‫לרופא‬
‫בעלון לרופא‬
‫בטיחות) בעלון‬
)‫מידע בטיחות‬
‫החמרה (( מידע‬
‫על החמרה‬
‫הודעה על‬
‫הודעה‬
__________________04.12.2011_____ ‫תאריך‬
Adacel Polio ______‫שם תכשיר באנגלית‬
_____________142603193800_______‫מספר רישום‬
‫שם בעל הרישום___מדיצ'י מדיקל בע"מ‬
‫ים‬/‫ים המבוקש‬/‫פרטים על השינוי‬
‫טקסט חדש‬
‫טקסט נוכחי‬
ADACEL-POLIO is indicated for active immunization against
diphtheria, tetanus, pertussis and poliomyelitis in persons from the
age of three years as a booster following primary immunization.
ADACEL-POLIO is not intended for primary immunization.
ADACEL-POLIO is not to be used for the treatment of disease
caused by B. pertussis, C. diphtheriae or C. tetani or Poliomyelitis
infections.
Persons who have had tetanus, diphtheria or pertussis should still be
immunized since these clinical infections do not always confer
immunity. Human Immunodeficiency Virus (HIV)-infected persons,
both asymptomatic and symptomatic, should be immunized against
tetanus, diphtheria and pertussis according to standard schedules
ADACEL-POLIO is indicated for active immunization
against diphtheria, tetanus, pertussis and poliomyelitis in
persons from the age of three years as a booster following
primary immunization.
ADACEL-POLIO is not intended for primary
immunization.
ADACEL-POLIO is not to be used for the treatment of
disease caused by B. pertussis, C. diphtheriae or C. tetani
or Poliomyelitis infections.
The use of ADACEL-POLIO should be determined on the basis of
official recommendations.
Recommended Dose
ADACEL®-POLIO should be administered as a single injection of 1
dose (0.5 mL) by the intramuscular route. The preferred site is the
deltoid muscle.
Fractional doses (doses <0.5 mL) should not be given. The effect of
fractional doses on safety and efficacy has not been determined.
Health-care professionals should refer to the National Advisory
Committee on Immunization (NACI) guidelines for tetanus
prophylaxis in routine wound management shown in Error!
Reference source not found.
A thorough attempt must be made to determine whether a patient has
completed primary immunization. Persons who have completed
primary immunization against tetanus and who sustain wounds that
are minor and uncontaminated, should receive a booster dose of a
tetanus toxoid-containing preparation if they have not received
tetanus toxoid within the preceding 10 years.
For tetanus-prone wounds (e.g., wounds contaminated with dirt,
feces, soil and saliva, puncture wounds, avulsions and wounds
resulting from missiles, crushing, burns or frostbite), a booster is
appropriate if the patient has not received a tetanus toxoid-containing
preparation within the preceding 5 years.
For adults who have not previously received a dose of acellular
pertussis vaccine, a single tetanus-diphtheria (Td) booster dose
should be replaced by a combined tetanus-diphtheria-acellular
pertussis vaccine (Tdap).
Method of administration
A single injection of one dose (0.5 mL) of ADACEL-POLIO should
be administered by intramuscular route. Administration should
preferably be performed in the deltoid muscle.
Inspect for extraneous particulate matter and/or discolouration before
use. If these conditions exist, the product should be discarded.
‫פרק בעלון‬
Indications
The use of ADACEL-POLIO should be determined on the
basis of official recommendations.
Posology
The same dosage, a single 0.5 mL intramuscular dose,
applies to all age groups. ADACEL-POLIO can be given
starting from the age of 3. The use of ADACEL-POLIO
in children aged 3 to 5 years is based upon studies in
which ADACEL-POLIO was given as the fourth dose
(first booster) of diphtheria, tetanus, pertussis and
poliomyelitis vaccines.
ADACEL-POLIO should be administered in accordance
with official recommendations and/or local practice
regarding the use of vaccines that provide low-dose
diphtheria toxoid plus tetanus toxoid in combination with
pertussis and poliomyelitis antigens.
Subjects who have not received a primary immunization
or whose primary immunization was incomplete with
respect to diphtheria and tetanus toxoids or polio antigens
should not be vaccinated with ADACEL-POLIO.
ADACEL-POLIO can be used in subjects who have not
been vaccinated or whose immunization status is
incomplete with respect to a previous pertussis
vaccination.
However, a booster response will only be elicited in
individuals who have been previously primed by
vaccination or by natural infection.
Booster injections for diphtheria and tetanus should be
given at intervals consistent with official
recommendations (generally 10 years). It is not necessary
to repeat primary vaccination, should the officially
recommended inter-booster interval be exceeded.
There are currently no data upon which to base a
recommendation for the optimal interval for administering
booster doses with ADACEL-POLIO to maintain
antibody levels against pertussis. There are no data on the
duration of protection against pertussis following
vaccination with ADACEL-POLIO.
ADACEL-POLIO has not been studied in subjects with
tetanus-prone injuries and should not be used in this
specific cases.
Method of administration
A single injection of one dose (0.5 mL) of ADACEL-
Posology and
method of
administration
Shake the vial or syringe well until a uniform, cloudy, suspension
results. When administering a dose from a stoppered vial, do not
remove either the stopper or the metal seal holding it in place. Use a
separate sterile needle and syringe, or a sterile disposable unit for
each individual patient to prevent disease transmission. Needles
should not be recapped but should be disposed of according to
biohazard waste guidelines.
POLIO should be administered by intramuscular route.
Administration should preferably be performed in the
deltoid muscle. ADACEL-POLIO should not be
administered into the buttock area.
Do not inject by intravascular route.
The subcutaneous route should not be used (for exception,
see section 4.4).
Before injection, the skin over the site to be injected should be
cleansed with a suitable germicide.
Hypersensitivity to the active substances, to any of the excipients or
any residual component carried over from manufacture
(formaldehyde, gluteraldehyde, streptomycin, neomycin and
polymyxin B).
■ Anaphylactic or other allergic reactions to a previous dose of a
vaccine containing diphtheria or tetanus toxoids, poliomyelitis
viruses or pertussis (acellular or whole cell).
■ Evolving encephalopathy: ADACEL-POLIO should not be
administered to subjects who experienced an encephalopathy of
unknown origin within 7 days of previous immunization with a
pertussis-containing vaccine, or to subjects who have experienced
other neurological complications following previous immunization
with any of the antigens in ADACEL-POLIO.
■ Hypersensitivity to the active substances, to any of the
excipients or any residual component carried over from
manufacture (formaldehyde, gluteraldehyde,
streptomycin, neomycin and polymyxin B).
■ Anaphylactic or other allergic reactions to a previous
dose of a vaccine containing diphtheria or tetanus toxoids,
poliomyelitis viruses or pertussis (acellular or whole cell).
■ Evolving encephalopathy: ADACEL-POLIO should not
be administered to subjects who experienced an
encephalopathy of unknown origin within 7 days of
previous immunization with a pertussis-containing
vaccine, or to subjects who have experienced other
neurological complications following previous
immunization with any of the antigens in ADACELPOLIO.
Vaccination should be deferred in the presence of any
acute illness, particularly febrile illness. A minor afebrile
illness such as mild upper respiratory infection does not
usually entail vaccination postpone.
ADACEL-POLIO should not be administered as primary
immunization or as boosters in children less than 3 years
of age.
The administration of ADACEL-POLIO, should be
preceded by asking the vaccinated subject's
parents/guardians about his/her personal and family
history his/her recent health status, including vaccination
The rates and severity of adverse events in recipients of tetanus
history, current health status and any undesirable effects
toxoid are influenced by the number of prior doses and level of prefollowing previous vaccinations.
existing antitoxins.
The rates and severity of adverse events in recipients of
As with any vaccine, ADACEL®-POLIO may not protect 100% of
tetanus toxoid are influenced by the number of prior doses
vaccinated persons.
and level of pre-existing antitoxins.
Febrile and Acute Disease: Vaccination should be postponed in
As with any vaccine, ADACEL®-POLIO may not protect
cases of an acute or febrile disease. However, a disease with low100% of vaccinated persons.
grade fever should not usually be a reason to postpone vaccination.
If Guillain-Barré syndrome has occurred of prior vaccine
Neurologic: ADACEL®-POLIO should not be administered to individuals
containing
with
tetanus toxoid, the decision to give
progressive neurological disorder, uncontrolled epilepsy, or progressive ADACEL®-POLIO or any vaccine containing tetanus
encephalopathy until a treatment regimen has been established and the condition
toxoid should
has be based on careful consideration of the
stabilized. A review by the US Institute of Medicine (IOM) found evidence
potential
for a benefits and possible risks such as whether the
causal relation between tetanus toxoid and both brachial neuritis and Guillain-Barré
primary immunization schedule is complete or not.
syndrome. If Guillain-Barré syndrome has occurred within 6 weeks of receipt
The decision
of
to administer the Adacel-Polio vaccine
prior vaccine containing tetanus toxoid, the decision to give ADACEL®-POLIO
should be
or taken with care in people who have already
any vaccine containing tetanus toxoid should be based on careful consideration
experienced
of
serious or severe reaction within 48 hours of
the potential benefits and possible risks
a previous injection of a vaccine containing the same
Immune The possibility of allergic reactions in persons sensitive to components
substances.
of
the vaccine should be evaluated. Hypersensitivity reactions may occur following the
use of ADACEL®-POLIO even in persons with no prior history of hypersensitivity
As with all injectable vaccines, appropriate medical
to the product components.
treatment should be readily available and supervision
As with all other products, epinephrine hydrochloride solution
provided in the event of rare anaphylactic reaction
(1:1,000) and other appropriate agents should be available for
following the administration of the vaccine.
immediate use in case an anaphylactic or acute hypersensitivity
reaction occurs. Health-care providers should be familiar with
current recommendations for the initial management of anaphylaxis
As with all other products, appropriate agents should be
in non-hospital settings, including proper airway management.
available for immediate use in case an anaphylactic or
Immunocompromised persons (whether from disease or treatment)
acute hypersensitivity reaction occurs.
may not achieve the expected immune response. If possible,
Immunocompromised persons (whether from disease or
consideration should be given to delaying vaccination until after the
treatment) may not achieve the expected immune
completion of any immunosuppressive treatment. Nevertheless,
response. If possible, consideration should be given to
vaccination of persons with chronic immunodeficiency, such as HIV
delaying vaccination until after the completion of any
infection, is recommended even if the immune response might be
immunosuppressive treatment. Nevertheless, vaccination
Contraindications
General
The administration of ADACEL-POLIO, should be preceded by
asking the vaccinated subject's parents/guardians about his/her
personal and family history his/her recent health status, including
vaccination history, current health status and any undesirable effects
following previous vaccinations.
Special warnings and
precautions for use
limited.
Administration Route Related Precautions Do not administer by
the intravascular route ensure that the needle does not penetrate a
blood vessel. Intradermal or subcutaneous routes of administration
are not to be utilized. ADACEL®-POLIO should not be administered
into the buttocks. Hematologic
Because any intramuscular injection can cause an injection site
hematoma in persons with any bleeding disorders, such as
haemophilia or thrombocytopenia, or in persons on anticoagulant
therapy, intramuscular injections with ADACEL®-POLIO should not
be administered to such persons unless the potential benefits
outweigh the risk of administration. If the decision is made to
administer any product by intramuscular injection to such persons, it
should be given with caution, with steps taken to avoid the risk of
hematoma formation following injection.
of persons with chronic immunodeficiency, such as HIV
infection, is recommended even if the immune response
might be limited.
Do not administer by the intravascular route. Once the
needle is inserted, aspirate in order to make sure the
needle has not penetrated a blood vessel.
Fractional doses (doses <0.5 mL) should not be given.
The effect of fractional doses on the frequency of serious
adverse events and on efficacy have not been determined.
Local recommendations should be followed with respect
to time interval before injection of a booster dose of
ADACEL-POLIO. However, in order to minimize the
risk of adverse reactions, a time interval of at least five
years is recommended between a booster dose of
ADACEL-POLIO and previous booster doses of vaccines
containing diphtheria and tetanus valences (DT, Td).
Because any intramuscular injection can cause an
injection site hematoma in persons with any bleeding
disorders, or in persons on anticoagulant therapy. In these
situations administration of ADACEL-POLIO by deep
subcutaneous injection may be considered, even if there is
an increased risk of local reactions.
If the decision is made to administer any product by
intramuscular injection to such persons, it should be given
with caution
As with all adsorbed vaccines, particularly if administered
into the superficial layers of the subcutaneous tissue, a
persistent nodule at the site of injection may occur.
Vaccination is usually justified for infants whose primary
immunization schedules are incomplete (i.e., less than
three doses administered).
Supportive data from a study conducted with ADACEL® suggests
that ADACEL®-POLIO may be used concomitantly with trivalent
influenza vaccine. ADACEL®-POLIO has been safely administered
concomitantly with measles-mumps-rubella vaccine in noncontrolled clinical studies in children 3 to 5 years of age. Data are not
available on concomitant use of ADACEL®-POLIO and varicella
vaccine.
Administering the most widely used live and inactivated vaccines
during the same patient visit has produced seroconversion rates and
rates of adverse reactions similar to those observed when the
vaccines are administered separately. Vaccines administered
concomitantly should be given using separate syringes at separate
sites. Simultaneous administration is suggested, particularly when
there is concern that a person may not return for subsequent
vaccination.
ADACEL®-POLIO should not be mixed in the same syringe with
other parenterals.
The effect of ADACEL-POLIO on embryo-foetal development has
not been assessed.
Limited post-marketing data is available following administration of
ADACEL®-POLIO in pregnant women. Vaccination in pregnancy is
not recommended unless there is a definite risk of acquiring
pertussis. As the vaccine is inactivated, risk to the embryo or the
fetus is improbable. The benefits versus the risks of administering
ADACEL®-POLIO during pregnancy should be carefully evaluated
when there is a high probable risk of exposure to a household contact
or during an outbreak in the community.
A clinical study has shown that ADACEL-POLIO can be
administered concomitantly with hepatitis B vaccine,
using a separate limb for the site of injection. No
interaction studies have been carried out with other
vaccines, biological products or medicinal products.
However, in accordance with commonly accepted
vaccination recomindations, as with any inactivated
vaccine, there is no theoretical reason why Adacel Polio
should not be administered concomitantly with other
vaccines or immunoglobulins at separate injection sites.
In the case of immunosuppressive therapy please refer to
section 4.4.
Interaction with
other medicinal
products and
other forms of
interaction
The effect of ADACEL-POLIO on embryo-foetal
development has not been assessed.
No teratogenic effect have been observed following
administration to pregnant women of vaccines containing
diphtheria or tetanus toxoids, or inactivated poliovirus.
There are no available data on the use of vaccines
containing acellular pertussis antigens in pregnant
women.
The use of this combined vaccine is not recommended
during pregnancy.
Pregnancy and
lactation
Because clinical trials are conducted under widely varying
conditions, adverse reaction rates observed in the clinical trials of a
vaccine cannot be directly compared to rates in the clinical trials of
another vaccine and may not reflect rates observed in practice. The
adverse reaction information from clinical trials does, however,
provide a basis for identifying the adverse events that appear to be
related to vaccine use and for approximating rates of those events.
The safety of ADACEL®-POLIO has been evaluated in a total of
1,636 participants who received a single dose of ADACEL®-POLIO
in 7 clinical trials (644 children 3 to 7 years of age, 992 adolescents
and adults 11 to 60 years of age). Pain was the most common
injection site reaction in all age groups. Most injection site reactions
occurred within 3 days following vaccination. The most frequent
systemic reaction was headache in adolescents and adults and
tiredness in children. These reactions were usually transient and of
mild to moderate intensity.
Table presents the frequencies of the solicited injection site and
systemic adverse events reported in 3 UK clinical trials in which
children previously primed with 3 doses of PEDIACEL® [Diphtheria
and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed
Combined with Inactivated Poliomyelitis Vaccine and Haemophilus
b Conjugate Vaccine (Tetanus Protein – Conjugate)] or a whole-cell
pertussis combination vaccine, received a pre-school booster dose of
ADACEL®-POLIO at 3 to 5 years of age. In addition, adverse events
of irritability (7.3%), injection site bruising (3.3%), injection site
pruritus (2.7%) and dermatitis (1.3%) were reported within 7 days of
vaccination in two of these studies. In clinical trials in children
ADACEL®-POLIO showed a comparable safety profile to that of
ADACEL® [Tetanus Toxoid, Reduced Diphtheria Toxoid and
Acellular Pertussis Vaccine Adsorbed]. Therefore, the safety of
ADACEL®-POLIO, in particular for use as a 4 to 6 years-old
booster dose is further supported by a study conducted with
ADACEL® in 298 children.
The frequency of the solicited injection site and systemic adverse
events reported in a Canadian clinical trial in adolescents and adults
are also presented in Table
Table 2:
Frequency (%) of Solicited Reactions
Observed in Clinical Trials in Children,
Adolescents and Adults, Following a Single
Booster Dose of ADACEL®-POLIO
Children
Adolescents
Adults
3 to 5 Years 12 to 18 Years of 19 to 60 Years
Ageii
of Ageii
Solicited
of Agei
Reactions
(N = 307)
(N = 350)
(N = 366)
Injection Site Reactions
Pain
46.5 – 71.3
88.3
86.3
Swelling
20.4 – 34.0
21.2
16.7
Redness
35.7 – 48.7
17.5
23.0
Data from clinical trials
In clinical trials conducted with ADACEL-POLIO, the
vaccine was administered to 1,384 children, adolescent
and adult subjects. The most commonly reported reactions
following vaccination were local injection site reactions
(pain, redness and swelling). These signs and symptoms
were usually of mild intensity and appeared within 48
hours of vaccination. They all resolved without sequelae.
Adverse reactions are ranked under headings of frequency
using the following convention:
Very
common
(
1/10)
Common
(
1/100 to <1/10)
Uncommon
(
1/1,000 to <1/100)
Rare
(
1/10,000 to <1/1,000)
Very Rare
(<1/10,000),
including individual cases
Adolescents and adults (994 subjects)
Clinical studies in which ADACEL-POLIO was
administered to adolescents and adults have shown that
the most frequently reported adverse reactions, whatever
the age group, appearing within 24 hours of vaccination
were as follows:
Nervous System Disorders
Very common:
Gastrointestinal Disorders
Very
Nausea
Common:
Common:
Headache
Nausea
Diarrhea
Vomiting
Body Ache
Sore or
Swollen
Joints
Tiredness
Chills
Rash
7.0 – 12.7
N.S.
N.S.
7.6 – 10.0
2.5 – 6.7
N.S.
14.2
41.3
17.5
5.4
3.2
26.1
2.7
37.7
14.5
15.8
2.5
24.0
1.3
11.2
11.2
35.7 – 52.7
N.S.
7.0 – 8.7
37.2
17.5
N.S.
29.8
11.2
N.S.
Adverse reactions reported within 7 days of
vaccination. Range of frequencies across 3 UK
studies.
Adverse reactions reported within 14 days of vaccination.
Fever was defined as temperature ≥37.5°C in children, 38.0°C
vomiting,
diarrhoea
Musculoskeletal and Connective
Tissue Disorders
Very Common:
Systemic Reactions
Feveriii
Headache
arthralgia/
joint
swelling,
myalgia
General Disorders and
Administration Site Conditions
Very common:
asthenia,
chills,
injection site
pain,
swelling,
erythema
Common:
fever
38.0°C
There was a trend for higher rates for local and general
reactions in adolescents than in adults. In both age groups,
injection site pain was the most common adverse reaction.
Late-onset local adverse reactions (i.e. a local adverse
reaction which had an onset or increase in severity 3 to 14
days after a vaccination), such as injection site pain,
erythema and swelling occurred in less than 1.2% of
cases.
Adverse events
in adolescents and adults. Fever was solicited up to 7 days postvaccination in children, up to 72 hours in adolescents and
adults.
N.S.: Not solicited.
Children 5 to 6 years old (240 subjects)
In a clinical trial, children received a primary
immunization with a combined diphtheria, tetanus and
acellular pertussis vaccine administered at 3, 5 and 12
months, with no additional dose in the second year of life.
These children received ADACEL-POLIO at the age of 5
to 6 years. The most frequently reported adverse reactions
observed undesirable effects appearing within 24 hours of
administration were as follows:
Data from postmarketing experienceIn addition to the data obtained
from clinical studies, the following adverse events have been
reported during the commercial use of ADACEL-POLIO. The
adverse events have been very rarely reported (<0.01%); however,
the exact incidence rates cannot precisely be assessed. Calculation is
based on the number of adverse events compared with the estimated
number of vaccinated subjects.
Blood and lymphatic disorders: Lymphadenopathy Nervous system
disorders: convulsions, vasovagal syncope, Guillain Barre
syndrome, facial palsy, myelitis, brachial neuritis, transient
paresthesia / hypoesthesia of vaccinated limb, dizziness.
General disorders and administrative site conditions: Injection site
indurations
Extensive limb swelling from the injection site beyond one or both
joints and frequently associated with erythema, sometimes with
blisters has been reported after the administration of ADACELPOLIO. Most reactions appeared within 48 hours of vaccination and
spontaneously resolved without sequelae whithin 4 days on average.
The risk seems to be dependent on the number of doses of d/DtaP
vaccine previously administered, with a risk increased after the 4 th
and 5th doses. Malaise, Pallor
Musculoskeletal and connective tissue disorders: pain in vaccinated
limb
Immune system disorders:Anaphylactic reactions, such as urticaria,
face oedema and dyspnea
Gastrointestinal
Disorders
Uncommo Diarrhoea,
n:
vomiting
General Disorders and
Administration Site
Conditions
Very
common:
fatigue,
injection
site pain,
swelling
Common:
fever
38.0°C,
injection
site
erythema
and
pruritus
The rates of general symptoms on the day after
vaccination and during the next 10 days were low; only
fever ( 38.0°C) and fatigue were reported in more than
10% of the cases. Severe transient swelling of the arm
have been reported in less than 1% of the cases.
Children 3 to 5 years old (150 subjects)
150 children received a primary immunization at 2, 3, and
4 months of age with a with a combined diphtheria,
tetanus and whole cell pertussis vaccine (with no
additional dose in the second year of life) were vaccinated
with ADACEL-POLIO at the age of 3 to 5 years. The
most frequently reported adverse reactions appearing
within the first 7 days after administration were as
follows:
Gastrointestinal
Disorders
Common:
nausea, vomiting, diarrhoea
Skin and Subcutaneous System Disorders
Common:
rash
General Disorders and Administration Site Conditions
Very common:
fatigue, fever 37.5°C, irritability,
injection site pain, swelling, erythema
Common:
Injection site bruising and dermatitis
Data from postmarketing experienceIn addition to the
data obtained from clinical studies, the following adverse
events have been reported during the commercial use of
ADACEL-POLIO. The adverse events have been very
rarely reported (<0.01%); however, the exact incidence
rates cannot precisely be assessed. Calculation is based on
the number of adverse events compared with the
estimated number of vaccinated subjects.
Blood and lymphatic disorders: Lymphadenopathy
General disorders and administrative site conditions:
Extensive limb swelling from the injection site beyond
one or both joints and frequently associated with
erythema, sometimes with blisters has been reported after
the administration of ADACEL-POLIO. Most reactions
appeared within 48 hours of vaccination and
spontaneously resolved without sequelae whithin 4 days
on average.
The risk seems to be dependent on the number of doses of
d/DtaP vaccine previously administered, with a risk
increased after the 4th and 5th doses. Malaise, Pallor
Immune system disorders:Anaphylactic reactions, such as
urticaria, face oedema and dyspnea
Potential adverse events
Other adverse events not mentioned above were reported
with other similar vaccines and should be considered as
potential adverse reactions of ADACEL-POLIO.
Brachial neuritis and Guillain-Barré syndrome after
administration of a tetanus toxoid containing vaccine.
i Adverse reactions reported within 7 days of vaccination. Range of frequencies across 3 UK studies.
ii Adverse reactions reported within 14 days of vaccination.
iii Fever was defined as temperature ≥37.5°C in children, 38.0°C in adolescents and adults. Fever was
solicited up to 7 days post-vaccination in children, up to 72 hours in adolescents and adults.
N.S.: Not solicited.