Pharmacology
Mechanism of Action
Promotes active immunity to diphtheria, tetanus, pertussis, hepatitis B, poliovirus (types 1, 2, and 3), and Haemophilus influenzae type B by inducing production of specific antibodies and antitoxins.
Pharmacokinetics/Pharmacodynamics
Onset of Action
Immune response observed to all components 1 month following the 3-dose series
Use: Labeled Indications
Note: Not approved in the US
Diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Haemophilus b disease prevention:
Active primary immunization against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and disease caused by Haemophilus influenzae type b in infants and children 6 weeks to 2 years of age; booster immunization (at 12 to 23 months) in infants who previously received a full primary vaccination course of each component of the vaccine
According to the National Advisory Committee on Immunization (NACI), the vaccine may be administered to children 2 years to <7 years if necessary (NACI 2015)
Contraindications
Hypersensitivity to any component of vaccine or formulation; encephalopathy of unknown etiology within 1 week following prior vaccination with a pertussis-containing vaccine; moderate or severe acute febrile illness or acute infection; children >7 years of age
Dosage and Administration
Dosing: Pediatric
Note: Vaccinate preterm infants according to their chronological age from birth. Vaccination usually begins at 2 months, but may be started at 6 weeks of age. Do not administer to infants <6 weeks of age.
Primary immunization: Infants and Children 6 weeks to 2 years: IM: 0.5 mL per dose; repeat 0.5 mL dose in intervals of at least 1 month for a total of 2 or 3 doses if full term at birth, or a total of 3 doses if preterm (born after at least 24 weeks gestational age)
Use in children previously vaccinated with one or more doses of hepatitis B vaccine: Children who received 1 dose of hepatitis B vaccine at birth (or shortly thereafter) may receive a 3-dose series of Infanrix Hexa beginning at ≥6 weeks of age. Use in infants who received more than 1 dose of hepatitis B vaccine has not been studied.
Where immunization against poliovirus is desired, Infanrix Hexa may be administered instead to infants scheduled to receive concurrent Infanrix (diphtheria, tetanus and acellular pertussis vaccine) and hepatitis B vaccine.
Booster immunization: IM: 0.5 mL dose administered at 12 to 23 months of age if the patient received 3-dose primary series or at 11 to 13 months of age if the patient received 2-dose primary series. Booster dose should be administered at least 6 months after the last priming dose and is intended for infants who have received a full primary vaccination course of each component of Infanrix Hexa.
Note: Dosing delays should not interfere with the final immunity achieved with Infanrix Hexa. Regardless of the time that elapses between doses, it is not necessary to restart the vaccination series.
Storage
Store at 2°C to 8°C (36°F to 46°F); do not freeze (discard if frozen). Protect from light. Immediate use after reconstitution is recommended; however, after reconstitution vaccine may be stored for 8 hours at 21°C (69.8°F) or up to 25°C (77°F) for 72 hours if necessary.
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
Meningococcal Polysaccharide (Groups A / C / Y and W-135) Tetanus Toxoid Conjugate Vaccine: May diminish the therapeutic effect of Tetanus Toxoids Vaccines. Management: When possible, administer the meningococcal polysaccharide (groups A / C / Y and W-135) tetanus toxoid conjugate vaccine either together with or at least one month before a tetanus toxoids-containing vaccine. 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
Haemophilus influenzae type b (Hib) capsular antigen may be present in urine within 1 to 2 weeks following vaccination; alternative diagnostic tests should be employed in suspected Hib disease during this time.
Adverse Reactions
>10%:
Central nervous system: Irritability (83%), hypersomnia (63%), sleep disorder (sleeping decreased: 51%), emotional lability (crying: 43%), fatigue, restlessness
Gastrointestinal: Anorexia (49%), diarrhea (36%), vomiting (25%)
Local: Erythema at injection site (49%), pain at injection site (43%), swelling at injection site (36%)
Miscellaneous: Fever (≥38°C [100.4°F]: 56%; >39.5°C [103.1°F]*)
1% to 10%:
Central nervous system: Nervousness
Local: Induration at injection site
<1%, postmarketing, and/or case reports: Angioedema, apnea, bronchitis, bronchospasm, cellulitis (inflammatory cellulitis without bacterial infection), collapse, cough, dermatitis, drowsiness, edema (diffuse edema of injected limb), hypersensitivity reaction (including anaphylactoid reaction and anaphylaxis), hypotonic/hyporesponsive episode, injection-site vesicle, lymphadenopathy, seizure (including febrile seizure), skin rash, thrombocytopenia, upper respiratory tract infection, 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]).
- Reactions from previous dose: Carefully consider use in patients with history of any of the following effects from previous administration of whole-cell DTP or acellular pertussis vaccine: Fever ≥105°F (40.5°C) within 48 hours of unknown cause; seizures with or without fever occurring within 3 days; persistent, inconsolable crying episodes lasting ≥3 hours and occurring within 48 hours; shock or collapse within 48 hours. Use is contraindicated in patients who have had encephalopathy within 7 days of a previous pertussis-containing vaccine.
- 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]; NACI 2014).
Disease-related concerns:
- Acute illness: Use is contraindicated in patients with moderate or severe acute illness (with or without fever); in general, vaccines may be administered to patients with mild acute illness (with or without fever) (NACI 2016).
- 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]; NACI 2015).
- Guillain-Barré syndrome: Patients who develop Guillain-Barre syndrome (GBS) within 6 weeks of receipt of a vaccine containing tetanus-toxoid should not receive any further doses; patients who develop GBS >6 weeks after immunization may receive subsequent doses of the vaccine (NACI 2016).
- Hepatitis B: Use for completion of hepatitis B vaccination series in infants born to HBsAG-positive mothers and previously vaccinated with hepatitis B immune globulin or born to mothers of unknown status, has not been evaluated.
- Neurologic disorders: Use with caution in patients with personal or immediate family (parent, sibling) history of progressive neurologic disease, or conditions predisposing to seizures; where appropriate, consider deferring immunization until health status can be assessed and condition stabilized. Antipyretics may be considered at the time of and for 24 hours following vaccination to patients at high risk for seizures to reduce the possibility of postvaccination fever (may occur within 2 to 3 days).
- Poliomyelitis: Defer administration during outbreaks of poliomyelitis.
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 NACI recommends simultaneous administration 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 (NACI 2016). An increased incidence of febrile reactions, convulsions (with or without fever) and hypotonic hyporesponsive episode have been observed with concomitant use of Infanrix hexa and pneumococcal conjugate vaccine.
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. May be used in patients with HIV infection. 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]).
- Premature infants: May be administered to infants born prematurely beginning at chronological age of 6 weeks; decreased immune response may be observed and the degree of clinical protection is unknown. Infants born ≤28 weeks gestation may be at greater risk for apnea; monitor respiratory function closely for 2 to 3 days following vaccination, particularly with history of respiratory immaturity.
Dosage form specific issues:
- Aluminum: Formulation may contain aluminum.
- Neomycin: Formulation contains trace amounts of neomycin; use caution in patients with prior hypersensitivity to neomycin.
- Polymyxin B: Formulation contains trace amounts of polymyxin B; use caution in patients with prior hypersensitivity to polymyxin B.
- Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer’s labeling.
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).
- 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]).
Monitoring Parameters
Signs/symptoms of hypersensitivity for 30 minutes after administration; respiratory function for 2 to 3 days following vaccination of infants born prematurely. Monitor for 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
Infanix Hexa is not approved for use in patients >2 years of age; animal reproduction studies have not been conducted.
