Haemophilus b Vaccine (Monograph)

Brand names: ActHIB, Hiberix, PedvaxHIB, Pentacel (combination)
Drug class: Vaccines
ATC class: J07AG51
VA class: IM100

Introduction

Inactivated (polysaccharide) vaccine.^{134 144 174 223} Commercially available in US as 2 different vaccine types: 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-T also commercially available 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 59 months of age.^{105 144 159 166 174 199 223} Also recommended in certain individuals ≥5 years of age^{† [off-label]} at increased risk for invasive Hib disease because of certain medical conditions.^{105 159 199 200}

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), principally in infants and children <5 years of age.^{105 159 166} Prior to availability of Hib vaccine, Hib was the most common cause of bacterial meningitis and other invasive bacterial disease in young children worldwide;^{105 166} case fatality rate was 3–6% despite appropriate 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 2012, there were 30 cases of invasive Hib disease reported in US children <5 years of age.¹⁶⁶ Nonencapsulated (nontypeable) H. influenzae now the leading cause of invasive H. influenzae disease in all age groups.¹⁰⁵

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 <5 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

Individuals at increased risk of invasive Hib infection because of certain medical conditions include those with functional or anatomic asplenia, sickle cell disease, immunoglobulin deficiency (including IgG₂ deficiency), early component complement deficiency, or HIV infection and those who have undergone hematopoietic stem cell transplantation (HSCT) or are receiving chemotherapy or radiation therapy for malignant neoplasms.^{105 134 159} Historically, invasive Hib was more common in American Indians (e.g., Apache and Navajo tribes),^{45 105 166} Alaskan natives,^{40 45 85 105} Hispanics,¹⁶⁶ blacks;^{29 105 166} boys;¹⁰⁵ daycare attendees;^{105 166} children living in crowded conditions;^{105 166} and children who were not breastfed.¹⁰⁵

PRP-OMP (PedvaxHIB) and PRP-T (ActHIB) are labeled by FDA for use in children through 5 years of age (prior to sixth birthday);^{144 174} PRP-T (Hiberix) is labeled by FDA for use in children through 4 years of age (prior to fifth birthday).²²³ Although efficacy and safety not established in older children or adults,^{144 174 223 224 225} ACIP, AAP, and others recommend a single dose of Hib vaccine in certain immunocompromised adults and children ≥5 years of age^{† [off-label]} at increased risk for invasive Hib disease.^{105 156 159 166 199 200} Consider that immune response to the vaccine may be reduced in immunocompromised individuals.^{105 134} (See Individuals with Altered Immunocompetence under Cautions.)

Hib vaccine will not provide protection against other types of H. influenzae (e.g., nonencapsulated [nontypeable] strains or against other pathogens that cause meningitis, septicemia, or other invasive infections.¹⁴⁴

Depending on age and vaccination status, Hib vaccine may be given as a monovalent vaccine containing PRP-OMP (PedvaxHIB),¹⁴⁴ monovalent vaccine containing PRP-T (ActHIB, Hiberix),^{174 223} or combination vaccine containing PRP-T (DTaP-IPV/Hib; Pentacel).²²⁴

ACIP and AAP state that PRP-OMP (PedvaxHIB) is preferred for primary immunization against invasive Hib disease in American Indian and Alaskan native children ≥6 weeks of age.^{105 159} Peak incidence of Hib meningitis in these populations occurs at a younger age (4–6 months) than in other US infants and there is evidence that PRP-OMP can induce protective antibody levels after first dose and provide earlier protection than vaccines containing PRP-T.^{105 159} These experts state that any available age-appropriate monovalent or combination Hib vaccine can be used in other individuals.^{105 159}

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 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-OMP; PedvaxHIB), (PRP-T; ActHIB, Hiberix): Administer by IM injection.^{144 174 223}

Combination Hib vaccine (DTaP-IPV/Hib; Pentacel): Administer by IM injection.²²⁴

Do not administer monovalent or combination Hib vaccines IV, sub-Q, or intradermally.^{144 174 223 224}

Depending on patient age, administer IM into anterolateral thigh or deltoid muscle.^{134 144 224}

Infants <12 months of age: Preferably give IM injection into anterolateral thigh.¹³⁴ In certain circumstances (e.g., physical obstruction at other sites and no reasonable indication to defer the vaccine dose), may consider IM injection into gluteal muscle using care to identify anatomical landmarks prior to injection.¹³⁴

Infants and children 1 through 2 years of age: Preferably give IM injection into anterolateral thigh; alternatively, deltoid muscle can be used if muscle mass is adequate.¹³⁴

Adults, adolescents, and children ≥3 years of age: Preferably give IM injection into deltoid muscle;¹³⁴ alternatively, anterolateral thigh can be used.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 judgment to avoid inadvertent underpenetration or overpenetration of muscle.^{208 209}

Some manufacturers state avoid injection into gluteal area or into or near blood vessels or nerves.^{144 224}

Syncope (vasovagal or vasodepressor reaction; fainting) may occur following vaccination;^{134 223} may be accompanied by transient neurologic signs (e.g., visual disturbance, paresthesia, tonic-clonic limb movements).²²³ Occurs most frequently in adolescents and young adults.¹³⁴ Have procedures in place to avoid falling injury and restore cerebral perfusion following syncope.^{134 223} 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 concurrently with other age-appropriate vaccines.^{105 134} When multiple vaccines are administered during a single health-care visit, give each parenteral vaccine using separate syringes and different injection sites.^{105 134} 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 single-dose vial well before withdrawing dose;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 0.6 mL of 0.4% sodium chloride diluent supplied by the manufacturer;¹⁷⁴ agitate thoroughly.¹⁷⁴ Should appear clear and colorless.¹⁷⁴ Consult manufacturer’s labeling for additional information regarding reconstitution.¹⁷⁴

Administer promptly after reconstitution or store at 2–8°C and administer within 24 hours after reconstitution.¹⁷⁴

Shake well prior to use.¹⁷⁴

Do not mix with any other vaccine or solution.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 additional information regarding reconstitution.²²³

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

Shake well before use.²²³

Do not mix with any other vaccine or solution.²²³

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 (i.e., number of doses) varies according to specific vaccine administered and age at which vaccination is started.^{144 159 174 223} Follow age-appropriate dosage recommendations for the specific preparation used.^{144 159 174 223}

PRP-OMP (PedvaxHIB) and PRP-T (ActHIB, Hiberix) monovalent Hib vaccines are considered interchangeable for both primary and booster immunization.^{105 159 166} If primary vaccination series included both PRP-OMB and PRP-T or if vaccine type previously given unknown, 3 primary doses and a booster dose are needed to complete the series.^{105 159 166}

ACIP and AAP recommend use of PRP-OMP (PedvaxHIB) for primary immunization in American Indian and Alaskan native children.^{105 159} (See Limitations of Vaccine Effectiveness under Cautions.)

Medically stable preterm infants should be vaccinated at the usual chronologic age using usual dosage.^{105 144 159} (See Pediatric Use under Cautions.)

If interruptions or delays result in an interval between doses longer than recommended, there is no need to administer additional doses or start the vaccination series over.^{134 144}

Pediatric Patients

Prevention of Haemophilus influenzae Type b (Hib) Infection

Infants and Children 2 Months 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.^{105 144 199} Manufacturer, ACIP, AAP, and others recommend that doses be given at 2, 4, and 12 through 15 months of age.^{144 159} Initial dose may be given as early as 6 weeks of age.¹⁹⁹ Minimum interval between first and second dose is 2 months (8 weeks).^{144 199} Give third dose (booster dose) no earlier than 2 months after second dose; third dose necessary only if second dose was given before 12 months of age.^{144 159}

Catch-up immunization in infants who receive first dose at 7 through 11 months of age: Give second dose at least 4 weeks after first dose and give third dose at 12 through 15 months of age or 8 weeks after second dose, whichever is later.^{159 199}

Catch-up immunization in previously unvaccinated infants 12 through 14 months of age: Give first dose immediately and give second dose 8 weeks after first dose.^{159 199} Third dose not needed.¹⁵⁹

Previously unvaccinated infants and children 15 through 59 months of age: Give single dose.¹⁹⁹

Infants and Children 2 Months through 5 years 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} Manufacturer recommends that doses be given at 2, 4, 6, and 15 through 18 months of age.¹⁷⁴ Initial dose may be given as early as 6 weeks of age.^{105 159 174 199}

Catch-up immunization in infants who receive first dose at 7 through 11 months of age: Give second dose at least 4 weeks after first dose and give third dose at 12 through 15 months of age or 8 weeks after second dose, whichever is later.^{159 199}

Catch-up immunization in previously unvaccinated infants 12 through 14 months of age: Give first dose immediately and give second dose 8 weeks after first dose.^{159 199} Third dose not needed.¹⁵⁹

Previously unvaccinated infants and children 15 through 59 months of age: Give single dose.¹⁹⁹

Infants and Children 6 Weeks through 4 Years of Age (PRP-T; Hiberix)

IM

Each dose is 0.5 mL.²²³

Routine primary immunization in early infancy consists of a series of 3 doses and a booster dose.^{105 199 223} ACIP, AAP, and others recommend that doses be given at 2, 4, 6, and 12 through 15 months of age.^{105 199} Manufacturer recommends that doses be given at 2, 4, 6, and 15 through 18 months of age.²²³ Initial dose may be given as early as 6 weeks of age.^{105 159 199 223}

Catch-up immunization in infants who receive first dose at 7 through 11 months of age: Give second dose at least 4 weeks after first dose and give third dose at 12 through 15 months of age or 8 weeks after second dose, whichever is later.^{159 199}

Catch-up immunization in previously unvaccinated infants 12 through 14 months of age: Give first dose immediately and give second dose 8 weeks after first dose.^{159 199} Third dose not needed.¹⁵⁹

Previously unvaccinated infants and children 15 through 59 months of age: Give single dose.¹⁹⁹

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 ACIP, AAP, and others recommend that doses be given at 2, 4, 6, and 12 through 15 months of age.^{105 199} Manufacturer recommends that doses be given 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: Give 2 doses of Hib vaccine 2 months (8 weeks) apart.^{105 159 199}

Previously received 2 doses of Hib vaccine before 12 months of age: Give 1 additional dose of Hib vaccine at least 8 weeks after last dose.^{105 159 199}

Previously received complete primary immunization series followed by a booster dose given at ≥12 months of age: No additional doses of Hib vaccine needed.^{105 159}

Children ≥5 Years of Age with Medical Conditions Associated with Increased Risk of Invasive Hib Disease† [off-label]

IM

Unvaccinated or incompletely vaccinated against Hib: ACIP, AAP, and others recommend a single dose of Hib vaccine in those at increased risk because of anatomic or functional asplenia, sickle cell disease, HIV infection, or IgG₂ deficiency.^{105 156 159 199}

Undergoing splenectomy: Give a single dose of Hib vaccine at least 14 days before surgery if previously unvaccinated.^{159 199} Some experts recommend a dose regardless of prior vaccination against Hib.¹⁵⁹ If not given before splenectomy, give as soon as possible ≥2 weeks after surgery when patient's condition is stable.^{105 134}

HSCT recipient: Starting 6–12 months after HSCT, give 3 doses of monovalent Hib vaccine at least 4 weeks apart, regardless of prior vaccination against Hib.^{159 199}

Adults

Adults with Medical Conditions Associated with Increased Risk of Invasive Hib Disease† [off-label]

IM

Anatomic or functional asplenia, sickle cell disease: Give a single dose of Hib vaccine if previously unvaccinated.^{134 200}

Undergoing splenectomy: Give a single dose of Hib vaccine at least 14 days before surgery if previously unvaccinated.^{159 200} Some experts recommend a dose regardless of prior vaccination against Hib.¹⁵⁹ If not given before splenectomy, give as soon as possible ≥2 weeks after surgery when patient's condition is stable.^{105 134}

HIV-infected adults: Hib vaccine not recommended unless patient also has anatomic or functional asplenia.^{155 159 200}

HSCT recipient: Starting 6–12 months after HSCT, give 3 doses of Hib vaccine at least 4 weeks apart, regardless of prior vaccination against Hib.^{159 200}

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): Hypersensitivity to any vaccine component.¹⁴⁴

• PRP-T (ActHIB, 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.^{174 223}

• 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, pruritus, urticaria) reported.^{174 223}

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}

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

Latex Sensitivity

Stopper on vial of PRP-OMP (PedvaxHIB) contains natural rubber latex,¹⁴⁴ which may cause sensitivity reactions in susceptible individuals.^{144 190 192}

Delayed-type (cell-mediated) allergic contact dermatitis is most common type of latex hypersensitivity; immediate-type allergic reactions reported rarely.¹³⁴

ACIP states that vaccines supplied in vials or syringes containing dry natural rubber or natural rubber latex may be administered to individuals with a history of contact allergy to latex.¹³⁴ Avoid use of such vaccines, if possible, in those with a history of severe (anaphylactic) latex allergy;¹³⁴ if used in such individuals, ensure that appropriate agents and equipment are available to treat anaphylaxis or other immediate allergic reaction to latex.¹³⁴

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 hypersensitivity usually manifests as a delayed-type (cell-mediated) contact dermatitis.¹³⁴

ACIP states that a history of delayed-type allergic reaction to neomycin is not a contraindication for use of vaccines containing trace amounts of neomycin.¹³⁴ However, individuals with a history of anaphylactic reaction to neomycin should be evaluated by an allergist before receiving a neomycin-containing vaccine.¹³⁴

Individuals with Altered Immunocompetence

May be administered to individuals immunosuppressed as the result of disease or immunosuppressive therapy.^{105 134 135 144 156} Consider possibility that immune responses to the vaccine and efficacy may be reduced in these individuals.^{105 134 135 144 174 223}

Manufacturer of PRP-T (Hiberix) states safety and efficacy not evaluated in immunosuppressed children.²²³

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 immune responses in HIV-infected individuals vary with the degree of immunocompromise.¹⁶⁶

ACIP, AAP, CDC, NIH, HIV Medicine Association of the IDSA, and others state that recommendations for use of Hib vaccine in HIV-infected children are the same as those for children not infected with HIV.¹⁵⁶

AAP states 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 scheduled for splenectomy (e.g., for Hodgkin’s disease, spherocytosis, immune thrombocytopenia, hypersplenism) may benefit from an additional dose of a Hib vaccine given ≥14 days before surgery.¹⁰⁵

Generally, administer prior to initiation of immunosuppressive therapy or defer until immunosuppressive therapy discontinued.^{105 134} (See Immunosuppressive Agents under Interactions.)

Concomitant Illness

Base decision to administer or delay vaccination in an individual with a current or recent acute illness on severity of symptoms and etiology of the illness.¹³⁴

ACIP states that mild acute illness generally does not preclude vaccination.¹³⁴

ACIP states that moderate or severe acute illness (with or without fever) is a precaution for vaccination;¹³⁴ defer vaccines until individual has recovered from the acute phase of the illness.¹³⁴ This avoids superimposing vaccine adverse effects on the underlying illness or mistakenly concluding that a manifestation of the underlying illness resulted from vaccine administration.¹³⁴

Guillain-Barré Syndrome

If Guillain-Barré syndrome (GBS) occurred within 6 weeks of receipt of a vaccine containing tetanus toxoid, manufacturers state base decision to administer a dose of PRP-T (ActHIB, Hiberix) on careful consideration of potential benefits and possible risks.^{174 223}

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 IM vaccines may be given to such individuals if a clinician familiar with the patient’s bleeding risk determines that the vaccines can be administered IM 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 In individuals receiving therapy for hemophilia, IM vaccines can be scheduled for shortly after a dose of such therapy.¹³⁴

Use of Combination Vaccines

When combination vaccine containing Hib and other antigens (DTaP-IPV/Hib; Pentacel) used, consider cautions, precautions, and contraindications associated with each antigen.²²⁴

Limitations of Vaccine Effectiveness

May not protect all vaccine recipients against Hib.^{144 174}

Hib vaccines will not provide protection against other types of H. influenzae (e.g., nonencapsulated [nontypeable] strains) or against other pathogens that cause meningitis, septicemia, or other invasive disease.¹⁴⁴

Hib vaccine does not result in protective antibodies immediately following vaccination.¹⁴⁴

There is some evidence that vaccines containing PRP-OMP (PedvaxHIB) result in more rapid seroconversion to protective antibody concentrations within the first 6 months of life compared with vaccines containing PRP-T (ActHIB, Hiberix).¹⁰⁵ 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 contains Hib antigen conjugated to outer membrane protein complex (OMPC) of Neisseria meningitidis and antibodies to OMPC have been demonstrated in individuals who received the vaccine, the clinical relevance of these antibodies not established.¹⁴⁴ PRP-OMP is not an immunizing agent against meningococcal disease.¹⁵⁹

Although PRP-T contains Hib antigen conjugated to tetanus toxoid, PRP-T is not a substitute for routine immunization against tetanus.²²³

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.^{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

Not labeled by FDA for use in adolescents or adults;^{144 174 223} not usually recommended for this age group.^{93 105 159}

No human or animal data available to assess risks of Hib vaccines during pregnancy.^{144 174 223 224}

ACIP states there is no evidence of risk to the fetus if inactivated vaccines are administered during pregnancy.¹³⁴

Lactation

Not labeled by FDA for use in adolescents or adults;^{144 174 223} not usually recommended for this age group.^{93 105 144 159 174 200}

Not known whether antigens contained in Hib vaccine are distributed into human milk, affect human milk production, or affect breast-fed infant.²²³

ACIP states that administration of inactivated vaccines to a woman who is breast-feeding does not pose any safety concerns for the woman or her breast-fed infant.¹³⁴

Pediatric Use

PRP-OMP (PedvaxHIB): Safety and efficacy not established in infants <6 weeks of age or in children ≥6 years of age.¹⁴⁴ Manufacturer states administration before 6 weeks of age may result in immunologic tolerance to the vaccine (i.e., impaired ability to respond to subsequent exposure to PRP antigen).¹⁴⁴

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

PRP-T (Hiberix): Safety and efficacy not established in infants <6 weeks of age or in children and adolescents 5–16 years of age.²²³

DTaP-IPV/Hib (Pentacel): Safety and efficacy not established in infants <6 weeks of age or in children 5–16 years of age.²²⁴

Do not administer Hib vaccine to infants <6 weeks of age.^{144 159}

Apnea reported following IM administration of vaccines in some infants born prematurely.^{223 224} 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.^{223 224}

Geriatric Use

Not labeled by FDA for use in adults, including geriatric adults;^{144 174 223 224} not usually recommended for this age group.^{93 105 159 200}

Common Adverse Effects

PRP-OMP (PedvaxHIB) or PRP-T (ActHIB Hiberix): Injection site reactions (pain, erythema, swelling), fever, irritability, lethargy, drowsiness, restlessness.^{144 174 223}

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

Drug Interactions

Immunosuppressive Agents

Immune responses to vaccines, including Hib vaccine, may be reduced in individuals receiving immunosuppressive agents.^{105 134 144 174 223 224}

Generally, give inactivated vaccines ≥2 weeks prior to initiation of immunosuppressive therapy and, because of possible suboptimal response, do not give during and for certain periods of time after immunosuppressive therapy discontinued.^{105 134 135} (See Specific Drugs under Interactions.)

Time to restoration of immune competence varies depending on type and intensity of immunosuppressive therapy, underlying disease, and other factors;¹⁰⁵ optimal timing for vaccine administration after discontinuance of immunosuppressive therapy not identified for every situation.¹⁰⁵

Vaccines

Although specific studies may not be available, concurrent administration with other age-appropriate vaccines, including live virus vaccines, toxoids, or inactivated or recombinant vaccines, during the same health-care visit 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 A, hepatitis B, influenza, measles, mumps, rubella, meningococcal disease, pneumococcal disease, poliovirus, rotavirus, and varicella.^{105 159 174} Administer each parenteral vaccine using separate syringes and different injection sites.^{105 134}

Specific Drugs and Laboratory Tests

Stability

Storage

Parenteral

For Injection, for IM Use

PRP-T (ActHIB) and 0.4% sodium chloride diluent: 2–8°C;¹⁷⁴ 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 0.9% sodium chloride diluent supplied by manufacturer at 2–8°C or room temperature <25°C;²²³ do not freeze;²²³ 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 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;¹⁴⁴ do not freeze.¹⁴⁴

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• Commercially available as monovalent PRP-OMP vaccine (PedvaxHIB)¹⁴⁴ and as monovalent PRP-T vaccine (ActHIB, Hiberix).^{174 223} PRP-T also available 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} 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)^{129 144 148 159 160} or tetanus toxoid (PRP-T; ActHIB) (PRP-T; Hiberix) (DTaP-IPV/Hib; Pentacel).^{174 223}

• Conjugation with a carrier protein results in a T-cell dependent polysaccharide antigen that induces 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}

• Studies using unconjugated Hib vaccines (no longer commercially available) indicate that antibody titers to H. influenzae capsular polysaccharide (anti-PRP) of ≥1 mcg/mL after vaccination correlate with long-term protection against invasive Hib disease.^{166 174 223}

• In clinical study using PRP-OMP (PedvaxHIB), 80% of infants developed protective antibody levels (anti-PRP >1 mcg/mL) after primary series of 2 doses initiated at 2–3 months of age;¹⁴⁴ 95% had protective antibody levels approximately 1 month after a booster dose given at 12–15 months of age.¹⁴⁴

• In clinical studies using PRP-T (ActHIB, Hiberix), 81–97% of infants developed protective antibody levels (anti-PRP ≥1 mcg/mL) after a primary immunization series of 3 doses given at 2, 4, and 6 months of age;^{174 223} 98–100% had protective antibody levels 1 month after a booster dose given at 15–23 months of age.^{174 223}

• If complete vaccination series administered as recommended, regimens that include PRP-OMP or PRP-T are considered equivalent.^{105 159} However, there is some evidence that vaccines containing PRP-OMP result in more rapid seroconversion to protective antibody concentrations within first 6 months of life compared with vaccines containing PRP-T.¹⁰⁵

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 [Web]).^{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 vaccination 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 [Web].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.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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