)‫בטיחות‬
)‫מידע בטיחות‬
‫החמרה (( מידע‬
‫על החמרה‬
‫הודעה על‬
‫הודעה‬
________0262.60202_______________ ‫תאריך‬
________ Infanrix HEXA __‫שם תכשיר באנגלית‬
_____133-20-30676 ________‫מספר רישום‬
_____GlaxoSmithKline (ISRAEL) Ltd. __‫שם בעל הרישום‬
‫השינויים המבוקשים על רקע צהוב‬
‫לרופא‬
‫בעלון לרופא‬
‫בעלון‬
‫ים‬/‫ים המבוקש‬/‫פרטים על השינוי‬
‫טקסט חדש‬
‫טקסט נוכחי‬
‫פרק בעלון‬
Infanrix hexa should not be administered
to subjects with known hypersensitivity
after
previous
administration
of
diphtheria, tetanus, pertussis, Hepatitis B,
polio or Hib vaccines or to the active
substances or to any of the excipients or
neomycin and polymixin.
Infanrix hexa should not be administered to
subjects with known hypersensitivity
after previous administration of diphtheria,
Containdications
tetanus, pertussis, Hepatitis B,
polio or Hib vaccines or to any component
of the vaccine (see 6.1)
4.4 Special warnings and special
precautions for use
4.4 Special warnings and special
precautions for use
Persistent, inconsolable crying
lasting  3 hours, occurring within
48 hours of vaccination.
Convulsions with or without fever,
occurring within 3 days of
vaccination.
There may be circumstances, such as a
high incidence of pertussis, when the
potential benefits outweigh possible risks.
Persistent, inconsolable crying
lasting  3 hours, occurring within 48
hours of vaccination.
Convulsions with or without fever,
occurring within 3 days of
vaccination.
There may be circumstances, such as a
high incidence of pertussis, when the
potential benefits outweigh possible risks.
As for any vaccination, the risk-benefit of
immunising with Infanrix hexa or
deferring this vaccination should be
weighed carefully in an infant or in a child
suffering from a new onset or progression
of a severe neurological disorder.
As with all injectable vaccines, appropriate
medical treatment and supervision should
always be readily available in case of a rare Warnings and
Precaution
anaphylactic event following the
administration of the vaccine.
As with all injectable vaccines,
appropriate medical treatment and
supervision should always be readily
available in case of a rare anaphylactic
event following the administration of the
vaccine.
Infanrix hexa should under no
circumstances be administered
intravascularly or intradermally.
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Infanrix hexa should under no
circumstances be administered
intravascularly.
Infanrix hexa contains traces of neomycin
and polymyxin. The vaccine should be
used with caution in patients with known
hypersensitivity to one of these antibiotics.
The hepatitis B component of the vaccine
will not prevent infection caused by other
agents such as hepatitis A, hepatitis C and
hepatitis E viruses and other pathogens
known to infect the liver.
Page 1 of 6
Infanrix hexa will not prevent disease
caused by pathogens other than
Corynebacterium diphtheriae,
Clostridium tetani, Bordetella pertussis,
hepatitis B virus, poliovirus or
Haemophilus influenzae type b. However,
it can be expected that hepatitis D will be
prevented by immunisation as hepatitis D
(caused by the delta agent) does not occur
in the absence of hepatitis B infection.
As with any vaccine, a protective immune
response may not be elicited in all
vaccinees (see section 5.1).
A history of febrile convulsions requires
special attention. A family history of
convulsions or a family history of Sudden
Infant Death Syndrome (SIDS) does not
constitute a contra-indication. Vaccines
with a history of febrile convulsions
should be closely followed up as such
adverse events may occur within 2 to 3
days post vaccination.
The Hib component of the vaccine does not
protect against diseases due to other
capsular serotypes than type b of
Haemophilus influenzae or against
meningitis caused by other organisms.
A history of febrile convulsions requires
special attention. A family history of
convulsions or a family history of Sudden
Infant Death Syndrome (SIDS) does not
constitute a contra-indication.
HIV infection is not considered as a contraindication. The expected immunological
response may not be obtained after
vaccination of immunosuppressed patients.
Excretion of capsular polysaccharide
antigen in the urine has been described
following receipt of Hib vaccines, and
therefore antigen detection may not have a
diagnostic value in suspected Hib disease
within 1-2 weeks of vaccination.
HIV infection is not considered as a
contra-indication. The expected
immunological response may not be
obtained after vaccination of
immunosuppressed patients.
Since the Hib capsular polysaccharide
antigen is excreted in the urine, a positive
urine test can be observed within 1-2
weeks following vaccination. Other tests
should be performed in order to confirm
Hib infection during this period.
Antipyretic treatment should be initiated
according to local treatment guidelines.
Limited data in 169 premature infants
indicate that Infanrix hexa can be given to
premature children. However, a lower
immune response may be observed and
the level of clinical protection remains
unknown.
The potential risk of apnoea and the need
for respiratory monitoring for 48-72h
should be considered when administering
the primary immunisation series to very
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premature infants (born ≤ 28 weeks of
gestation) and particularly for those with a
previous history of respiratory immaturity.
As the benefit of the vaccination is high in
this group of infants, vaccination should
not be withheld or delayed.
Clinical trials on primary vaccination:

Clinical trials:
The safety profile presented below is
based on data from more than 16,000
subjects.
As has been observed for DTPa and
DTPa-containing combinations, an
increase in local reactogenicity and fever
was reported after booster vaccination
with Infanrix hexa with respect to the
primary course.
Tabulated summary of adverse reactions
(clinical trials):
Within each frequency grouping,
undesirable effects are presented in order
of decreasing seriousness.
Frequencies per dose are defined as
follows:
Very common:
Common:
Uncommon:
Rare:
Very rare:
(≥1/10)
(≥1/100 to <1/10)
(≥1/1,000 to <1/100)
(≥1/10,000 to <1/1,000)
(<1/10,000)
Nervous system disorders:
Uncommon: somnolence
Very rare: convulsions (with or without
fever)
Respiratory, thoracic and mediastinal
disorders
Uncommon: cough
Gastrointestinal disorders:
Common: diarrhoea, vomiting
Skin and subcutaneous tissue disorders
Rare: rash
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Clinical trials involved the administration
of over 13,500 doses of Infanrix hexa to
4,590 healthy infants from 6 weeks of age
as primary vaccination.
In two large randomised controlled studies,
infants were enrolled to receive a three
dose primary series of Infanrix hexa
(N=2121) or separate injections of
commercially-available DTPa-IPV/Hib and
hepatitis B (HBV) vaccines given
simultaneously at separate sites (N=708).
In these trials, Infanrix hexa was shown to
be as safe as the licensed vaccines. For
both groups, solicited local reactions were
reported in 54 to 70% of subjects. In the
study where measurement of temperature
was specifically requested, fever of
>39.5°C was reported for 1.4% of infants
administered Infanrix hexa; fever of >40°C
was reported for 0.2% (values for infants Undesirable
administered licensed vaccines were effects
respectively 1.6% and 0%).
No increase in the incidence or severity of
these undesirable events was seen with
subsequent doses of the primary
vaccination series.
In a smaller randomised comparative trial,
severe undesirable events after Infanrix
hexa were reported with a lower frequency
as compared to a commercial diphtheria,
tetanus, pertussis (DTP) whole cell
vaccine.

Clinical
trials
on booster
vaccination:
A total of 2,358 infants 12 to 24 months of
age received a booster dose of Infanrix
hexa; 1,220 of these subjects received
Infanrix hexa for both the primary and
booster doses (for a total of 4 doses of
vaccine).
Page 3 of 6
Very rare: dermatitis
As has been observed for DTPa and DTPacontaining combinations, an increase in
reactogenicity was reported after booster
vaccination with Infanrix hexa with respect
General disorders and administration site to the primary course; however, the
incidence of symptoms graded as severe
conditions:
was low.
Very common: fever  38°C, local
Oedematous swelling, occasionally leading
swelling at the injection site (≤ 50 mm),
to an increased circumference of the
fatigue, pain, redness
injected limb, has been observed in clinical
Common: fever >39.5°C, injection site
trials evaluating booster doses of Infanrix
reactions, including induration, local
swelling at the injection site (> 50 mm)*, hexa at an incidence of 2.3% when
solicited.
injection site reaction
All these reactions resolved without
Uncommon: diffuse swelling of the
sequelae.
injected limb, sometimes involving the
adjacent joint*
Irrespective of the vaccine used for the
primary course, fever >39.5°C was
Psychiatric disorders:
reported for overall 3.3% of infants
Very common: crying abnormal,
administered Infanrix hexa as a booster
irritability, restlessness
dose. The incidence of fever >39.5°C in a
Common: nervousness
control group of infants boosted with
commercially-available DTPa-IPV/Hib +

Post marketing surveillance:
HBV vaccines was 2.9%. The incidences
of fever > 40°C were respectively 0.9% for
Blood and lymphatic system disorders
Infanrix hexa and 0.8% for the licensed
Lymphadenopathy
vaccines.
Nervous system disorders:
Collapse or shock-like state (hypotonic- In a randomised comparative trial, infants
primed with Infanrix hexa were boosted
hyporesponsiveness episode)
with the same vaccine (N = 543) or
received a booster dose with commercially
Respiratory, thoracic and mediastinal
available DTPa-IPV/Hib (with or without
disorders:
HBV administered separately at a different
Apnoea [see section 4.4 for apnoea in
site) (N = 331). The incidences of the
very premature infants (≤ 28 weeks of
solicited general and local symptoms
gestation)]
following the booster dose were similar in
both groups. Fever of >39.5°C was
Skin and subcutaneous tissue disorders
reported for 3.5% of infants administered
Angioedema
Infanrix hexa; fever of >40°C was reported
General disorders and administration site for 0.7% (values for infants administered
licensed vaccines were respectively 3.6%
conditions:
and 0.9%).
Swelling of the entire injected limb*,
extensive swelling reactions, injection site

Post marketing surveillance:
mass, injection site vesicles
Metabolism and nutrition disorders
Very common: appetite lost
Immune system disorders
Anaphylactic reactions, anaphylactoid
reactions (including urticaria), allergic
reactions (including pruritus)
During post marketing surveillance, other
reactions have been reported in temporal
association with Infanrix hexa. None of the
reactions were reported with a frequency
higher than 0.01%.
* Children primed with acellular pertussis
vaccines are more likely to experience
swelling reactions after booster

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Tabulated summary of undesirable
effects:
Page 4 of 6
administration in comparison with
children primed with whole cell vaccines. Undesirable effects reported in clinical
These reactions resolve over an average of trials (following primary immunisation or
booster dose) or reported during post
4 days.
marketing surveillance are listed here

Experience with hepatitis B vaccine: below per system organ class. For those
symptoms reported both during clinical
trials and during PMS, invariably the
In extremely rare cases, paralysis,
highest frequencies were under controlled
neuropathy, Guillain-Barré syndrome,
clinical trial conditions.
encephalopathy, encephalitis and
meningitis have been reported. The causal
Frequencies are defined as follows:
relationship to the vaccine has not been
established.
 10%
Thrombocytopenia has been reported with Very common:
Common:
 1% and < 10%
hepatitis B vaccines.
Uncommon:  0.1% and < 1%
Rare:
 0.01% and < 0.1%
Very rare:
< 0.01%
Application site
very common: pain, redness, swelling,
peripheral oedema
common: injection site reaction
very rare: injection site mass*, extensive
swelling reaction*
Body as a whole
very common: fever 38C
common: abnormal crying, restlessness
uncommon: fatigue
very rare: allergic reactions (including
rash* and angiooedema), anaphylactoid
reactions (including urticaria)*
Gastro-intestinal system
very common: loss of appetite
common: diarrhoea, enteritis, gastroenteritis
uncommon: abdominal pain, vomiting,
constipation
Neurological disorders
very rare: convulsions (with or without
fever)*, collapse or shock-like state
(hypotonic-hyporesponsiveness episode)*
Psychiatric
very common: drowsiness, irritability
uncommon: somnolence
Resistance mechanism
common: viral infection, moniliasis, otitis
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Page 5 of 6
media
uncommon: infection
Respiratory system
common: upper respiratory tract infection,
bronchitis, coughing, rhinitis, pharynigitis
uncommon: bronchospasm, laryngitis,
stridor
Skin and appendages
common: rash erythematous, dermatitis
uncommon: eczema
very rare: pruritus*
Vision
common: conjunctivitis
* Reported only during post-marketing
surveillance

Experience with hepatitis B vaccine:
Nearly 100 million doses of Engerix
B
10
µg,
GlaxoSmithKline
Biologicals’ hepatitis B vaccine,
have been distributed for infants < 2
years old. In extremely rare cases,
paralysis, neuropathy, Guillain-Barré
syndrome,
encephalopathy,
encephalitis and meningitis have
been reported.
The causal
relationship to the vaccine has not
been established.
Thrombocytopenia has been reported
very rarely with hepatitis B vaccines.
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