PNU-IMUNE 23 (Wyeth-Ayerst)
Pneumococcal Vaccine Polyvalent,
FOR INTRAMUSCULAR OR SUBCUTANEOUS USE ONLY
Pneumococcal Vaccine Polyvalent, Pnu-Imune 23 is a sterile liquid preparation intended for intramuscular or subcutaneous use. Pnu-Imune 23 consists of a mixture of purified capsular polysaccharides from the 23 most prevalent serotypes of Streptococcus pneumoniae (pneumococci) which are responsible for approximately 90% of serious pneumococcal disease in the United States (US). 1,2 The six serotypes (6B, 9V, 14, 19A, 19F, and 23F) that most frequently cause invasive drug-resistant pneumococcal infection in the U.S. are represented in the 23-valent vaccine. 3
Danish 1 2 3 4 5 6B 7F 8 9N 9V 10A 11A 12F 14 15B 17A 18C 19F 19A 20 22F 23F 33F
Each of the pneumococcal polysaccharide serotypes is produced separately to assure a high degree of purity. Cultures of pneumococcal serotypes are grown individually in a standard pneumococcal fermentation medium (modified Holt's medium supplemented with dextrose). Polysaccharide is separated from the bacterial cell and purified by a series of steps including ethanol fractionation. The vaccine is formulated to contain 25 Âµg of each of the 23 purified polysaccharide serotypes per 0.5 mL dose of vaccine. Each 0.5 mL dose contains approximately 50 Âµg of the preservative thimerosal (a mercury derivative) at a final concentration of 0.01%. The vaccine is a clear, colorless liquid formulation.
Streptococcus pneumoniae (pneumococcus) causes illness and death among the elderly and persons who have certain underlying medical conditions.
Pneumococci colonize the upper respiratory tract where, by appropriate culturing, they can be detected in 5% to 10% of healthy adults and 20% to 40% of healthy children. 4 If the organisms are carried into tissues from which they are not readily cleared, they may cause: a) disseminated invasive infections, including bacteremia and meningitis, b) pneumonia and other lower respiratory tract infections. 3
S. pneumoniae is the most common cause of community-acquired bacterial pneumonia, accounting for approximately 25% to 35% of cases in persons requiring hospitalization. 3 During the years 1995-98, the overall incidence of invasive pneumococcal disease was 23.2/100,000 population. Invasive disease in persons 65 to 79 years of age was 46/100,000, and in persons 80 years and older, 98.5/100,000. 5 In the age group 65 to 79 years, bacteremia accounted for 13.6/100,000; meningitis for 1.5/100,000 and pneumonia for 30.8/100,000. The incidence of the same diseases in persons older than 80 years was higher: 20.4/100,000 of bacteremia, 1.9/100,000 of meningitis and 75.4/100,000 of pneumonia. 5 The case-fatality rate of patients with underlying disease in the age group 18 to 64 years was 12/100,000. In 1999, the overall incidence of invasive disease due to pneumococcal infections had reportedly increased to 61.5/100,000 in persons 65 years and older and a case-fatality rate of 13/100,000. 6
Certain ethnic backgrounds, (ie, Alaskan Native, Native American, and African-American), are associated with higher disease rates in adult populations. 7,8,9,10 Alaskan Natives over the age of 19 years have a 7-fold higher rate of meningitis and a 4-fold higher rate of mortality than non-native Alaskans. 7 White mountain Apache populations 20 to 59 years of age have a 13- to 25-fold higher rate of invasive pneumococcal disease than the general US population. 8 African-Americans over 65 years of age have a 2.7-fold higher rate of pneumococcal bacteremia than age-matched Caucasians. 10
Pneumococcal infection caused an estimated 43,940 deaths in adults in the United States in 1998. 5 The estimated case-fatality rate due to culture-confirmed invasive pneumococcal disease in the US in 1998 increased with increasing age as follows: 13% in the 50 to 64 year age group, 16% in persons 65 to 79 years of age and 18% in individuals 80 years and older. 5 Individuals 65 years or older accounted for 51% of all deaths due to invasive pneumococcal disease in 1998. 5 Case-fatality rates were higher for pneumococcal meningitis than for pneumonia or bacteremia at all ages. Persons 80 years old and above with meningitis had a case-fatality rate of 50%. Reported case fatality rates range from 25% to 38% in adults with pneumococcal bacteremia. 11,12,13 Extrapulmonary infections with pneumococcus have been associated with 62% case fatality rate in all adults and an 88% case fatality rate in adults over 50 years of age. 12
Predisposing Medical Conditions (Risk Factors)
Persons 65 years of age or older and patients with certain underlying medical conditions are at increased risk for developing pneumococcal infection or experiencing severe disease and complications. Adults at increased risk include those who are generally immunocompetent and have chronic cardiovascular diseases (eg, congestive heart failure [CHF], coronary artery disease or cardiomyopathy), chronic obstructive pulmonary disease, chronic liver diseases (eg, cirrhosis), diabetes mellitus and renal failure requiring dialysis. 3,5 The incidence of pneumococcal infection is increased for persons who have liver disease as a result of alcohol abuse. 5 The case fatality rate for patients with alcoholic cirrhosis and concomitant pneumococcal infections is 18.3%, ie, 4- to 5-fold greater than those individuals with no indication for vaccination. 5
Persons with functional or anatomic asplenia (eg, sickle cell disease or splenectomy) are at greatly increased risk for pneumococcal infection due to resultant reduced clearance of encapsulated bacteria from the bloodstream. Pediatric patients who have sickle cell disease or have had a splenectomy are at increased risk for fulminant pneumococcal sepsis associated with high mortality. 3
Other patients at greater risk include those who have decreased responsiveness to polysaccharide antigens or more rapid decline in serum antibody concentrations as a result of immunosuppressive conditions (eg, congenital immunodeficiency, human immunodeficiency virus [HIV] infection, leukemia, Hodgkin's disease, lymphoma, multiple myeloma, or generalized malignancy), chronic renal failure or nephrotic syndrome, organ or bone marrow transplantation, or therapy with alkylating agents, antimetabolites, or systemic corticosteroids. 3
Recurrent pneumococcal meningitis may occur in patients with cerebrospinal fluid leakage that complicates skull fractures or neurologic procedures. 3
As many as 91% of adults who have invasive pneumococcal infection have at least one of the previously mentioned underlying medical conditions, or are >/=65 years of age. 3
Patients with underlying medical conditions have high rates of deaths following infection with S. pneumoniae . The case-fatality rate is highest in patients with CHF (27%), followed by patients with a non-hematologic malignancy (22%) and those with renal failure requiring dialysis (20%). Patients with coronary artery disease have a 19% case-fatality rate. 5
A 5-month surveillance study in 1997 of pneumococcal isolates in 21 US medical centers found that 43.8% of these isolates were penicillin-nonsusceptible (MIC >/=0.12 Âµg/mL). High-level penicillin resistance (MIC >/=2 Âµg/mL) was found in 16% of these isolates and the highly penicillin resistant isolates were frequently resistant to other antibiotics, including cephalosporins, macrolides, and trimethoprim-sulfamethoxazole. 14 In 1999, the prevalence of penicillin nonsusceptible isolates was 26.8%, of which 16.5% were resistant (MIC >/=2 Âµg/mL). 6
Approximately 90 serotypes of S. pneumoniae have been identified based on antigenic differences in their capsular polysaccharides. Vaccine serotypes found to be most commonly associated with antimicrobial resistance in an 11-state sampling were 3, 4, 6B, 9V, 12F, 14, 18C, 19A, 19F, 22F, and 23F. 15 Six of these serotypes - 6B, 9V, 14, 19A, 19F, and 23F - accounted for nearly 85% of penicillin-resistant S. pneumoniae in a 13-state survey. 16
Results of Clinical Evaluations
Controlled clinical trials in South Africa involving 12,000 young, adult, male gold miners have shown a 6-valent and a 13-valent pneumococcal vaccine to be 78.5% effective in preventing type-specific pneumococcal pneumonia and 82.3% effective in preventing pneumococcal bacteremia with the serotypes contained in the vaccine. 17
In addition, case-control and serotype-prevalence studies have provided evidence for pneumococcal vaccine effectiveness against invasive disease. These studies have shown a wide variation in vaccine efficacy. In a study of an 8-valent polysaccharide vaccine in a group consisting of 77 patients with sickle cell disease and 19 asplenic persons, there were no pneumococcal infections in the immunized patients within two years of immunization. There were eight cases of pneumococcal infection in 106 unimmunized, age-matched patients with sickle cell disease within a two-year follow-up period, and none in 77 immunized patients. Antibody response of the asplenic patients was comparable to that of normal controls. 18
In a double-blind study of a 14-valent pneumococcal polysaccharide vaccine carried out in 11,958 persons, (5,946 subjects received vaccine and 6,012 subjects received placebo) 10 years of age and over, in Papua, New Guinea, pneumococcal infection (confirmed by blood culture and lung aspirate) was 86% lower (p<0.005) and mortality from pneumonia uncomplicated by chronic lung disease, was 42% lower in the immunized group. 19
Effectiveness of 23-valent pneumococcal polysaccharide vaccine against invasive disease, including bacteremic pneumonia, in case-control studies generally has ranged from 56% to 81%. 20,21,22,23 Analysis of data from national surveillance for pneumococcal disease, using indirect cohort analysis, of 2,837 persons, 6 years of age and older (median age, 57 years in vaccinated group and 50 years in unvaccinated group) demonstrated 60% (95% CI: 30% to 77%) overall protective effectiveness against invasive infections caused by serotypes included in the 23-valent vaccine. 2 Efficacy was 58% (95% CI: 45% to 67%) for bacteremic disease and 46% (95% CI: 12% to 74%) for patients with a cerebrospinal fluid isolate. Vaccine effectiveness of 65% to 84% also was demonstrated among specific patient groups (eg, persons having diabetes mellitus, coronary vascular disease, CHF, chronic pulmonary disease, and anatomic asplenia); vaccine effectiveness could not be demonstrated for other patient groups (alcoholism/cirrhosis, sickle cell disease, chronic renal failure, immunoglobulin deficiency, Hodgkin's disease, non-Hodgkin's lymphoma, leukemia, multiple myeloma). Effectiveness in immunocompetent persons 65 years and older, was 75% (95% CI: 57% to 85%). 2 In contrast, one study with small sample size (N=89) and incomplete ascertainment of immunization status of patients failed to show efficacy in preventing pneumococcal bacteremia. 24
A prospective study of 1,686 elderly (mean age 74 years) nursing home residents in France found that the 14-valent pneumococcal polysaccharide vaccine was 77% effective (CI: 51% to 89%) in reducing the incidence of pneumonia. 25 In another trial of the 14-valent polysaccharide vaccine in 2,295 high-risk United States Veteran's Administration patients (defined as age >55 years with chronic disease) there was no evidence of vaccine efficacy against proven or probable pneumococcal pneumonia or bronchitis. 26 In a Swedish study of a 23-valent pneumococcal polysaccharide vaccine in 691 immunocompetent older adults (50 to 85 years) with previous community-acquired-pneumonia, the vaccine did not protect against new pneumonia, pneumococcal pneumonia, or death. 27
The 23-valent pneumococcal polysaccharide vaccine is not effective for the prevention of common upper respiratory diseases (eg, sinusitis or acute otitis media) in pediatric patients. 28
The polysaccharide capsules of pneumococci enable these organisms to resist the phagocytic action of polymorphonuclear leukocytes and monocytes. Type-specific antibodies that are induced by the 23-valent pneumococcal capsular polysaccharide antigens following immunization facilitate destruction of pneumococci in the body by the mechanism of complement-mediated lysis. 3
In an open-label, single-group study, 31 subjects between the ages of 45 and 65 years were administered one 0.5 mL dose IM of Pneumococcal Vaccine Polyvalent, Pnu-Imune 23. At one month post-immunization, 97% to 100% of subjects showed >/=2-fold increase in antibody titer for each serotype compared to pre-immunization titers. Post-immunization GMTs per serotype showed >/=4-fold increase compared to pre-immunization GMTs. Results are shown in Table 1 below.
In a double-blind, comparative study of 104 healthy adults, subjects were randomly assigned to one of four groups receiving (1) a single dose of a 22-valent pneumococcal vaccine containing 50 Âµg of each serotype; or (2) two vaccinations one month apart of an 8-valent and a 14-valent vaccine containing 50 Âµg of each serotype; or (3) a single dose of a 22-valent vaccine containing 25 Âµg of each serotype; or (4) two vaccinations one month apart of an 8-valent and a 14-valent vaccine containing 25 Âµg of each serotype. Serum antibody responses induced by the capsular antigen serotypes (either 25 Âµg or 50 Âµg) in each vaccine preparation were compared to each other. Two-fold responses to 20 of 22 serotypes were seen when the vaccine was administered as a single dose at either 25 Âµg or 50 Âµg. Serotypes 10A and 11A in the 50 Âµg preparation and serotypes 11A and 12F in the 25 Âµg preparation failed to show a 2-fold increase. Results are displayed in Table 2 below:
Persistence of antibodies was evaluated at 12 months after vaccination. All serotypes except serotypes 5 and 8 maintained or demonstrated >/=2-fold increase over pre-vaccination titers, including the serotypes that had lower fold-rises at one month post-vaccination. 29
Antibody responses to some capsular polysaccharides were lower in elderly bronchitics (>/=55 years; mean age 62 years, n=11) than in healthy young adults (20 to 34 years; mean age 26 years, n=15). 30
Bacterial capsular polysaccharides induce an antibody response primarily by T-cell independent mechanisms. Therefore, children under two years of age, whose immune systems are immature, respond poorly or inconsistently to most capsular polysaccharide serotypes in the vaccine. Responses to some pneumococcal serotypes which occur commonly in pediatric populations (eg, 6A and 14) also are decreased in children 2 to 5 years of age. 3
Patients over the age of 2 years, with anatomical or functional asplenia and otherwise intact lymphoid function, respond to pneumococcal polysaccharide vaccines with antibody levels, measured by a radioimmunoassay technique, comparable with those observed in healthy individuals of the same age. 31
Data on sequential immunization with Prevnar followed by 23-valent pneumococccal polysaccharide vaccine are limited. In a randomized study, 23 children >/=2 years of age with sickle cell disease were administered either 2 doses of Prevnar followed by a dose of polysaccharide vaccine or a single dose of polysaccharide vaccine alone. In this small study, safety and immune responses with the combined schedule were similar to polysaccharide vaccine alone. 32
Patients with acquired immunodeficiency syndrome (AIDS) may show no response to vaccination. 33,34 If they do respond similarly to normal individuals, antibody levels decline within 9 months. 35
Following immunization of healthy adults with pneumococcal polysaccharide vaccines, antibody levels remain elevated (at least 1.4 times increase over pre-immunization levels) for at least 5 years. However, depending on the pneumococcal capsular serotype, antibody levels decline in 30% to 80% of vaccinees within 10 years. 36,37 A more rapid decline in antibodies may occur in certain pediatric patients, particularly those who have undergone a splenectomy, those with sickle cell disease, and those with nephrotic syndrome, in whom antibodies to some serotypes can fall to preimmunization levels 3 to 5 years after immunization. 38,39,40 Antibody concentrations also may decline to pre-immunization levels after 5 to 10 years in healthy adults and the elderly (20 to 79 years). 37,41,42,43
Indications and Usage
Pneumococcal Vaccine Polyvalent, Pnu-Imune 23 is indicated for active immunization against invasive pneumococcal disease and pneumococcal pneumonia caused by those pneumococcal serotypes included in the vaccine. As with any vaccine, Pnu-Imune 23 may not protect 100% of individuals receiving the vaccine. If earlier immunization status is unknown, the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control (CDC) has recommended that persons in the categories below should be vaccinated. 3 Pnu-Imune 23 is not indicated for children under two years of age, since antibody response to most capsular polysaccharide serotypes is poor in this age group. 3 Efficacy in this age group has not been demonstrated.
Available data do not support the routine immunization of healthy individuals with 23-valent pneumococcal polysaccharide vaccine. Recurrent upper respiratory tract diseases, including otitis media and sinusitis, are not specific indications for 23-valent pneumococcal polysaccharide vaccine.
- Immunocompetent adults 65 years of age or older should be immunized, including previously unvaccinated persons and persons who have not received the vaccine within 5 years and were less than 65 years of age at the time of immunization, with emphasis on immunization of the older adult while in good health. 3
- Immunocompetent adults up to 64 years who are at increased risk for pneumococcal disease or its complications if they become infected should be immunized. Persons at increased risk for severe pneumococcal disease include those with chronic illnesses such as cardiovascular disease (eg, CHF or cardiomyopathies), chronic pulmonary diseases (eg, COPD or emphysema), diabetes mellitus, chronic liver disease (eg, cirrhosis), or cerebrospinal fluid leaks. 3
- Otherwise immunocompetent adults up to age 64 who have functional or anatomic asplenia (eg, SCD sickle cell disease or splenectomy) should be immunized. Such persons or their guardians should be informed that immunization may not protect against fulminant pneumococcal disease. 3
Children Aged 24 to 59 months at High Risk of Pneumococcal Infection
- Children aged 24 to 59 months with underlying medical conditions that predispose to pneumococcal infection should receive a single dose of 23-valent pneumococcal polysaccharide vaccine at least 2 months after a 2 dose series of 7-valent pneumococcal conjugate vaccine, Prevnar. Pneumococcal 23-valent polysaccharide vaccine immunization does not substitute for penicillin prophylaxis in children less than 5 years of age with sickle cell disease. 44
- Children aged 24 to 59 months who are Alaskan Natives or in certain Native American populations may benefit from a single dose of 23-valent pneumococcal polysaccharide vaccine at least 2 months after a single dose of 7-valent pneumococcal conjugate vaccine, Prevnar. 44
Children Aged Over 5 Years to Adults at High Risk of Pneumococcal Infection
- Children over 5 years of age to adults with high risk conditions, (such as anatomic or functional asplenia [including sickle cell disease], nephrotic syndrome, cerebrospinal fluid leaks, and conditions associated with immunosuppression) should receive 23-valent pneumococcal polysaccharide vaccine. If these patients receive the 7-valent pneumococcal conjugate vaccine, Prevnar, prior to the 23-valent polysaccharide vaccine, then the 23-valent polysaccharide vaccine should be given at least 2 months after the 7-valent pneumococcal conjugate vaccine, Prevnar. 44
Immunocompromised persons aged 2 years and older, including persons with HIV infection, leukemia, lymphoma, Hodgkin's disease, multiple myeloma, generalized malignancy, chronic renal failure, nephrotic syndrome, or other conditions associated with immunosuppression (eg, organ or bone marrow transplantation); and persons receiving immunosuppressive chemotherapy, including long-term systemic corticosteroids, should be vaccinated. If earlier immunization status is unknown, immunocompromised persons should receive 23-valent pneumococcal polysaccharide vaccine. 3 If immunocompromised persons received 7-valent pneumococcal conjugate vaccine, Prevnar, previously, at least 2 months should elapse before administering 23-valent pneumococcal polysaccharide vaccine. 44
In persons with HIV infection, some studies have shown a transient increase in plasma HIV levels after pneumococcal immunization, while other studies have not demonstrated such an elevation. 41 However, no adverse effects of pneumococcal immunization on HIV patient survival have been reported (see ADVERSE REACTIONS ). 3
Timing of Immunization
When elective splenectomy is being considered, 23-valent pneumococcal polysaccharide vaccine should be given at least two weeks before surgery, if possible. 3
Individuals receiving therapy with immunosuppressive agents (large amounts of corticosteroids, antimetabolites, alkylating agents, cytotoxic agents) may not respond optimally to active immunization procedures. 45 For planning cancer chemotherapy or other immunosuppressive therapy, 23-valent pneumococcal polysaccharide vaccine should be given at least two weeks before initiation of therapy. Immunization during chemotherapy or radiation therapy should be avoided (see WARNINGS ). 3
Persons with asymptomatic or symptomatic HIV infection should be vaccinated as soon as possible after their diagnosis is confirmed. 3
Reimmunization after Previous 23-valent Pneumococcal Polysaccharide Immunization
The ACIP recommends reimmunization as follows:
- Immunocompromised children or children with functional (eg, sickle cell disease) or anatomic (eg, splenectomy), asplenia, nephrotic syndrome, renal failure, renal transplantation, HIV infection, leukemia, lymphoma, Hodgkin's disease, multiple myeloma, generalized malignancies, chronic renal failure and other conditions associated with immunosuppression (organ or bone marrow transplants) and those on immunosuppressive chemotherapy (eg, on long-term corticosteroids) and who are over 10 years of age should be reimmunized with 23-valent pneumococcal polysaccharide vaccine provided 5 years has elapsed since receipt of the first dose of 23-valent pneumococcal polysaccharide vaccine. 4,44
- High-risk children less than 10 years of age should be considered for a single reimmunization with 23-valent pneumococcal polysaccharide vaccine 3 to 5 years after the previous dose of 23-valent pneumococcal polysaccharide vaccine. 4,44
- Persons aged 65 years and older should be administered a second dose of vaccine if they received the vaccine 5 years or more previously and were less than 65 years of age at the time of primary vaccination. Elderly persons with unknown vaccination status should be administered one dose of vaccine. 3
Health care professionals should not administer a second dose of 23-valent pneumococcal polysaccharide vaccine any earlier than 3 years after an initial dose of 23-valent pneumococcal polysaccharide vaccine.
Data are limited regarding adverse events related to 23-valent pneumococcal polysaccharide vaccine administered after 7-valent pneumococcal conjugate vaccine, Prevnar. 44
An early study indicated that local reactions (ie, 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 immunization. 46
Self-limited local injection site reactions of at least 10 cm in diameter occurred more frequently following reimmunization 5 years after the first immunization. However, this risk does not represent a contraindication to reimmunization with 23-valent pneumococcal polysaccharide vaccine for recommended groups. 47
Insufficient data are available to assess the safety of 23-valent pneumococcal polysaccharide vaccine when administered three or more times. Therefore, reimmunization following a second dose is not recommended. 3
HYPERSENSITIVITY TO ANY COMPONENT OF THE VACCINE, INCLUDING THIMEROSAL, A MERCURY DERIVATIVE, IS A CONTRAINDICATION TO THE USE OF THE PRODUCT. THE OCCURRENCE OF ANY TYPE OF AN IMMEDIATE OR DELAYED HYPERSENSITIVITY REACTION OR THE OCCURRENCE OF NEUROLOGICAL SYMPTOMS OR SIGNS FOLLOWING ADMINISTRATION OF THIS PRODUCT IS A CONTRAINDICATION TO FURTHER USE.
Reimmunization is contraindicated for persons who had a severe reaction (eg, anaphylactic reactions or severe local arthus-type reactions) to the initial dose they received. 3
The decision to administer or delay immunization because of a current or recent febrile illness depends largely on the severity of the symptoms and their etiology. Although a severe or even a moderate febrile illness is sufficient reason to postpone immunizations, minor illnesses, such as a mild upper respiratory infection with or without low-grade fever, are not generally contraindications. 48
THIS VACCINE WILL NOT PROTECT AGAINST S. PNEUMONIAE DISEASE OTHER THAN THAT CAUSED BY THE TWENTY-THREE SEROTYPES INCLUDED IN THE VACCINE, NOR WILL IT PROTECT AGAINST OTHER MICROORGANISMS THAT CAUSE PNEUMONIA, MENINGITIS, OR OTHER INVASIVE DISEASE.
Pneumococcal Vaccine Polyvalent, Pnu-Imune 23 is not indicated for children under two years of age, since antibody response to most capsular polysaccharide serotypes is poor in this age group. 3 Efficacy in this age group has not been demonstrated. A 7-valent pneumococcal conjugate vaccine, Prevnar, is licensed for use in children less than 2 years of age. Please see prescribing information for indications and usage for the 7-valent pneumococcal conjugate vaccine, Prevnar.
Immunization may not protect against fulminant pneumococcal disease in patients with functional or anatomic asplenia. 3
Patients with impaired immune responsiveness whether due to the use of immunosuppressive therapy, a genetic defect, HIV infection, or other causes may have a reduced antibody response to any immunization, including 23-valent pneumococcal polysaccharide vaccine. 3
Patients who have received extensive chemotherapy and/or splenectomy for the treatment of Hodgkin's disease have been shown to have an impaired serum antibody response to pneumococcal vaccine. 49,50
In one study, administration of the vaccine to patients on immunosuppressive drugs and/or irradiation for Hodgkin's disease resulted in reduction of pre-existing antibody levels in several patients. 50 It is unclear whether this effect was due to the vaccine or to the effects of irradiation and/or chemotherapy.
Pneumococcal Vaccine Polyvalent, Pnu-Imune 23 should be given with caution to patients with thrombocytopenia, or any coagulation disorder, or to those receiving anticoagulant therapy; the preferred route of administration in these patients is subcutaneous injection.
At least two weeks should elapse between immunization and the initiation of chemotherapy or immunosuppressive therapy. 3 Immunization during chemotherapy or radiation therapy should be avoided. 3
Routine reimmunization with this vaccine is not recommended. Â Â For recommendations regarding reimmunization of individuals at highest risk of fatal pneumococcal infection (see INDICATIONS AND USAGE -- Reimmunization ).
Patients who have had episodes of pneumococcal pneumonia or other pneumococcal infection may have high levels of preexisting pneumococcal antibodies that may result in increased reactions to Pnu-Imune 23, mostly local, but occasionally systemic. 51 Caution should be exercised if such patients are considered for immunization with Pnu-Imune 23.
DO NOT ADMINISTER THE VACCINE INTRAVENOUSLY OR INTRADERMALLY SINCE SEVERE REACTIONS MAY OCCUR.
Health care professionals should prescribe and/or administer this product with caution to patients with a possible history of latex sensitivity since this package contains dry natural rubber.
- This product should not be used in children under 2 years of age.
- PRIOR TO ADMINISTRATION OF ANY DOSE OF PNU-IMUNE 23, THE PARENT, GUARDIAN, OR ADULT PATIENT SHOULD BE ASKED ABOUT THE RECENT HEALTH STATUS, MEDICAL AND IMMUNIZATION HISTORY OF THE PATIENT TO BE IMMUNIZED TO DETERMINE THE EXISTENCE OF ANY CONTRAINDICATION TO IMMUNIZATION WITH PNEUMOCOCCAL VACCINE AND TO ALLOW AN ASSESSMENT OF RISKS AND BENEFITS (SEE CONTRAINDICATIONS AND WARNINGS ).
- BEFORE ADMINISTRATION OF ANY BIOLOGICAL, THE HEALTH CARE PROFESSIONAL SHOULD TAKE ALL PRECAUTIONS KNOWN FOR THE PREVENTION OF ALLERGIC OR ANY OTHER ADVERSE REACTIONS. This should include a review of the patient's history regarding possible sensitivity; the ready availability of epinephrine 1:1,000 and other appropriate agents used for control of immediate allergic reactions; and a knowledge of the recent literature pertaining to use of the biological concerned, including the nature of side effects and adverse reactions that may follow its use.
- A separate sterile syringe and needle or a sterile disposable unit should be used for each individual patient to prevent transmission of infectious agents from one person to another.
- Do not inject intradermally, or into or near a blood vessel or nerve.
- Health care professionals should administer this product with caution to patients with a possible history of latex sensitivity, since its packaging contains dry natural rubber.
- Do not mix with other vaccines.
Information for Patients
PRIOR TO ADMINISTRATION OF THIS VACCINE, THE HEALTH CARE PROFESSIONAL SHOULD INFORM THE PARENT, GUARDIAN, OR ADULT PATIENT OF THE POTENTIAL BENEFITS AND RISKS TO THE PATIENT (SEE ADVERSE REACTIONS AND WARNINGS SECTIONS). PARENTS, GUARDIANS, OR THE ADULT PATIENT SHOULD BE INSTRUCTED TO REPORT ANY SUSPECTED ADVERSE REACTIONS TO THEIR HEALTH CARE PROFESSIONAL. THE HEALTH CARE PROFESSIONAL SHOULD PROVIDE VACCINE INFORMATION STATEMENTS PRIOR TO EACH IMMUNIZATION.
Individuals receiving therapy with immunosuppressive agents may not respond optimally to active immunization procedures. At least two weeks should elapse between immunization and subsequent initiation of chemotherapy or immunosuppressive therapy. 3
Immunization during chemotherapy or radiation therapy should be avoided (see WARNINGS ). 3
Carcinogenesis, Mutagenesis, and Impairment of Fertility
Pnu-Imune 23 has not been evaluated for its carcinogenic or mutagenic potential or for its effects on fertility.
Pregnancy: Teratogenic Effects
Pregnancy Category C: Â Â Animal reproduction studies have not been conducted with Pnu-Imune 23. It is also not known whether Pnu-Imune 23 can cause fetal harm when administered to a pregnant woman or affect reproductive capacity. Pnu-Imune 23 is not recommended for use in pregnant women.
It is not known whether the vaccine antigens or antibodies resulting from stimulation by vaccine polysaccharides are excreted in human milk. Therefore, in the absence of data, caution should be exercised when Pnu-Imune 23 is administered to a nursing woman.
The safety and effectiveness of 23-valent pneumococcal polysaccharide vaccine in pediatric populations under 2 years of age have not been established. Children under 2 years of age respond poorly or inconsistently to most capsular polysaccharide serotypes in the vaccine (see CLINICAL PHARMACOLOGY -- Immunogenicity , INDICATIONS AND USAGE , and DOSAGE AND ADMINISTRATION ). 3
Twenty-three-valent pneumococcal polysaccharide vaccine is recommended for persons >/=65 years of age, including previously unvaccinated persons and persons who have not received 23-valent pneumococcal polysaccharide vaccine within 5 years (and were <65 years of age at the time of immunization). 3
After immunization, antibody concentrations and responses to individual antigens may be lower in the elderly than those seen among healthy young adults. However, the levels of antibodies that correlate with pneumococcal disease protection have not been clearly defined. 3
Adverse events reported in a pre-licensure United States clinical trial (N=31) with Pnu-Imune 23 included:
Local:Â Â Injection site pain or tenderness, erythema, induration, swelling
Systemic:Â Â Fever, chills, malaise, myalgia, headache, irritability, poor appetite, rash
Additional adverse events reported in post-marketing experience include:
Injection Site: Â Â inflammation, skin discoloration, warmth, mass, hypersensitivity reaction
Body as a Whole: Â Â fatigue
Dermatologic: Â Â vesiculobullous rash
Digestive System: Â Â nausea, vomiting
Hematologic/Lymphatic: Â Â adenitis, relapse of thrombocytopenia in patients with stabilized idiopathic thrombocytopenic purpura
Hypersensitivity: Â Â anaphylactoid reactions, urticaria, pruritus
Musculoskeletal System: Â Â arthritis, arthralgia
Nervous System: Â Â dizziness, paresthesias, acute radiculoneuropathy, including Guillain-BarrÃ© syndrome
In a comparative study of adults aged 50 to 74 years, local injection site reactions were significantly more common among subjects who received revaccination of Pneumococcal Vaccine Polyvalent, Pnu-Imune 23 >/=5 years after their first vaccination than among those being vaccinated for the first time. Specifically, within the first two days following vaccination, arm soreness was reported among 74% of 513 revaccinated subjects as compared to 57% of 901 subjects vaccinated for the first time. Sizable local reactions are shown in Table 3 excerpted from JAMA 1999. 47
Preliminary data have suggested that the 23-valent pneumococcal polysaccharide vaccine may cause a transient increase in plasma HIV levels; however, the importance of this occurrence is not known (see INDICATIONS AND USAGE -- Immunocompromised Patients ). 3
Health care professionals should report suspected adverse events after administration of Pnu-Imune 23 to the Vaccine Adverse Event Reporting System (VAERS) by calling (800) 822-7967. 3
There have been reports of overdose with Pnu-Imune 23. Most cases have involved inadvertent reimmunization at varying intervals following initial immunization. Most individuals were asymptomatic. Events experienced primarily consisted of injection site reactions.
Dosage and Administration
The immunization schedule consists of a single 0.5 mL dose given intramuscularly or subcutaneously. Intradermal administration should be avoided. Do not inject into or near a blood vessel or nerve.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration (see DESCRIPTION ).
Before injection, the skin at the injection site should be cleansed with a suitable germicide. After insertion of the needle, aspirate and wait to see if any blood appears in the syringe, which will help avoid inadvertent injection into a blood vessel. If blood appears, withdraw the needle and prepare for a new injection at another site.
Simultaneous Administration with Other Vaccines
A comparative study of simultaneous administration of influenza and pneumococcal vaccines versus sequential administration of influenza followed by pneumococcal vaccine a month later, in 152 adults with chronic respiratory disease, showed no difference in immunogenicity of either the pneumococcal (Pnu-Imune 23) or of the influenza vaccine. There was no increase in the incidence or severity of adverse effects when the vaccines were administered concomitantly. 52 In a cohort study conducted in a managed care organization among elderly individuals with chronic lung disease, receipt of both influenza and pneumococcal vaccines was associated with a 63% reduction (95% CI: 29% to 90%) in the risk of hospitalization for pneumonia and 81% reduction (95% CI: 68% to 88%) in the risk of death, when compared to no vaccination. There was no evidence of interaction of vaccines. 53
The ACIP advises that influenza vaccine may be given simultaneously with 23-valent pneumococcal polysaccharide vaccine at a different site (by separate injection in the other arm). 3 However, influenza vaccine is administered annually, while pneumococcal vaccine typically is administered only once for persons in most groups (see INDICATIONS AND USAGE -- Reimmunization ). The ACIP states that 23-valent pneumococcal polysaccharide vaccine also may be administered concurrently with other vaccines. 3 However, data are unavailable concerning the effects on safety and immune response of Pnu-Imune 23 when given concurrently with DT, DTP, DTaP, Td, or poliovirus vaccines.
Pnu-Imune 23 is supplied as follows:
NDC 0005-2309-31 2.5 mL Vial, for use with syringe only.
NDC 0005-2309-33 5 Ã— One Dose, 0.5 mL fill in 1 mL size (25 gauge Ã— 5/8" needle) LEDERJECT Disposable Syringes.
DO NOT FREEZE. STORE REFRIGERATED, AWAY FROM FREEZER COMPARTMENT AT 2Â°C to 8Â°C (36Â°F to 46Â°F).
Directions for Use of the LEDERJECT Disposable Syringe
- Twist the plunger rod clockwise to be sure the rod is secure to rubber plunger base.
- Hold needle shield in place with index finger and thumb of one hand while, with the other thumb, exert light pressure on plunger rod until the plunger base has been freed and demonstrates slight movement when pressure is applied.
- Grasp the plastic shield at its base; twist and pull to remove.
- To prevent needle-stick injuries, needles should not be recapped, purposely bent, or broken by hand. Pneumococcal Vaccine Polyvalent, Pnu-Imune 23 disposable LEDERJECT syringes must never be reused. The syringe should be discarded into an impenetrable sharps container without recapping.
- Robbins JB, Austrian R, Lee CJ, et al. Considerations for formulating the second-generation pneumococcal capsular polysaccharide vaccine with emphasis on the cross-reactive types within groups. J Infect Dis. 1983;148(6):1136-1159.
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- Mandell GL, Bennett, JE, Dolin R. Principles and Practices of Infectious Diseases . 4th ed. New York, N.Y. Churchill Livingstone Inc; 1995:1812-1813.
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- Centers for Disease Control and Prevention. Active bacterial core surveillance (ABCs) Report. Emerging infections program network: Streptococcus pneumoniae , 1999. 2000; Nov 15.
- Davidson M, Parkinson AJ, Bulkow LR, Fitzgerald MA, Peters HV, Parks DJ. The epidemiology of invasive pneumococcal disease in Alaska, 1986-1990-Ethnic differences and opportunities for prevention. J. Infect Dis. 1994;170:368-376.
- Cortese MM, Wolff M, Almeido-Hill J, Reid R, Ketcham J, Santosham M. High incidence rates of invasive pneumococcal disease in the White Mountain Apache population. Arch Intern Med. 1992; 152:2277-2282.
- Breiman RB, Spika JS, Navarro VJ, Darden PM, Darby CP. Pneumococcal bacteremia in Charleston County, South Carolina. Arch Intern Med. 150:1401-1405.
- Bennett NM, Buffington J, LaForce FM. Pneumococcal bacteremia in Monroe County, New York. Am J Public Health 1992;82:1513-1516.
- Hook EW, Horton CA, Schaberg DR. Failure of intensive care unit support to influence mortality from pneumococcal bacteremia. JAMA. 1983;249(8):1055-1057.
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- Doern GV, Pfaller MA, Kugler K, Freeman J, Jones RN. Prevalence of antimicrobial resistance among respiratory tract isolates of Streptococcus pneumoniae in North America: 1997 results from the SENTRY antimicrobial surveillance program. Clin Infect Dis. 1998;27:764-770.
- Butler JC, Hofmann J, Cetron MS, Elliott JA, Facklam RR, Breiman RF, and the Pneumococcal Sentinel Surveillance Working Group. The continued emergence of drug-resistant Streptococcus pneumoniae in the United States: An update from the Centers for Disease Control and Prevention's Pneumococcal Sentinel Surveillance System. J Infect Dis. 1996;174:986-993.
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- Austrian R, Douglas RM, Schiffman G, et al. Prevention of pneumococcal pneumonia by vaccination. Trans Assoc Am Phys. 1976;89:184-194.
- Ammann AJ, Addiego J, Wara DW, Lubin B, Smith WB, Mentzer WC. Polyvalent pneumococcal-polysaccharide immunization of patients with sickle cell anemia and patients with splenectomy. N Engl J Med. 1977;297:897-900.
- Riley ID, Tarr PI, Andrews M, et al. Immunisation with a polyvalent pneumococcal vaccine: Reduction of adult respiratory mortality in a New Guinea Highlands community. Lancet. 1977;1:1338-1341.
- Shapiro ED, Berg AT, Austrian R, et al. The protective efficacy of polyvalent pneumococcal polysaccharide vaccine. N Engl J Med. 1991;325(21):1453-1460.
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- Ortqvist A, Hedlund J, Burman L-A, et al and the Swedish Pneumococcal Vaccination Study Group. Randomised trial of 23-valent pneumococcal capsular polysaccharide vaccine in prevention of pneumonia in middle-aged and elderly people. Lancet . 1998;351:399-403.
- Douglas RM, Miles HB. Vaccination against Streptococcus pneumoniae in childhood: Lack of demonstrable benefit in young Australian children. J Infect Dis. 1984;149(6):861-869.
- Data on file, Lederle Laboratories.
- Musher DM, Luchi MJ, Watson DA, Hamilton R, Baughn RE. Pneumococcal polysaccharide vaccine in young adults and older bronchitics: Determination of IgG responses by ELISA and the effect of adsorption of serum with non-type specific cell wall polysaccharide. J Infect Dis. 1990;161:728-735.
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- Vernacchio L, Neufeld EJ, MacDonald K, et al. Combined schedule of 7-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal vaccine in children and young adults with sickle cell disease. J. Pediatr . 1998;133(2):275-278.
- Carson PJ, Schut RL, Simpson ML, O'Brien J, Janoff EN. Antibody class and subclass responses to pneumococcal polysaccharides following immunization of human immunodeficiency virus-infected patients. J Infec Dis. 1995;172:340-345.
- Rodriquez-Barradas MC, Groover JE, Lacke CE, et al. IgG antibody to pneumococcal capsular polysaccharide in human immunodeficiency virus-infected subjects: persistence of antibody in responders, revaccination in non-responders, and relationship of immunoglobulin allotype to response. J Infect Dis. 1996;173:1347-1353.
- Mascart-Lemone F, Gerard M, Libin M, et al. Differential effect of human immunodeficiency virus infection on the IgA and IgG antibody responses to pneumococcal vaccine. J Infect Dis. 1995;172:1253-1260.
- Mufson MA, Krause HE, Schiffman G. Long term persistence of antibodies following immunization with pneumococcal polysaccharide vaccine. Proc Soc Exp Bio Med. 1983;173:270-275.
- Mufson MA, Krause HE, Schiffman G, Hughey DF. Pneumococcal antibody levels one decade after immunization of healthy adults. Am J Med Sci. 1987;293(5):279-284.
- Giebink GS, Le CT, Schiffman G. Decline of serum antibody in splenectomized children after vaccination with pneumococcal capsular polysaccharides. J Pediatr. 1984;105:576-582.
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- Siber GR, Gorham C, Martin P, Corkery JC, Schiffman G. Antibody response to pre-treatment immunization and post-treatment boosting with bacterial polysaccharide vaccines in patients with Hodgkin's disease. Ann Intern Med. 1986;104:467-475.
- Siber GR, Weitzman SA, Aisenberg AC, Weinstein HJ, Schiffman G. Impaired antibody response to pneumococcal vaccine after treatment for Hodgkin's disease. N Engl J Med. 1978;299:442-448.
- Ponka A, Leinonen M. Adverse reactions to polyvalent pneumococcal vaccine. Scand J Infect Dis. 1982;14:67-71.
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Division American Cyanamid Company
Pearl River, NY 10965 USA
US GOVT. LICENSE NO. 17
Â Â V A C C I N E S
Philadelphia, PA 19101 USA
CI 7576-1 Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Issued May 10, 2002
PRODUCT PHOTO(S):NOTE: These photos can be used only for identification by shape, color, and imprint. They do not depict actual or relative size.
The product samples shown here have been supplied by the manufacturer. While every effort has been made to assure accurate reproduction, please remember that any visual identification should be considered preliminary. In cases of poisoning or suspected overdosage, the drug's identity should be verified by chemical analysis.