Hiberix

MIMS Abbreviated Prescribing Information
haemophilus B conjugate vaccine
SmithKline Beecham Pharmaceuticals
Section: 10(a) Vaccines - Immunology
Pregnancy Category: B2
Permitted in sport

Use: Active immunisation against Haemophilus influenzae type b in children 2
months-5 years
Contraindications: Acute severe febrile illness; IVI
Precautions: Immunosuppression; thrombocytopenia, bleeding disorders (SCI
recommended); pregnancy, lactation
Adverse Reactions: Local erythema; fever; loss of appetite; GI upset;
restlessness; unusual crying; others, see MIMS Annual or Supplement

Hiberix (Injection) Rx
Haemophilus influenzae type b purified capsular polysaccharide bound to
tetanus toxiod 30 mcg; NaCl, lactose; prefilled syringe
Pack 10 mcg/0.5 mL [1]
Dose 0.5 mL IMI at 2, 4 and 6 months; booster dose at 18 months. 12 months:
anterolateral thigh; > 12 months: deltoid region or anterolateral thigh
MIMS Annual 1998, Suppl. No. 2, p. 149


HiberixMIMS Full Prescribing Information
SmithKline Beecham International - Pharmaceuticals
MIMS revision date: 1/08/1998
 Composition Active. Haemophilus influenzae type b capsular polysaccharide.
Inactive. Tetanus toxoid.
Reconstituted vaccine: lactose, sodium chloride, water for injection.
 Description Hiberix is a noninfectious vaccine containing purified
polyribosylribitol phosphate capsular polysaccharide (PRP) of Haemophilus
influenzae type b covalently bound to tetanus toxoid.
Hiberix is supplied as a white lyophilised pellet for reconstitution with
sterile saline solution 0.9%. Each 0.5 mL dose contains 10 microgram of
purified capsular polysaccharide of Hib covalently bound to approximately 30
microgram of tetanus toxoid.
The Hiberix Hib polysaccharide is extracted from a culture of Haemophilus
influenzae type b strain 20,752. After activation with cyanogen bromide and
derivatisation with an adipic hydrazide spacer, the Hib polysaccharide is
coupled to tetanus toxoid via carbodiimide condensation. After purification,
the Hib conjugate is lyophilised in the presence of a lactose stabiliser.
Hiberix meets the World Health Organization requirements for the manufacture
of biological substances and Hib conjugate vaccines.
 Actions Pharmacology. The protective efficacy of Hiberix has not been
studied in field trials. Hiberix has however been shown to induce anti-PRP
antibodies above the level known to be protective against invasive disease
due to Haemophilus influenzae type b. An anti-PRP antibody titre greater
than or equal to 0.15 microgram/mL correlates with immediate protection
against Hib infection and greater than or equal to 1.0 microgram/mL
correlates with long term protection.
The immunogenicity of Hiberix has been investigated in clinical studies
involving over 300 infants (over two months of age) using a three dose
primary vaccination schedule. Protective anti-PRP antibody titres were
demonstrated in 95 to 100% (greater than or equal to 0.15 microgram/mL) and
87 to 90% (greater than or equal to 1.0 microgram/mL) of infants one month
after completion of the primary schedule.
Clinical trials have demonstrated the immunogenicity of Hiberix is unaltered
by administration of different primary vaccination schedules. One month
after completion of a two, four, six month or three, four, five month
primary schedule, over 95% of infants in each group obtained anti-PRP titres
greater than or equal to 0.15 microgram/mL.
A boosting dose of Hiberix was given either separately (n = 19) or in
combination with DTPa (n = 56) to infants aged between 15 and 18 months who
had previously received primary immunisation with Hiberix and DTPa given at
separate sites. One month after administration of this booster dose, an
anamnestic response was observed with anti-PRP antibody titres of greater
than or equal to 0.15 microgram/mL and greater than or equal to 1.0
microgram/mL being obtained in 100% and greater than 94% of infants
respectively.
 Indications Active immunisation against Haemophilus influenzae type b
infection in children aged from two months to five years.
 

Contraindications
Known hypersensitivity to any component of the vaccine,
or to subjects having shown signs of hypersensitivity after previous
administration of Hib vaccines.
As for any vaccine, Hiberix should not be administered to subjects suffering
from acute severe febrile illness. However, the presence of minor infection
does not contraindicate vaccination.

 Precautions
Hiberix should never be administered intravenously.
It is good clinical practice that any vaccination be preceded by a review of
medical history (especially with regard to previous vaccinations and
possible adverse events) and a clinical examination.
As with all injectable vaccines, appropriate medical treatment and
supervision should always be readily available in case of anaphylactic
reactions following the administration of the vaccine.
Native populations (native Alaskans, native American Indians) with a high
incidence of Haemophilus influenzae type b disease have shown a reduced
antibody response to conjugated Haemophilus influenzae type b vaccines. The
immunogenicity of Hiberix has not been studied in the Australian Aboriginal
population and the possibility of a lower antibody response than that seen
in clinical studies should be borne in mind.
Human immunodeficiency virus (HIV) infection is not a contraindication to
vaccination. However an adequate antibody response may not be obtained in
patients with an immunodeficiency disorder or in patients receiving
immunosuppressive therapy (see Interactions).
Hiberix should be administered subcutaneously in patients with
thrombocytopenia or bleeding disorders (e.g. haemophiliacs) since bleeding
after intramuscular injection may occur in these patients (see Dosage and
Administration).
Urinary excretion of the capsular polysaccharide antigen has been reported
following Hib vaccination. Therefore antigen detection within one to two
weeks of vaccination may not be of diagnostic value in suspected Hib
disease.
An immune response to the tetanus toxoid component may occur following
Hiberix vaccination, however this does not substitute for routine tetanus
vaccination.
Hiberix will not protect against diseases caused by other types of
Haemophilus influenzae, or meningitis caused by other organisms.
Use in pregnancy. (Category B2)
The effect of Hiberix on fetal development is unknown. Therefore,
vaccination of pregnant women cannot be recommended.
Use in lactation. The effect of Hiberix in lactation has not been assessed,
as the vaccine is not intended for adult use.
 

Adverse Reactions
Clinical trial data. In controlled clinical trials, signs
and symptoms were actively monitored for the first four to eight days
following Hiberix vaccination and recorded on diary cards. The vaccine was
generally well tolerated and most local adverse events were considered to be
mild and transient. The incidence of local adverse events did not increase
with subsequent vaccine doses. As Hiberix was coadministered with either a
diphtheria-tetanus-acellular pertussis vaccine or a diphtheria-tetanus-whole
cell pertussis vaccine, systemic adverse events cannot be specifically
attributed to either vaccine. Most systemic events were mild and resolved
spontaneously.
Events are listed within body systems and categorised by frequency according
to the following definitions. Very common events reported at a frequency of
greater or equal to 1/10 patients; common events reported at a frequency of
less than 1/10 but greater or equal to 1/100 patients; uncommon events
reported at a frequency of less than 1/100 but greater or equal to 1/1,000
patients; rare events reported at a frequency of less than 1/1,000 patients.
Local reactions. Very common: redness (> 2 cm). Common: pain, swelling (> 2
cm).
Body as a whole. Very common: fever. Common: viral infection. Uncommon:
asthenia, fatigue, injury.
Dermatological. Common: erythematous rash, injection site reaction.
Uncommon: sweating increased, purpura.
Gastrointestinal. Very common: loss of appetite, vomiting, diarrhoea.
Common: gastroenteritis. Uncommon: abdominal pain.
Musculoskeletal. Uncommon: spastic paralysis.
Nervous system. Very common: restlessness, unusual crying. Common:
nervousness, somnolence. Uncommon: insomnia, emotional lability.
Respiratory. Common: rhinitis, coughing, respiratory disorder, upper
respiratory tract infection, bronchitis.
Special senses. Common: conjunctivitis, otitis media.
No serious adverse event was considered by investigators to be related to
Hiberix alone. In two serious adverse events considered related or possibly
related to vaccination, Hiberix was administered simultaneously with an
acellular DTP vaccine.
Postmarketing data. Postmarketing experience with Hiberix is currently
limited.
 Interactions Hiberix may be administered either simultaneously, or at any
time before or after different live or inactivated vaccines. However,
different injectable vaccines administered concurrently should always be
given in separate sites using separate syringes.
Clinical trials have shown concomitant administration of Hiberix and the
diphtheria-tetanus-pertussis (acellular or whole cell) combination vaccines
does not affect the immunogenicity of either vaccine, provided the vaccines
are given at separate sites and not mixed prior to administration.
As with other vaccines, it may be expected patients receiving
immunosuppressive therapy (e.g. high dose steroids or cyclosporin) or
patients with an immunodeficiency may not achieve an adequate immune
response (see Precautions.)
Hiberix must not be mixed with other vaccines in the same syringe.
 Dosage and Administration Hiberix is supplied as a white lyophilised pellet
for reconstitution with sterile 0.9% saline diluent. Hiberix is prepared by
adding the entire contents of the diluent container to the vial containing
the Hib vaccine pellet. The reconstituted solution must be shaken well
before use, and must not be injected prior to complete dissolution of the
Hib pellet. All parenteral drug and vaccine products should be inspected
visually prior to administration for foreign particulate matter and/or
discolouration. If either are observed, discard the diluent or reconstituted
vaccine. After reconstitution Hiberix should be used promptly or kept in a
refrigerator. If it is not used within 24 hours, it should be discarded
because of the risk of contamination.
The recommended dose is 0.5 mL.
Hiberix vaccine must be administered by intramuscular injection. In infants
and children under 12 months of age it is preferable to inject the vaccine
in the anterolateral thigh because of the small size of their deltoid
muscle. In children over 12 months of age the injection can alternatively be
given in the deltoid region. The vaccine should be administered
subcutaneously in patients with thrombocytopenia or bleeding tendencies,
e.g. haemophiliacs (see Precautions).
Note. Hiberix must not be given intravenously.
The recommended primary vaccination course consists of three doses at two,
four and six months of age. A booster dose is recommended at 18 months of
age to ensure long term protection.
This is consistent with the National Health and Medical Research Council
recommendations for Haemophilus influenzae type b vaccination.
 Presentation Prefilled syringe (white pellet with clear, colourless saline
0.9% diluent in glass vial): 1's.
 Storage Store between 2 deg. C to 8 deg. C. Protect from light.
Lyophilised Hib vaccine is not affected by freezing.
Shelf life: 3 years.
The sterile 0.9% saline diluent may be refrigerated or stored at ambient
temperature, but must not be frozen.
 Poison Schedule S4.
 Date of TGA approval or last amendment 17/02/1998

Source AVN