Haemophilus b Polysaccharide Vaccine (Systemic )


VA CLASSIFICATION
Primary: IM100


Note: This monograph applies only to the polysaccharide vaccine.
It is recommended that, whenever possible, children with indications for haemophilus b vaccine be immunized with the more immunogenic conjugate vaccine instead of with this polysaccharide vaccine {01}. This is especially important for children under 24 months of age {01}. See Haemophilus b Conjugate Vaccine (Systemic) for information on the conjugate vaccine.

Commonly used names are:
Haemophilus influenzae type b polysaccharide vaccine ; HbPV ; Hib CPS ; Hib polysaccharide vaccine ; and PRP .
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

*Not commercially available in the U.S.

Not commercially available in Canada.



Category:


Immunizing agent (active)—

Indications

Accepted

Haemophilus influenzae type b disease (prophylaxis)—Haemophilus b polysaccharide vaccine is indicated for routine immunization of children 24 months to {02} 5 years of age (i.e., up to the 5th {02} birthday) {03} {04} against diseases caused by Haemophilus influenzae type b (Hib). Although the polysaccharide vaccine was licensed for use up to the 6th birthday, pediatric experts recommend that the vaccine be used only up to the 5th birthday {02}.
—In addition, immunization with haemophilus b polysaccharide vaccine should be considered for children 18 to 24 months of age, especially those in known high-risk groups, only {02} if the more immunogenic conjugate vaccine is not available. These groups include:    • Children attending day-care facilities {03} {05}.
   • Children in residential institutions, such as orphanages {02}.
   • Children with chronic illnesses associated with increased risk of Hib disease {08}. These illnesses include asplenia, sickle cell disease, antibody deficiency syndromes, immunosuppression, and Hodgkin's disease {03} {05}. Children scheduled to undergo immunosuppressive therapy {02}, including that for Hodgkin's disease, should receive the polysaccharide vaccine at least 10 to 14 days prior to the initiation of therapy {02}. The interval between discontinuation of immunosuppressive therapy and the restoration of the patient's ability to respond to an active immunizing agent depends on the intensity and type of immunosuppression-causing therapy, the underlying disease, and other factors; estimates vary from 3 months to 1 year {02} {06}. Children with immunodeficiency syndromes secondary to deficient synthesis of immunoglobulins (e.g., agammaglobulinemia) probably will not benefit from immunization with the polysaccharide vaccine {04}. Instead, passive immunity should be maintained in these children {04}.
   • Children under 24 months of age who have already had invasive Hib disease {07}. Most children under 24 months of age do not develop an immune response to Hib disease and may contract the disease again if they are not immunized {07}. The vaccine should be administered to these children no sooner than 2 months following Hib disease {02} and not until they have reached 24 months of age {02}. Children 24 months of age or older who contract Hib disease do not need to be immunized, since most children in this age group will develop protective levels of antibody from their illnesses {02}.
   • Children with asymptomatic or symptomatic human immunodeficiency virus (HIV) infection {08}. Immunization is recommended even though immunization of symptomatic children may be less effective than it would be for immunocompetent children {08}.
   • Children of certain racial groups, such as American Indian and Alaskan Eskimo {02} {03} {04} {05}. These racial groups appear to be at increased risk of Hib disease {02} {03} {04}.
   • Children of low socioeconomic status {03} {04}. Low socioeconomic status is often associated with crowded living conditions, which increase a child's risk of contact with Hib-infected persons {02} {04}.

—Even though they may be protected from invasive disease themselves, household, nursery, and day-care contacts, both adults and children, exposed to children with Hib disease may become asymptomatic carriers of Hib organisms and may infect unimmunized contacts {01} {02} {09}. There is an increased risk of invasive Hib disease among unimmunized household contacts less than 4 years of age {02} {09}; in addition, unimmunized nursery and day-care contacts may also be at increased risk, especially if they are younger than 2 years of age {02} {09}. In households where there is at least one contact younger than 48 months of age, it is recommended that all household contacts, both adults and children, receive rifampin chemoprophylaxis, regardless of the immunization status of any of the contacts {02} {09}. For nursery and day-care contacts where the facility provides for children less than 2 years of age for at least 25 hours per week, rifampin chemoprophylaxis is recommended for all contacts, both adults and children, regardless of the immunization status of any of the contacts {02} {09}. For nursery and day-care facilities where all contacts are more than 2 years of age, rifampin chemoprophylaxis is not necessary {02} {09}.
—Since satisfactory response to the polysaccharide vaccine is not consistent among children 18 to 24 months of age, most authorities believe that these children should be reimmunized {07}. The optimal timing of this second dose is not known; however, it appears that reimmunization of these children should occur at or after 24 months of age, with 2 to 18 months having elapsed between the first immunization and the second one {07}. Previous immunization does not affect the immune response or adverse reaction to a subsequent dose of the vaccine {07}.

Unaccepted
Because the polysaccharide vaccine protects against only Haemophilus influenzae type b (Hib), protection against other strains of H. influenzae , such as nonencapsulated strains associated with recurrent upper respiratory disease (including otitis media and sinusitis), should not be anticipated following administration of this vaccine {02} {03} {05} {08}.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Source—
    Purified capsular polysaccharide {03} {04}, a polymer of ribose, ribitol, and phosphate (PRP), {05} from the bacterium Haemophilus influenzae type b (Hib) {03} {04}.

Mechanism of action/Effect:

Haemophilus influenzae type b (Hib) bacteria are surrounded by polysaccharide capsules, which make the bacteria resistant to attack by white blood cells. However, human blood serum contains antibodies, which render the bacteria vulnerable to attack. The vaccine, which is composed of the purified polysaccharide {02} from Hib bacterial cells, stimulates production of anticapsular {04} antibodies and provides active immunity to the Haemophilus influenzae type b bacteria represented by the polysaccharide {02} in the vaccine.

Haemophilus b polysaccharide vaccine, unlike the conjugate vaccine, predominantly stimulates B-cells to produce antibodies {01} {02}. This is known as being T-cell independent and is characteristic of polysaccharide vaccines {02}. The initial stimulation of T-cells followed by stimulation of B cells (known as a T-cell response) is particularly important in young children to ensure adequate and persisting antibody production {02}. Stimulation of T-cells also results in an anamnestic response to future doses of the vaccine and future natural exposure to Haemophilus influenzae type b {02} {04}. The poor T-cell response stimulated by the polysaccharide vaccine is thought to be one reason why the polysaccharide vaccine is not adequately immunogenic in children up to 18 months of age and may not be fully immunogenic in children 18 to 24 months of age {01} {02}. In addition, lack of initial T-cell stimulation probably is the reason that repeat doses of the polysaccharide vaccine do not boost the antibody response consistently {01} {02}.


Protective efficacy

The exact protective level of anti-Haemophilus b polysaccharide antibody has not been established; however, 0.15 mcg/mL is considered by many experts {02} to be protective, and 1 mcg/mL in post-immunization sera {02} is considered indicative of long-term protection {01}.

Antibody response to the vaccine is age related in children. Children up to 18 months of age develop very little immunologic {02} response to the vaccine. Children 18 to 24 months of age have inconsistent and less than optimal response to the vaccine {01}. Children over 24 months of age have a high rate of seroconversion. Antibody response continues to improve until it reaches adult levels in children approximately 6 years of age.


Time to protective efficacy

Approximately 1 week for onset of an antibody response to the vaccine; approximately 3 weeks for attainment of the protective level of 1 mcg per mL, which is considered indicative of long-term protection.


Duration of protective effect

The duration of immunity after a single dose of the polysaccharide vaccine has not been completely described {02}. However, it may be less than the duration of immunity following administration of the conjugate vaccine, which is expected to be at least 1.5 to 3 years {02}.

Duration of antibody response is age related in children {01}. In one study of children 15 to 24 months of age, an antibody concentration of 1 mcg per mL, which is considered indicative of long-term protection, was reached in less than 30% of children {01} {02}.


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to haemophilus b conjugate vaccine may be sensitive to the polysaccharide vaccine also.

Pediatrics

For children up to 18 months of age—Immunization is not recommended {04}, since children in this age group will not have an adequate antibody response to the polysaccharide vaccine {04}.

For children 18 to 24 months of age—Immunization is recommended for children in this age group, especially those in known high risk groups. However, the efficacy of the polysaccharide vaccine in these children appears to be less than in children 24 months of age or older, and some of these children will not have an adequate antibody response to the polysaccharide vaccine. It is recommended that, whenever possible, the more immunogenic conjugate vaccine be used instead of the polysaccharide vaccine.


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.

Immunosuppressive agents{04} or
Radiation therapy{04}    (because immunosuppressive agents and radiation therapy suppress normal defense mechanisms, the patient's antibody response to the polysaccharide vaccine may be decreased {04}. If possible, children who are to undergo therapy with agents that cause immunosuppression, including that for Hodgkin's disease, should receive the vaccine at least 10 days, and preferably more than 14 days, prior to receiving the immunosuppression-causing agent {02} {04}; otherwise, it may be preferable to postpone the immunization until after the immunosuppression-causing therapy is completed {02} {04}. The interval between discontinuation of therapy that causes immunosuppression and the restoration of the patient's ability to respond to an active immunizing agent depends on the intensity and type of immunosuppression-causing therapy, the underlying disease, and other factors; estimates vary from 3 months to 1 year {02}. The precaution does not apply to corticosteroids used as replacement therapy, for short-term [less than 2 weeks] systemic therapy, or by other routes of administration that do not cause immunosuppression)



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With diagnostic test results
Antigen detection tests    (the polysaccharide vaccine may interfere with interpretation of antigen detection tests, such as latex agglutination and countercurrent immunoelectrophoresis, that are used for diagnosis of systemic Hib disease {04}. Antigenuria from administration of the haemophilus b polysaccharide vaccine can produce {02} positive urinary latex agglutination tests for up to 11 days after immunization {02} {04})


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).


Except under special circumstances, this medication should not be used when the following medical problem exists:
» Illness, acute or febrile{04}    (administration of the polysaccharide vaccine should be postponed {04} to avoid confusing the symptoms of the illness with the side effects of the vaccine; minor illnesses, such as mild upper respiratory infections, do not preclude administration of the vaccine {04})


Risk-benefit should be considered when the following medical problem exists
Sensitivity to haemophilus b polysaccharide vaccine


Side/Adverse Effects

Note: Side effects generally are minor {03} {11} {12}, occur within 24 hours, and last 24 hours or less {03} {04}.
There are no significant differences in the frequency or types of side effects between haemophilus b polysaccharide vaccine and haemophilus b conjugate vaccine {01} {04} {11}.

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 rare
    
Anaphylactic reaction{13} (difficulty in breathing or swallowing; hives; itching, especially of soles or palms; reddening of skin, especially around ears; swelling of eyes, face, or inside of nose; unusual tiredness or weakness, sudden and severe)
    
convulsions{13}



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Anorexia {11}(lack of appetite)
    
diarrhea{11}
    
erythema at injection site {04}{11}(redness at place of injection)
    
fever up to 39 °C (102.2 °F){11} —usually resolves within 48 hours{11}
    
irritability{04}{11}
    
lethargy {11}(lack of interest; reduced physical activity)
    
tenderness at injection site{04}{11}

Incidence less frequent or rare
    
Fever over 39 °C (over 102.2 °F){01}{04}{11} —usually resolves within 48 hours{11}
    
induration at injection site {04}{11}(hard lump at place of injection)
    
serum sickness–like reaction{13} {13}(itching; skin rash; swelling of face; arthralgia; joint pain)
    
sleep disturbance (trouble in sleeping)
    
swelling at injection site{04}
    
vomiting{11}{13}





Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Haemophilus b Polysaccharide Vaccine (Systemic) .

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

Before receiving this vaccine
»   Conditions affecting use, especially:
Sensitivity to haemophilus b polysaccharide vaccine or haemophilus b conjugate vaccine





Use in children—Not recommended for use in children up to 18 months of age

Other medical problems, especially fever or serious illness

Proper use of this vaccine

» Proper dosing


Side/adverse effects
Signs of potential side effects, especially anaphylactic reaction or convulsions


General Dosing Information
When sterilizing syringes and skin before vaccination, care should be taken to avoid use of preservatives, antiseptics, detergents, and disinfectants, since the polysaccharide vaccine may be inactivated by these substances.

The polysaccharide vaccine is for intramuscular or subcutaneous administration {03}. It should not be administered intradermally or intravenously {03}.

To prevent inactivation of the vaccine, it is recommended that only the diluent provided by the manufacturer be used for vaccine reconstitution.

Persons infected with human immunodeficiency virus (HIV) may receive this vaccine whether they have asymptomatic or symptomatic HIV infection {08}.

Polysaccharide vaccines, including haemophilus b polysaccharide vaccine, may be administered concurrently with the following, using separate body sites, separate syringes, and the precautions that apply to each immunizing agent:    • Polysaccharide vaccines, other, such as meningococcal polysaccharide vaccine or pneumococcal polyvalent vaccine.
   • Influenza vaccine, whole or split virus.
   • Diphtheria toxoid, tetanus toxoid, and/or pertussis vaccine.
   • Live virus vaccines, such as measles, mumps, and/or rubella vaccines.
   • Poliovirus vaccines (oral [OPV], inactivated [IPV], or enhanced-potency inactivated [enhanced-potency IPV]).
   • Hepatitis B recombinant or plasma-derived vaccine.
   • Immune globulin and disease-specific immune globulins.
   • Inactivated vaccines, except cholera, typhoid, and plague. It is recommended that cholera, typhoid, and plague vaccines be administered on separate occasions because there are no data available on the concurrent administration of haemophilus b polysaccharide vaccine and these vaccines and because of these vaccines' propensity to cause side/adverse effects.


Parents should be informed that the polysaccharide vaccine is not as effective in children 18 to 24 months of age as it is in older children and that reimmunization may be necessary {04}.

Most authorities believe that children immunized between 18 and 24 months of age should be reimmunized {07}. The optimal timing of this second dose is not known {07}; however, it appears that reimmunization of these children should occur at or after 24 months of age, with 2 to 18 months having elapsed between the first immunization and the second one {07}. Previous immunization does not affect the immune response or adverse reaction to a subsequent dose of the vaccine {07}.

For treatment of adverse effects


Recommended treatment consists of the following:
For children

   • If anaphylaxis occurs, 0.01 mg of epinephrine per kg of body weight or 0.3 mg of epinephrine per square meter of body surface, up to a maximum of 0.5 mg per dose, may be administered subcutaneously, the dose being repeated every fifteen minutes for two doses, then administered every four hours as needed.
   • If anaphylactic shock occurs, 0.01 mg of epinephrine per kg of body weight, up to a maximum of 0.3 mg, may be administered intramuscularly or subcutaneously, the dose being repeated every five minutes if necessary. If there is an inadequate response to the intramuscular or subcutaneous dosage, 0.01 mg of epinephrine per kg of body weight may be administered intravenously every five to fifteen minutes as needed.



Parenteral Dosage Forms

HAEMOPHILUS B POLYSACCHARIDE VACCINE (FOR INJECTION)

Usual adult and adolescent dose
Use is not recommended.

Usual pediatric dose
Children up to 18 months of age—Use is not recommended.

Children 18 to 24 months of age (especially if they are in known high risk groups) and

Children 24 months to 5 years of age {02} (i.e., up to the 5th birthday)—Intramuscular or subcutaneous, 0.5 mL, into the outer aspect of the upper arm (deltoid) or into the lateral mid thigh (vastus lateralis).

Note: Since satisfactory response to the polysaccharide vaccine is not consistent among children 18 to 24 months of age, most authorities believe that these children should be reimmunized {07}. The optimal timing of this second dose is not known {07}; however, it appears that reimmunization of these children should occur at or after 24 months of age with 2 to 18 months having elapsed between the first immunization and the second one {07}. Previous immunization does not affect the immune response or adverse reaction to a subsequent dose of the vaccine {07}.


Strength(s) usually available
U.S.—
Not commercially available {14}.

Canada—
Not commercially available.

Packaging and storage:
Store lyophilized and reconstituted polysaccharide vaccine and diluent between 2 to 8 °C (35 to 46 °F), unless otherwise specified by manufacturer. Do not freeze.

Preparation of dosage form:
The appropriate measured amount of the sterile diluent supplied by the manufacturer should be injected into the vial of lyophilized polysaccharide vaccine and then the vial should be gently shaken to dissolve the contents; the lyophilized vaccine dissolves rapidly. The reconstituted solution is clear and colorless.

Stability:
The reconstituted polysaccharide vaccine should be administered as soon as possible; discard unused reconstituted vaccine after 8 hours.

The date and time of reconstitution should be recorded on the label of the vaccine vial.



Revised: 03/29/1994



References
  1. Centers for Disease Control and Prevention. ACIP Update: Prevention of haemophilus influenzae type b disease. MMWR 1988 Jan 22: 13-6.
  1. Panel comments, 5/9/89.
  1. McEvoy GK, editor. AHFS Drug information. Bethesda, MD: American Society of Hospital Pharmacists, 1986, Supplement B: 10B–15B.
  1. McEvoy GK, editor. AHFS Drug Information. Bethesda, MD: American Society of Hospital Pharmacists 1988: 1922-8.
  1. Centers for Disease Control and Prevention. ACIP: Polysaccharide vaccine for prevention of haemophilus influenzae type b disease. MMWR 1985 Apr 19: 201-5.
  1. Centers for Disease Control and Prevention. ACIP: General recommendations on immunization. MMWR 1989 Apr 7; 38(13): 205-27.
  1. Centers for Disease Control and Prevention. ACIP Update: Prevention of haemophilus influenzae type b disease. MMWR 1986 Mar 21: 170-80.
  1. Centers for Disease Control and Prevention. ACIP: Immunization of children infected with HTLV-III/LAV lymphadenopathy-associated virus. MMWR 1986 Sep 26; 35: 595-606.
  1. Committee on Infectious Diseases. American Academy of Pediatrics. Report of the committee on infectious diseases 1988 (Red Book). 21st ed. Elk Grove Village, Ill: American Academy of Pediatrics; 1988.
  1. Moxon ER. Commentaries—Haemophilus influenzae vaccine. Pediatrics 1986 Feb; 77(2): 258-60.
  1. Berkowitz CD, et al. Safety and immunogenicity of haemophilus influenzae type b polysaccharide and polysaccharide diphtheria toxoid conjugate vaccines in children 15 to 24 months of age. J Pediatr 1987 Apr: 509-14.
  1. Frank AL, et al. Haemophilus influenzae type b immunization of children with sickle cell diseases. Pediatrics 1988 Oct; 82(4): 571-5.
  1. Milstien, Gross, Kuritsky (FDA). Adverse reactions reported following receipt of haemophilus influenzae type b vaccine: An analysis after 1 year of marketing. Pediatrics 1987 Aug; 80(2): 270-4.
  1. Centers for Disease Control and Prevention. ACIP: Update on adult immunization—Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 1991 Nov 15; 40(RR-12): 40-1.
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