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DIPHTHERIA AND TETANUS TOXOIDS AND PERTUSSIS VACCINE ADSORBED AND HAEMOPHILUS B CONJUGATE VACCINE (Systemic)

This monograph includes information on the following:

1) Diphtheria and tetanus toxoids combined with whole-cell pertussis vaccine and Haemophilus b conjugate vaccine (HbOC—diphtheria CRM 197 protein conjugate) {01} {02}
2) Diphtheria and tetanus toxoids combined with whole-cell pertussis vaccine and Haemophilus b conjugate vaccine (PRP-D—diphtheria toxoid conjugate) {19} *

VA CLASSIFICATION
Primary: IM900

Commonly used brand name(s): DPT-Hib2; Tetramune1.

Other commonly used names are:


DTP-HbOC —Diphtheria and tetanus toxoids combined with whole-cell pertussis vaccine and Haemophilus b conjugate vaccine (HbOC—diphtheria CRM 197 protein conjugate)
{01} {03} {13}


DTP-Hib —Diphtheria and tetanus toxoids combined with whole-cell pertussis vaccine and Haemophilus b conjugate vaccine (HbOC—diphtheria CRM 197 protein conjugate)
or —Diphtheria and tetanus toxoids combined with whole-cell pertussis vaccine and Haemophilus b conjugate vaccine (PRP-D—diphtheria toxoid conjugate)
{01} {03} {13} {19}


DTP-PRP-D —Diphtheria and tetanus toxoids combined with whole-cell pertussis vaccine and Haemophilus b conjugate vaccine (PRP-D—diphtheria toxoid conjugate)
{03} {13} {19}
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.



Category:


Immunizing agent (active){01}

Indications

Accepted

Diphtheria, tetanus, pertussis, and Haemophilus influenzae type b diseases (prophylaxis)—Diphtheria and tetanus toxoids and pertussis vaccine adsorbed and Haemophilus b conjugate vaccine combination (DTP-Hib) is indicated for immunization against the diseases caused by diphtheria, tetanus, pertussis, and Haemophilus influenzae type b organisms in infants and children up to 5 years of age when the schedules for immunization with the separate vaccines, diphtheria and tetanus toxoids and pertussis vaccine (DTP) and Haemophilus b conjugate vaccine (Hib), coincide. {01} {02} {03}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Source—
    Diphtheria and tetanus: Diphtheria toxoid is prepared from Corynebacterium diphtheriae toxin {24} and tetanus toxoid is prepared from Clostridium tetani toxin {24}. Both toxins are detoxified with formaldehyde. The toxoids are adsorbed onto aluminum phosphate {01} {05}
    Pertussis: Pertussis vaccine is prepared from Bordetella {24} {25} pertussis bacteria, which are inactivated with thimerosal {01} {05}
    Haemophilus b: Purified capsular polysaccharide, a polymer of ribose, ribitol, and phosphate (PRP), is derived from the bacterium Haemophilus influenzae type b. It is conjugated in one of the following ways. {19}
    For the diphtheria CRM 197 protein conjugate: Oligosaccharides are derived from the polysaccharide and bound directly to CRM 197 (a nontoxic variant of diphtheria toxin) by reductive amination {01} {13}
    For the diphtheria toxoid conjugate: The polysaccharide is conjugated to the diphtheria toxoid {15} {19} via a 6-carbon linker molecule {16} {18}

Mechanism of action/Effect:

Diphtheria—Following intramuscular injection, diphtheria toxoid induces the formation of diphtheria antitoxin. {06}

Tetanus—Following intramuscular injection, tetanus toxoid induces the formation of tetanus antitoxin. {06}

Pertussis—Following intramuscular injection, pertussis vaccine induces the formation of several antibodies thought to be clinically protective. The exact mechanism of protection is not known. {08}

Haemophilus b— Haemophilus influenzae type b (Hib) bacteria are surrounded by polysaccharide capsules, which make these bacteria resistant to attack by white blood cells. The vaccine, which is derived from the purified polysaccharide from Hib cells, stimulates production of anticapsular antibodies and provides active immunity to the Hib bacteria. Whereas the nonconjugated polysaccharide vaccine predominantly stimulates B-cells to produce antibodies (known as being T-cell independent), Haemophilus b conjugate vaccine stimulates T-cells also. The additional stimulation of T-cells (known as being T-cell dependent) is particularly important in young children to ensure an adequate and persistent antibody response. 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 Hib, resulting in elevated antibody titers. {01} {02} {03} {13} {15} {16} {17} {24}


Protective effect

Diphtheria—The protective titer of diphtheria antitoxin in serum is considered to be {24} 0.01 unit per mL. {07}

Tetanus—The protective titer of tetanus antitoxin in serum is considered to be {24} 0.01 unit per mL. {07}

Pertussis—The potency of the inactivated B. pertussis cells in the vaccine is assayed by comparison with the U.S. standard pertussis vaccine in the intracerebral mouse protection test. The protective efficacy of pertussis vaccines for humans has been shown to correlate with the measure of vaccine potency. {01} {05}

Haemophilus b—Antibody response to Haemophilus b conjugate vaccine is age related in children, with the immune response improving with increasing age. The titer of antibody from Haemophilus b conjugate vaccine required for protection against invasive disease has not been clearly established. However, in studies using Haemophilus b polysaccharide vaccine, a geometric mean titer (GMT) of 1 mcg per mL of serum 3 weeks after immunization correlated with protection and suggests long-term protection from invasive disease. {03} {12} {13}


Duration of protective effect

Diphtheria—At least 10 years for diphtheria toxoid following a completed primary immunizing series of injections. {01} {05} {06}

Tetanus—At least 10 years for tetanus toxoid following a completed primary immunizing series of injections. {01} {05} {06}

Pertussis—Following a completed primary immunizing series of injections, immunity to pertussis usually persists throughout childhood, but is thought to decrease over time. Lifelong immunity is probably attained through subsequent mild pertussis infection. {05} {09} {10} {11}

Haemophilus b—The duration of immunity is unknown. {03} {15} {17} {18}


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to diphtheria or tetanus toxoid, whole cell or acellular pertussis vaccine, Haemophilus b polysaccharide vaccine, or any type of Haemophilus b conjugate vaccine may be sensitive to diphtheria and tetanus toxoids and pertussis vaccine adsorbed and Haemophilus b conjugate vaccine combination (DTP-Hib) also.

Carcinogenicity/Mutagenicity

Studies have not been done. {01}

Pregnancy/Reproduction
Fertility—
Studies have not been done. {01}

Pregnancy—
Studies have not been done in humans. DTP-Hib is not recommended for use in persons 7 years of age or older. {03} {19}

Studies have not been done in animals. {01}

FDA Pregnancy Category C. {01}

Pediatrics

Safety and efficacy have not been established for children younger than 6 weeks of age for DTP-Hib (HbOC—diphtheria CRM 197 protein conjugate) {01} {02} or younger than 18 months of age for DTP-Hib (PRP-D—diphtheria toxoid conjugate). {19} DTP-Hib is not recommended for use in children 7 years of age or older. {01} {02} {03} {19} (The DTP component is not recommended for use in persons 7 years of age or older, because of the increased risk of side/adverse reactions {05}; the Hib component is not recommended for use in persons 5 years of age or older, except for patients with certain chronic conditions associated with an increased risk of Hib disease.) {13}

Immunization with DTP-Hib is contraindicated if a previous immunization with a DTP- or pertussis-containing vaccine was temporally related to an immediate anaphylactic reaction or encephalopathy occurring within 7 days after immunization {01} {05}. See also General Dosing Information.

Although the following events were considered contraindications in previous recommendations of the Advisory Committee of Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC), they are now considered precautions. Immunization with DTP-Hib should be carefully considered if a previous immunization with a DTP- or pertussis-containing vaccine was temporally related to fever of ³ 40.5 °C (105 °F) occurring within 48 hours; hypotonic-hyporesponsive episode (collapse or shock-like state) occurring within 48 hours; persistent and inconsolable crying lasting 3 or more hours and occurring within 48 hours; or seizures with or without fever occurring within 3 days. {05} See also General Dosing Information.


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 vaccine.

Immunosuppressive agents
Radiation therapy    (because normal defense mechanisms are suppressed by immunosuppressive agents or radiation treatment, the patient's antibody response to DTP-Hib may be decreased. 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; otherwise, it may be preferable to postpone the immunization until after the immunosuppressive therapy is completed. 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 therapy used, the underlying disease, and other factors; estimates vary from 3 months to 1 year. 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 {01} {05} {08} {16} {18} {20} {21})



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 {16} 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. {16} For example, purified capsular polysaccharide [a polymer of ribose, ribitol, and phosphate (PRP)], which is associated with Haemophilus b vaccines, was detected in the urine of some persons for up to 7 days following immunization with an Haemophilus b vaccine conjugated with meningococcal protein [PRP-OMP] {16} {23} {25} {26})


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 vaccine should not be used when the following medical problems exist:
» Central nervous system (CNS) disorders, evolving or changing, whether or not the disorder is associated with seizure activity{01}    (there appears to be an increased risk of the appearance of manifestations of the underlying neurological disorder within 2 or 3 days after immunization. This may lead to confusion in interpretation of the neurological disorder. However, prolonged manifestations, increased progression, or exacerbation of the disorder has not been identified {05} {24})


» Febrile illness or
» Infection, acute    (administration of DTP-Hib should be postponed until the acute symptoms of the patient's illness have abated to avoid confusing the symptoms of the illness with the side effects of the vaccine; however, minor illnesses, such as mild upper-respiratory infections with or without low-grade fever are not contraindications {01} {02} {03} {05} {19} {21} {29})


» Sensitivity to DTP-Hib{01}
Risk-benefit should be considered when the following medical problems exist
Neurological disease, suspected    (initiation of DTP, but not other childhood vaccines, should be delayed until there is clarification of the child's neurological status; however, the decision whether or not to commence immunization with DTP should be made by the child's first birthday. When making the decision, it should be recognized that neurologically disabled children may be at increased risk of pertussis because of their attendance at special schools or clinics where many of the other children attending may not be immunized. In addition, neurologically disabled children may be at increased risk from complications of pertussis {05})

    (See also General Dosing Information.)


Seizures    (children who have had seizures prior to DTP administration, whether febrile or afebrile, appear to be more likely to have seizures following DTP immunization than children without such histories. {01} {05} However, current evidence indicates that seizures following DTP immunization do not cause permanent brain damage. A seizure occurring within 3 days of DTP immunization in a child with a history of seizures may be initiated by vaccine-induced fever in a child prone to febrile seizures, induced by the pertussis component, or unrelated to the vaccine. Therefore, it is prudent to delay DTP immunization in infants and children with a history of seizures until the child's status has been fully assessed and the condition has been stabilized. However, it should be noted that delaying DTP immunization until the second 6 months of life will increase the risk of febrile seizures among predisposed children. Children with a history of seizures should be given acetaminophen, 15 mg per kg of body weight (mg/kg), at the time of immunization and every 4 hours for the next 24 hours {05} {21})

    (See also General Dosing Information.)


Seizures or other CNS disorders, family history of{24}    (children with a family history of seizures or other CNS disorders appear to be more likely to have seizures following DTP immunization than do children without such histories {01} {05}; however, these seizures are usually caused by fever. Acetaminophen, 15 mg/kg, should be given to these children at the time of immunization and every 4 hours for the next 24 hours {05} {21} {22})


Sensitivity to thimerosal{01}{02}{19}{27}


Side/Adverse Effects

Note: Children who have had seizures previously, whether febrile or afebrile, appear to be more likely to have seizures following a diphtheria and tetanus toxoids and pertussis vaccine (DTP)–containing immunization than children without such histories. However, current evidence indicates that seizures following a DTP-containing immunization do not cause permanent brain damage. {05} See also General Dosing Information.
Fever that does not begin until 24 or more hours after immunization or persists for more than 24 hours after immunization should not be assumed to be due to a DTP-containing immunization. {05}

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{01}{02}{05} (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, with or without fever, occurring within 3 days{01}{02}{05}
    
crying, persistent and inconsolable, occurring within 48 hours and lasting 3 or more hours{01}{02}{05}{19}
    
encephalopathy, occurring within 7 days{01}{02}{05} (severe alterations in consciousness, with generalized or focal neurological signs; confusion; severe or continuing headache; unusual and continuing irritability; excessive sleepiness; severe or continuing vomiting)
    
fever of 40.5 °C (105 °F) or more, occurring within 48 hours{01}{02}{05}
    
hypotonic-hyporesponsive episode, occurring within 48 hours{01}{02}{05} (collapse or shock-like state)



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Drowsiness{01}{02}{05}{19}
    
erythema{01}{02}{03}{05}{13}{19} , swelling{01}{02}{03}{05}{13}{19} , or warm feeling{01}{02}{13} at injection site (redness, swelling, or warm feeling at place of injection)
    
fever up to 39 °C (102.2 °F) —usually lasting up to, but no longer than, 48 hours; may be accompanied by fretfulness, drowsiness, vomiting, and anorexia
    
fretfulness{05}{19}
    
irritability{01}{02}{03}{19}
    
lump at injection site{19} —may be present for a few weeks after injection
    
pain{01}{02}{03}{05}{19} or tenderness{01}{02}{03}{19} at injection site

Incidence less frequent
    
Anorexia{01}{02}{03}{05}{19} (loss of appetite)
    
diarrhea{01}{02}{03}
    
fever between 39 and 40 °C (102.2 and 104 °F){01}{02}{05}{19} —usually lasting up to, but no longer than, 48 hours; may be accompanied by fretfulness, drowsiness, vomiting, and anorexia
    
induration{19} at injection site (hard lump)—may be present for a few days after injection
    
vomiting{01}{02}{03}{05}{19}

Incidence rare
    
Abscess, sterile{05}{28} (redness, swelling, tenderness, or pain at injection site)
    
fever between 40 and 40.4 °C (104 and 104.8 °F){05} —usually lasting up to, but no longer than, 48 hours; may be accompanied by fretfulness, drowsiness, vomiting, and anorexia; incidence 1 to 5%
    
lethargy{03} (lack of interest; reduced physical activity)
    
skin rash{01}{02}{03}{05}





Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Diphtheria and Tetanus Toxoids and Pertussis Vaccine Adsorbed and 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 diphtheria or tetanus toxoid, whole cell or acellular pertussis vaccine, Haemophilus b polysaccharide vaccine, any type of Haemophilus b conjugate vaccine, or thimerosal





Use in children—Safety and efficacy have not been established for children younger than 6 weeks of age (administration usually begins at 2 months of age); not recommended for use in children 7 years of age or older

Other medical problems, especially acute infection; evolving or changing central nervous system (CNS) disorders, whether or not the disorder is associated with seizure activity; or febrile illness

Proper use of this vaccine

» Proper dosing

After receiving this vaccine
Possibly receiving acetaminophen at time of injection; possibly continuing acetaminophen every 4 hours for 24 hours following injection; checking with physician if there are questions

Possibility of vaccine interfering with laboratory tests that check for Hib disease; informing physician of recent DTP-Hib vaccination if treated for a severe infection within 2 weeks after administration


Side/adverse effects
Signs of potential side effects, especially anaphylactic reaction; convulsions, with or without fever, occurring within 3 days; crying, persistent and inconsolable, occurring within 48 hours and lasting 3 or more hours; encephalopathy, occurring within 7 days; fever of 40.5 °C (105 °F) or more, occurring within 48 hours; and hypotonic-hyporesponsive episode, occurring within 48 hours


General Dosing Information
Diphtheria and tetanus toxoids and pertussis vaccine adsorbed and Haemophilus b conjugate vaccine combination (DTP-Hib) is not recommended for use in persons 7 years of age or older. {01} {02} {03} {19} (The DTP component is not recommended for use in persons 7 years of age or older, because of the increased risk of side/adverse reactions {05}; the Hib component is not recommended for use in persons 5 years of age or older, except for patients with certain chronic conditions associated with an increased risk of Hib disease.) {13}

DTP-Hib vaccine may be administered concurrently with the following, using separate body sites and syringes for the parenterals, and the precautions that apply to each immunizing agent:    • Hepatitis B recombinant or plasma-derived vaccine. {03}
   • Influenza virus vaccine. {03} In the past it was recommended that influenza virus vaccine and a pertussis-containing vaccine should not be administered within 3 days of one another. Since both influenza virus vaccine and pertussis vaccine may cause febrile reactions in young children, the time interval was recommended so that the cause of any adverse effect was clear. However, the American Academy of Pediatrics (AAP) now accepts {26} concurrent administration of these vaccines. {01} {21}
   • Measles, mumps, and rubella vaccine (MMR). {03}
   • Poliovirus vaccines (oral [OPV], inactivated [IPV], or enhanced-potency inactivated [enhanced-potency IPV]). {03}


Preterm infants should be immunized according to their chronological age from birth. {05}

Continued use of this vaccine is contraindicated because of its DTP component, according to the Advisory Committee Immunization Practices (ACIP), when the following medical problems occur:    • Anaphylactic reaction, immediate. {01} {05} Because of uncertainty as to which component of the vaccine may be responsible, it is recommended that no further immunization be carried out with any of the three antigens in DTP. Alternatively, because of the importance of tetanus immunization, such individuals should be referred to an allergist for evaluation and desensitized to tetanus toxoid if specific allergy can be demonstrated. {05}
   • Encephalopathy, {01} {05} not due to another identifiable cause. {05} Encephalopathy is defined as an acute, severe CNS disorder occurring within 7 days following immunization and generally consisting of major alterations in consciousness, unresponsiveness, generalized or focal seizures that persist more than a few hours, and failure to recover within 24 hours. {01} {05} Even though causation by DTP cannot be established, subsequent doses of the pertussis component should not be given. In addition, it may be desirable to delay for a period of months so that the child's neurological status can clarify before continuing the immunization series with diphtheria and tetanus toxoids combination (DT) instead of DTP. {05}


Although the following events were considered contraindications to continued use of pertussis vaccine, in previous ACIP recommendations, they are now considered precautions. There may be circumstances, such as a high incidence of pertussis in the community, in which the potential benefits outweigh possible risks, particularly since these events are not associated with permanent sequelae. Therefore, continued use of this vaccine should be carefully considered because of its pertussis component when the following medical problems occur:    • Fever ³ 40.5 °C (105 °F) occurring within 48 hours and not due to other causes. This is considered a precaution because of the likelihood that fever following a subsequent dose of DTP vaccine also will be high. Because such febrile reactions are usually attributed to the pertussis component, the immunization series should be continued with DT. {05}
   • Hypotonic-hyporesponsive episode (collapse or shock-like state) occurring within 48 hours. Although these uncommon events have not been recognized to cause death or to induce permanent neurological sequelae, it is prudent to omit the pertussis component and continue the immunization series with DT. {05}
   • Persistent and inconsolable crying lasting 3 or more hours and occurring within 48 hours. Follow-up of infants who have cried inconsolably following DTP immunization has indicated that this reaction is without long-term sequelae and is not associated with other reactions of greater significance. Inconsolable crying occurs most frequently following the first dose of DTP. However, crying for longer than 30 minutes following a DTP injection can be a predictor of increased likelihood of persistent crying following subsequent doses. Children who react with persistent crying have had a higher rate of substantial local reactions than did children who had other DTP-associated reactions (including high fever, seizures, and hypotonic-hyporesponsive episodes), suggesting that prolonged crying was really a pain reaction. {05}
   • Seizures, with or without fever, occurring within 3 days. Short-lived seizures, with or without fever, have not been shown to cause permanent sequelae. Furthermore, the occurrence of prolonged febrile seizures (i.e., status epilepticus, defined as any seizure lasting longer than 30 minutes or recurrent seizures lasting a total of 30 minutes without the child fully regaining consciousness), irrespective of their cause, involving an otherwise normal child does not substantially increase the risk for subsequent febrile (brief or prolonged) or afebrile seizures. The risk is significantly increased only among those children who are neurologically abnormal before their episode of status epilepticus. Accordingly, although a seizure following DTP immunization previously has been considered a contraindication to further doses of the pertussis component, under certain circumstances subsequent doses may be indicated, particularly if the risk of pertussis in the community is high. If a child has a seizure following the first or second dose of DTP, it is desirable to delay subsequent doses until the child's neurologic status is better defined. By the child's first birthday, the presence of an underlying neurologic disorder has usually been determined. A decision should be made whether to continue with DTP instead of automatically switching to DT. Regardless of whether DTP or DT is chosen, acetaminophen, 15 mg per kg of body weight (mg/kg), should be given at the time of immunization and every 4 hours for the next 24 hours. {05}


Continued use of this vaccine should be carefully considered because of its DTP component if a neurological event (e.g., seizure) occurs between doses of, but not temporally associated with, this vaccine. If the event occurs before the child's first birthday and the child has not received all 3 doses of the primary DTP series, further doses of DTP, but not other childhood vaccines, should be deferred until there is clarification of the child's neurological status; however, the decision whether or not to continue immunization with DTP should be made no later than the child's first birthday and should be based on the nature of the neurological event and the risk/benefit associated with the vaccine. If the event occurs after the child's first birthday, the child's neurological status should be evaluated to ensure that the disorder is stable before immunization with DTP is continued. {05} See also Medical considerations/Contraindications.

Children with stable neurologic conditions, including well-controlled seizures, may be immunized with a DTP-containing vaccine. {05} The occurrence of a single seizure that is not temporally associated with DTP does not contraindicate DTP immunization, particularly if the seizure can be explained. {05} {29} Parents of children with histories of seizures should be informed of the increased risk of postimmunization seizures. In addition, acetaminophen, 15 mg/kg, should be given at the time of immunization and every 4 hours for the next 24 hours to reduce the possibility of postimmunization fever. {05} See also Medical considerations/Contraindications.

Immunization with a DTP-containing vaccine is recommended for children with certain neurologic problems, such as hydrocephalus (following placement of a shunt and if the child is without seizures) or neonatal hypocalcemic tetany, that have been corrected or have clearly subsided without residua. {05}

Before each additional dose of DTP-Hib, the health status of the patient should be assessed. In addition, information should be obtained regarding any symptom or sign of an adverse reaction that occurred after the previous dose. {05} {21}

If tetanus immune globulin (TIG) or diphtheria antitoxin is being administered at the same time as DTP-Hib, separate body sites and separate syringes should be used. {01}

For treatment of adverse effects {19}
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.


DIPHTHERIA AND TETANUS TOXOIDS AND PERTUSSIS VACCINE ADSORBED AND HAEMOPHILUS B CONJUGATE VACCINE (HbOC—DIPHTHERIA CRM 197 PROTEIN CONJUGATE)


Parenteral Dosage Forms

DIPHTHERIA AND TETANUS TOXOIDS AND PERTUSSIS VACCINE ADSORBED AND HAEMOPHILUS B CONJUGATE VACCINE(HbOC—diphtheria CRM 197 protein conjugate)INJECTION

Note: Diphtheria and tetanus toxoids and pertussis vaccine adsorbed and Haemophilus b conjugate vaccine combination (DTP-Hib) may be used whenever the schedules for immunization with the separate vaccines, diphtheria and tetanus toxoids and pertussis vaccine (DTP) and Haemophilus b conjugate vaccine (Hib), coincide. {01} {02} {03}


Usual adult and adolescent dose
Use is not recommended. {01}

Usual pediatric dose
Active immunizing agent
Intramuscular, 0.5 mL into the outer aspect of the upper arm (deltoid) or into the lateral mid thigh (vastus lateralis)
Children up to 2 months of age—Use is not recommended. {01} {03}

Children 2 to 6 months of age at the first dose—Three doses, at least two months apart. Then, a fourth dose at 12 to 18 months of age {01} {02} {03} after at least a 6-month interval {03} following the third dose. {01} {02} {03}

Note: Alternatively, Hib vaccine {01} {02} {03} and either acellular DTP (DTaP) {01} {03} or whole-cell DTP {02} may be administered as separate injections for the fourth dose at 12 to 18 months of age. {01} {02} {03} (DTaP is preferred for doses four and five of the five-dose DTP series {03} in order to reduce the chance of side effects.) {21}


Children 7 to 11 months of age at the first dose—Two doses, at least two months apart, followed by appropriate doses of DTP or Hib (or DTP-Hib, where use of the two vaccines coincides) to complete each vaccine's immunization schedule. {03} (A child 7 to 11 months of age should receive a total of 3 doses of a product containing HbOC.) {01} {03} {13}

Children 12 to 14 months of age at the first dose—One dose, followed by appropriate doses of DTP or Hib (or DTP-Hib, when use of the two vaccines coincides) to complete each vaccine's immunization schedule. (A child 12 to 14 months of age should receive a total of 2 doses of a product containing HbOC.) {01} {03} {13} {29} {30}

Children 15 to 59 months of age at the first dose—One dose, followed by appropriate doses of DTP to complete the immunization schedule for DTP. (A child 15 to 59 months of age should receive a single dose of a product containing HbOC.) {01} {03} {05} {13} {30}



Note: The above dosage schedules do not negate the necessity of any additional doses or boosters of DTP or Hib that are required.
The above doses assume that neither DTP nor Hib vaccine has been administered previously.
DTP-Hib vaccine may be used also to complete an immunization series already initiated with any Hib vaccine and/or any DTP vaccine in those instances where the two vaccine schedules coincide. {03}
Although any Hib vaccine type (licensed for use in that particular age group) {03} {26} may be used where the individual vaccine is required, use of the same Hib vaccine type throughout a primary immunization series is preferable. {03}


Strength(s) usually available
U.S.—


12.5 Lf of diphtheria toxoid, 5 Lf of tetanus toxoid, 4 protective units of pertussis vaccine, 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 diphtheria toxin), per 0.5 mL dose. Each 0.5-mL dose contains not more than 850 mcg (0.85 mg) of aluminum (Rx) [Tetramune{01} (thimerosal 1:10,000)]

Canada—


12.5 Lf of diphtheria toxoid, 5 Lf of tetanus toxoid, 4 protective units of pertussis vaccine, 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 diphtheria toxin), per 0.5 mL dose. Each 0.5-mL dose contains not more than 850 mcg (0.85 mg) of aluminum (Rx) [Tetramune{02} (thimerosal 1:10,000)]

Note: Lf is the quantity of toxoid as assessed by flocculation.


Packaging and storage:
Store between 2 and 8 °C (36 and 46 °F), unless otherwise specified by manufacturer. Protect from freezing. {01} {02}

Preparation of dosage form:
The product should be shaken well immediately before withdrawing each dose. The product should be discarded if clumps remain after vigorous agitation. {01} {02}

Stability:
The vaccine should be refrigerated, but kept away from the freezer compartment {01} {02}. Vaccine that has been frozen should be discarded. {19} {26}

Auxiliary labeling:
   • Shake well. {01} {02}
   • Do not freeze. {01} {02}


DIPHTHERIA AND TETANUS TOXOIDS AND PERTUSSIS VACCINE ADSORBED AND HAEMOPHILUS B CONJUGATE VACCINE (PRP-D—DIPHTHERIA TOXOID CONJUGATE)


Parenteral Dosage Forms

DIPHTHERIA AND TETANUS TOXOIDS AND PERTUSSIS VACCINE ADSORBED AND HAEMOPHILUS B CONJUGATE VACCINE(PRP-D—diphtheria toxoid conjugate)INJECTION

Usual adult and adolescent dose
Use is not recommended. {19}

Usual pediatric dose
Active immunizing agent
Intramuscular, 0.5 mL into the outer aspect of the upper arm (deltoid) or into the lateral mid thigh (vastus lateralis):
Children up to 18 months of age—Use is not recommended. {19}

Children 18 to 59 months of age—DTP-Hib may be administered when the single dose of Hib coincides with the fourth or fifth scheduled dose of DTP. {19} {31}



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

Canada—


25 Lf of diphtheria toxoid, 5 Lf of tetanus toxoid, 4 to 12 protective units of pertussis vaccine, 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. Each 0.5-mL dose contains 1.5 mg of aluminum phosphate (Rx) [DPT-Hib{19} (thimerosal 0.01%)]

Note: Lf is the quantity of toxoid as assessed by flocculation.


Packaging and storage:
Store between 2 and 8 °C (36 and 46 °F), unless otherwise specified by manufacturer. Protect from freezing. {19}

Preparation of dosage form:
The product should be shaken well immediately before withdrawing each dose. The product should be discarded if clumps remain after vigorous agitation. {19}

Stability:
The vaccine should be refrigerated, but kept away from the freezer compartment. Vaccine that has been frozen should be discarded. {19} {26}

Auxiliary labeling:
   • Shake well. {19}
   • Do not freeze. {19}



Developed: 11/27/1996



References
  1. Tetramune package insert (Lederle—US), Rev 4/94, Rec 10/94.
  1. Tetramune package insert (Lederle—Canada), Rev 4/94, Rec 11/94.
  1. Centers for Disease Control and Prevention. Recommendations for use of Haemophilus b conjugate vaccines and a combined diphtheria, tetanus, pertussis, and Haemophilus b vaccine. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1993 Sep 17; 42(RR-13): 1-15.
  1. Open.
  1. Centers for Disease Control and Prevention. Diphtheria, tetanus, and pertussis: recommendations for vaccine use and other preventive measures: recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 1991 Aug 8; 40(RR-10): 1-28.
  1. Diphtheria and Tetanus Toxoids Adsorbed (generic, Lederle). In: PDR Physicians' desk reference. 48th ed. 1994. Montvale, NJ: Medical Economics Data, 1994: 1158.
  1. Diphtheria and Tetanus Toxoids Adsorbed package insert (generic, Connaught— US), Rev 4/84, Rec 10/94.
  1. Diphtheria and Tetanus Toxoids and Pertussis Vaccine (Acel-Imune, Lederle). In: PDR Physician's desk reference. 48th ed. 1994. Montvale, NJ: Medical Economics Data, 1994: 1149.
  1. Panel comments on Diphtheria and Tetanus Toxoids and Pertussis Vaccine monograph revision of 8/7/86.
  1. Panel comments on Diphtheria and Tetanus Toxoids and Pertussis Vaccine monograph revision of 10/14/86.
  1. Panel comments on Diphtheria and Tetanus Toxoids and Pertussis Vaccine monograph revision of 6/88.
  1. ACIP. Supplementary statement: change in administration schedule for Haemophilus b conjugate vaccines. MMWR 1990 Apr 13; 39(14): 232-3.
  1. Centers for Disease Control and Prevention. 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. Open.
  1. Centers for Disease Control and Prevention. ACIP update: prevention of Haemophilus influenzae type b disease. MMWR 1988 Jan 22; 37: 13-6.
  1. Panel comments on Haemophilus b conjugate vaccine monograph, 5/9/89.
  1. Panel comments on Haemophilus b conjugate vaccine monograph, 9/19/90.
  1. Panel comments on Haemophilus b conjugate vaccine monograph, 3/16/93.
  1. DPT-Hib package insert (Connaught—Canada), Rev 2/92, Rec 12/94.
  1. Centers for Disease Control and Prevention. Recommendations of the Advisory Committee on Immunization Practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence. MMWR 1993 Apr 9; 42(RR-4): 1-18.
  1. American Academy of Pediatrics. Peter G, editor. 1994 Red Book: Report of the Committee on Infectious Diseases. 23rd ed. Elk Grove Village, IL: American Academy of Pediatrics, 1994: 35, 54, 59, 281, 355-67.
  1. Centers for Disease Control and Prevention. Pertussis immunization: family history of convulsions and use of antipyretics—supplementary ACIP statement: recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 1987 May 15; 36(18): 281-2.
  1. McEvoy GK, editor. AHFS Drug Information 88. Bethesda, MD: American Society of Hospital Pharmacists, 1988: 1922-8.
  1. Panel comment, 6/1/95.
  1. Panel comment, 6/1/95.
  1. Panel comment, 6/1/95.
  1. Reviewers' consensus on monograph revision of 6/1/95.
  1. Panel comment, 6/1/95.
  1. Manufacturer's comment, 6/1/95.
  1. Reviewers' consensus on monograph revision of 6/1/95.
  1. Reviewers' consensus on monograph revision of 6/1/95.
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