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Haemophilus b Vaccine

Class: Vaccines
ATC Class: J07AG51
VA Class: IM100
Brands: ActHIB, Comvax, Hiberix, MenHibrix (combination), PedvaxHIB, Pentacel (combination)

Introduction

Inactivated (polysaccharide) vaccine.134 144 174 223 Commercially available in US as 2 different monovalent vaccines: Haemophilus b (Hib) conjugate vaccine (meningococcal protein conjugate) (PRP-OMP; PedvaxHIB)144 and Hib conjugate vaccine (tetanus toxoid conjugate) (PRP-T; ActHIB, Hiberix).174 223 PRP-OMP also commercially available in fixed combination with hepatitis B vaccine (Hib-HepB; Comvax);77 PRP-T also commercially available in fixed combination with meningococcal groups C and Y antigens (Hib-MenCY; MenHibrix)227 and in a combination vaccine containing diphtheria, tetanus, pertussis, poliovirus, and Hib antigens (DTaP-IPV/Hib; Pentacel).224

Uses for Haemophilus b Vaccine

Prevention of Haemophilus influenzae type b (Hib) Infection

Prevention of Hib infection in infants and children 2 through 71 months of age (usually 2 through 59 months of age).105 144 159 166 174 199 223

Hib is a gram-negative bacterium that causes meningitis and other serious infections (e.g., pneumonia, epiglottitis, sepsis, cellulitis, septic arthritis, osteomyelitis, endocarditis, purulent pericarditis) in young children.23 105 166 Prior to availability of Hib vaccine, Hib was the most common cause of bacterial meningitis and other invasive bacterial disease in infants and children <5 years of age;105 166 case fatality rate was 2–5% despite anti-infective treatment and 15–30% of meningitis survivors had hearing loss or neurologic sequelae.166 Incidence of invasive Hib in the US decreased 99% after Hib conjugate vaccines became available.105 166 Most cases now occur in unvaccinated or incompletely vaccinated infants and children, including infants <6 months of age who are too young to have received a complete vaccination series.105 166 During 2009, there were 35 cases of invasive Hib disease and 178 cases caused by unknown serotypes of H. influenzae in US children <5 years of age.166

USPHS Advisory Committee on Immunization Practices (ACIP), AAP, and others recommend routine vaccination against Hib in all infants using an appropriate vaccine regimen initiated in early infancy at 2 months of age (minimum age 6 weeks).105 159 199

Catch-up vaccination recommended by ACIP, AAP, and others for all children <5 years of age who are unvaccinated or incompletely vaccinated against Hib.105 159 199

Unvaccinated children <4 years of age are at increased risk of invasive Hib disease, especially if in prolonged close contact (e.g., household contact) with a child with invasive Hib disease.105 Other factors associated with increased risk of invasive Hib infection include asplenia,105 166 sickle cell disease,105 166 antibody deficiency syndromes,166 HIV infection,105 156 166 other immunodeficiency syndromes,38 105 166 and Hodgkin’s disease79 or other malignancies (especially during chemotherapy).105 166 Historically, invasive Hib was more common in boys;105 American Indians (e.g., Apache and Navajo tribes),45 105 166 Alaskan natives,40 45 85 105 Hispanics,166 and blacks;29 105 166 daycare attendees;105 166 children living in crowded conditions;105 166 and children who were not breastfed.105 (See Limitations of Vaccine Effectiveness under Cautions.)

Not labeled by FDA for use in children ≥5 years of age, adolescents, or adults.77 144 174 223 224 227 Although efficacy data not available on which to base recommendations, ACIP, AAP, and others recommend a single dose of Hib vaccine in children ≥5 years of age who are unvaccinated or incompletely vaccinated against Hib and are at increased risk for invasive Hib disease because of altered immunocompetence (e.g., sickle cell disease, leukemia, anatomic or function asplenia, HIV infection, IgG2 deficiency, chemotherapy, hematopoietic stem cell transplantation).105 134 156 159 166 199 200 These experts also state consider a single dose of Hib vaccine in adults with sickle cell disease, leukemia, HIV infection, or anatomic or functional asplenia if they have not previously received the vaccine.134 200 Consider that immune response to the vaccine may be less in immunocompromised individuals.105 134 (See Individuals with Altered Immunocompetence under Cautions.)

Ensure that children with a cochlear implant have received age-appropriate Hib vaccination;114 cochlear implant recipients may be at increased risk of invasive Hib disease (i.e., meningitis).114

For internationally adopted children with uncertain immune status, ACIP recommends revaccination with an age-appropriate Hib vaccine regimen.134

Hib vaccine will not provide protection against other types of H. influenzae (e.g., nonencapsulated [nontypeable] strains associated with otitis media and sinusitis) or against other pathogens that cause meningitis or septicemia.144 174

Depending on age and vaccination status, Hib vaccine may be given as a monovalent vaccine (ActHIB, PedvaxHIB, Hiberix)144 174 223 or a combination vaccine containing Hib and other antigens.77 174 224 227 ACIP, AAP, and others state a combination vaccine generally preferred over separate injections of the equivalent component vaccines;134 199 considerations include provider assessment (e.g., number of injections, vaccine availability, likelihood of improved coverage, likelihood of patient return, storage requirements, cost), patient preference, and potential for adverse effects.134

Hib-HepB (Comvax): May be used in infants 6 weeks to 15 months of age born to HBsAg-negative women when vaccination against HBV and Hib indicated.77 Although not labeled by FDA for use in infants born to HBsAg-positive women,77 ACIP states Hib-HepB (Comvax) may be used to complete the HBV vaccination series in infants 6 weeks to 15 months of age born to HBsAg-positive women.137

Hib-MenCY (MenHibrix): May be used in infants 6 weeks through 18 months of age when vaccination against Hib and meningococcal serogroups C and Y indicated.162 227 228 Although routine vaccination against meningococcal disease not recommended in infants who are not at increased risk,105 162 228 ACIP, AAP, and others state Hib-MenCY (MenHibrix) may be used for primary immunization against Hib in infants 6 weeks through 18 months of age who are at increased risk for meningococcal disease because they have certain chronic medical conditions (e.g., persistent complement component deficiencies or anatomic or functional asplenia, including sickle cell disease) or reside in communities with outbreaks of meningococcal serogroup C or Y.162 199 228 Does not provide adequate protection for infants and children traveling to or residing in areas with high endemic rates of meningococcal disease (e.g., “meningitis belt” of sub-Saharan Africa) since it does not provide protection against meningococcal serogroups A and W-135.162 199 228 Administration in infancy unlikely to provide persistent protection against meningococcal disease until 11 through 12 years of age, the age of recommended routine adolescent meningococcal vaccination.162

DTaP-IPV/Hib (Pentacel): May be used in infants and children 6 weeks through 4 years of age when doses of DTaP, IPV, and Hib indicated and there are no contraindications to any of the individual components.207 224 For prevention of Hib, ACIP states that DTaP-IPV/Hib (Pentacel) may be used for primary immunization doses and the booster dose at 12 through 15 months of age.207

Haemophilus b Vaccine Dosage and Administration

Administration

IM Administration

Monovalent Hib vaccines (PRP-T; ActHIB, Hiberix) (PRP-OMP; PedvaxHIB): Administer by IM injection.77 144 174 223

Hib-HepB (Comvax), Hib-MenCY (MenHibrix), DTaP-IPV/Hib (Pentacel): Administer by IM injection.77 224 227

Do not administer monovalent Hib vaccines or combination vaccines containing Hib and other antigens IV, sub-Q, or intradermally.77 144 174 223 224 227

Depending on patient age, administer IM into deltoid muscle or anterolateral thigh.134 144 224 227 In infants and children 6 weeks to 2 years of age, anterolateral thigh is preferred;134 alternatively, deltoid muscle can be used in those 1 through 2 years of age if muscle mass is adequate.134 In children ≥3 years of age, deltoid muscle preferred.134

To ensure delivery into muscle, make IM injections at a 90° angle to the skin using a needle length appropriate for the individual’s age and body mass, thickness of adipose tissue and muscle at injection site, and injection technique.134 208 209 Consider anatomic variability, especially in the deltoid; use clinical judgement to avoid inadvertent underpenetration or overpenetration of muscle.208 209

Avoid injection into gluteal area or into or near blood vessels or nerves.77 134 144 174 224 Generally do not administer vaccines into gluteal area or any area where there may be a major nerve trunk.134 If the gluteal muscle is chosen for infants <12 months of age because of special circumstances (e.g., physical obstruction of other sites), it is essential that clinician identify anatomical landmarks prior to injection.134

Syncope (vasovagal or vasodepressor reaction; fainting) may occur following vaccination;134 223 227 may be accompanied by transient neurologic signs (e.g., visual disturbance, paresthesia, tonic-clonic limb movements).223 227 Occurs most frequently in adolescents and young adults.134 Have procedures in place to avoid falling injury and restore cerebral perfusion following syncope.223 227 Syncope and secondary injuries may be averted if vaccinees sit or lie down during and for 15 minutes after vaccination.134 If syncope occurs, observe patient until symptoms resolve.134

May be given simultaneously with other age-appropriate vaccines.134 When multiple vaccines are administered during a single health-care visit, give each parenteral vaccine with a different syringe and at different injection site.134 Separate injection sites by at least 1 inch (if anatomically feasible) to allow appropriate attribution of any local adverse effects that may occur.134

PRP-OMP (PedvaxHIB)

Do not dilute.144

Shake well before use;144 thorough agitation necessary to maintain suspension.144 Should appear as slightly opaque white suspension.144

PRP-T (ActHIB)

Reconstitute single-dose vial of lyophilized PRP-T (ActHIB) by adding entire amount of 0.4% sodium chloride diluent supplied by the manufacturer; agitate thoroughly.174 Consult manufacturer’s labeling for specific information regarding reconstitution.174

Administer within 24 hours after reconstitution.174

PRP-T (Hiberix)

Reconstitute single-dose vial of lyophilized PRP-T (Hiberix) by adding entire amount of 0.9% sodium chloride diluent supplied by the manufacturer;223 agitate thoroughly.223 Consult manufacturer’s labeling for specific information regarding reconstitution.223

Administer promptly after reconstitution or store at 2–8°C and administer within 24 hours.223

Shake vigorously before use.223

Do not mix with any other vaccine or solution.223

Hib-HepB (Comvax)

Do not dilute.77

Shake well before use;77 thorough agitation necessary to maintain suspension.77 Should appear as slightly opaque white suspension.77

Hib-MenCY (MenHibrix)

Reconstitute single-dose vial of lyophilized Hib-MenCY (MenHibrix) by adding 0.6 mL of 0.9% sodium chloride diluent supplied by the manufacturer;227 shake well.227 Consult manufacturer’s labeling for specific information regarding reconstitution.227

Administer immediately after reconstitution.227

Do not mix with any other vaccine.227

DTaP-IPV/Hib (Pentacel)

DTaP-IPV/Hib (Pentacel) is commercially available as a kit containing single-dose vial of fixed-combination vaccine containing diphtheria, tetanus, pertussis, and poliovirus antigens (DTaP-IPV vaccine) and single-dose vial of lyophilized Hib vaccine (PRP-T; ActHIB).224

Prior to administration, reconstitute vial of lyophilized PRP-T (ActHIB) vaccine by adding entire contents of vial of DTaP-IPV vaccine in the kit according to manufacturer’s instructions to provide a combination vaccine containing diphtheria, tetanus, pertussis, IPV, and Hib antigens.224 Gently swirl until cloudy, uniform, white to off-white (yellow tinge) suspension is obtained.224

Administer immediately after reconstitution.224

Dosage

Dosing schedule varies according to specific vaccine administered and age at which vaccination is started.144 159 174 223 227 Follow dosage recommendations for the specific preparation used.144 159 174 223 227

PRP-T (ActHIB) and PRP-OMP (PedvaxHIB) monovalent Hib vaccines can be considered interchangeable for both primary and booster immunization.105 166 If the primary vaccination series included both PRP-T (ActHIB) and PRP-OMP (PedvaxHIB), 3 primary doses and a booster dose are needed to complete the series.166

AAP recommends use of a vaccine preparation that includes PRP-OMP (PedvaxHIB or Comvax) for the first primary dose in American Indian and Alaskan native children.105 (See Limitations of Vaccine Effectiveness under Cautions.)

Medically stable preterm and low birthweight infants should be vaccinated at the usual chronologic age using usual dosage.105 144 170 174 (See Pediatric Use under Cautions.)

Interruptions resulting in an interval between doses longer than recommended should not interfere with the final immunity achieved; there is no need to administer additional doses or start the vaccination series over.134 144 174

Pediatric Patients

Prevention of Haemophilus influenzae Type b (Hib) Infection
Infants 2 through 18 Months of Age (PRP-T; ActHIB)
IM

Each dose is 0.5 mL.174

Routine primary immunization in early infancy consists of a series of 3 doses and a booster dose.105 174 199 ACIP, AAP, and others recommend that doses be given at 2, 4, 6, and 12 through 15 months of age.105 199 Initial dose may be given as early as 6 weeks of age.105 199

Catch-up vaccination using the age-appropriate number of doses indicated below is recommended in those who are unvaccinated or incompletely vaccinated.199

Previously unvaccinated infants 7 through 11 months of age: Primary immunization consists of a series of 2 doses and a booster dose.105 174 199 ACIP, AAP, and others recommend a minimum interval of 4 weeks between first and second dose and third (final) dose at 12 through 15 months of age (regardless of Hib vaccine used for first dose).199 Manufacturer recommends that 2 doses be given 8 weeks apart and a third dose (booster dose) be given at 15 through 18 months of age.174

Previously unvaccinated infants 12 through 14 months of age: Primary immunization consists of 2 doses given at least 8 weeks apart.174 199

Previously unvaccinated infants 15 through 18 months of age: Single dose.105 199

Infants and Children 2 through 71 Months of Age (PRP-OMP; PedvaxHIB)
IM

Each dose is 0.5 mL.144

Routine primary immunization in early infancy consists of a series of 2 doses and a booster dose.105 144 Manufacturer, ACIP, AAP, and others recommend that doses be given at 2, 4, and 12 through 15 months of age.105 144 159 Initial dose may be given as early as 6 weeks of age.105 199 Minimum interval between doses is 2 months.144

Catch-up vaccination using the age-appropriate number of doses indicated below is recommended in all children up to 71 months of age who are unvaccinated or incompletely vaccinated.199

Previously unvaccinated infants 7 through 11 months of age: Primary immunization consists of a series of 2 doses and a booster dose.105 199 ACIP, AAP, and others recommend a minimum interval of 4 weeks between first and second dose with third (final) dose at 12 through 15 months of age (regardless of Hib vaccine used for first dose).199

Previously unvaccinated infants 12 through 14 months of age: Primary immunization consists of 2 doses given at least 8 weeks apart.199

Previously unvaccinated infants and children 15 through 71 months of age: Single dose.105 144 199

Infants and Children 15 Months through 4 Years of Age (PRP-T; Hiberix)
IM

A single dose consisting of entire contents of reconstituted vial (approximately 0.5 mL).223

Used as a booster dose in infants and children 15 months through 4 years of age who received a primary series of an appropriate Hib vaccine (primary series consists of 2 or 3 doses depending on the manufacturer).223 225

To facilitate timely administration of Hib booster dose for routine or catch-up vaccination, ACIP states that booster dose of PRP-T (Hiberix) may be given as early as 12 months of age.199 225

Do not use for primary immunization.199 223 225 However, if PRP-T (Hiberix) is inadvertently given during primary vaccination series, ACIP states that the dose may be counted as a valid PRP-T primary dose if it was administered at an appropriate interval according to the recommended PRP-T primary vaccination schedule.225

Infants 6 Weeks to 15 Months of Age (Hib-HepB; Comvax)
IM

Each dose is 0.5 mL.77

May be used when primary immunization against Hib and HBV is indicated in infants and children 6 weeks to 15 months of age born to HBsAg-negative women.77

Primary immunization consists of a series of 3 doses given ideally at 2, 4, and 12–15 months of age.77

Minimum interval between first 2 doses is 6 weeks; make interval between second and third dose as close to 8–11 months as possible.77

Infants 6 Weeks through 18 Months of Age (Hib-MenCY; MenHibrix)
IM

Each dose is 0.5 mL.227

Primary immunization in previously unvaccinated infants: Use a series of 4 doses.162 199 227 228 Give doses at 2, 4, 6, and 12 through 15 months of age.199 227 228

Initial dose usually given at 2 months of age, but may be given as early as 6 weeks of age.162 227 228 Fourth dose may be given as late as 18 months of age.162 227 228

If first dose given at ≥12 months of age, give a series of 2 doses at least 8 weeks apart.162 228

For those who remain at prolonged increased risk for meningococcal disease, ACIP recommends a dose of meningococcal vaccine (MCV4) 3 years after completion of Hib-MenCY (MenHibrix) primary immunization series and every 5 years thereafter.228

Infants and Children 6 Weeks through 4 Years of Age (DTaP-IPV/Hib; Pentacel)
IM

Each dose is 0.5 mL.224

May be used when immunization against diphtheria, tetanus, pertussis, poliovirus, and Hib is indicated in children 6 weeks through 4 years of age.207 224

Previously unvaccinated: Use a series of 4 doses.224 Give doses at 2, 4, 6, and 15 through 18 months of age.224 Initial dose usually given at 2 months of age, but may be given as early as 6 weeks of age.224

Previously received ≥1 dose of Hib vaccine: Can be used to complete the Hib vaccination series when doses of IPV and DTaP also are indicated and there are no contraindications to any of the individual components.207 224

To complete recommended primary and booster vaccination series against diphtheria, tetanus, and pertussis in children who received the 4-dose series of DTaP-IPV/Hib (Pentacel): Give a fifth dose of DTaP (Daptacel) at 4 through 6 years of age.224 Do not use DTaP-IPV/Hib (Pentacel) for booster dose of DTaP indicated at 4 through 6 years of age; however, if dose of DTaP-IPV/Hib (Pentacel) is inadvertently given to a child ≥5 years of age or older, ACIP states the dose may be counted as a valid dose.207

To complete recommended vaccination against poliovirus in children who received the 4-dose series of DTaP-IPV/Hib (Pentacel): Give additional booster dose of age-appropriate vaccine containing IPV (IPOL or Kinrix) at 4 through 6 years of age.224

Children 12 through 59 Months of Age with Medical Conditions Associated with Increased Risk of Invasive Hib Disease
IM

Unvaccinated or previously received 1 dose of Hib vaccine before 12 months of age: AAP recommends 2 doses of Hib vaccine given 2 months apart.105

Previously received 2 doses of Hib vaccine before 12 months of age: AAP recommends 1 dose of Hib vaccine.105

Children ≥5 Years of Age with Medical Conditions Associated with Increased Risk of Invasive Hib Disease
IM

Unvaccinated or incompletely vaccinated against Hib: ACIP, AAP, and others recommend a single dose in those at increased risk because of sickle cell disease, leukemia, anatomic or functional asplenia, HIV infection, IgG2 deficiency, chemotherapy, or hematopoietic stem cell transplantation.105 134 156 159 199

Adults

Adults with Medical Conditions Associated with Increased Risk of Invasive Hib Disease
IM

Unvaccinated against Hib: ACIP, AAP, and others state consider a single dose in those at increased risk because of sickle cell disease, leukemia, HIV infection, or anatomic or functional asplenia.134 200

Special Populations

Hepatic Impairment

No specific dosage recommendations.144 174 223 227

Renal Impairment

No specific dosage recommendations.144 174 223 227

Cautions for Haemophilus b Vaccine

Contraindications

  • PRP-OMP (PedvaxHIB) and PRP-T (ActHIB): Hypersensitivity to any vaccine component.144 174

  • PRP-T (Hiberix): Severe allergic reaction (e.g., anaphylaxis) after dose of any Hib vaccine, dose of any vaccine containing tetanus toxoid, or any component in PRP-T (Hiberix).223

  • Hib-HepB (Comvax): Hypersensitivity to yeast or any vaccine component.77

  • Hib-MenCY (MenHibrix): Severe allergic reaction (e.g., anaphylaxis) to the vaccine, any vaccine component, or any vaccine containing meningococcal, Hib, or tetanus antigens.227

  • DTaP-IPV/Hib (Pentacel): Severe allergic reaction (e.g., anaphylaxis) to any ingredient in the vaccine or after previous dose of the vaccine or any vaccine containing diphtheria, tetanus, pertussis, poliovirus, or Hib antigens.224 Also contraindicated (because of the pertussis antigen) in individuals who had encephalopathy (e.g., coma, decreased consciousness, prolonged seizures) within 7 days of a dose of pertussis-containing vaccine and in individuals with progressive neurologic disorder, including infantile spasms, uncontrolled epilepsy, or progressive encephalopathy.224

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions (e.g., anaphylaxis, anaphylactoid reaction, angioedema, rash, urticaria) reported.223 227

Prior to administration, take all known precautions to prevent adverse reactions, including a review of the patient’s history with respect to possible hypersensitivity to the vaccine or similar vaccines.144 174 223 227

Epinephrine and other appropriate agents and equipment should be readily available in case an immediate allergic reaction occurs.144 174 223 227

Do not administer additional doses to individuals with symptoms of hypersensitivity after a previous dose.144

Latex Sensitivity

Stopper on vial of sodium chloride diluent supplied with PRP-T (ActHIB) contains dry natural latex;174 stoppers on vials of Hib-HepB (Comvax) and PRP-OMP (PedvaxHIB) contain natural rubber latex.77 144

Some components (i.e., tip cap) of single-dose prefilled syringes of sodium chloride diluent supplied with PRP-T (Hiberix) contain dry natural latex;223 rubber plungers of these syringes and stoppers on vials of the lyophilized vaccine are latex-free.223

Some individuals may be hypersensitive to natural latex proteins.134 190 192 193 223 Take appropriate precautions if these preparations are administered to individuals with history of latex sensitivity.77 134 144 174 190 192 193

ACIP states that vaccines supplied in vials or syringes containing dry natural rubber or natural rubber latex may be administered to individuals with latex allergies other than anaphylactic allergies (e.g., history of contact allergy to latex gloves), but should not be used in those with a history of severe (anaphylactic) allergy to latex unless benefits of vaccination outweigh risks of a potential allergic reaction.134 Contact-type allergy is the most common type of latex sensitivity.134

Yeast Allergy

Hib-HepB (Comvax): Manufacturing process for HepB vaccine component involves baker’s yeast (Saccharomyces cerevisiae) and final product contains yeast protein (≤1%).77 Contraindicated in individuals hypersensitive to yeast.77

Neomycin and/or Polymyxin B Allergy

DTaP-IPV/Hib (Pentacel): Contains trace amounts of neomycin sulfate (≤4 pg) and polymyxin B (≤4 pg).224

Neomycin allergy usually results in delayed-type (cell-mediated) hypersensitivity reactions manifested as contact dermatitis.105 134 ACIP and AAP state that vaccines containing trace amounts of neomycin should not be used in individuals with history of anaphylactic reaction to neomycin, but use may be considered in those with history of delayed-type neomycin hypersensitivity if benefits of vaccination outweigh risks.105 134

Use of Combination Vaccines

Do not administer vaccine containing Hib antigen with any other Hib-containing vaccine.228

When combination vaccine containing Hib and other antigens ([Hib-HepB; Comvax], [Hib-MenCY; MenHibrix], [DTaP-IPV/Hib; Pentacel]) is used, consider cautions, precautions, and contraindications associated with each antigen.227

Limitations of Vaccine Effectiveness

May not protect all vaccine recipients against Hib.144 174

Protection against Hib disease may not be provided until 1–2 weeks after primary immunization with 2 or 3 doses of Hib vaccine.144 148 174

When a complete vaccine series is administered as recommended, regimens that include PRP-T (ActHIB) or PRP-OMP (PedvaxHIB, Comvax) are considered equivalent.105 144 166

There is some evidence that vaccines containing PRP-OMP (PedvaxHIB, Comvax) result in more rapid seroconversion to protective antibody concentrations within the first 6 months of life compared with vaccines containing PRP-T (ActHIB).105 207 This is particularly important in American Indian and Alaskan native children because these children are at increased risk for Hib disease during the first 6 months of life.105

Although PRP-OMP (PedvaxHIB) contains Hib antigen conjugated to outer membrane protein complex (OMPC) of Neisseria meningitidis and antibodies to OMPC have been demonstrated in patients who received the vaccine, the clinical relevance of these antibodies not established.144 PRP-OMP (PedvaxHIB) is not an immunizing agent against meningococcal disease.159

Although PRP-T (Hiberix) and Hib-MenCY (MenHibrix) contain Hib antigen conjugated to tetanus toxoid, these vaccines are not a substitute for routine immunization against tetanus.223 227

Individuals with Altered Immunocompetence

May be administered to individuals immunosuppressed as the result of disease or immunosuppressive therapy.77 105 134 144 156 174 Consider possibility that the immune response to the vaccine may be reduced in individuals with altered immunocompetence (e.g., HIV infection, immunoglobulin deficiency, stem cell transplant recipients, cancer patients receiving chemotherapy).77 105 134 144 174 223 227

Immune responses have been obtained following administration of Hib vaccine in patients with sickle cell disease, leukemia, or HIV infection, and in those who have undergone splenectomies;166 response in HIV-infected individuals varies with the degree of immunocompromise.166

Manufacturer of PRP-T (Hiberix) and Hib-MenCY (MenHibrix) states that safety and efficacy not evaluated in immunosuppressed children.223 227

AAP states that children who have received the usual age-appropriate regimen of Hib vaccine (primary and booster doses) and have decreased or absent splenic function do not need additional doses of the vaccine;105 however, those who are scheduled for splenectomy (e.g., for Hodgkin’s disease, spherocytosis, immune thrombocytopenia, hypersplenism) may benefit from an additional dose of a Hib vaccine given at least 7–10 days before surgery.105

Although children with HIV infection or IgG2 deficiency or those receiving chemotherapy are at increased risk of invasive Hib disease, it is unclear whether these children would benefit from additional doses of Hib vaccine after completion of the usual age-appropriate vaccination regimen.105

Concomitant Illness

Delay administration in individuals with acute febrile illness until symptoms have subsided.134 ACIP states that minor illness (with or without fever) generally does not preclude vaccination.134

Guillain-Barré Syndrome

If Guillain-Barré syndrome (GBS) occurred within 6 weeks of receipt of a vaccine containing tetanus toxoid, base a decision to administer a dose of a vaccine containing tetanus toxoid, including PRP-T (Hiberix) or Hib-MenCY (MenHibrix), on careful consideration of potential benefits and possible risks.223 227

Individuals with Bleeding Disorders

Advise individuals who have bleeding disorders or are receiving anticoagulant therapy and/or their family members about the risk of hematoma from IM injections.134

ACIP states that vaccines may be given IM to such individuals if a clinician familiar with the patient’s bleeding risk determines that the preparation can be administered with reasonable safety.134 In these cases, use a fine needle (23 gauge or smaller) to administer the vaccine and apply firm pressure to the injection site (without rubbing) for ≥2 minutes.134 If patient is receiving therapy for hemophilia, administer the IM vaccine shortly after a scheduled dose of such therapy.134

Improper Storage and Handling

Improper storage or handling of vaccines may reduce vaccine potency resulting in reduced or inadequate immune responses in vaccinees.134

Inspect all vaccines upon delivery and monitor during storage to ensure that the appropriate temperature is maintained.134 (See Storage under Stability.)

Do not administer monovalent Hib vaccines or combination vaccines containing Hib and other antigens that have been mishandled or have not been stored at the recommended temperature.77 134 144 174

If there are concerns about mishandling, contact the manufacturer or state or local immunization or health departments for guidance on whether the vaccine is usable.134

Specific Populations

Pregnancy

Category C.77 144 174 223 227 Not labeled by FDA for use in adults144 174 223 227 and not usually recommended for this age group.93 105 170

Lactation

Not labeled by FDA for use in adults144 174 223 227 and not usually recommended for this age group.93 105 144 170 174 200

Pediatric Use

PRP-OMP (PedvaxHIB): Safety and efficacy not established in infants <6 weeks of age or in children ≥6 years of age.144

PRP-T (ActHIB): Safety and efficacy not established in infants <6 weeks of age or in infants or children >18 months of age.174

PRP-T (Hiberix): Safety and efficacy not established in infants <15 months of age or in children ≥5 years of age.223 Safety and efficacy for use in infants 15 through 18 months of age established based on clinical studies in this age group;223 safety and efficacy in infants and children 19 months through 4 years of age supported by evidence in children 15 through 18 months of age.223

Hib-HepB (Comvax): Safety and efficacy not established in infants <6 weeks of age or in infants or children >15 months of age.77

Hib-MenCY (MenHibrix): Safety and efficacy not established in infants <6 weeks of age or in infants and children >18 months of age.227

DTaP-IPV/Hib (Pentacel): Safety and efficacy not established in infants <6 weeks of age or in children ≥5 years of age.224

Do not administer Hib vaccine to infants <6 weeks of age;77 144 limited data indicate that infants who receive Hib vaccine before 6 weeks of age may develop immunologic tolerance resulting in reduced response to subsequent doses of the vaccine.166

Apnea reported following IM administration of vaccines in some infants born prematurely.224 227 Base decisions regarding when to administer an IM vaccine in premature infants on consideration of the individual infant's medical status and potential benefits and possible risks of vaccination.224 227

Geriatric Use

Not labeled by FDA for use in adults, including geriatric adults;,77 144 174 223 224 227 not usually recommended for this age group.93 105 170 200

Common Adverse Effects

PRP-T (ActHIB) or PRP-OMP (PedvaxHIB): Injection site reactions (pain, erythema, swelling), fever, irritability, lethargy.144 174

PRP-T (Hiberix): Injection site reactions (e.g., redness, pain, swelling) and systemic effects (e.g., fever, fussiness, loss of appetite, restlessness, sleepiness, diarrhea, vomiting) when given concomitantly with a combination vaccine containing diphtheria, tetanus, pertussis, hepatitis B, and poliovirus antigens (DTaP-HBV-IPV) administered at a different site. 223

Hib-HepB (Comvax): Adverse effects similar in type and frequency to those reported in infants who receive monovalent PRP-OMP (PedvaxHIB) vaccine and monovalent HepB vaccine (Recombivax HB) simultaneously at separate sites.77

Hib-MenCY (MenHibrix): Injection site reactions (e.g., pain, redness, swelling), systemic effects (e.g., fever, irritability, drowsiness, loss of appetite).227

DTaP-IPV/Hib (Pentacel): Injection site reactions (tenderness, redness, swelling), systemic effects (fever, decreased activity/lethargy, inconsolable crying, fussiness/irritability).224

Interactions for Haemophilus b Vaccine

Other Vaccines

Simultaneous administration with other age-appropriate vaccines, including live virus vaccines, toxoids, or inactivated or recombinant vaccines, during the same health-care visit is not expected to affect immunologic responses or adverse reactions to any of the preparations.105 134 174 Immunization against Hib can be integrated with immunization against diphtheria, tetanus, pertussis, hepatitis B, influenza, pneumococcal disease, poliovirus, rotavirus, measles, mumps, rubella, and varicella.77 105 159 174 Each parenteral vaccine should be administered using a different syringe and different injection site.105 134

Specific Drugs and Laboratory Tests

Drug

Interaction

Comments

Diphtheria and tetanus toxoids and pertussis vaccine adsorbed (DTaP)

Hib-MenCY (MenHibrix): Concurrent administration with DTaP-HepB-IPV (Pediarix) and pneumococcal 7-valent conjugate vaccine (PCV7; (Prevnar; no longer commercially available in US) in infants at 2, 4, and 6 months of age did not reduce antibody response to DTaP or the other antigens227

Hepatitis A vaccine (HepA)

HepA (Havrix, Vaqta): Concomitant administration with Hib vaccine at different site (with or without other concurrent vaccines) resulted in immune responses and adverse effects similar to those reported when the vaccines were administered at different times76 198

Hepatitis B vaccine (HepB)

Hib-MenCY (MenHibrix): Concurrent administration with DTaP-HepB-IPV (Pediarix) and PCV7 (Prevnar) in infants at 2, 4, and 6 months of age did not reduce antibody response to HepB or the other antigens227

HepB and Hib vaccine may be administered simultaneously (using separate syringes and separate injection sites)105 163 170

Alternatively, fixed-combination vaccine (Hib-HepB; Comvax) can be used when dose of HepB and dose of Hib vaccine are indicated in infant 6 weeks to 15 months of age77

Do not prepare extemporaneous combinations of HepB and Hib vaccine163

Immune globulin (immune globulin IM [IGIM], immune globulin IV [IGIV]) or specific hyperimmune globulin (hepatitis B immune globulin [HBIG], rabies immune globulin [RIG], tetanus immune globulin [TIG], varicella zoster immune globulin [VZIG])

No evidence that immune globulin preparations interfere with immune response to Hib vaccine134

Hib vaccine may be given simultaneously with (using different syringes and different injection sites) or at any interval before or after immune globulin or specific hyperimmune globulin134

Immunosuppressive agents (e.g., alkylating agents, antimetabolites, corticosteroids, radiation)

Potential for decreased antibody response to vaccines134 174 223 227

Vaccines generally should be administered 2 weeks prior to initiation of immunosuppressive therapy or deferred until ≥3 months after such therapy is discontinued and immunocompetence restored79 134

Measles, mumps, and rubella vaccine (MMR)

Simultaneous administration of MMR and Hib vaccine does not interfere with the immune response or increase adverse effects of either vaccine174 162 227

Hib-MenCY (MenHibrix): Concurrent administration with MMR, varicella vaccine (VAR), and PCV7 (Prevnar) in infants 12 through 15 months of age did not interfere with immune response to MMR227

MMR and Hib vaccine may be administered simultaneously (using different syringes and different injection sites)134 159 174

Meningococcal vaccine

Hib and meningococcal vaccines may be administered simultaneously (using separate syringes and separate injection sites)105 159

Alternatively, fixed-combination vaccine (Hib-MenCY; MenHibrix) can be used when Hib vaccine is indicated in infant 6 weeks through 18 months of age at increased risk for meningococcal disease162 227 228

Pneumococcal vaccine

Hib-MenCY (MenHibrix): Concurrent administration with PCV7 (Prevnar) and DTaP-HepB-IPV (Pediarix) in infants at 2, 4, and 6 months of age did not reduce antibody response to PCV7 or the other antigens;227 manufacturer states data insufficient to evaluate potential interference when Hib-MenCY (MenHibrix) administered concomitantly with fourth dose of PCV7 (Prevnar) at 12–15 months of age227

Hib-MenCY (MenHibrix): May be administered concomitantly with pneumococcal 13-valent conjugate vaccine (PCV13; Prevnar 13) in infants 2 through 18 months of age228

Rotavirus vaccine

Rotavirus vaccines (Rotarix, RotaTeq) have been administered concomitantly with Hib vaccines without decreased immune response to either vaccine219 221 222

Tests to diagnose Hib disease

May interfere with interpretation of antigen tests used to diagnose Hib disease;88 93 223 227 administration of Hib vaccine results in antigenuria144 174 227

Urine antigen detection may not have diagnostic value in evaluating suspected Hib disease in children within 1–2 weeks following administration of a Hib vaccine88 93 174 223 227

Antigen testing of urine and serum specimens no longer recommended for diagnosis of Hib infection105 166

Vaccines, inactivated or toxoids

Hib vaccine does not affect immune response to diphtheria or tetanus toxoids, pertussis vaccine, HepB vaccine, or pneumococcal vaccine77 174 195

May be administered concomitantly with or at any interval before or after inactivated vaccines or toxoids routinely used in infants and children134

Varicella vaccine (VAR)

Simultaneous administration of VAR and Hib vaccine does not increase risk of breakthrough varicella infection32 162 227

Hib-MenCY (MenHibrix): Concurrent administration with VAR, MMR, and PCV7 (Prevnar) in infants 12 through 15 months of age did not interfere with immune response to VAR227

VAR and Hib vaccine may be administered simultaneously (using different syringes and different injection sites)134

Stability

Storage

Parenteral

For Injection, for IM Use

PRP-T (ActHIB) and sodium chloride diluent: 2–8°C; do not freeze.174 Following reconstitution with diluent provided by manufacturer, store at 2–8°C and use within 24 hours.174

PRP-T (Hiberix): 2–8°C; protect from light.223 Store sodium chloride diluent supplied by manufacturer at 2–8°C or 20–25°C; do not freeze; discard if freezing occurs.223 Following reconstitution with diluent provided by manufacturer, store at 2–8°C and use within 24 hours; do not freeze.223 Discard reconstituted vaccine if frozen or if not used within 24 hours.223

Hib-MenCY (MenHibrix): 2–8°C; protect from light.227 Store 0.9% sodium chloride diluent supplied by manufacturer at 2–25°C; do not freeze; discard if freezing occurs.227 Use immediately after reconstitution.227 Discard reconstituted vaccine if frozen.227

Kit containing DTaP-IPV and ActHIB (DTaP-IPV/Hib; Pentacel): 2–8°C.224 Do not freeze; if freezing occurs, discard vaccine.224 Use immediately after reconstitution.224

Suspension, for IM Use

PRP-OMP (PedvaxHIB): 2–8°C; do not freeze.144

Hib-HepB (Comvax): 2–8°C; do not freeze.77

Actions

  • Commercially available as monovalent vaccines (ActHIB, Hiberix, PedvaxHIB).144 174 223 Also available as a fixed-combination vaccine containing Hib and hepatitis B antigens (Hib-HepB; Comvax);77 fixed-combination vaccine containing Hib and meningococcal groups C and Y antigens (Hib-MenCY; MenHibrix);227 and in a kit used to provide a combination vaccine containing diphtheria, tetanus, pertussis, poliovirus, and Hib antigens (DTaP-IPV/Hib; Pentacel).224

  • Hib vaccines contain antigenic capsular polysaccharides extracted from Hib.144 159 174 223 227 Vaccine capsular polysaccharides are derived from polyribosylribitol phosphate (PRP), a major Hib virulence factor.159 166

  • All currently available Hib vaccines contain Hib antigen conjugated to a T-cell-dependent protein antigen (carrier), either N. meningitidis outer membrane protein complex (OMPC) (PRP-OMP; PedvaxHIB) (Hib-HepB; Comvax)77 129 144 148 159 160 or tetanus toxoid (PRP-T; ActHIB) (PRP-T; Hiberix) (Hib-MenCY; MenHibrix) (DTaP-IPV/Hib; Pentacel).174 223 227

  • Conjugation with a carrier protein results in a T-cell dependent polysaccharide antigen that elicits an improved immunologic response compared with unconjugated Hib vaccines previously available.129 159 166 174

  • Hib vaccines stimulate active immunity to Hib infection by inducing production of specific antibodies.38 111 117 144 166 Hib capsular polysaccharide present in the vaccines promotes production of Hib anticapsular antibody; this antibody provides protection against Hib infection.6 7 14 38 55 59 75 117 159 166

  • At least 95% of infants develop protective antibody levels after a primary series of 2 or 3 doses of conjugated Hib vaccine.166

  • Although the exact level of Hib anticapsular antibody that provides protection against Hib infection is not known,159 170 geometric mean titers of 1 mcg/mL 3 weeks after vaccination appear to correlate with long-term protection from Hib infection.159 170

Advice to Patients

  • Prior to administration of each vaccine dose, provide a copy of the appropriate CDC Vaccine Information Statement (VIS) to the patient or patient’s legal representative as required by the National Childhood Vaccine Injury Act (VISs are available at ).144 174 203 223 227

  • Advise patient and/or patient’s parent or guardian of the risks and benefits of vaccination against Hib.144 174 223 227

  • Importance of receiving the complete primary vaccination series to ensure the highest level of protection against Hib.144 174 227

  • Importance of informing clinicians if any severe or unusual adverse reactions occur.203 223 227 Clinicians or individuals can report any adverse reactions that occur following vaccination to Vaccine Adverse Event Reporting System (VAERS) at 800-822-7967 or .203

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.144 174 223 227

  • Importance of informing patients and/or patient’s parent or guardian of other important precautionary information.144 174 223 227 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate) (PRP-OMP)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injectable suspension, for IM use

7.5 mcg of Haemophilus b capsular polysaccharide conjugated to 125 mcg of Neisseria meningitidis OMPC protein carrier per 0.5 mL

Liquid PedvaxHIB

Merck

Haemophilus b Conjugate Vaccine (Tetanus Toxoid Conjugate) (PRP-T)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injectable suspension, for IM use

10 mcg of Haemophilus b capsular polysaccharide conjugated to 24 mcg of tetanus toxoid protein carrier per 0.5 mL

ActHIB

Sanofi Pasteur

For injection, for IM use

10 mcg of Haemophilus b capsular polysaccharide conjugated to 25 mcg of tetanus toxoid protein carrier per 0.5 mL

Hiberix

GlaxoSmithKline

Haemophilus b Conjugate (Meningococcal Protein Conjugate) and Hepatitis B (Recombinant) Vaccine (Hib-HepB)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injectable suspension, for IM use

7.5 mcg of Haemophilus b capsular polysaccharide conjugated to 125 mcg of Neisseria meningitidis OMPC protein carrier per 0.5 mL and 5 mcg of hepatitis B surface antigen per 0.5 mL

Comvax

Merck

Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus b Conjugate (Tetanus Toxoid Conjugate) Vaccine (DTaP-IPV/Hib)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Kit, for IM use

Injection, for IM use, Diphtheria Toxoid 15 Lf units, Tetanus Toxoid 5 Lf units, Acellular Pertussis Vaccine 48 mcg (of pertussis antigen), Poliovirus Type 1 40 DU, Poliovirus Type 2 8 DU, and Poliovirus Type 3 32 DU per 0.5 mL

For injectable suspension, for IM use, 10 mcg of Haemophilus b polysaccharide conjugated to 24 mcg of tetanus toxoid protein carrier per 0.5 mL, ActHIB

Pentacel

Sanofi Pasteur

Meningococcal Groups C and Y and Haemophilus b Tetanus Toxoid Conjugate Vaccine (Hib-MenCY)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IM use

5 mcg of meningococcal C capsular polysaccharide conjugated to approximately 5 mcg of tetanus toxoid protein carrier, 5 mcg of meningococcal Y capsular polysaccharide conjugated to approximately 6.5 mcg of tetanus toxoid protein carrier, and 2.5 mcg of Haemophilus b capsular polysaccharide conjugated to approximately 6.25 mcg of tetanus toxoid protein carrier per 0.5 mL

MenHibrix

GlaxoSmithKline

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions January 2, 2014. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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