Haemophilus b Vaccine

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

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 (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

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

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

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

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

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

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

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

Storage

Parenteral

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

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

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

• 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