Pharmaceutical Name

Trade (marketing or proprietary) name: ActHIB, PedvaxHIB, Hiberix

Generic (nonproprietary or active ingredient) name: Haemophilus b Conjugate Vaccine (Tetanus Toxoid Conjugate) Solution for Intramuscular Injection, Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate)

Indication and Usage

Reason the product has been approved for sale on the market.

• ActHIB is a vaccine indicated for the prevention of invasive disease caused by Haemophilus influenzae type b. ActHIB vaccine is approved for use as a four dose series in infants and children 2 months through 5 years of age
• Liquid PedvaxHIB is indicated for routine vaccination against invasive disease caused by Haemophilus influenzae type b in infants and children 2 to 71 months of age. Liquid PedvaxHIB will not protect against disease caused by Haemophilus influenzae other than type b or against other microorganisms that cause invasive disease such as meningitis or sepsis. As with any vaccine, vaccination with Liquid PedvaxHIB may not result in a protective antibody response in all individuals given the vaccine.
• HIBERIX is a vaccine indicated for active immunization for the prevention of invasive disease caused by Haemophilus influenzae type b. HIBERIX is approved for use in children aged 6 weeks through 4 years (prior to fifth birthday).

Manufacturer Insert

Ingredients

Also known as “excipients” for vaccines.

ActHIB: The vaccine consists of the Haemophilus influenzae type b capsular polysaccharide (polyribosyl-ribitol-phosphate, PRP), a high-molecularweight polymer prepared from the H. influenzae type b strain 1482 grown in a semi-synthetic medium, covalently bound to tetanus toxoid. The lyophilized ActHIB vaccine powder and saline diluent contain no preservative. The tetanus toxoid is prepared by extraction, ammonium sulfate purification, and formalin inactivation of the toxin from cultures of Clostridium tetani (Harvard strain) grown in a modified Mueller and Miller medium. (5) The culture medium contains milk derived raw materials (casein derivatives). Further manufacturing process steps reduce residual formaldehyde to levels below 0.5 micrograms (mcg) per dose by calculation. The toxoid is filter sterilized prior to the conjugation process. Potency of ActHIB vaccine is specified on each lot by limits on the content of PRP polysaccharide and protein in each dose and the proportion of polysaccharide and protein in the vaccine that is characterized as high molecular weight conjugate. When ActHIB is reconstituted with saline diluent (0.4% Sodium Chloride), each 0.5-mL dose is formulated to contain 10 mcg of purified capsular polysaccharide conjugated to 24 mcg of inactivated tetanus toxoid and 8.5% of sucrose. The vial stoppers for ActHIB vaccine and diluent are not made with natural rubber latex.

PedvaxHIB: Liquid PedvaxHIB is ready to use and does not require a diluent. Each 0.5 mL dose of Liquid PedvaxHIB is a sterile product formulated to contain: 7.5 mcg of Haemophilus b PRP, 125 mcg of Neisseria meningitidis OMPC and 225 mcg of aluminum as amorphous aluminum hydroxyphosphate sulfate (previously referred to as aluminum hydroxide), in 0.9% sodium chloride, but does not contain lactose or thimerosal. Liquid PedvaxHIB is a slightly opaque white suspension. This vaccine is for intramuscular administration and not for intravenous injection.

Hiberix: HIBERIX contains Haemophilus b capsular polysaccharide (polyribosyl-ribitol-phosphate [PRP]), a high molecular weight polymer prepared from the H. influenzae type b strain 20,752 grown in a synthetic medium that undergoes heat inactivation and purification. The tetanus toxin, prepared from Clostridium tetani grown in a semi-synthetic medium, is detoxified with formaldehyde and purified. The capsular polysaccharide is covalently bound to the tetanus toxoid. After purification, the conjugate is lyophilized in the presence of lactose as a stabilizer. The diluent for HIBERIX is a sterile saline solution (0.9% sodium chloride) supplied in vials or prefilled syringes. After reconstitution, each approximately 0.5-mL dose of HIBERIX contains 10 mcg of purified capsular polysaccharide conjugated to approximately 25 mcg of tetanus toxoid, 12.6 mg of lactose, and ≤0.5 mcg of residual formaldehyde. HIBERIX does not contain a preservative. The stopper of the vial containing Lyophilized Antigen Component or Sterile Saline Diluent and the tip cap and rubber plunger stopper of the prefilled syringe containing Sterile Saline Diluent are not made with natural rubber latex.

Contraindications

Per the FDA, contraindications are conditions in a recipient that increases the risk for a serious adverse reaction. Product should not be administered when a patient has a listed contraindication.

ActHIB: Hypersensitivity Severe allergic reaction (e.g., anaphylaxis) after a previous dose of any H. influenzae type b or tetanus toxoid-containing vaccine or any component of the vaccine is a contraindication to administration of ActHIB vaccine

PedvaxHIB: Hypersensitivity to any component of the vaccine or the diluent. Persons who develop symptoms suggestive of hypersensitivity after an injection should not receive further injections of the vaccine.

Hiberix: Severe allergic reaction (e.g., anaphylaxis) after a previous dose of any H. influenzae type b- or tetanus toxoid-containing vaccine or any component of the vaccine is a contraindication to administration of HIBERIX.

Warnings and Precautions

Per the FDA, warnings are clinically significant adverse reactions or risks. According to the CDC, a precaution is a condition in a recipient that might increase the risk for a serious adverse reaction, might cause diagnostic confusion, or might compromise the effectiveness of the product. In general, a product should be deferred when a precaution is present.

ActHIB

Management of Acute Allergic Reactions: Epinephrine and other appropriate agents must be available should an acute anaphylactic reaction occur.

Guillain-Barré Syndrome: If Guillain-Barré syndrome has occurred within 6 weeks of receipt of a prior vaccine containing tetanus toxoid, the decision to give any tetanus toxoid-containing vaccine, including ActHIB vaccine, should be based on careful consideration of the potential benefits and possible risks.

Altered Immunocompetence: In immunosuppressed persons, including those receiving immunosuppressive therapy, the expected antibody responses may not be obtained.

Limitations of Vaccine Effectiveness: Vaccination with ActHIB vaccine may not protect 100% of individuals.

Tetanus Immunization: Immunization with ActHIB vaccine does not substitute for routine tetanus immunization.

Interference with Laboratory Tests: Urine antigen detection may not have a diagnostic value in suspected disease due to H. influenzae type b within 1 to 2 weeks after receipt of a H. influenzae type b-containing vaccine, including ActHIB.

Immunosuppressive Treatments: Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs, and corticosteroids (used in greater than physiologic doses) may reduce the immune response to ActHIB vaccine.

PedvaxHIB

As for any vaccine, adequate treatment provisions, including epinephrine, should be available for immediate use should an anaphylactoid reaction occur. Use caution when vaccinating latex-sensitive individuals since the vial stopper contains dry natural latex rubber that may cause allergic reactions.

Special care should be taken to ensure that the injection does not enter a blood vessel. It is important to use a separate sterile syringe and needle for each patient to prevent
transmission of hepatitis B or other infectious agents from one person to another.

As with other vaccines, Liquid PedvaxHIB may not induce protective antibody levels
immediately following vaccination. As reported with Haemophilus b Polysaccharide Vaccine and another Haemophilus b Conjugate Vaccine, cases of Hib disease may occur in the week after vaccination, prior to the onset of the protective effects of the vaccines. There is insufficient evidence that Liquid PedvaxHIB given immediately after exposure to
natural Haemophilus influenzae type b will prevent illness.

The decision to administer or delay vaccination because of current or recent febrile illness depends on the severity of symptoms and on the etiology of the disease. The Advisory Committee on Immunization Practices (ACIP) has recommended that vaccination should be delayed during the course of an acute febrile illness. All vaccines can be administered to persons with minor illnesses such as diarrhea, mild upper-respiratory infection with or without low-grade fever, or other low-grade febrile illness. Persons with moderate or severe febrile illness should be vaccinated as soon as they have recovered from the acute phase of the illness. If PedvaxHIB is used in persons with malignancies or those receiving immunosuppressive therapy or who are otherwise immunocompromised, the expected immune response may not be obtained.

Hiberix

Guillain-Barré Syndrome: If Guillain-Barré syndrome has occurred within 6 weeks of receipt of a prior vaccine containing tetanus toxoid, the decision to give any tetanus toxoid-containing vaccine, including HIBERIX, should be based on careful consideration of the potential benefits and possible risks.

Syncope: Syncope (fainting) can occur in association with administration of injectable vaccines, including HIBERIX. Syncope can be accompanied by transient neurological signs such as visual disturbance, paresthesia, and tonic-clonic limb movements. Procedures should be in place to avoid falling injury and to restore cerebral perfusion following syncope.

Apnea in Premature Infants: Apnea following intramuscular vaccination has been observed in some infants born prematurely. Decisions about when to administer an intramuscular vaccine, including HIBERIX, to infants born prematurely should be based on consideration of the individual infant’s medical status, and the potential benefits and possible risks of vaccination.

Preventing and Managing Allergic Vaccine Reactions: Prior to administration, the healthcare provider should review the patient’s immunization history for possible vaccine hypersensitivity. Epinephrine and other appropriate agents used for the control of immediate allergic reactions must be immediately available should an acute anaphylactic reaction occur.

Altered Immunocompetence: Safety and effectiveness of HIBERIX in immunosuppressed children have not been evaluated. If HIBERIX is administered to immunosuppressed children, including children receiving immunosuppressive therapy, the expected immune response may not be obtained.

Interference with Laboratory Tests: Urine antigen detection may not have a diagnostic value in suspected disease due to H. influenzae type b within 1 to 2 weeks after receipt of a H. influenzae type b-containing vaccine, including HIBERIX.

Tetanus Immunization: Immunization with HIBERIX does not substitute for routine tetanus immunization.

Immunosuppressive Therapies: Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs, and corticosteroids (used in greater than physiologic doses), may reduce the immune response to HIBERIX.

Manufacturer-Listed Adverse Reactions

Per the CDC, adverse reactions are an undesirable medical condition that has been demonstrated to be caused by a vaccine. Evidence for the causal relation is usually obtained through randomized clinical trials, controlled epidemiologic studies, isolation of the vaccine strain from the pathogenic site, or recurrence of the condition with repeated vaccination (i.e., rechallenge); synonyms include side effect and adverse effect.

ActHIB can  cause: Anaphylaxis, Urticaria (Hives), Angioedema (facial swelling), Convulsions, Extensive limb swelling, Peripheral edema, Pruritus (itchy skin), Rash.

PedvaxHIB can cause: Early onset Hib disease, Guillain-Barré syndrome, Lymphadenopathy, Febrile seizures, Sterile injection site abscess, Angioedema.

Hiberix can  cause: Extensive swelling, Injection site induration, Anaphylactic/Anaphylactoid reactions, Angioedema, Convulsions, Hypotonic-Hyporesponsive Episode, Somnolence (sleepiness), Syncope, Vasovagal responses to injection (fainting), Apnea, Rash/Uticaria (Hives).

Limitations of Vaccine Effectiveness

Vaccination with ActHIB vaccine may not protect 100% of individuals.

Specific Populations

Pregnancy

ActHIB is not approved for use in individuals 6 years of age and older. No human or animal data are available to assess vaccine-associated risks in pregnancy.

Pregnancy Category C: Animal reproduction studies have not been conducted with PedvaxHIB. Liquid PedvaxHIB is not recommended for use in individuals 6 years of age and older.

Breastfeeding

ActHIB is not approved for use in individuals 6 years of age and older. Human or animal data are not available to assess the impact of ActHIB on milk production, its presence in breast milk, or its effects on the breastfed infant.

Fertility

ActHIB/Liquid PedvaxHIB/HIBERIX vaccine has not been evaluated for its carcinogenic or mutagenic potential or impairment of male fertility.

Pediatric

Safety and effectiveness of ActHIB have not been established in infants below the age of 6 weeks and children and adolescents 6 years of age and older.

Safety and effectiveness in infants below the age of 2 months and in children 6 years of age
and older have not been established. In addition, Liquid PedvaxHIB should not be used in infants younger than 6 weeks of age because this will lead to a reduced anti-PRP response and may lead to immune tolerance (impaired ability to respond to subsequent exposure to the PRP antigen). Liquid PedvaxHIB is not recommended for use in individuals 6 years of age and older because they are generally not at risk of Hib disease.

Safety and effectiveness of HIBERIX in children younger than 6 weeks and in children aged 5 to 16 years have not been established.

Mechanism of Action

This is the specific biochemical interaction through which a drug or vaccine substance produces its pharmacological effect. This section also includes the minimum protective level designated for a certain disease.

ActHIB: Antibody titers to H. influenzae capsular polysaccharide (anti-PRP) of >1.0 mcg/mL following vaccination with unconjugated PRP vaccine correlated with long-term protection against invasive H. influenzae type b disease in children older than 24 months of age. Although the relevance of this threshold to clinical protection after immunization with conjugate vaccines is not known, particularly in light of the induced, immunologic memory, this level continues to be considered as indicative of long-term protection.

PedvaxHIB: Nonconjugated PRP vaccines are capable of stimulating B-lymphocytes to produce antibody without the help of T-lymphocytes (T-independent). The responses to many other antigens are augmented by helper T-lymphocytes (T-dependent). PedvaxHIB is a PRP-conjugate vaccine in which the PRP is covalently bound to the OMPC carrier producing an antigen which is postulated to convert the T-independent antigen (PRP alone) into a T-dependent antigen resulting in both an enhanced antibody response and immunologic memory.

Hiberix: Specific levels of antibodies to polyribosyl-ribitol-phosphate (anti-PRP) have been shown to correlate with protection against invasive disease due to H. influenzae type b. Based on data from passive antibody studies and a clinical efficacy study with unconjugated Haemophilus b polysaccharide vaccine, an anti-PRP concentration of 0.15 mcg/mL has been accepted as a minimal protective level. Data from an efficacy study with unconjugated Haemophilus b polysaccharide vaccine indicate that an anti-PRP concentration of ≥1.0 mcg/mL predicts protection through at least a 1-year period. These antibody levels have been used to evaluate the effectiveness of Haemophilus b Conjugate Vaccines, including HIBERIX.

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