Haemophilus b Vaccine

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

Introduction

Inactivated (polysaccharide) vaccine.^{134 144 174 223} Haemophilus b (Hib) vaccine is used to stimulate active immunity to Haemophilus influenzae type b (Hib) infection.^{105 144 159 174 205 223} Commercially available in the US as 2 different monovalent vaccines: 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 (PedvaxHIB) also commercially available in fixed combination with hepatitis B vaccine (Hib-HepB; Comvax)⁷⁷ and PRP-T (ActHIB) also commercially available in a kit used to provide a combination vaccine containing diphtheria, tetanus, pertussis, and Hib antigens (DTaP/Hib; TriHIBit)^{174 202} and in a kit used to provide a combination vaccine containing diphtheria, tetanus, pertussis, poliovirus, and Hib antigens (DTaP-IPV/Hib; Pentacel).²⁰⁶

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).^{105 144 159 174 199}

Hib is a gram-negative bacteria that causes meningitis and other serious systemic infections (e.g., epiglottitis, sepsis, cellulitis, septic arthritis, osteomyelitis, pericarditis, pneumonia) in young children.^{23 105 205} Before Hib vaccine became available, Hib infection was the most common cause of bacterial meningitis in children.^{105 205} There were about 20,000 cases of invasive Hib each year in the US, principally in infants and children <5 years of age;²⁰⁵ the case fatality rate was 2–5% despite anti-infective treatment and 15–30% of meningitis survivors had hearing loss or neurologic sequelae.²⁰⁵ The incidence of invasive Hib in the US decreased ≥99% after Hib conjugate vaccines became available.^{105 205} Most cases now occur in infants and children who are unvaccinated or incompletely vaccinated, including infants <6 months of age who are too young to have received a complete vaccination series.^{105 205} The average annual rate of invasive Hib disease reported in children <5 years of age during 1998–2000 was 0.3 cases per 100,000 children.²²⁰ During 2007, there were 22 cases of invasive Hib disease and 180 cases caused by unknown serotypes of H. influenzae in US children <5 years of age.²⁰⁵

USPHS Advisory Committee on Immunization Practices (ACIP), AAP, American Academy of Family Physicians (AAFP), and other experts recommend that all infants be vaccinated against Hib with an appropriate vaccine regimen initiated in early infancy at 2 months of age (minimum age 6 weeks), unless contraindicated.^{105 159 199} (See Contraindications under Cautions.)

ACIP and AAP also recommend catch-up vaccination 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 they are in prolonged close contact (e.g., household contact) with a child with invasive Hib disease.¹⁰⁵ Other factors associated with an increased risk of developing invasive Hib infection include asplenia,^{105 205} sickle cell anemia,^{105 205} antibody deficiency syndromes,²⁰⁵ HIV infection,^{105 156 205} other immunodeficiency syndromes,^{38 105 205} and Hodgkin’s disease⁷⁹ or other malignancies (especially during chemotherapy).^{105 205} Historically, invasive Hib was more common in boys¹⁰⁵ and in American Indians (e.g., Apache and Navajo tribes),^{45 105 205} Alaskan natives,^{40 45 85 105} Hispanics,²⁰⁵ and blacks.^{29 105 205} (See Limitations of Vaccine Effectiveness under Cautions.)

ACIP and AAP do not recommend routine use of Hib vaccine in children ≥5 years of age.^{105 146 170 199} Although efficacy data not available on which to base recommendations regarding use of Hib vaccine in these age groups, use of Hib vaccine can be considered in children ≥5 years of age† or adults† who did not receive the vaccine in early childhood and are at increased risk for invasive Hib disease because of altered immunocompetence (e.g., sickle cell disease, leukemia, splenectomy, HIV infection, IgG₂ deficiency, chemotherapy, hematopoietic stem cell transplantation).^{105 134 159 172 199 200 205} The fact that the vaccine may be less immunogenic in immunocompromised individuals should be considered.^{105 134} (See Individuals with Altered Immunocompetence under Cautions.)

Cochlear implant recipients may be at increased risk of invasive Hib disease (i.e., meningitis).¹¹⁴ Any child <5 years of age with a cochlear implant who has not received Hib vaccine should be vaccinated.¹¹⁴

For internationally adopted children whose immune status is uncertain, vaccinations can be repeated or serologic tests performed to confirm immunity.^{115 134} For Hib vaccine, ACIP recommends revaccination with the age-appropriate vaccination regimen.¹³⁴ (See Dosage and Administration.)

Hib vaccine will not provide protection against other types of H. influenzae (e.g., nonencapsulated 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 as a fixed-combination vaccine containing Hib and other antigens.^{77 174 206} ACIP, AAP, and AAFP state that use of a combination vaccine generally is preferred over separate injections of the equivalent component vaccines;^{199 226} considerations should include provider assessment (e.g., number of injections, vaccine availability, likelihood of improved coverage, likelihood of patient return, storage and cost considerations), patient preference, and potential for adverse effects.^{199 226}

When vaccination against both hepatitis B virus (HBV) and Hib is indicated in an infant 6 weeks to 15 months of age born to HBsAg-negative women, the commercially available fixed-combination bivalent vaccine containing Hib polysaccharide conjugate (meningococcal protein conjugate) vaccine and hepatitis B vaccine (Hib-HepB; Comvax) can be used.⁷⁷ ACIP states this fixed-combination vaccine also may be used to complete the HBV vaccine series in infants 6 weeks to 15 months of age born to HBsAg-positive women†.¹⁶²

When a fourth dose of DTaP and a fourth dose of Hib vaccine are indicated in a child 15 through 18 months of age, a kit (DTaP/Hib; TriHIBit) containing both DTaP (Tripedia) and Hib polysaccharide conjugate (tetanus toxoid conjugate) vaccine (ActHIB) may be used.^{165 174 179 202 205} ActHIB in the kit is reconstituted with Tripedia to provide a combination vaccine containing diphtheria, tetanus, pertussis, and Hib antigens.^{174 202} TriHIBit should not be used for the first 3 doses in the primary DTaP or Hib vaccination series.^{165 179 205} Other commercially available Hib vaccines and DTaP vaccines should not be mixed extemporaneously to provide a combination vaccine.^{186 205}

When doses of DTaP, poliovirus vaccine (IPV), and Hib vaccine are indicated in infants and children 6 weeks through 4 years of age and there are no contraindications to any of the individual components, a kit (DTaP-IPV/Hib; Pentacel) containing a fixed-combination DTaP-IPV vaccine and Hib vaccine (ActHIB) can be used.^{206 207} ActHIB in the kit is reconstituted with the fixed-combination of DTaP-IPV in the kit to provide a combination vaccine containing diphtheria, tetanus, pertussis, poliovirus, and Hib antigens.^{206 207} For prevention of Hib, ACIP states that Pentacel may be used for the 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 (ActHIB, Hiberix, PedvaxHIB) are administered by IM injection.^{77 144 174 223}

Hib-HepB (Comvax),⁷⁷ DTaP/Hib (TriHIBit),^{174 202} and DTaP-IPV/Hib (Pentacel)²⁰⁶ are administered by IM injection.

Do not administer monovalent Hib vaccines or combination vaccines containing Hib and other antigens IV, sub-Q, or intradermally.^{77 144 174 202 206 223}

Shake vaccine before administering.^{77 144 202 206 223}

Depending on patient age, administer IM into the deltoid muscle or anterolateral thigh.^{134 144 174 202 206} In infants and children 6 weeks to 2 years of age, use anterolateral thigh;¹³⁴ alternatively, deltoid muscle can be used in those 1–2 years of age if muscle mass is adequate.¹³⁴ In adults, adolescents, and children ≥3 years of age, deltoid muscle is preferred.¹³⁴

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

Take care to avoid injection into the gluteal area or into or near blood vessels or nerves.^{77 134 144 174 202 206} Generally do not administer vaccines into buttock muscle in children because of potential for injection-associated injury to sciatic nerve.¹³⁴

Although some experts state that aspiration (i.e., pulling back on the syringe plunger after needle insertion and before injection) can be performed to ensure that a blood vessel has not been entered, ACIP and AAP state this procedure is not required because large blood vessels are not present at recommended IM injection sites.¹³⁴

Syncope (vasovagal or vasodepressor reaction) may occur following vaccination, most frequently in adolescents and young adults.¹³⁴ 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 during the same health-care visit (using different syringes and different injection sites).¹³⁴

When multiple vaccines are administered during a single health-care visit, each vaccine should be given with a different syringe and at different injection sites.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

Reconstitution (ActHIB)

Reconstitute lyophilized 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

Reconstitution (Hiberix)

Reconstitute lyophilized 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 or store at 2–8°C and administer within 24 hours.²²³

Do not mix with any other vaccine or solution.²²³

Reconstitution (TriHIBit)

TriHIBit is commercially available as a kit containing single-dose vials of lyophilized Hib (ActHIB) and single-dose vials of DTaP (Tripedia).^{174 202}

Prior to administration, reconstitute a vial of lyophilized ActHIB by adding 0.6 mL of the Tripedia vaccine according to manufacturer’s instructions to provide a combination vaccine containing diphtheria, tetanus, pertussis, and Hib antigens.¹⁷⁴ Agitate thoroughly.¹⁷⁴ Do not mix with any other vaccine or solution.¹⁷⁴

Administer TriHIBit immediately (within 30 minutes) after reconstitution.^{174 202}

Reconstitution (Pentacel)

Pentacel is commercially available as a kit containing single-dose vials of a fixed-combination vaccine containing diphtheria, tetanus, pertussis, and poliovirus antigens (DTaP-IPV vaccine) and single-dose vials of lyophilized Hib vaccine (ActHIB).²⁰⁶

Prior to administration, reconstitute a vial of lyophilized ActHIB vaccine by adding the entire contents of a vial of the DTaP-IPV vaccine according to manufacturer’s instructions to provide a combination vaccine containing diphtheria, tetanus, pertussis, IPV, and Hib antigens.²⁰⁶ Shake thoroughly until a cloudy, uniform suspension is obtained.²⁰⁶

Administer Pentacel immediately after reconstitution.²⁰⁶

Dosage

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

Commercially available PedvaxHIB and ActHIB monovalent Hib vaccines can be considered interchangeable for both primary and booster immunization.^{105 205} If both PedvaxHIB and ActHIB are administered as part of the primary series, 3 primary doses and a booster dose are needed to complete the series.²⁰⁵

ACIP and AAP recommend use of a vaccine preparation that includes PRP-OMP (PedvaxHIB or Comvax) for the first primary dose in American Indian and Alaskan native children.^{105 207} (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}

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}

PRP-OMP (PedvaxHIB): Used in infants and children 2 through 71 months of age.¹⁴⁴

PRP-T (ActHIB): Used in infants 2 through 18 months of age.¹⁷⁴

PRP-T (Hiberix): Used in infants and children 15 months through 4 years of age.²²³

Hib-HepB (Comvax): Used in infants 6 weeks to 15 months of age.⁷⁷

DTaP/Hib (TriHIBit): Used when a fourth dose of DTaP and a fourth dose of Hib vaccine are both indicated in infants 15 through 18 months of age.^{165 174}

DTaP-IPV/Hib (Pentacel): Used in infants and children 6 weeks through 4 years of age.²⁰⁶

Pediatric Patients

Prevention of Haemophilus influenzae Type b (Hib) Infection

Infants 2 through 18 Months of Age (PRP-T; ActHIB)

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 AAFP 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 children 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 AAFP recommend that first 2 doses be given 2 months apart (minimum interval 4 weeks) and the third dose be given at 12 through 15 months of age (at least 8 weeks after second dose).^{105 199} 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 children 12 through 14 months of age: Primary immunization consists of 2 doses given 8 weeks apart.^{105 174 199}

Previously unvaccinated children 15 through 18 months of age: Single dose.^{105 199}

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

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} ACIP, AAP, AAFP, and manufacturer 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 children 7 through 11 months: Primary immunization consists of a series of 2 doses and a booster dose.^{105 199} Give first 2 doses 2 months apart (minimum interval is 4 weeks); give third dose at 12 through 15 months of age (at least 8 weeks after second dose).^{105 199}

Previously unvaccinated children 12 through 14 months of age: Primary immunization consists of 2 doses given 8 weeks apart.^{105 199}

Previously unvaccinated children 15 through 71 months of age: Single dose.^{105 144 199}

Infants and Children 15 Months through 4 Years of Age (Hiberix)

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 a booster dose of Hib vaccine for routine or catch-up vaccination, ACIP states that the booster dose of Hiberix may be given as early as 12 months of age†.^{199 225}

Do not use for primary immunization.^{199 223 225} However, if Hiberix is inadvertently given during the 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)

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

Interval between first 2 doses should be at least 6 weeks and interval between second and third dose should be as close as possible to 8–11 months.⁷⁷

Infants 15 through 18 Months of Age (DTaP/Hib; TriHIBit)

A single 0.5-mL dose.¹⁷⁴

May be used whenever a fourth dose of DTaP is indicated in addition to a fourth dose of Hib vaccine in children 15 through 18 months of age.^{105 165 174} ACIP, AAP, and AAFP state may be used in children ≤12 months of age, provided at least 6 months have elapsed since the last DTaP dose.¹⁹⁹

Do not use for first 3 doses of the primary series.^{165 174 179 205}

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

Each dose is 0.5 mL.²⁰⁶

May be used when immunization against diphtheria, tetanus, pertussis, poliovirus, and Hib is indicated in children 6 weeks through 4 years of age.^{206 207}

In previously unvaccinated children 6 weeks through 4 years of age, Pentacel is given in a series of 4 doses.²⁰⁶ Give doses at 2, 4, 6, and 15 through 18 months of age.²⁰⁶ Initial dose usually given at 2 months of age, but may be given as early as 6 weeks of age.²⁰⁶ To complete the recommended primary and booster regimen against diphtheria, tetanus, and pertussis, children who received the 4-dose series of Pentacel should receive a fifth dose of DTaP (Daptacel) at 4 through 6 years of age.²⁰⁶ Pentacel should not be used for the booster dose of DTaP indicated at 4 through 6 years of age; however, if a dose of Pentacel is inadvertently given to a child ≥5 years of age, ACIP states the dose may be counted as a valid dose.²⁰⁷

In children 6 weeks through 4 years of age who previously received 1 or more doses of IPV, Pentacel can be used to complete the IPV series when doses of IPV and DTaP also are indicated and there are no contraindications to any of the individual components.^{206 207}

In children 6 weeks through 4 years of age who previously received 1 or more doses of DTaP (Daptacel), Pentacel can be used to complete the DTaP series when doses of IPV and Hib vaccine also are indicated and there are no contraindications to any of the individual components.^{206 207}

In children 6 weeks through 4 years of age who previously received 1 or more doses of Hib vaccine, Pentacel can be used to complete the Hib series when doses of IPV and DTaP, and Hib vaccine also are indicated and there are no contraindications to any of the individual components.^{206 207}

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

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

Unvaccinated: Although safety and efficacy not established, ACIP, AAP, and AAFP state that 1 dose of Hib vaccine can be considered in those with sickle cell disease, leukemia, HIV infection, or splenectomy.¹⁹⁹ Based on limited data, AAP suggests 2 doses of Hib vaccine given at least 1–2 months apart in those with HIV infection or IgG₂ deficiency.^{105 156}

Special Populations

Hepatic Impairment

No specific dosage recommendations.^{144 174 223}

Renal Impairment

No specific dosage recommendations.^{144 174 223}

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 a dose of any Hib vaccine, a dose of any vaccine containing tetanus toxoid, or any component in Hiberix.²²³

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

• DTaP/Hib (TriHIBit): Hypersensitivity to any ingredient in the vaccine.^{174 202} Also contraindicated (because of the pertussis antigen) in individuals who had encephalopathy (e.g., coma, decreased level of consciousness, prolonged seizures) within 7 days of a previous dose of a vaccine containing pertussis antigens that is not attributable to another identifiable cause and in individuals with progressive neurologic disorder, including infantile spasms, uncontrolled epilepsy, or progressive encephalopathy.²⁰²

• 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.²⁰⁶ 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.²⁰⁶

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

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}

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

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

Latex Sensitivity

Stopper on vial of sodium chloride diluent supplied with ActHIB contains dry natural latex;¹⁷⁴ stoppers on vials of Comvax and PedvaxHIB contain natural rubber latex.^{77 144} Some components (i.e., tip cap) of single-dose prefilled syringes of sodium chloride diluent supplied with 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 a history of latex sensitivity.^{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 the benefits of vaccination outweigh the risk 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 Manufacturer states the vaccine is 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).²⁰⁶

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 a history of anaphylactic reaction to neomycin, but use of such vaccines may be considered in those with a history of delayed-type neomycin hypersensitivity if benefits of vaccination outweigh risks.^{105 134}

General Precautions

Use of Fixed Combinations

When the combination vaccine containing Hib and hepatitis B antigens (Hib-HepB; Comvax) is used, consider the cautions and precautions associated with both antigens.⁷⁷

When the combination vaccine containing diphtheria, tetanus, pertussis, and Hib antigens (DTaP/Hib; TriHIBit) is used, consider the cautions and precautions associated with each antigen.¹⁷⁴

When the combination vaccine containing diphtheria, tetanus, pertussis, poliovirus, and Hib antigens (DTaP-IPV/Hib; Pentacel) is used, consider the cautions and precautions associated with each antigen.²⁰⁶

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.^{144 146 148 174}

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}

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).^{105 204 207} 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.^{105 204}

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

Although Hiberix contains Hib antigen conjugated to tetanus toxoid, the vaccine is not a substitute for routine immunization against tetanus.²²³

Individuals with Altered Immunocompetence

May be administered to individuals immunosuppressed as the result of disease or immunosuppressive therapy.^{77 105 134 144 156 172 174} 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}

Immune responses have been obtained following administration of Hib vaccine in patients with sickle disease, leukemia, or HIV infection, and in those who have undergone splenectomies;²⁰⁵ response in HIV-infected individuals varies with the degree of immunocompromise.²⁰⁵

Manufacturer of Hiberix monovalent Hib vaccine states that safety and efficacy not evaluated in immunosuppressed children.²²³

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 also 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, a decision to administer a dose of a vaccine containing tetanus toxoid, including Hiberix, should be based on careful consideration of potential benefits and possible risks.²²³

Individuals with Bleeding Disorders

ACIP states that vaccines may be given IM to individuals who have bleeding disorders or are receiving anticoagulant therapy 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) 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

Advise individual and/or their family about the risk of hematoma from IM injections.¹³⁴

Thimerosal Precautions

Although there is no convincing evidence that the low concentrations of thimerosal (a mercury-containing preservative) contained in some vaccines is harmful to vaccine recipients,^{134 210 211 212 213 214 215 216 217 218} efforts to eliminate or reduce the thimerosal content in vaccines is recommended as a prudent measure to reduce mercury exposure in infants and children and part of an overall strategy to reduce mercury exposures from all sources, including food and drugs.^{134 187 188 189 196}

ActHIB, PedvaxHIB, Hiberix, Comvax, and Pentacel do not contain thimerosal or any other preservatives.^{77 144 174 206 223}

When the kit (TriHIBit) containing both DTaP (Tripedia) and Hib vaccine (ActHIB) is used, the reconstituted vaccine contains trace amounts of thimerosal from the DTaP manufacturing process (≤0.3 mcg of mercury per 0.5-mL dose).^{174 202} FDA states that trace amounts of thimerosal from the manufacturing process are not considered clinically important.¹⁹⁶

Improper Storage and Handling

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

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} (See Storage under Stability.)

Inspect all vaccines upon delivery and monitor during storage to ensure that the appropriate temperature is maintained.¹³⁴ If there are concerns about mishandling, contact the manufacturer or state or local health departments for guidance on whether the vaccine is usable.¹³⁴

Specific Populations

Pregnancy

Category C.^{77 144 174 223} Not labeled by FDA for use in adults^{144 174 223} and not usually recommended for this age group.^{93 105 146 170}

Lactation

Not labeled by FDA for use in adults^{144 174 223} and not usually recommended for this age group.^{93 105 144 146 170 174 200}

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 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

DTaP/Hib (TriHIBit): Safety and efficacy not established in infants <15 months of age or in infants or children >18 months of age.¹⁷⁴

DTaP-IPV/Hib (Pentacel): Safety and efficacy not established in infants <6 weeks of age or in children ≥5 years of age.²⁰⁶

Limited data indicate that infants who receive Hib vaccine before 6 weeks of age may develop immunologic tolerance resulting in a reduced response to subsequent doses of the vaccine.²⁰⁵ Therefore, Hib vaccine should not be administered to infants <6 weeks of age.^{77 144}

Geriatric Use

Not labeled by FDA for use in adults, including geriatric adults,^{144 174 223} and not usually recommended for this age group.^{93 105 146 170 200}

Common Adverse Effects

ActHIB and PedvaxHIB: Injection site reactions (pain, erythema, swelling), fever, irritability, lethargy.^{144 174}

Hiberix: Local effects (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 reported in infants who receive the fixed-combination bivalent vaccine are similar in type and frequency to those reported in infants who receive monovalent PedvaxHIB vaccine and monovalent HepB vaccine (Recombivax HB) simultaneously at separate sites.⁷⁷

DTaP/Hib (TriHIBit): Adverse effects reported in infants 15–18 months of age who receive the combination vaccine are similar in type and frequency to those reported in infants who receive monovalent Hib vaccine (ActHIB) and DTaP vaccine (Tripedia) simultaneously at separate sites.^{165 174}

DTaP-IPV/Hib (Pentacel): Injection site reactions (tenderness, redness, swelling), fever, decreased activity/lethargy, inconsolable crying, fussiness/irritability.²⁰⁶

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} However, each vaccine should be administered using a different syringe and different injection site.^{105 134}

Specific Drugs and Laboratory Tests

Stability

Storage

Parenteral

For Injection, for IM Use

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

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

Kit containing Tripedia and ActHIB (DTaP-Hib; TriHIBit): 2–8°C; do not freeze.¹⁷⁴ Use immediately (within 30 minutes) after reconstitution.^{174 202}

Kit containing DTaP-IPV and ActHIB (DTaP-IPV/Hib; Pentacel): 2–8°C.²⁰⁶ Do not freeze; if freezing occurs, discard vaccine.²⁰⁶ Use immediately after reconstitution.²⁰⁶

Suspension, for IM Use

PedvaxHIB: 2–8°C; do not freeze.¹⁴⁴

Comvax: 2–8°C; do not freeze.⁷⁷

Actions

• Commercially available as monovalent vaccine (ActHIB, Hiberix, PedvaxHIB).^{144 174 223} Also available as a bivalent vaccine containing both Hib and hepatitis B antigens (Hib-HepB; Comvax);⁷⁷ in a kit (DTaP/Hib; TriHIBit) containing both DTaP and Hib antigens;^{144 174} and in a kit used to provide a combination vaccine containing diphtheria, tetanus, pertussis, poliovirus, and Hib antigens (DTaP-IPV/Hib; Pentacel).²⁰⁶

• Hib vaccine is a noninfectious, bacteria-derived vaccine containing antigenic capsular polysaccharides extracted from Haemophilus influenzae (Hib) type b.^{144 159 174 223} The capsular polysaccharides present in the vaccine are derived from polyribosylribitol phosphate (PRP), a major virulence factor for the organism, and are conjugated with T-cell dependent protein antigens (carriers).^{159 205}

• Commercially available Hib vaccines contain either the polysaccharide conjugate of Neisseria meningitidis outer membrane protein complex (PRP-OMP; PedvaxHIB, Hib-HepB; Comvax)^{77 129 144 148 159 160} or the polysaccharide conjugate of tetanus toxoid (PRP-T; ActHIB, Hiberix, DTaP-Hib; TriHIBit, DTaP-IPV/Hib; Pentacel).^{174 223} These conjugated vaccines differ in the protein carrier, polysaccharide size, and method of conjugation, including use of a spacer (linking moiety) between the PRP and protein carrier.^{129 159}

• Conjugation with a carrier protein results in a T-cell dependent polysaccharide antigen that elicits an improved immunologic response compared with unconjugated polysaccharide vaccines previously available.^{129 159 174 205}

• Hib vaccines stimulate active immunity to Hib infection by inducing production of specific antibodies.^{38 111 117 144 205} 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 75 117 159 205}

• At least 95% of infants develop protective antibody levels after a primary series of 2 or 3 doses of conjugated Hib vaccine.²⁰⁵

• 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}

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

• Importance of receiving the complete primary immunization series to ensure the highest level of protection against Hib.^{144 174}

• Importance of informing clinicians if any severe or unusual adverse reactions occur.^{203 223} 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}

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

Preparations

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