Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution:
Hiberix: Haemophilus b capsular polysaccharide 10 mcg [bound to tetanus toxoid 25 mcg] per 0.5 mL
Injection, powder for reconstitution [preservative free]:
ActHIB: Haemophilus b capsular polysaccharide 10 mcg [bound to tetanus toxoid 24 mcg] per 0.5 mL [contains formaldehyde; may be reconstituted with provided diluent (forms solution)]
Hiberix: Haemophilus b capsular polysaccharide 10 mcg [bound to tetanus toxoid 25 mcg] per 0.5 mL [contains lactose 12.6 mg] [DSC]
Injection, suspension:
PedvaxHIB: Haemophilus b capsular polysaccharide 7.5 mcg [bound to Neisseria meningitidis OMPC 125 mcg] per 0.5 mL (0.5 mL) [contains aluminum; natural rubber/natural latex in packaging]
Pharmacology
Mechanism of Action
Stimulates production of anticapsular antibodies and provides active immunity to Haemophilus influenzae type b. Vaccination provides protective antibodies in >95% of infants who are vaccinated with a 2- or 3-dose series (CDC 2012). An anti-PRP concentration of ≥1.0 mcg/mL predicts long-term protection.
Pharmacokinetics/Pharmacodynamics
Onset of Action
Immunity develops progressively with each dose. Immunity can be inferred ~ 2 weeks after the initial series is complete.
Efficacy: The initial unconjugated polysaccharide Hib vaccines produced 45% to 88% reduction in disease incidence among children at least 18 to 24 months of age. The initial protein-conjugated Hib vaccines produced >90% protection in infants after a multidose series. After the initial Hib conjugate vaccines were licensed, subsequent formulations were licensed based on noninferior antibody responses.
Duration of Action
Antibody concentrations exceeding 0.15 mcg/mL correlate with clinical protection from disease. Antibody concentrations exceeding 1 mcg/mL correlate with prolonged protection from disease, generally implying several years of protection.
Use: Labeled Indications
Active immunization for the prevention of invasive disease caused by Haemophilus influenzae type b (Hib):
ActHIB: Immunization of infants and children 2 months to 5 years of age.
Hiberix: Immunization of infants and children 6 weeks to 4 years of age (prior to fifth birthday).
PedvaxHIB: Routine vaccination of infants and children 2 to 71 months of age.
The Advisory Committee on Immunization Practices (ACIP) recommends vaccination for the following (CDC/ACIP [Briere 2014]):
- Routine immunization of all infants and children through age 59 months
- Unimmunized (defined as those who have not received a primary series and booster dose or at least 1 dose of a Hib vaccine after 14 months of age) children 12 to 59 months including chemotherapy recipients, anatomic or functional asplenia (including sickle cell disease), HIV infection, immunoglobulin deficiency or early component complement deficiency
Efficacy data are not available for use in older children and adults with chronic conditions associated with an increased risk of Hib disease. However, use may be considered for:
- Unimmunized (defined as those who have not received a primary series and booster dose or at least 1 dose of a Hib vaccine after 14 months of age) children ≥5 years, adolescents and adults with functional or anatomic asplenia, (including sickle cell disease)
- Unimmunized (defined as those who have not received a primary series and booster dose or at least 1 dose of a Hib vaccine after 14 months of age) children ≥5 years and adolescents with HIV infection
- Children <5 years undergoing chemotherapy or radiation treatment
- Successful hematopoietic stem cell transplant recipients
- Children ≥15 months and adolescents undergoing elective splenectomy
Contraindications
Hypersensitivity to Haemophilus b polysaccharide, tetanus toxoid-containing vaccine (Hiberix and ActHIB only), or any component of the formulation
Dosage and Administration
Dosing: Adult
Immunization: IM:
Adults who have not received the childhood Hib series and are at increased risk for invasive Hib disease due to sickle cell disease, anatomic/functional asplenia or splenectomy. ACIP recommendations: One dose (0.5 mL); may use any of the Hib conjugate vaccines (CDC/ACIP [Briere 2014])
Adults who are recipients of a successful hematopoietic stem cell transplant: Revaccinate with a 3-dose regimen beginning 6-12 months after the transplant, regardless of vaccination history. Doses should be administered ≥4 weeks apart (CDC/ACIP [Briere 2014]).
Dosing: Pediatric
Note: Consult CDC/ACIP annual immunization schedules for additional information including specific detailed recommendations for catch-up scenarios and/or care of patients with high-risk conditions. According to ACIP, doses administered ≤4 days before minimum interval or age are considered valid; however, local or state mandates may supersede this timeframe (ACIP [Kroger 2017]).
Primary immunization: Note: Preterm infants should be vaccinated according to their chronological age, beginning at 2 months of age; number of doses for completion of Hib series dependent upon products including some combination formulations (3 doses: ActHIB, Hiberix; 2 doses: PedvaxHIB) (CDC/ACIP [Briere 2014]) (see combination product monographs for specific dosing information)
Infants 6 weeks to 6 months: Minimum age for first dose is 6 weeks.
ActHIB, Hiberix (PRP-T): IM: 0.5 mL per dose for a total of 3 doses administered as follows: 2, 4, and 6 months of age
PedvaxHIB (PRP-OMP): IM: 0.5 mL per dose for a total of 2 doses administered as follows: 2 and 4 months of age
Booster immunization: ACIP recommendation: ActHIB, Hiberix, PedvaxHIB: Children 12 to 15 months: IM: 0.5 mL as a single dose (CDC/ACIP [Briere 2014])
Catch-up immunization: Note: Do not restart the series. If doses have been given, refer to current immunization guidelines for specific schedule and timing of dose based on patient age and previous number of doses.
Infants and Children 4 to 59 months: IM: 0.5 mL per dose for a total of 1 to 4 doses:
Children ≥5 years and Adolescents; unimmunized and are at increased risk for invasive Hib disease due to anatomic/functional asplenia or splenectomy, HIV infection, immunoglobulin deficiency, early component complement deficiency, or chemotherapy or radiation therapy: IM: 0.5 mL as a single dose; may use any of the Hib conjugate vaccines (CDC/ACIP [Briere 2014]). Unimmunized defined as persons who have not received a primary series and booster dose or at least 1 dose of a Hib vaccine after 14 months of age.
Repeat immunization for high-risk conditions (CDC/ACIP [Briere 2014):
Invasive Hib disease: Infants and Children <24 months: Revaccinate with a second primary series beginning 4 weeks after onset of disease
Undergoing chemotherapy or radiation therapy: Infants and Children <60 months: If dose administered within 14 days of starting or given during therapy: Repeat the doses at least 3 months after therapy completion
Hematopoietic stem cell transplant recipient: Children and Adolescents: Revaccinate with a 3-dose regimen beginning 6 to 12 months after successful transplant, regardless of vaccination history. Doses should be administered ≥4 weeks apart.
Reconstitution
ActHIB: Dilute with 0.6 mL of provided saline diluent (sodium chloride 0.4%); agitate to form a clear, colorless solution. Withdraw 0.5 mL of reconstituted vaccine for administration. Shake well prior to use
Hiberix: Dilute with provided saline diluent only. Transfer entire contents of prefilled syringe containing diluent into the vial; with needle still inserted, shake vigorously until it becomes a clear, colorless solution. Withdraw entire contents of vial (~0.5 mL) for administration. Shake well prior to use.
PedvaxHIB: Used as supplied; no reconstitution is necessary. Shake well; thorough agitation is necessary to maintain suspension of the vaccine.
Administration
IM: For IM administration; do not inject IV, intradermally, or subcutaneously. Shake well prior to use. Administer into the anterolateral thigh or deltoid. Do not administer into buttocks due to potential risk of injury to sciatic nerve. Do not mix with other vaccines or injections; separate needles and syringes should be used for each injection. To prevent syncope related injuries, patients should be vaccinated while seated or lying down (ACIP [Kroger 2017]). US law requires that the date of administration, the vaccine manufacturer, lot number of vaccine, and the administering person's name, title, and address be entered into the patient's permanent medical record.
ActHIB, PedvaxHIB: If the primary series is delayed or interrupted, there is no need to start the series over, regardless of the interval between doses.
Hiberix: If Hiberix is inadvertently administered during the primary vaccination series, the dose can be counted as a valid PRP-T dose that does not need to be repeated if administered according to schedule. In this case, a total of 3 doses completes the primary series (CDC 58[36] 2009).
For patients at risk of hemorrhage following intramuscular injection, the vaccine should be administered intramuscularly if, in the opinion of the physician familiar with the patient's bleeding risk, the vaccine can be administered by this route with reasonable safety. If the patient receives antihemophilia or other similar therapy, intramuscular vaccination can be scheduled shortly after such therapy is administered. A fine needle (23 gauge or smaller) can be used for the vaccination and firm pressure applied to the site (without rubbing) for at least 2 minutes. The patient should be instructed concerning the risk of hematoma from the injection. Patients on anticoagulant therapy should be considered to have the same bleeding risks and treated as those with clotting factor disorders (ACIP [Kroger 2017]).
Storage
ActHIB: Store lyophilized powder and diluent under refrigeration at 2°C to 8°C (36°F to 46°F); do not freeze. If not used immediately after reconstitution, may store under refrigeration for up to 24 hours.
Hiberix: Prior to reconstitution, store powder under refrigeration at 2°C to 8°C (36°F to 46°F). Protect from light. Diluent may be stored under refrigeration or at room temperature; do not freeze, discard diluent if frozen. If not used immediately after reconstitution, may store under refrigeration for up to 24 hours.
PedvaxHIB: Store under refrigeration at 2°C to 8°C (36°F to 46°F); do not freeze.
Drug Interactions
Fingolimod: May diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting fingolimod. If vaccinated during fingolimod therapy, revaccinate 2 to 3 months after fingolimod discontinuation. Consider therapy modification
Immunosuppressants: May diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Exceptions: Cytarabine (Liposomal). Consider therapy modification
Siponimod: May diminish the therapeutic effect of Vaccines (Inactivated). Management: Avoid administration of vaccines (inactivated) during treatment with siponimod and for 1 month after discontinuation due to potential decreased vaccine efficacy. Consider therapy modification
Venetoclax: May diminish the therapeutic effect of Vaccines (Inactivated). Monitor therapy
Test Interactions
May interfere with interpretation of urine antigen detection tests; antigenuria may occur up to 2 weeks following immunization
Adverse Reactions
>10%:
Central nervous system: Irritability (infants: 67% to 76%; children: 13% to 60%), drowsiness (infants: 49% to 66%; children: 13% to 39%)
Gastrointestinal: Anorexia (6% to 34%)
Local: Pain at injection site (41% to 57%), erythema at injection site (≤32%), swelling at injection site (≤22%), tenderness at injection site (children: ≤20%)
Miscellaneous: Fever (≤19%)
1% to 10%:
Central nervous system: Excessive crying (>4 hours, infants: >1%), pain (infants: >1%)
Dermatologic: Skin rash (infants: >1%)
Gastrointestinal: Diarrhea (infants: >1%)
Local: Induration at injection site (children: ≤6%), local soreness/soreness at injection site (infants: >1%)
Otic: Otitis media (infants: >1%)
Respiratory: Upper respiratory tract infection (infants: >1%)
Miscellaneous: Crying (>1%; may be unusual or high-pitched)
Frequency not defined:
Central nervous system: Guillain-Barré syndrome
Gastrointestinal: Vomiting
Infection: Bacterial infection (Hib early-onset)
<1%, postmarketing, and/or case reports: Abscess at injection site (sterile), anaphylaxis, angioedema, apnea, asthenia, febrile seizures, hypersensitivity reaction, hypotonic/hyporesponsive episode, lymphadenopathy, nonimmune anaphylaxis, peripheral edema, pneumonia, pruritus, seizure, swelling of extremities, swelling of the injected limb (extensive), syncope, thrombocytopenia, tracheitis, urticaria
Warnings/Precautions
Concerns related to adverse effects:
- Anaphylactoid/hypersensitivity reactions: Immediate treatment (including epinephrine 1 mg/mL) for anaphylactoid and/or hypersensitivity reactions should be available during vaccine use (ACIP [Kroger 2017]).
- Syncope: Syncope has been reported with use of injectable vaccines and may result in serious secondary injury (eg, skull fracture, cerebral hemorrhage); typically reported in adolescents and young adults and within 15 minutes after vaccination. Procedures should be in place to avoid injuries from falling and to restore cerebral perfusion if syncope occurs (ACIP [Kroger 2017]).
Disease-related concerns:
- Acute illness: The decision to administer or delay vaccination because of current or recent febrile illness depends on the severity of symptoms and the etiology of the disease. Defer administration in patients with moderate or severe acute illness (with or without fever); vaccination should not be delayed for patients with mild acute illness (with or without fever) (ACIP [Kroger 2017]).
- Bleeding disorders: Use with caution in patients with a history of bleeding disorders (including thrombocytopenia); bleeding/hematoma may occur from IM administration; if the patient receives antihemophilia or other similar therapy, IM injection can be scheduled shortly after such therapy is administered (ACIP [Kroger 2017]).
- Guillain-Barré syndrome (GBS): ActHIB, Hiberix: Use with caution in patients with history of GBS; carefully consider risks and benefits to vaccination in patients known to have experienced GBS within 6 weeks following previous tetanus-containing vaccination.
- Tetanus immunization: Immunization with ActHIB or Hiberix does not substitute for routine tetanus immunization.
Concurrent drug therapy issues:
- Anticoagulant therapy: Use with caution in patients receiving anticoagulant therapy; bleeding/hematoma may occur from IM administration (ACIP [Kroger 2017]).
- Vaccines: In order to maximize vaccination rates, the ACIP recommends simultaneous administration (ie, >1 vaccine on the same day at different anatomic sites) of all age-appropriate vaccines (live or inactivated) for which a person is eligible at a single clinic visit, unless contraindications exist. The use of combination vaccines is generally preferred over separate injections, taking into consideration provider assessment, patient preference, and adverse events. When using combination vaccines, the minimum age for administration is the oldest minimum age for any individual component; the minimum interval between dosing is the greatest minimum interval between any individual components. The ACIP prefers each dose of Hib containing combination vaccines in a series come from the same manufacturer when possible; however, vaccination should not be deferred because a specific brand name is unavailable. According to the ACIP, monovalent Hib vaccines are interchangeable; however, if different brands are used in the primary series and the number of doses required for series completion varies, then the higher number of doses is recommended for series completion (ACIP [Kroger 2017]).
Special populations:
- Altered immunocompetence: Consider deferring immunization during periods of severe immunosuppression (eg, patients receiving chemo/radiation therapy or other immunosuppressive therapy [including high-dose corticosteroids]); may have a reduced response to vaccination (ACIP [Kroger 2017]). In general, household and close contacts of persons with altered immunocompetence may receive all age appropriate vaccines). Inactivated vaccines should be administered ≥2 weeks prior to planned immunosuppression when feasible; inactivated vaccines administered during chemotherapy should be readministered after immune competence is regained (ACIP [Kroger 2017]; IDSA [Rubin 2014]).
- Pediatric: Apnea has occurred following intramuscular vaccine administration in premature infants; consider clinical status implications. In general, preterm infants should be vaccinated at the same chronological age as full-term infants (ACIP [Kroger 2017]).
Dosage form specific issues:
- Lactose: Some products may contain lactose.
- Latex: Packaging may contain natural latex rubber.
Other warnings/precautions:
- Antipyretics: Antipyretics have not been shown to prevent febrile seizures; antipyretics may be used to treat fever or discomfort following vaccination (ACIP [Kroger 2017]). One study reported that routine prophylactic administration of acetaminophen to prevent fever prior to vaccination decreased the immune response of some vaccines; the clinical significance of this reduction in immune response has not been established (Prymula 2009).
- Appropriate use: Use of this vaccine for specific medical and/or other indications (eg, immunocompromising conditions, hepatic or kidney disease, diabetes) is also addressed in the annual ACIP Recommended Immunization Schedules (refer to CDC schedule for detailed information). Specific recommendations for vaccination in immunocompromised patients with asplenia, cancer, HIV infection, cerebrospinal fluid leaks, cochlear implants, hematopoietic stem cell transplant (prior to or after), sickle cell disease, solid organ transplant (prior to or after), or those receiving immunosuppressive therapy for chronic conditions are available from the IDSA (Rubin 2014).
- Effective immunity: Vaccination may not result in effective immunity in all patients. Response depends upon multiple factors (eg, type of vaccine, age of patient) and may be improved by administering the vaccine at the recommended dose, route, and interval. Vaccines may not be effective if administered during periods of altered immune competence (ACIP [Kroger 2017]). Infection may occur within the week of vaccination, prior to the onset of the vaccine.
Monitoring Parameters
Monitor for anaphylaxis and syncope for 15 minutes following administration (ACIP [Kroger 2017]). If seizure-like activity associated with syncope occurs, maintain patient in supine or Trendelenburg position to reestablish adequate cerebral perfusion.
Pregnancy
Pregnancy Considerations
Animal reproduction studies have not been conducted. Inactivated vaccines have not been shown to cause increased risks to the fetus (ACIP [Kroger 2017]).
Patient Education
What is this drug used for?
- It is used to prevent Haemophilus influenzae type b disease.
Frequently reported side effects of this drug
- Injection site pain, swelling, or irritation
- Irritability
- Fatigue
- Lack of appetite
- Agitation
- Diarrhea
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Burning or numbness feeling
- Facial paralysis
- Abnormal movements
- Severe dizziness
- Passing out
- Muscle weakness
- Vision changes
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
