Haemophilus b Conjugate Vaccine (Systemic)

This monograph includes information on the following:

1) Haemophilus b conjugate vaccine (HbOC—diptheria CRM 197 protein conjugate)
2) Haemophilus b conjugate vaccine (PRP-D—diphtheria toxoid conjugate)
3) Haemophilus b conjugate vaccine (PRP-OMP—meningococcal protein conjugate)
4) Haemophilus b conjugate vaccine (PRP-T—tetanus protein conjugate)

Note: It is recommended that, whenever possible, persons with indications for haemophilus b (Hib) vaccine be immunized with this newer, more immunogenic conjugate vaccine instead of with the polysaccharide vaccine {05} {13}. This is especially important for children 2 months {09} to 24 months of age {09} {26}. See Haemophilus b Polysaccharide Vaccine (Systemic) for information on the polysaccharide vaccine.
This vaccine is not an immunizing agent against diphtheria, meningococcal disease {15}, or tetanus {05} {09} {30} {32}.


VA CLASSIFICATION
Primary: IM100

Commonly used brand name(s): Act-Hib4; Hibtiter1; Pedvaxhib3; Prohibit2.

Other commonly used names for HbOC are
oligo-CRM and PRP-HbOC .
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Immunizing agent (active)—

Indications

Accepted

Haemophilus influenzae type b disease (prophylaxis) —Haemophilus b conjugate vaccine is indicated for routine immunization of all children 2 to 59 months of age {09} {30} {32} against diseases caused by Haemophilus influenzae type b (Hib) {01} {05} {06} {09} {10}.
—[Fractional-dose regimens of Hib conjugate vaccines may be used in developing countries where cost has limited their use]1{33}{34}.
—Hib is a major cause of serious bacterial infection in early childhood. In developing countries, pneumonia and meningitis due to Hib are common in children under 12 months of age and the mortality from meningitis is high. Hib conjugate vaccines have brought Hib disease under control in industrialized countries. However, the cost of Hib conjugate vaccines has limited their use in developing countries. Fractional (one-half or one-third) doses of Hib conjugate vaccine have been shown to be highly effective. The use of fractional-dose regimens and the savings afforded by these regimens may represent the difference between vaccinating and not vaccinating infants against Hib in developing countries (See Pharmacology/Pharmacokinetics){33}{34}.

Note: Act-Hib (PRP-T), Hibtiter(HbOC), and Pedvaxhib (PRP-OMP) are licensed for use in infants and children 2 months of age and older {09} {24} {25} {30}.
Prohibit (PRP-D) is licensed for use in children 15 months of age and older (U.S.) and in children 18 months of age and older (Canada) {09} {15} {19}.
There are no efficacy data available on the use of Hib vaccine for children 5 years of age and older and adults. Moreover, healthy adults and children 5 and older are not at risk for invasive Hib disease. However, studies suggest that patients in this age group who have chronic conditions associated with an increased risk of Hib disease, such as sickle cell disease, leukemia, splenectomy, or HIV infection, demonstrate good immune responses {15} when immunized with Hib vaccine and may benefit {15} from such immunization {08} {09} {11} {19}. Persons infected with human immunodeficiency virus (HIV) may receive this vaccine whether they are asymptomatic {11} {27} {28} or symptomatic {11} {27} {28}.

—The following children should be included:    • Children attending day-care facilities {05} {09}.
   • Children in residential institutions, such as orphanages {32}.
   • Children with chronic illnesses associated with increased risk of Hib disease {05}. These illnesses include asplenia, sickle cell disease, antibody deficiency syndromes, immunosuppression, and Hodgkin's disease {05}. Children scheduled to undergo immunosuppressive therapy {32}, including that for Hodgkin's disease, should receive the conjugate vaccine at least 10 to 14 days prior to the therapy's {32} initiation {22} {32}. 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 immunosuppressive {15} therapy used, the underlying disease, and other factors; estimates vary from 3 months to 1 year {32}. Children with immunodeficiency syndromes secondary to deficient synthesis of immunoglobulins (e.g., agammaglobulinemia) probably will not benefit from immunization with the conjugate vaccine {22}. Instead, passive immunity should be considered {08} in these children {22} {32}.
   • Infants and {08} children under 24 months of age {09} {31} who have already had invasive Hib disease {04} {05} {08} {09} {13}. Many {09} infants and children under 24 months of age do not develop an adequate {09} immune response to Hib disease and may contract the disease again if they are not immunized {04} {05} {09} {13}. The vaccine series can be initiated, or continued, at the time of discharge from the hospital {09}. 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 {13}.
   • Children with asymptomatic or symptomatic human immunodeficiency virus (HIV) infection {27}. Immunization is recommended even though immunization {15} may be less effective than it would be for immunocompetent children {27}.
   • Children of certain racial groups, such as American Indian and Alaskan Eskimo {14} {21} {22} {32}. These racial groups appear to be at increased risk of Hib disease {14} {31} {32}.
   • Children of low socioeconomic status {21} {22}. Low socioeconomic status is often associated with crowded living conditions, which increase a child's risk of contact with Hib-infected persons {21} {22} {32}.
   • Children who have been previously immunized with the polysaccharide vaccine {05} {13}. Children previously immunized before 24 months of age should be reimmunized with the conjugate vaccine {05} {13}. Reimmunization should take place at least 2 months after the polysaccharide immunization {05} {13}. Children previously immunized at 24 months of age or older do not need to be reimmunized {05} {13}.

—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 {05} {09} {32}. Therefore, the Immunization Practices Advisory Committee (ACIP) recommends that all contacts (whether immunized or unimmunized) of children with Hib disease receive rifampin chemoprophylaxis {09} {11} with the precautions that apply to the medication {11}. Immunization of unimmunized contacts should not be used to prevent Hib disease in these contacts, because of the time required to generate an immunologic response {09}. In addition, routinely immunizing health-care and day-care workers who may come into close contact with children with invasive Hib disease is not necessary, because healthy adults are not at risk for invasive Hib disease {11}.

Unaccepted
This vaccine should not be used as an immunizing agent against diphtheria, tetanus, or meningococcal disease, even though there will be some increase in serum diphtheria or tetanus {15} {30} antitoxin levels or antibody levels to the outer membrane protein complex (OMPC) of Neisseria meningitidis, respectively, following immunization {05} {09}. No changes in the schedule for administration of diphtheria or tetanus {30} {15} toxoid or meningococcal vaccine are necessitated by the administration of this vaccine {05} {09}.

The conjugate vaccine protects against only Haemophilus influenzae type b (Hib). Protection against other strains of H. influenzae {01}, such as nonencapsulated strains associated with recurrent upper respiratory disease (including otitis media and sinusitis) should not be anticipated following administration of this vaccine {21} {32}.

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Source—
    Purified capsular polysaccharide {01} {10}, a polymer of ribose, ribitol, and phosphate (PRP), from the bacterium Haemophilus influenzae type b (Hib) {01} {10}. It has been conjugated in one of the following ways:    • For the diphtheria toxoid conjugate—The polysaccharide has been conjugated to the diphtheria toxoid {01} {05} {10} via a 6-carbon linker {15} molecule {32}.
   • For the diphtheria CRM 197 protein conjugate—The oligosaccharide has been derived from the polysaccharide and has been bound directly to CRM 197 {32} (a nontoxic variant of diphtheria toxin) by reductive amination {32}.
   • For the meningococcal protein conjugate—The polysaccharide has been covalently bound to an outer membrane protein complex (OMPC) of the B11 strain of Neisseria meningitidis serogroup B.
   • For the tetanus protein conjugate—The polysaccharide has been covalently bound to tetanus toxoid protein {15} {30}.


Mechanism of action/Effect:

Haemophilus influenzae type b (Hib) bacteria are surrounded by polysaccharide capsules, which make these {15} bacteria resistant to attack by white blood cells. However, human blood serum contains antibodies that render the bacteria vulnerable to attack. The vaccine, which is derived from {32} the purified polysaccharide {32} from Hib {15} cells, stimulates production of anticapsular {10} antibodies and provides active immunity to the Haemophilus influenzae type b bacteria {08} {32}.

Whereas the nonconjugated polysaccharide vaccine predominantly {32} stimulates {08} B-cells to produce antibodies (known as being T-cell independent), haemophilus b conjugate vaccine stimulates T-cells also {01} {05} {14}. The additional stimulation of T-cells (known as being T-cell dependent) is particularly important in young children to ensure an adequate and persistent {08} antibody response {14}. Stimulation of T-cells also results in an anamnestic response to future doses of the conjugate or nonconjugate vaccine and to future natural exposure to Haemophilus influenzae type b {05} {08} {10} {32}, resulting in elevated antibody levels {08}.


Protective effect

The exact protective level of anti-Haemophilus b polysaccharide antibody has not been established; however, 0.15 mcg per mL is considered by many experts {32} to be protective, and 1 mcg per mL in post-immunization sera {26} {32} is considered indicative of long-term protection {05}.

A study has shown that fractional (one-half or one-third) doses of Hib conjugate vaccines (PRP-T and PRP-CRM197) can stimulate ³ 0.15 mcg per mL antibody concentrations in 91–100% of immunized infants. This rate is similar to the 93% rate at which three full doses stimulated seroprotective concentrations. Therefore, the use of alternative regimens (i.e., fractional-dose regimens) and the savings afforded by fractional-dose regimens may represent the difference between vaccinating and not vaccinating infants against Hib in developing countries{33}{34}.

Antibody response to the vaccine is age related in children, with the immune response improving with increasing age {26}.

Some differences in immunogenicity may exist among the different conjugates of haemophilus b conjugate vaccine {23} {26}; however, further studies are needed to confirm these {08} differences and to {08} evaluate their clinical relevance {26}.

Haemophilus b conjugate vaccine is significantly more immunogenic than the nonconjugated polysaccharide vaccine {05} {07}.


Time to protective effect

Approximately 1 to 2 weeks {15} for onset of a detectable {08} antibody response to the vaccine {01} {23} {30}.


Duration of protective effect

The duration of immunity of the conjugate vaccine is unknown {05} {08} {15}.


Precautions to Consider

Cross-sensitivity and/or related problems

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

Patients sensitive to diphtheria toxoid, meningococcal vaccine {01}, or tetanus toxoid {15} protein {30} may be sensitive to the conjugate vaccines available in the U.S. and Canada. These vaccines contain either diphtheria toxoid, a nontoxic variant of diphtheria {32} toxin, an outer membrane protein complex (OMPC) of Neisseria meningitidis {01}, or tetanus toxoid protein {15} {30}.

Carcinogenicity/Mutagenicity

The conjugate vaccine has not been evaluated for its carcinogenic or mutagenic potential {01}.

Pregnancy/Reproduction

Pregnancy—
Studies have not been done in humans or animals {17} {18}.

FDA Pregnancy Category C {17} {18}.

Breast-feeding

Problems in humans have not been documented.

Pediatrics

Immunization is not recommended for children less than 2 months {09} of age, since the safety and efficacy of the conjugate vaccine have not been established in this age group {01} {10}.


Geriatrics


Appropriate studies on the relationship of age to the effects of Hib vaccine have not been performed in the geriatric population. However, no geriatrics-specific problems have been documented to date.

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 or
Radiation therapy    (because normal defense mechanisms are suppressed by immunosuppressive agents or radiation treatment, the patient's antibody response to the conjugate vaccine may be decreased {01} {22}. If possible, children who are to undergo therapy with agents that cause immunosuppression, including treatment for Hodgkin's disease, should receive the vaccine at least 10 days, and preferably more than 14 days, before receiving the immunosuppressive agent {15} {22} {32}; otherwise, it may be preferable to postpone the immunization until after the immunosuppressive {15} therapy is completed {32} {22}. 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 immunosuppressive {15} therapy used, the underlying disease, and other factors; estimates vary from 3 months to 1 year {15} {22}. 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    (there is a possibility {32} that the conjugate 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 {32}. PRP [a polymer of ribose, ribitol, and phosphate] derived from haemophilus b meningococcal protein conjugate vaccine may be detected in the urine of some persons for up to 7 days following immunization {10} {32})


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 problems exist:
» Illness, acute or febrile    (administration of the conjugate vaccine should be postponed {01} {10} 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 {10})


Risk-benefit should be considered when the following medical problem exists
Sensitivity to haemophilus b conjugate vaccine{32}


Side/Adverse Effects

Note: Side effects generally are minor {05} {07} {09} {10} and last 48 hours or less {07}; in addition, no serious systemic reactions have been observed {01} {05} {07} {09}.
In one person, thrombocytopenia was temporally noted; however, no causative relationship was established {01}.
There are no significant differences in the frequency or types of side effects between haemophilus b polysaccharide vaccine and haemophilus b conjugate vaccine {05} {07} {10}.

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 {12}(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{12}{31}



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Anorexia {07}(loss of appetite)
    
erythema at injection site{01}{07}{09}{10} (redness)
    
fever up to 39 °C (102.2 °F){07} (usually resolves within 48 hours)
    
irritability{07}
    
lethargy {07}(lack of interest; reduced physical activity)
    
tenderness at injection site{01}{07}{10}

Incidence less frequent
    
Diarrhea{01}{07}
    
fever over 39 °C (over 102.2 °F){01}{05}{07} {07}(usually resolves within 48 hours)
    
induration (hard lump)
    
swelling, or warm feeling at injection site{01}{07}{09}
    
skin rash
    
urticaria (hives)
    
vomiting{01}{07}





Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Haemophilus b Conjugate 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 conjugate vaccine, haemophilus b polysaccharide vaccine, diphtheria toxoid, meningococcal vaccine, or tetanus toxoid





Use in children—Not recommended for use in children up to 2 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 before vaccination, care should be taken to avoid use of preservatives, antiseptics, detergents, and disinfectants, since the conjugate vaccine may be inactivated by these substances. Disposable syringes and needles are recommended {08}.

The conjugate vaccine is for intramuscular administration only {01} {09}. It should not be administered intravenously {01}.

This vaccine should not be used as an immunizing agent against diphtheria, meningococcal meningitis {09}, or tetanus {30}, even though there may be some slight {32} increase in serum antitoxin or antibody levels following immunization {01} {05} {10} {30}. No changes in the schedule for administration of diphtheria or tetanus toxoid or meningococcal vaccine are necessitated by the administration of this vaccine {05} {09} {30}.

Polysaccharide vaccines, including haemophilus b conjugate vaccine, may be administered concurrently with the vaccines listed below, using separate syringes for the parenterals {15}, and the precautions that apply to each immunizing agent. If DTP, MMR, and IPV are administered concurrently with Hib conjugate vaccine, any 2 of the vaccines may be administered in the same deltoid, and any of these vaccines may be administered in the thigh {09}. If any of the other vaccines listed below is to be administered concurrently with Hib conjugate vaccine, each parenteral {15} vaccine should be administered at a separate body site.    • Polysaccharide vaccines, other, such as meningococcal polysaccharide vaccine {09} or pneumococcal polyvalent vaccine {09}.
   • Influenza vaccine, whole or split virus.
   • Diphtheria toxoid, tetanus toxoid, and/or pertussis vaccine {09}.
   • Live virus vaccines, such as measles, mumps, and/or rubella vaccines {09}.
   • Poliovirus vaccines (oral [OPV], inactivated [IPV], or enhanced-potency inactivated [enhanced-potency IPV]) {09}.
   • Hepatitis B recombinant or plasma-derived vaccine.
   • Immune globulin and disease-specific immune globulins.
   • Inactivated vaccines, except cholera, typhoid (parenteral) {15}, and plague. It is recommended that cholera, typhoid (parenteral) {15}, and plague vaccines be administered on separate occasions because there are no data available on the concurrent administration of haemophilus b conjugate vaccine and these vaccines and because of these vaccines' propensity for causing side/adverse effects.


The first conjugate vaccine was licensed for use in the U.S. in December 1987 {06} {13}. Persons immunized against Hib disease before that date can be presumed to have received the polysaccharide vaccine.

For treatment of adverse effects
Recommended treatment includes:

   • For mild hypersensitivity reaction—Administering antihistamines, and, if necessary, glucocorticoids.
   • For severe hypersensitivity or anaphylactic reaction—Administering epinephrine. Antihistamines or glucocorticoids may also be administered as required.

HAEMOPHILUS B CONJUGATE VACCINE (HbOC—DIPTHERIA CRM 197 PROTEIN CONJUGATE)


Parenteral Dosage Forms

HAEMOPHILUS B CONJUGATE VACCINE INJECTION (HbOC—diphtheria CRM 197 protein conjugate)

Usual adult and adolescent dose
Active immunizing agent
Use is not recommended {01} in these age groups {15}, except for patients with certain chronic conditions associated with an increased risk of Hib disease {08} {09} {11}.


Usual pediatric dose

Note: In countries where the cost of Hib conjugate vaccines has limited their use, fractional dose (one-half or one-third of the usual pediatric dose) regimens may be used as an alternative to the usual pediatric dose (See Indications){33}{34}.

Active immunizing agent
Intramuscular, 0.5 mL, into the outer aspect of the upper arm (deltoid) or into the lateral mid thigh (vastus lateralis), according to the following dosage schedules {09} {16} {17} {18} {30}:


In the U.S.—:


Infants—
First dose—At 2 months of age {09} {17}.

Note: The vaccine series may be initiated as early as 6 weeks of age {09}.


Second dose—At 4 months of age {09} {17}.

Third dose—At 6 months of age {09} {17}.

Booster—At 15 months of age {09} {17}.



Children up to 59 months of age who did not follow the above schedule —
Age 2 to 6 months of age at first dose—Three doses, two months apart, then a booster dose at 15 months of age or as soon as possible thereafter, but not less than two months after previous dose {09} {17}.

Age 7 to 11 months of age at first dose—Two doses, two months apart, then a booster dose at 15 months of age or as soon as possible thereafter, but not less than two months after previous dose {09} {17}.

Age 12 to 14 months of age at first dose—One dose, then a booster dose at 15 months of age or as soon as possible thereafter, but not less than two months after previous dose {09} {17}.

Age 15 to 59 months of age at first dose—One dose {09} {17}.

Note: An interval as short as 1 month between doses is acceptable, but is not optimal {09}.
Any of the other conjugate vaccines may be used for the booster dose; however, there are no data demonstrating that a booster response will occur if one of these other vaccines is used {09}. Ideally, the same conjugate vaccine should be used throughout the vaccination series, including the booster {09}.




Children 5 years of age and older—
Use is not recommended, except for patients with certain chronic conditions associated with an increased risk of Hib disease {09}.




In Canada—:


Infants—
First dose—At 2 months of age {18}.

Note: The vaccine series may be initiated as early as 6 weeks of age {09}.


Second dose—At 4 months of age {18}.

Third dose—At 6 months of age {18}.

Booster—At 15 to 18 months of age {18}.



Children up to 59 months of age who did not follow the above schedule —
Age 2 to 6 months of age at first dose—Three doses, two months apart, then a booster dose at 15 to 18 months of age or as soon as possible thereafter, but not less than two months after previous dose {18}.

Age 7 to 11 months of age at first dose—Two doses, two months apart, then a booster dose at 15 to 18 months of age or as soon as possible thereafter, but not less than two months after previous dose {18}.

Age 12 to 17 months of age at first dose—One dose, then a booster dose at 15 to 18 months of age or as soon as possible thereafter, but not less than two months after previous dose {18}.

Age 18 to 59 months of age at first dose—One dose {18}.

Note: An interval as short as 1 month between doses is acceptable, but is not optimal {09}.
Any of the other conjugate vaccines may be used for the booster dose; however, there are no data demonstrating that a booster response will occur if one of these other vaccines is used {09}. Ideally, the same conjugate vaccine should be used throughout the vaccination series, including the booster {09}.




Children 5 years of age and older—
Use is not recommended.

Note: Children 5 years of age and older with certain chronic conditions associated with an increased risk of Hib disease may profit from Hib immunization {09}.





Strength(s) usually available
U.S.—


10 mcg (0.01 mg) of purified haemophilus b saccharide and approximately 25 mcg (0.025 mg) of CRM 197 protein, a nontoxic variant of {32} diphtheria toxin, per 0.5 mL dose (Rx) [Hibtiter (in multidose vials—thimerosal 1:10,000)]{32}

Canada—


10 mcg (0.01 mg) of purified haemophilus b saccharide and approximately 25 mcg (0.025 mg) of CRM 197 protein, a nontoxic variant of {32} diphtheria toxin, per 0.5 mL dose (Rx) [Hibtiter{18}]

Packaging and storage:
Store between 2 and 8 °C (35 and 46 °F) {01} {30}, unless otherwise specified by manufacturer. Do not freeze {01} {30}.


HAEMOPHILUS B CONJUGATE VACCINE (PRP-D—DIPHTHERIA TOXOID CONJUGATE)


Parenteral Dosage Forms

HAEMOPHILUS B CONJUGATE VACCINE INJECTION (PRP-D—diphtheria toxoid conjugate)

Usual adult and adolescent dose
Active immunizing agent
Use is not recommended in these age groups, except for patients with certain chronic conditions associated with an increased risk of Hib disease {01} {08} {09} {11} {15}.


Usual pediatric dose

Note: In countries where the cost of Hib conjugate vaccines has limited their use, fractional dose (one-half or one-third of the usual pediatric dose) regimens may be used as an alternative to the usual pediatric dose (See Indications){33}{34}.

Active immunizing agent
Intramuscular, 0.5 mL, into the outer aspect of the upper arm (deltoid) or into the lateral mid thigh (vastus lateralis), according to the following dosage schedules {16} {17} {30}:


In the U.S.:
Infants and children up to 15 months of age: Use is not recommended {02} {09}.

Children 15 to 59 months of age who were not previously immunized: One dose {02} {09}.

Children 5 years of age and older: Use is not recommended {02}, except for patients with certain chronic conditions associated with an increased risk of Hib disease {09}.



In Canada:
Infants and children up to 18 months of age: Use is not recommended. {19}

Children 18 to 60 months of age who were not previously immunized {19}: One dose {19}.

Children 5 years of age and older: Use is not recommended, except for patients with certain chronic conditions associated with an increased risk of Hib disease {19}.



Strength(s) usually available
U.S.—


25 mcg (0.025 mg) of purified haemophilus b capsular polysaccharide and 18 mcg (0.018 mg) of diphtheria toxoid protein, per 0.5 mL dose {01} (Rx) [Prohibit (thimerosal 1:10,000)]{01}

Canada—


25 mcg (0.025 mg) of purified haemophilus b capsular polysaccharide and 18 mcg (0.018 mg) of diphtheria toxoid protein, per 0.5 mL dose (Rx) [Prohibit ( thimerosal 1:10,000)]{19}

Packaging and storage:
Store between 2 and 8 °C (35 and 46 °F) {01} {30}, unless otherwise specified by manufacturer. Do not freeze {01} {30}.


HAEMOPHILUS B CONJUGATE VACCINE (PRP-OMP—MENINGOCOCCAL PROTEIN CONJUGATE)


Parenteral Dosage Forms

HAEMOPHILUS B CONJUGATE VACCINE INJECTION (PRP-OMP—meningococcal protein conjugate)

Usual adult and adolescent dose
Active immunizing agent
Use is not recommended in these age groups, except for patients with certain chronic conditions associated with an increased risk of Hib disease {01} {08} {09} {11} {15}.


Usual pediatric dose

Note: In countries where the cost of Hib conjugate vaccines has limited their use, fractional dose (one-half or one-third of the usual pediatric dose) regimens may be used as an alternative to the usual pediatric dose (See Indications){33}{34}.

Active immunizing agent
Intramuscular, 0.5 mL, into the outer aspect of the upper arm (deltoid) or into the lateral mid thigh (vastus lateralis), according to the following dosage schedules {30} {16} {18}:


In the U.S.:


Infants—
First dose—At 2 months of age {03} {09}.

Note: the vaccine series may be initiated as early as 6 weeks of age {09}.


Second dose—At 4 months of age {03} {09}.

Booster—At 12 months of age {03} {09}.



Children up to 59 months of age who did not follow the above schedule —
Age 2 to 6 months of age at first dose—Two doses, two months apart, then a booster dose at 12 months of age or as soon as possible thereafter, but not less than two months after previous dose {09}.

Age 7 to 11 months of age at first dose—Two doses, two months apart, then a booster dose at 15 months of age or as soon as possible thereafter, but not less than two months after previous dose {09}.

Age 12 to 14 months of age at first dose—One dose, then a booster dose at 15 months of age or as soon as possible thereafter, but not less than two months after previous dose {09}.

Age 15 to 59 months of age at first dose—One dose {09}.

Note: The U.S. manufacturer"s labeling gives the age ranges and dosages as: 2 to 10 months of age at first dose—2 doses, 2 months apart, with a booster at 12 to 15 months; 11 to 14 months of age at first dose—2 doses, 2 months apart; 15 to 71 months of age at first dose—1 dose {03}. These recommendations differ somewhat from those of the Immunization Practices Advisory Committee (ACIP) {09} that are used above {15}.
An interval as short as 1 month between doses is acceptable, but is not optimal {09}.
Any of the other conjugate vaccines may be used for the 15-month booster dose; however, there are no data demonstrating that a booster response will occur if one of these other vaccines is used {09}. Ideally, the same conjugate vaccine should be used throughout the vaccination series, including the booster {09}.




Children 5 years of age and older—
Use is not recommended, except for patients with certain chronic conditions associated with an increased risk of Hib disease {09}.




In Canada:


Infants—
First dose—At 2 months of age {20}.

Note: The vaccine series may be initiated as early as 6 weeks of age {09}.


Second dose—At 4 months of age {20}.

Booster—At 12 months of age {20}.



Children up to 59 months of age who did not follow the above schedule —
Age 2 to 6 months of age at first dose—Two doses, two months apart, then a booster dose at 12 months of age or as soon as possible thereafter, but not less than two months after previous dose {20}.

Age 7 to 11 months of age at first dose—Two doses, two months apart, then a booster dose at 15 months of age or as soon as possible thereafter, but not less than two months after previous dose {20}.

Age to 12 to 17 months of age at first dose—One dose, then a booster dose at 18 months of age or as soon as possible thereafter, but not less than two months after previous dose {20}.

Age 18 to 59 months of age at first dose—One dose {20}.

Note: An interval as short as 1 month between doses is acceptable, but is not optimal {09}.
Any of the other conjugate vaccines may be used for the 15- or 18-month booster dose; however, there are no data demonstrating that a booster response will occur if one of these other vaccines is used {09}. Ideally, the same conjugate vaccine should be used throughout the vaccination series, including the booster {09}.




Children 5 years of age and older—
Use is not recommended.

Note: Children 5 years of age and older with certain chronic conditions associated with an increased risk of Hib disease may profit from Hib immunization {09}.





Strength(s) usually available
U.S.—


15 mcg (0.015 mg) of purified haemophilus b capsular polysaccharide and 250 mcg (0.25 mg) of an outer membrane protein complex (OMPC) of the B11 strain of Neisseria meningitidis serogroup B, per 0.5 mL dose (Rx) [Pedvaxhib (in lyophilized product—lactose 2 mg) ( in diluent—aluminum 225 mcg as aluminum hydroxide) ( thimerosal 1:20,000)]

Canada—


15 mcg (0.015 mg) of purified haemophilus b capsular polysaccharide and 250 mcg (0.25 mg) of an outer membrane protein complex (OMPC) of the B11 strain of Neisseria meningitidis serogroup B, per 0.5 mL dose (Rx) [Pedvaxhib (in lyophilized product—lactose 2 mg) ( in diluent—aluminum 225 mcg as aluminum hydroxide) ( thimerosal 1:20,000)]{20}

Packaging and storage:
Store between 2 and 8 °C (35 and 45 °F) {01} {30}, unless otherwise specified by manufacturer. Do not freeze {01} {30} reconstituted vaccine or aluminum hydroxide diluent {20}.

Preparation of dosage form:
Pedvaxhib should be reconstituted only with the aluminum hydroxide diluent that is supplied. The diluent should be agitated prior to its withdrawal. The vaccine should be agitated at the time of reconstitution, prior to withdrawal of the vaccine dose into the syringe, and prior to injection.

Stability:
Pedvaxhib should be used as soon as possible after reconstitution. Reconstituted vaccine should be stored between 2 and 8 °C (35 and 46 °F) and discarded if not used within 24 hours.

Auxiliary labeling:
   • Shake gently before use.


HAEMOPHILUS B CONJUGATE VACCINE (PRP-T—TETANUS PROTEIN CONJUGATE)


Parenteral Dosage Forms

HAEMOPHILUS B CONJUGATE VACCINE INJECTION (PRP-T—tetanus protein conjugate)

Usual adult and adolescent dose
Active immunizing agent
Use is not recommended in these age groups, except for patients with certain chronic conditions associated with an increased risk of Hib disease {01} {08} {09} {11} {15}.


Usual pediatric dose

Note: In countries where the cost of Hib conjugate vaccines has limited their use, fractional dose (one-half or one-third of the usual pediatric dose) regimens may be used as an alternative to the usual pediatric dose (See Indications){33}{34}.

Active immunizing agent
Intramuscular, 0.5 mL, into the outer aspect of the upper arm (deltoid) or into the lateral mid thigh (vastus lateralis), according to the following dosage schedules {15} {16} {17} {24} {25} {30}:


In the U.S.:


Infants—
First dose—At 2 months of age {24}.

Note: The vaccine series may be initiated as early as 6 weeks of age {09}.


Second dose—At 4 months of age {24}.

Third dose—At 6 months of age {24}.

Booster—At 15 months of age {24}.



Children up to 59 months of age who did not follow the above schedule —
Age 2 to 6 months of age at first dose—Three doses, two months apart, then a booster dose at 15 months of age or as soon as possible thereafter, but not less than two months after previous dose {24}.

Age 7 to 11 months of age at first dose—Two doses, two months apart, then a booster dose at 15 months of age or as soon as possible thereafter, but not less than two months after previous dose {24}.

Age 12 to 14 months of age at first dose—One dose, then a booster dose at 15 months of age or as soon as possible thereafter, but not less than two months after previous dose {24}.

Age 15 to 59 months of age at first dose—One dose {24}.

Note: An interval as short as 1 month between doses is acceptable, but is not optimal {09}.
Any of the other conjugate vaccines may be used for the booster dose; however, there are no data demonstrating that a booster response will occur if one of these other vaccines is used {09}. Ideally, the same conjugate vaccine should be used throughout the vaccination series, including the booster {09}.




Children 5 years of age and older—
Use is not recommended, except for patients with certain chronic conditions associated with an increased risk of Hib disease {24}.




In Canada:


Infants—
First dose—At 2 months of age {25} {29} {30}.

Note: The vaccine series may be initiated as early as 6 weeks of age {09}.


Second dose—At 4 months of age {25} {29} {30}.

Third dose—At 6 months of age {25} {29} {30}.

Booster—At 18 months of age {25} {29} {30}.



Children up to 59 months of age who did not follow the above schedule —
Age 3 to 6 months of age at first dose—Three doses, two months apart, then a booster dose at 18 months of age or as soon as possible thereafter, but not less than two months after previous dose {25} {29} {30}.

Age 7 to 11 months of age at first dose—Two doses, two months apart, then a booster dose at 18 months of age or as soon as possible thereafter, but not less than two months after previous dose {25} {29} {30}.

Age 12 to 14 months of age at first dose—One dose, then a booster dose at 18 months of age or as soon as possible thereafter, but not less than two months after previous dose {25} {29} {30}.

Age 15 to 59 months of age at first dose—One dose {25} {29} {30}.

Note: An interval as short as 1 month between doses is acceptable, but is not optimal {09}.
The booster dose may be given as early as 15 months of age or as soon as possible thereafter, but not less than two months after previous dose {25} {29}.
Any of the other conjugate vaccines may be used for the booster dose; however, there are no data demonstrating that a booster response will occur if one of these other vaccines is used {09}. Ideally, the same conjugate vaccine should be used throughout the vaccination series, including the booster {09}.




Children 5 years of age and older—
Use is not recommended, except for patients with certain chronic conditions associated with an increased risk of Hib disease {25} {29} {30}.




Strength(s) usually available
U.S.—


10 mcg (0.01 mg) of purified haemophilus b capsular polysaccharide and 20 mcg (0.02 mg) of tetanus protein, per 0.5 mL dose (Rx) [Act-Hib{24}]

Canada—


10 mcg (0.01 mg) of purified haemophilus b capsular polysaccharide and 20 mcg (0.02 mg) of tetanus protein, per 0.5 mL dose (Rx) [Act-Hib{25}{30}]

Packaging and storage:
Store between 2 and 8 °C (35 and 46 °F) {01} {30}, unless otherwise specified by manufacturer. Do not freeze {01} {30} the reconstituted vaccine.

Preparation of dosage form:
Act-Hib should be reconstituted only with the 0.4% saline diluent that is supplied. The vaccine should be shaken gently until a clear, colorless solution results {30}. (In Canada, Act-Hib may be reconstituted also with the Connaught-Canada brand of DTP vaccine) {15} {30}.

Stability:
Act-Hib should be discarded if it is not used immediately after reconstitution {30}.



Revised: 08/16/2000



References
  1. Prohibit package insert (Connaught—US), Rev 12/87, Rec 10/88.
  1. Prohibit package insert (Connaught—US), PDR Physicians' desk reference. 47th ed. 1993. Montvale NJ: Medical Economics Data, 1993: 919.
  1. Pedvaxhib package insert (MSD—US), Rev 1/92, Rec 1/93.
  1. ACIP. Prevention of Haemophilus type b disease. MMWR 1986 Mar 21: 170-80.
  1. Centers for Disease Control. ACIP update: prevention of Haemophilus influenzae type b disease. MMWR 1988 Jan 22; 37: 13-6.
  1. ACIP. Haemophilus influenzae type b vaccine. MMWR 1988 Jan 1: 832.
  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. Reviewer comments of 9/19/90.
  1. Centers for Disease Control. Haemophilus b conjugate vaccines for prevention of Haemophilus influenzae type b disease among infants and children two months of age and older: recommendation of the Immunization Practices Advisory Committee (ACIP). MMWR 1991 Jan 11: 40 (RR-1).
  1. AHFS Drug Information 1988: 1922-8.
  1. Centers for Disease Control. Update on adult immunization: recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 1991 Nov 15: 40 (RR-12).
  1. Milstien JB, Gross TP, Kuritsky JN (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. Weinberg GA, Granoff DM. Polysaccharide-protein conjugate vaccines for the prevention of Haemophilus influenzae type b disease. J Pediatr 1988 Oct; 113(4): 621-31.
  1. Conjugated Haemophilus influenzae type b vaccine. Med Lett Drugs Ther 1988 Apr 22; 30 (Issue 764): 47-8.
  1. Panel comments, 3/16/93.
  1. Pedvaxhib package insert (MSD—US), Rev 10/91, Rec 12/91.
  1. Hibtiter package insert (Lederle—US), PDR Physicians' desk reference. 46th ed. 1992. Montvale NJ: Medical Economics Data, 1992: 1206.
  1. Hibtiter package insert and product monograph (Lederle—Canada), Rev 8/91 and 9/91, Rec 9/92.
  1. Prohibit package insert (Connaught—Canada), Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 27th ed. Ottawa; Canadian Pharmaceutical Association, 1992: 928.
  1. Pedvaxhib package insert (MSD—Canada), Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 27th ed. Ottawa: Canadian Pharmaceutical Association, 1992: 856.
  1. AHFS Drug Information, 1986 Suppl B: 10B-15B.
  1. AHFS Drug Information, 1988: 1922-8.
  1. Rothstein ED, et al. Comparison of antigenuria following immunization with three Haemophilus influenzae type b conjugate vaccines. 1992. Under review for The Pediatric Infectious Disease Journal.
  1. FDA. FDA approval of use of a new Haemophilus b conjugate vaccine and a combined diptheria-tetanus-pertussis and Haemophilus b conjugate vaccine for infants and children. MMWR 1993 Apr 23; 42(15): 296-8.
  1. Act-Hib product monograph (Connaught—Canada), Rev 3/93, Rec 4/93.
  1. ACIP. Supplementary statement: change in administration schedule for Haemophilus b conjugate vaccines. MMWR 1990 Apr 13; 39(14): 232-3.
  1. ACIP. Immunization of children infected with human immunodeficiency virus (HIV) - Supplementary ACIP Statement. MMWR 1988 Apr 1; 37: 181-3.
  1. Reviewer comments of 7/88 for measles monograph that also apply to Hib vaccine.
  1. Panel comment, 4/30/93.
  1. Act-Hib package insert (Connaught—Canada), Rec 1/93.
  1. Reviewer comments on original draft, 11/88-12/88.
  1. Reviewer comments of 5/9/89.
  1. Panel consensus, 2/2000.
  1. Lagos R, Valenzuela MT, Levine OS, et al. Economization of vaccination against Haemophilus influenzae type b: randomized trial of immunogenicity of fractional-dose and two-dose regimens. Lancet 1998; 351: 1472-6.
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