earlier study, 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. ^1,28

Duration of Immunity

Following pneumococcal vaccination, serotype-specific antibody levels decline after 5-10 years.¹ A more rapid decline in antibody levels may occur in some groups (e.g., children). Limited published data suggest that antibody levels may decline in the elderly >60 years of age. ^29,30

The Advisory Committee on Immunization Practices (ACIP) states that these findings indicate that revaccination may be needed to provide continued protection. ¹ (See INDICATIONS, Revaccination.)

The results from one epidemiologic study suggest that vaccination may provide protection for at least nine years after receipt of the initial dose. ²² Decreasing estimates of effectiveness with increasing interval since vaccination, particularly among the very elderly (persons aged 85 years) have been reported. ²³

The healthcare provider should inform the patient, parent or guardian of the benefits and risks associated with vaccination. For risks associated with vaccination, see WARNINGS, PRECAUTIONS, and ADVERSE REACTIONS.

Patients, parents, and guardians should be instructed to report any serious adverse reactions to their healthcare 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), 1-800-822-7967.32

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

PNEUMOCOCCAL VACCINE - INJECTION

(NEU-mo-KOK-al)

COMMON BRAND NAME(S): Pneumovax 23, Pnu-Imune 23

USES: This vaccine helps protect against serious infection (e.g., meningitis, bacteria in the blood) due to certain bacteria (Streptococcus pneumoniae). This vaccine is important for preventing infection in individuals at risk (e.g., those with heart disease, lung disease, liver disease, diabetes, alcoholism, spleen problems, sickle cell anemia, or HIV, or those living in a nursing home).

HOW TO USE: This vaccine is injected into a muscle or under the skin by a health care professional as directed by your doctor.

Before using, check this product visually for particles or discoloration. If either is present, do not use the liquid.

This vaccine should not be injected too deep under the skin (intradermally) or into a vein. Doing so may increase your risk of side effects. When injected into a muscle, this vaccine should be injected into the back of the upper arm or into the outside of the thigh.

You may need to have another dose of vaccine if you are still at high risk for infection. This is especially true if you are younger than 65 years old when you receive the first dose of this vaccine. A second dose should not be given until 5 years after your first dose. Ask your doctor for more details.

If you are receiving this vaccination before spleen surgery or before receiving cancer chemotherapy or other drugs that decrease your immune system function, it should be given at least 2 weeks before these procedures to be effective. Talk to your doctor or pharmacist for more information.

SIDE EFFECTS: Injection site reactions (e.g., pain, redness, swelling, hard lump), muscle/joint aches, or fever may occur. Ask your doctor whether you should take a fever/pain reducer (e.g., acetaminophen) to help treat these symptoms. Nausea and vomiting may also occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: unusual weakness, tingling/numbness of the hands/feet, easy bleeding/bruising, swollen glands.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice any other effects not listed, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using this vaccine, tell your doctor or pharmacist if you are allergic to it; or to the preservative phenol; or to latex or dry natural rubber in the vial stopper; or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: your vaccination/immunization history, recent illness/fever.

This vaccine is not recommended for use in children younger than 2 years.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is not known whether this drug passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: "blood thinners" (e.g., warfarin or heparins), cancer chemotherapy drugs, corticosteroids (e.g., dexamethasone, prednisone), drugs that weaken your immune system (e.g., cyclosporine, efalizumab, tacrolimus).

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: It is important to understand the risks and benefits of vaccinations. Discuss this with your doctor.

Talk to your doctor or pharmacist about the need for other vaccines to prevent possibly severe illness (e.g., flu shots).

Make sure all of your doctors know you have received this vaccine. Make sure a note is placed in your medical record of having received this vaccine.

MISSED DOSE: Not applicable.

STORAGE: Refrigerate the vaccine between 36-46 degrees F (2-8 degrees C) away from light. Do not freeze. Discard any unused portion as directed. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.