| PNEUMOVAX® 23 |
|Pneumococcal Vaccine, Polyvalent |
|Pneumococcal Infection Immunization |
|Action And Clinical Pharmacology: Pneumococcal infection is a leading cause of death throughout the world and a major cause of pneumonia, meningitis and otitis media. The emergence of strains of pneumococci with increased resistance to one or more of the common antibiotics and recent isolations of pneumococci with multiple antibiotic resistance emphasize the importance of vaccine prophylaxis against pneumococcal disease. Based on projection from limited observations in the United States, it has been estimated that 400 000 to 500 000 cases of pneumococcal pneumonia may occur annually. The overall case fatality rate ranges from 5 to 10%. About 25% of all persons with pneumococcal pneumonia develop bacteremia. Death occurs in about 28% of these bacteremic patients more than 50 years of age.
The annual incidence of pneumococcal meningitis is 1.1 per 100 000 population with an overall fatality rate of 19% (children, 6%; adults, 30%). Children with sickle cell disease have been estimated to have a risk of pneumococcal meningitis nearly 600 times greater than normal children.
Invasive pneumococcal disease causes high morbidity and mortality in spite of effective antimicrobial control by antibiotics. These effects of pneumococcal disease appear due to irreversible physiologic damage caused by the bacteria during the first 5 days following onset of illness, and occur irrespective of antimicrobial therapy. Older persons, individuals with chronic debilitating diseases, and persons with absent or impaired splenic function, including those with homozygous sickle cell anemia and sickle thalassemia, are especially susceptible to severe pneumococcal disease.
Presently, there are 83 known pneumococcal capsular types. However, the preponderance of pneumococcal disease is caused by only some capsular types. For example, a 10-year (1952 to 1962) surveillance at a New York medical center showed that 56% of all deaths due to pneumococcal pneumonia were caused by 6 capsular types and that approximately 78% of all pneumococcal pneumonias were caused by 12 capsular types. Such unequal distribution of pneumococcal capsular types causing disease has been shown throughout the world. It is on the basis of this information that the pneumococcal vaccine is composed of 23 capsular types, designed to provide coverage of approximately 90% of the most frequently reported types.
It has been established that the purified pneumococcal capsular polysaccharides induce antibody production and that such antibody is effective in preventing pneumococcal disease. Studies in humans have demonstrated the immunogenicity (antibody-stimulating capability) of each of the 23 capsular types when tested in polyvalent vaccines. Adults of all ages responded immunologically to the vaccines. Earlier studies with 12- and 14-valent pneumococcal vaccines in children 2 years of age and older and in adults showed immunogenic responses.
The protective efficacy of pneumococcal vaccines containing 6 and 12 capsular polysaccharides was investigated in controlled studies of gold miners in South Africa, in whom there is a high attack rate for pneumococcal pneumonia. Capsular type-specific attack rates for pneumococcal pneumonia were observed for the period from 2 weeks through about 1 year after vaccination. The rates for pneumonia caused by the same capsular types represented in the vaccines are given below. See Table I. Protective efficacy was 76% and 92%, respectively, in the 2 studies for the capsular types represented.
In similar studies carried out by Dr. R. Austrian and associates using similar pneumococcal vaccines, prepared for the National Institutes of Allergy and Infectious Disease by a different source, the reduction in pneumonias caused by the vaccine capsular types was 79%. Type-specific reduction in pneumococcal bacteremia was 82%. A preliminary report suggests efficacy of the vaccine in persons over 2 years of age in preventing severe pneumococcal disease and bacteremia in patients with sickle cell anemia and in individuals without spleens or those who have impaired splenic function.
The duration of protective effect of pneumococcal vaccine is presently unknown, but it has been shown in previous studies with other pneumococcal vaccines that antibody induced by the vaccine may persist for as long as 5 years. Type-specific antibody levels induced by pneumococcal vaccine (14-valent) have been observed to decline over a 42-month period of observation, but remain significantly above prevaccination levels in almost all recipients who manifest an initial response.
Indications And Clinical Uses: For immunization against pneumonia and bacteremia, caused by those types of pneumococci included in the vaccine, in all persons 2 years of age or older in whom there is an increased risk of morbidity and mortality from pneumococcal pneumonia. These include: (1) persons having chronic physical conditions such as chronic heart disease of any etiology, chronic bronchopulmonary diseases, chronic renal failure, and chronic metabolic disorders; (2) persons convalescing from severe disease; (3) persons 50 years of age or older who in the opinion of their physician are at increased risk of pneumococcal pneumonia.
Earlier studies suggest the 12- and 14-valent pneumococcal vaccines are efficacious for preventing severe pneumonic disease and bacteremia in persons over 2 years of age with sickle cell anemia and in individuals who have had a splenectomy or who have impaired splenic function, and in pediatric patients over 2 years of age with nephrotic syndrome. It is expected also that the vaccine will be found effective in preventing pneumococcal meningitis of bacteremic origin. However, pneumococcal vaccine may not be effective in preventing infection resulting from basilar skull fracture or from external communication with cerebrospinal fluid.
Use with other Vaccines: Simultaneous administration of pneumococcal polysaccharide vaccine and whole-virus influenza vaccine gives satisfactory antibody response without increasing the occurrence of adverse reactions. Simultaneous administration of the pneumococcal vaccine and split-virus influenza vaccine may also be expected to yield satisfactory results.
Revaccination: Adults: Routine revaccination of adults is not recommended; however, revaccination is recommended for adults with chronic conditions which increase the risk of fatal pneumococcal infection and for those shown to have a rapid decline in pneumococcal antibody levels (e.g., patients with nephrotic syndrome, renal failure, or transplant recipients).
One hundred ninety-eight subjects, participated in a randomized, double-blind, placebo-controlled study to compare the safety and tolerance of pneumococcal vaccine revaccination to placebo, in a group of subjects who had been immunized 4 or more years previously. Twenty-five subjects with no prior history of pneumococcal vaccination were in an open study group which served as a positive control for the lot of pneumococcal vaccine used. The demographic characteristics of the subjects enrolled in this study are shown in Table II.
The rate of local injection site reactions was higher for the Pneumovax 23 revaccination group than the placebo group, and the local reactions in the Pneumovax 23 revaccination group tended to have slightly longer duration than did those in the placebo group. However, the rate and duration of local injection site reactions in the Pneumovax 23 revaccination group were not significantly different from those in the primary vaccinee group, and almost all of the local reactions in the Pneumovax 23 revaccination group were of mild intensity. All 3 groups had similar rates of systemic adverse events.
Based on the above-mentioned clinical study, revaccination with pneumococcal vaccine is recommended for adults at highest risk of fatal pneumococcal infection who were initially vaccinated with pneumococcal vaccine 4 or more years previously without a serious or severe reaction.
In addition, the National Advisory Committee on Immunization (NACI) and the U.S. Immunization Practices Advisory Committee (ACIP) recommend that revaccination should be considered for adults at highest risk who received the 23-valent vaccine 6 or more years previously.
Because of an increased incidence and severity of adverse reactions among healthy adults revaccinated with pneumococcal vaccines at intervals under 3 years, routine revaccination with pneumococcal vaccine is not recommended. This was probably due to sustained high antibody levels. Also, persons who received the 14-valent vaccine should not be routinely revaccinated with the 23-valent vaccine, as increased coverage is modest and duration of protection is not well defined.
Children: The National Advisory Committee on Immunization (NACI) and the U.S. Immunization Practices Advisory Committee (ACIP) recommend that revaccination after 3 to 5 years should be considered for children at highest risk for pneumococcal infection (e.g., children with asplenia, sickle cell disease or nephrotic syndrome) who would be 10 years old or younger at revaccination.
Children at highest risk for pneumococcal infection may have lower peak antibody levels and/or more rapid antibody decline than do healthy adults. There is evidence that some of these high-risk children (e.g., asplenic children) benefit from revaccination with vaccine containing antigen 7F, 8, 19F.
Contra-Indications: Hypersensitivity to any component of the vaccine. Epinephrine injection (1:1 000) must be immediately available should an acute anaphylactoid reaction occur due to any component of the vaccine.
Revaccination with pneumococcal vaccine is contraindicated except as described under Indications.
Patients with Hodgkin's disease immunized less than 7 to 10 days prior to immunosuppressive therapy have in some instances been found to have postimmunization antibody levels below their preimmunization levels. Because of these results immunization less than 10 days prior to or during treatment is contraindicated. Patients with Hodgkin's disease who have received extensive chemotherapy and/or nodal irradiation have been shown to have an impaired antibody response to a 12-valent pneumococcal vaccine. Because, in some intensively treated patients, administration of that vaccine depressed pre-existing levels of antibody to some pneumococcal types, pneumococcal vaccine is not recommended at this time for patients who have received these forms of therapy for Hodgkin's disease.
Manufacturers' Warnings In Clinical States: The pneumococcal vaccine will not immunize against capsular types of pneumococcus other than those contained in the vaccine.
If the vaccine is used in persons receiving immunosuppressive therapy, the expected serum antibody response may not be obtained.
Intradermal administration may cause severe local reactions.
In patients who require penicillin (or other antibiotics) prophylaxis against pneumococcal infection, such prophylaxis should not be discontinued after immunization with pneumococcal vaccine.
Precautions: General: Any febrile respiratory illness or other active infection is reason for delaying use of pneumococcal vaccine, except when, in the opinion of the physician, withholding the agent entails even greater risk.
Caution and appropriate care should be exercised in administering pneumococcal vaccine to individuals with severely compromised cardiac and/or pulmonary function in whom a systemic reaction would pose a significant risk.
Pregnancy: It is not known whether pneumococcal vaccine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. The pneumococcal vaccine should be given to a pregnant woman only if clearly needed.
Lactation : It is not known whether this vaccine is excreted in human milk. Caution should be exercised when pneumococcal vaccine is administered to a nursing woman.
Children: Children under 2 years of age may not obtain a satisfactory antibody response to pneumococcal capsular types. Safety and effectiveness in children below the age of 2 years have not been established. Therefore, the vaccine should not be used in this age group.
Adverse Reactions: Common: local injection site soreness, erythema and induration.
Occasional: Body as a whole: low grade fever (<38.3°C).
Rare: Body as a whole: headache, fever (>39°C), malaise, asthenia.
Hypersensitivity: anaphylactoid reactions, serum sickness.
Musculoskeletal: arthralgia, myalgia, arthritis.
Skin: rash, urticaria.
Patients with otherwise stabilized idiopathic thrombocytopenic purpura have, on rare occasions, experienced a relapse in their thrombocytopenia, occurring 2 to 14 days after vaccination, and lasting up to 2 weeks.
Reactions of greater severity, duration, or extent are unusual. Neurological disorders such as paresthesias and acute radiculoneuropathy including Guillain-Barré syndrome have been rarely reported in temporal association with administration of pneumococcal vaccine. No cause and effect relationship has been established.
Dosage And Administration: Do not inject i.v.
REG>Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The pneumococcal vaccine is a clear, colorless solution.
Administer a single 0.5 mL dose of the pneumococcal vaccine s.c. or i.m. (preferably in the deltoid muscle or lateral midthigh), with appropriate precautions to avoid intravascular administration (see Indications). Intradermal administration should be avoided.
The vaccine is used directly as supplied. No dilution or reconstitution is necessary. Phenol in 0.25% concentration is present in the vaccine as a preservative.
Use a separate sterile syringe and needle free of preservatives, antiseptics and detergents for each individual patient.
It is important to use a separate sterile syringe and needle for each individual patient to prevent transmission of hepatitis B and other infectious agents from one person to another.
Availability And Storage: Each 0.5 mL dose contains: 25 µg of each polysaccharide type dissolved in isotonic saline solution containing phenol 0.25% as preservative. See Table III.
Single dose vials. Cartons of 1, boxes of 5. Store vials at 2 to 8°C. All vaccines must be discarded by the expiration date.