Pnu-Imune 23 (Pneumococcal Vaccine)

PNU-IMUNE® 23

Wyeth-Ayerst

Pneumococcal Vaccine Polyvalent

Active Immunizing Agent

Action And Clinical Pharmacology: Disease caused by S. pneumonia remains an important cause of morbidity and mortality particularly in the very young, the elderly and persons with certain high-risk conditions. The overall incidence of pneumococcal infections in Canada is not known. In 1992, 132 cases of pneumococcal meningitis were reported in Canada. In England, 34% of pneumonias in adults have been attributed to the pneumococcus.

Studies in the United States have detected rates of pneumococcal bacteremia of 15 to 19/100 000 for all persons, 50/100 000 for persons ³65 years of age and 160/100 000 for children £2 years old. Certain population groups, e.g., Native Americans, may have considerably higher disease rates.

Mortality from pneumococcal disease is highest in patients with bacteremia or meningitis, patients with underlying medical conditions, and older persons. In some high-risk patients, mortality has been reported to be over 40% for bacteremic disease and 55% for meningitis, despite appropriate antimicrobial therapy.

In addition to the young and persons 65 years of age and older, patients with certain chronic conditions are at increased risk of developing pneumococcal infection and severe pneumococcal illness. Patients with chronic cardiovascular or pulmonary disease, diabetes mellitus, alcoholism and cirrhosis are generally immunocompetent but have increased risk. Other patients at greater risk because of decreased responsiveness to polysaccharide antigens or more rapid decline in serum antibody include those with functional or anatomic asplenia (e.g., sickle cell disease or splenectomy), Hodgkin’s disease, lymphoma, multiple myeloma, chronic renal failure, nephrotic syndrome and organ transplantation. Studies indicate that patients with acquired immunodeficiency syndrome (AIDS) are also at increased risk of pneumococcal disease. Recurrent pneumococcal meningitis may occur in patients with cerebrospinal fluid leakage that complicates skull fractures or neurologic procedures.

The polysaccharide capsules of pneumococci give these organisms resistance to the phagocytic action of polymorphonuclear leukocytes and monocytes. However, type-specific antibody facilitates their destruction in the body by the mechanism of complement-medicated lysis.

Most healthy adults, including the elderly, demonstrate at least a 2-fold rise in type-specific antibodies within 2 or 3 weeks of immunization. Similar antibody responses have been reported in patients with alcoholic cirrhosis and diabetes mellitus. In contrast, elderly individuals with chronic pulmonary disease failed to mount a comparable immune response. In immunocompromised patients, the response to immunization may also be lower. Children under 2 years of age respond poorly to most capsular polysaccharide types. Further, response to some pneumococcal types (e.g., 6A and 14) important in pediatric infection is decreased in children less than 5 years of age.

In clinical studies with pneumococcal vaccine polyvalent, more than 90% of all adults showed 2-fold or greater increase in geometric mean antibody titre for each capsular type contained in the vaccine.

Patients over the age of 2 years with anatomical or functional asplenia and otherwise intact lymphoid function generally respond to pneumococcal vaccines with a serological conversion comparable to that observed in healthy individuals of the same age.

Patients with acquired immunodeficiency syndrome (AIDS) may have an impaired antibody response to pneumococcal vaccine. However, asymptomatic human immunodeficiency virus (HIV)-infected patients, or those with generalized lymphadenopathy, respond to the 23-valent pneumococcal vaccine.

Following immunization of healthy adults, antibody levels remain elevated for at least 5 years, but in some individuals these may fall to preimmunization levels within 10 years. A more rapid decline in antibodies may occur in children, particulary those who have undergone a splenectomy and those with sickle cell disease, in whom antibodies for some types can fall to preimmunization levels 3 to 5 years after immunization. Similar rates of decline can occur in children with nephrotic syndrome.

Controlled clinical trials in South Africa involving 12 000 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 types contained in the vaccine. In a preliminary 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 2 years of immunization. There were 8 cases of pneumococcal infection in 106 unimmunized, age-matched patients with sickle-cell disease. Antibody response to the asplenic patients was comparable to that of normal controls.

In a study carried out by Austrian and colleagues with 13-valent pneumococcal vaccines prepared for the National Institute of Allergy and Infectious Disease, the reduction in pneumonias caused by the capsular types present in the vaccines was 79%. Reduction in type-specific pneumococcal bacteremia was 82%.

In a double-blind study of a 14-valent pneumococcal vaccine carried out in Papua, New Guinea, pneumococcal infection was 84% lower in the immunized group and mortality from pneumonia 44% lower.

Five case-control studies in the U.S. have evaluated the efficacy of pneumococcal vaccine in the prevention of serious pneumococcal disease. Four of these studies showed the vaccine to be efficacious, with point estimates of efficacy ranging from 61 to 70%. One study failed to show efficacy in preventing pneumococcal bacteremia. This study was judged inadequate in determination of vaccination status and the selection of controls was considered potentially biased.

A prospective study failed to demonstrate efficacy against pneumococcal pneumonia and bronchitis. This study has been criticized for methodological flaws. In contrast, a prospective French study found pneumococcal vaccine to be 77% effective in reducing the incidence of pneumonia among nursing home residents.

Despite conflicting findings, the data continue to support the use of pneumococcal vaccine for certain well-defined groups at risk.

Indications And Clinical Uses: For immunization against pneumococcal disease caused by those pneumococcal types included in the vaccine.

Children: Children 2 years of age or older with chronic illnesses specifically associated with increased risk of pneumococcal disease or its complications (e.g., anatomic or functional asplenia [including sickle-cell disease], nephrotic syndrome, cerebrospinal fluid leaks, and conditions associated with immunosuppression).

Adults: All adults 65 or older with emphasis on immunization of the older adult while in good health.

Immunocompetent adults who are at increased risk of pneumococcal disease or its complications because of chronic illness (e.g., cardiovascular or pulmonary disease, diabetes mellitus, alcoholism, cirrhosis, or cerebrospinal fluid leaks).

Immunocompromised adults at increased risk of pneumococcal disease or its complications (e.g., splenic dysfunction or anatomic asplenia, Hodgkin’s disease, lymphoma, multiple myeloma, chronic renal failure, nephrotic syndrome, or conditions such as organ transplantation associated with immunosuppression).

Special Groups: Persons living in special environments or social settings with an identified increased risk of pneumococcal disease or its complications.

Patients with acquired immunodeficiency syndrome (AIDS) have been shown to have an impaired antibody response to pneumococcal vaccine. However, asymptomatic or symptomatic human immunodeficiency virus (HIV)-infected patients or those with persistent generalized lymphadenopathy respond to the 23-valent vaccine.

Timing of Immunization: When elective splenectomy is being considered, pneumococcal vaccine should be given at least 2 weeks before surgery, if possible.

For planning cancer chemotherapy or other immunosuppressive therapy, the interval between immunization and initiation of chemotherapy or immunosuppression should be at least 2 weeks.

Contra-Indications: Hypersensitivity to any component of the vaccine, including thimerosal, a mercury derivative, is a contraindication to the use of the product.

Revaccination of adults is contraindicated. Adults previously immunized with any polyvalent pneumococcal vaccine should not receive pneumococcal vaccine polyvalent since an increased incidence and severity of adverse reactions among healthy adults receiving such reinjections have been noted most likely due to sustained high antibody levels.

The occurrence of any type of neurological symptoms or signs following administration of this product is a contraindication to further use.

Immunization should be deferred during the course of any febrile illness or acute infection. A minor illness such as mild upper respiratory infection is usually not a reason to defer immunization.

The clinical judgment of the attending physician should prevail at all times.

Manufacturers’ Warnings In Clinical States: Pneumococcal vaccine polyvalent is not recommended for children under two years of age, since antibody response to most capsular polysaccharide types is poor in this age group.

Pneumococcal Vaccine Polyvalent is not an effective agent for prophylaxis against capsular types of pneumococcus other than those contained in the vaccine.

Patients with impaired immune responsiveness whether due to the use of immunosuppressive therapy, a genetic defect, human immunodeficiency virus (HIV) infection, or other causes may have a reduced antibody response to active immunization procedures (see Precautions).

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.

In 1 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. It is unclear whether this effect was due to the vaccine or to the effects of irradiation and/or chemotherapy.

At least 2 weeks should elapse between immunization and the initiation of chemotherapy or immunosuppressive therapy.

Routine reimmunization with this vaccine is not recommended. For reimmunization (including recommendations regarding reimmunization of individuals at highest risk of fatal pneumococcal infection), see Dosage.

In 1 study, local reactions after reimmunization were more severe than after initial immunization when the interval between immunizations was 13 months.

Patients who have had episodes of pneumococcal pneumonia or other pneumococcal infection may have high levels of pre-existing pneumococcal antibodies that may result in increased reactions to pneumococcal vaccine polyvalent, mostly local, but occasionally systemic. Caution should be exercised if such patients are considered for immunization with pneumococcal vaccine polyvalent.

Do not administer the vaccine intradermally since severe reactions may occur.

As with other i.m. injections, pneumococcal vaccine polyvalent should be given with caution to individuals with thrombocytopenia or any coagulation disorder that would contraindicate i.m. injection (see Precautions, Drug Interactions).

As with any vaccine, pneumococcal vaccine polyvalent may not protect 100% of individuals receiving the vaccine.

In patients who require penicillin (or other antibiotics) prophylaxis against pneumococcal infection, such prophylaxis should not be discontinued after immunization with the pneumococcal vaccine.

Precautions: Pneumococcal vaccine polyvalent is for i.m. or s.c. use only.

Pneumococcal vaccine polyvalent should not be used in children under 2 years of age.

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.

Prior to administration of any dose of pneumococcal vaccine polyvalent, the parent, guardian, or adult patient should be asked about the personal history, family history, recent health status and immunization history of the patient to be immunized to determine the existence of any contraindication to immunization with pneumococcal vaccine (see Contraindications and Warnings).

Before administration of any biological, the physician should take all known precautions for prevention of allergic or any other reactions. This includes: 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. Needles should be disposed of properly and should not be recapped.

Patients with impaired immune responsiveness, whether due to use of immunosuppressive therapy (including irradiation, corticosteroids, antimetabolites, alkylating agents, any cytotoxic agents), a genetic defect, human immunodeficiency virus (HIV) infection or other causes, may have reduced antibody response to active immunization procedures. Deferral of administration of vaccine may be considered in individuals receiving immunosuppressive therapy.

This product is not contraindicated for use in individuals with HIV.

Special care should be taken to prevent injection into a blood vessel.

Children: Pneumococcal vaccine polyvalent should not be used in children under 2 years of age.

Pregnancy: Animal reproduction studies have not been conducted with pneumococcal vaccine polyvalent. It is also not known whether pneumococcal vaccine polyvalent can cause fetal harm when administered to a pregnant woman or effect reproduction capacity. Pneumococcal vaccine polyvalent is not recommended for use in pregnant women.

Lactation: It is not known whether the drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when pneumococcal vaccine polyvalent is administered to a nursing woman.

Carcinogenesis, Mutagenesis, Impairment of Fertility: Pneumococcal vaccine polyvalent has not been evaluated for its carcinogenic or mutagenic potential, or impairment of fertility.

Drug Interactions: Simultaneous immunization is possible with attenuated live vaccines, inactivated vaccines and immunoglobulins, if the application is given at separate sites.

Children receiving immunosuppressive therapy may have a reduced response to active immunization procedures.

As with other i.m. injections, pneumococcal vaccine polyvalent should be given with caution to children on anticoagulant therapy.

Information to be Provided to the Patient: Prior to administration of this vaccine, health care personnel should inform the parent, guardian, or adult patient of the benefits and risks of immunization with pneumococcal vaccine. Guidance should be provided on measures to be taken should adverse events occur, such as, antipyretic measures for elevated temperatures and the need to report adverse events to the health care provider.

Adverse Reactions: Pneumococcal vaccine polyvalent is associated with a relatively low incidence of adverse reactions. The adverse reactivity observed in clinical studies was of short duration and not serious.

In a study of 32 individuals who received pneumococcal vaccine polyvalent, 23 (72%) experienced local reaction characterized by soreness at the injection site within 3 days after immunization.

Low grade fever (less than 37.8°C) and mild myalgia occur occasionally and are usually confined to the 24-hour period following immunization. Rash and arthralgia have been reported infrequently.

Although rare, fever over 38.9°C and marked local swelling have been reported with pneumococcal polysaccharide vaccine. Rash, urticaria, arthritis, arthralgia and adenitis have been reported rarely.

Patients with otherwise stabilized idiopathic thrombocytopenic purpura have, on rare occasions, experienced a relapse in their thrombocytopenia, occurring 2 to 14 days after immunization and lasting up to 2 weeks.

Reactions of greater severity or extent are unusual. Rarely, anaphylactoid reactions have been reported.

Temporal association of neurological disorders such as paresthesias and acute radiculoneuropathy, including Guillain-Barr© syndrome, have been reported following parenteral injections of biological products including pneumococcal vaccine.

Symptoms And Treatment Of Overdose: Symptoms and Treatment: In case of anaphylactic reactions, the usual procedures for shock therapy apply.

Dosage And Administration: The immunization schedule consists of a single 0.5 mL dose given i.m. or s.c.

Administration: Shake vigorously before withdrawing each dose to resuspend the contents of vial or syringe.

The preferred sites are the anterolateral aspect of the thigh or the deltoid muscle of the upper arm. The vaccine should not be injected in the gluteal area or areas where there may be a major nerve trunk. Before injection, the skin at the injection site should be cleansed with a suitable germicide. After insertion of the needle, aspirate to help avoid inadvertent injection into a blood vessel.

The vaccine should be injected i.m. or s.c. Intradermal administration should be avoided. Do not inject i.v. (Vaccines applied mistakenly i.v. can result in anaphylactic reactions, including shock.)

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.

Directions for Use of the Lederject Disposable Syringe (see package insert for illustrations): Twist the plunger rod clockwise to be sure the rod is secure to rubber plunger base. Shake syringe to resuspend contents.

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 rubber needle 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.

Do not use this vaccine past the expiration date.

Simultaneous Administration with Other Vaccines: Many patients who receive pneumococcal vaccine should also be immunized with influenza vaccine which may be given simultaneously at a different site. In contrast to pneumococcal vaccine, influenza vaccine is recommended annually.

Reimmunization: The incidence of local reactions after reimmunization were found to be more severe than after initial immunization when the interval between immunizations was 13 months. Reports of reimmunization after longer intervals in children and adults, including a large group of elderly persons reimmunized at least 4 years after primary immunization, suggest a similar incidence of such reactions.

The USA Immunization Practices Advisory Committee (ACIP) recommendations regarding reimmunization are as follows: Persons who receive the 14-valent vaccine should not routinely be reimmunized with the 23-valent vaccine. However, reimmunization with 23-valent vaccine should be strongly considered for persons who received the 14-valent vaccine if they are at highest risk of fatal pneumococcal infection (e.g., asplenic patients). Reimmunization should also be carefully considered for adults at highest risk who received the 23-valent vaccine more than 6 years before and for those shown to have a rapid decline in antibody levels (e.g., patients with nephrotic syndrome, renal failure, or transplant patients). Reimmunization should be carefully considered after 3 to 5 years for children with nephrotic syndrome, asplenia, or sickle-cell anemia who would be 10 years old or younger at the time of reimmunization.

Availability And Storage: Each dose (0.5 mL) of clear, colorless liquid contains: 25 g of each of the 23 purified capsular polysaccharide types of S. pneumoniae. See Table I. Nonmedicinal ingredients: 2-(ethylmeralrithio) benzoic acid, phosphate buffer, sodium salt and thimerosal. Thimerosal (mercury derivative) is added to the vaccine to a final concentration of 1:10 000.

Vials of 2.5 mL (5 doses), for use with syringe only, packages of 1. Lederject disposable syringes of 0.5 mL (single dose), packages of 5. Store refrigerated away from the freezer compartment at 2 to 8°C. Do not freeze. Do not use vaccine past expiration date.

PNU-IMUNE® 23 Wyeth-Ayerst Pneumococcal Vaccine Polyvalent Active Immunizing Agent

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