Pneumococcal Conjugate Vaccine (Systemic)

VA CLASSIFICATION
Primary: IM100


Note: This monograph refers to the 7–valent conjugate vaccine (Diphtheria CRM₁₉₇ protein conjugate) licensed in the U.S.

Commonly used brand name(s): Prevnar™.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Immunizing agent (active) —

Indications

General considerations
Streptococcus pneumoniae is a bacterial pathogen that causes invasive infections, such as bacteremia and meningitis, as well as pneumonia and upper respiratory tract infections, in adults and children worldwide ^{01}. In children older than 1 month, S. pneumoniae is the most common cause of invasive disease^{01}. Children in group child care have an increased risk of invasive pneumococcal disease^{01}. Pneumococcal meningitis in children between 1 and 23 months of age occurs at a rate of approximately 7 cases per 100,000 persons per year and has been associated with 8% mortality^{01}. Survivors may suffer neurological sequelae (25%) and hearing loss (32%)^{01}.

Twenty to forty percent of cases of acute otitis media are associated with S. pneumoniae. The 7 serotypes contained in the pneumococcal 7–valent conjugate vaccine account for 60% of acute otitis media due to S. pneumoniae^{01}. Seventy percent of cases of community-acquired bacterial pneumonia are caused by S. pneumoniae ^{01}. Approximately 80% of invasive pneumococcal disease in children under 6 years of age in the U.S. is attributable to the 7 serotypes of S. pneumoniae represented in the 7–valent conjugate vaccine^{01}.

Accepted

Pneumococcal disease (prophylaxis)—Pneumococcal 7–valent conjugate vaccine is indicated for active immunization of infants and toddlers against invasive disease caused by S. pneumoniae of capsular serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F^{01}.
—The vaccine is not intended for active infection^{01}.
—The use of this vaccine does not replace the use of 23–valent pneumococcal polysaccharide vaccine in children >24 months of age with sickle cell disease, asplenia, HIV infection, chronic illness, or who are immunocompromised^{01}.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Source—
    The 7–valent conjugate vaccine contains the saccharides of the capsular antigens of the 7 Streptococcus pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F, which cause 80% of invasive pneumococcal disease in children under 6 years of age in the U.S.^{01}. Polysaccharides derived from the serotypes are purified and chemically activated to make saccharides, which are then conjugated to the protein carrier CRM₁₉₇ to form the glycoconjugate^{01}. CRM₁₉₇ is a nontoxic variant of diphtheria toxin isolated from cultures of Corynebacterium diphtheriae^{01}. The individual glycoconjugates are compounded to formulate the 7–valent conjugate vaccine, which provides 2 mcg of each saccharide of serotypes 4, 9V, 14, 18C, 19F, and 23F, and 4 mcg of serotype 6B per 0.5 mL dose. Each 0.5 mL dose also contains 20 mcg of CRM ₁₉₇ and 0.125 mg of aluminum as aluminum phosphate adjuvant^{01}.

Mechanism of action/Effect:

The 7–valent conjugate vaccine induces functional antibodies to all vaccine serotypes, as measured by opsonophagocytosis following 3 doses^{01}.


Protective effect—

In a double-blind clinical trial, 37,816 infants were randomized to receive pneumococcal 7–valent conjugate vaccine or an investigational meningococcal group C conjugate vaccine (control) at 2, 4, 6 and 12 to 15 months of age. Per protocol analysis of the primary endpoint for efficacy included cases of pneumococcal disease due to serotypes represented in the 7–valent vaccine occurring 14 or more days after the third dose. At the time when 17 cases had occurred in the control group, no cases had occurred in the pneumococcal vaccine group^{01}. Preliminary efficacy data through an extended follow-up period to April, 1999 (4.5 years after the start of the study), showed 1 case in the pneumococcal vaccine group and 39 cases in the control group^{01}. Intent-to-treat analysis (including all cases among children who had received at least one dose of vaccine) showed similar efficacy: 3 cases in the pneumococcal vaccine group and 49 cases in the control group^{01}.

This vaccine does not protect against S. pneumoniae disease other than that caused by the 7 serotypes included in the vaccine, nor will it protect against other microorganisms that cause similar disease. It is not intended to replace the 23–valent vaccine in children > 24 months of age with sickle cell disease, asplenia, HIV infection, chronic illness or who are immunocompromised. It is also not recommended for use in adult populations.

Immunization with this vaccine does not substitute for routine diphtheria immunization^{01}.


Precautions to Consider

Carcinogenicity/Tumorigenicity/Mutagenicity

The pneumococcal 7–valent conjugate vaccine has not been evaluated for any carcinogenic or mutagenic potential ^{01}.

Pregnancy/Reproduction
Fertility—
This vaccine has not been evaluated for impairment of fertility^{01}.

Pregnancy—
Studies have not been done in humans^{01}. The pneumococcal 7–valent conjugate vaccine is not recommended for use in pregnant women^{01}.

FDA Pregnancy Category C^{01}.

Breast-feeding

It is not known whether vaccine antigens or antibodies are distributed into breast milk^{01}. This vaccine is not recommended for use in nursing mothers^{01}.

Pediatrics

Infants younger than 6 weeks of age—The safety and effectiveness of this vaccine in children below the age of 6 weeks has not been established^{01}.

Infants born prematurely—Immune responses elicited by this vaccine in infants born prematurely have not been studied^{01}.

Children 7 months through 9 years of age —Immune responses of previously unvaccinated children in this age group to this vaccine appear to be comparable to responses of younger children^{01}.


Geriatrics


This vaccine is not recommended for use in adult populations and is not to be used as a substitute for the 23–valent pneumococcal polysaccharide vaccine in geriatric populations^{01}.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Anticoagulant therapy    (increased risk of bleeding with intramuscular injection^{01})


Immunosuppressive agents    (impaired immunoresponsiveness may reduce the antibody response to immunization^{01})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
Febrile illness, moderate to severe    (minor illnesses, such as a mild upper respiratory infection with or without low-grade fever, do not preclude administration of the vaccine^{01})


Impaired immune responsiveness    (may reduce antibody response to active immunization^{01})


Sensitivity to pneumococcal vaccine, including diptheria toxoid^{01}    (antigens of pneumococcal serotypes are conjugated to diptheria toxin^{01})


Sensitivity to latex    (packaging contains dry natural rubber^{01})


Thrombocytopenia or other coagulation disorder    (intramuscular administration may cause excessive bleeding^{01})




Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence less frequent
    
Fever over 39 °C (102.2 °F) ^{01}

Incidence rare
    
Hypotonic-hyporesponsive episode (collapse or shock-like state)—3 cases reported; all received concurrent DTP vaccine^{01}
    
seizures (convulsions )
^{01}


Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Decreased appetite
diarrhea ( increase in bowel movements; loose stools; soft stools)
    
drowsiness
    
fever of less than 39 °C (102.2 °F)
    
irritability
    
redness, soreness, hard lump, swelling, or pain at injection site
    
restless sleep
    
vomiting
^{01}
Incidence less frequent
    
Skin rash or hives
^{01}




Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Pneumococcal Conjugate Vaccine (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to pneumococcal vaccine components, including diphtheria toxoid and latex




Use in children——Safety and efficacy in infants below 6 weeks of age not established






Use in the elderly—Not recommended for use in adult populations

Proper use of this vaccine

» Proper dosing

Precautions after receiving this vaccine
» Notifying all patient's physicians that patient has received pneumococcal conjugate vaccine so that the information can be included in patient's medical records


Side/adverse effects
Signs of potential side effects, especially fever over 39 °C (102.2 °F), hypotonic-hyporesponsive episode, and seizures


General Dosing Information
Pneumococcal conjugate vaccine is usually well tolerated in infants^{01}. However, as with any biological, appropriate precautions should be taken prior to vaccine administration to prevent allergic or any other unwanted reactions. Precautions should include review of the patient's history regarding possible sensitivity and the ready availability of 1:1000 epinephrine injection and other appropriate agents used for control of immediate allergic reactions^{01}.

Pneumococcal conjugate is administered by intramuscular injection only^{01}. Care should be taken to prevent injection into or near a blood vessel or nerve.

A single dose is the same for all individuals; however, the number of doses depends on age at which the first dose is received^{01}.

Pneumococcal conjugate vaccine may be administered simultaneously with other vaccines (at separate sites)^{01}. In clinical studies, pneumococcal conjugate vaccine has been administered with DTP-HbOC, DTaP and HbOC, OPV or IPV, Hep B vaccines, MMR, and varicella vaccine^{01}.

The use of pneumococcal conjugate vaccine does not replace the use of 23–valent pneumococcal polysaccharide vaccine in children over 24 months of age with sickle cell disease, HIV infection, chronic illness, or who are immunocompromised^{01}.


Parenteral Dosage Forms

PNEUMOCOCCAL CONJUGATE VACCINE INJECTION

Usual adult dose
Use of pneumococcal conjugate vaccine is not recommended in adults^{01}

Usual Pediatric Dose
Immunizing agent (active)
Intramuscular, 0.5 mL, preferably in the anterolateral aspect of the thigh in infants or the deltoid muscle of the upper arm in toddlers and young children, according to the following dosing schedules^{01}:


Infants:
First dose—At 2 months of age^{01}.

Note: The vaccine series may be initiated as early as 6 weeks of age. The recommended dosing interval is 4 to 8 weeks^{01}.


Second dose—At 4 months of age^{01}.

Third dose—6 months of age^{01}.

Fourth dose—12 to 15 months of age^{01}.



Older infants and children:
Age 7 to 11 months at first dose—Two doses, two months apart, then a third dose after the 1–year birthday, separated from the second dose by at least 2 months^{01}.

Age 12 to 23 months—Two doses at least 2 months apart^{01}.

Age 24 months through 9 years—One dose^{01}.



Usual Geriatric Dose
Use of pneumococcal conjugate vaccine is not recommended in geriatric patients^{01}.

Strength(s) usually available
U.S.—


16 mcg total saccharide (2 mcg of each saccharide for serotypes 4, 9V, 14, 18C, 19F, and 23F, and 4 mcg of serotype 6B) and 20 mcg of diphtheria CRM ₁₉₇ protein (Rx) [Prevnar™ (single dose vials; 5 per package) (0.125 mg of aluminum per 0.5 mL dose as aluminum phosphate adjuvant )]

Packaging and storage:
Store between 2 and 8°C (36 and 46 °F). Do not freeze.^{01}

Auxiliary labeling:
   • Shake the vial vigorously immediately before use in order to resuspend the contents.


Caution:
The vaccine should not be used if it cannot be resuspended^{01}.

Additional information:
After shaking, the vaccine is a homogeneous suspension^{01}.

Developed: 5/5/2000

References

1. Product Information: Prevnar™, pneumococcal 7–valent conjugate vaccine (diphtheria CRM₁₉₇protein). Wyeth Lederle, Philadelphia, PA (PI revised 2/2000) reviewed 4/2000.