ADACEL POLIO

אפורל ןולעב )תוחיטב עדימ ( הרמחה לע העדוה אפורל ןולעב )תוחיטב עדימ ( הרמחה לע העדוה _____ ךיראת

27.03.2014

__________________

______תילגנאב רישכת םש

Adacel Polio

_______םושיר רפסמ

142603193800

_____________

מ"עב לקידמ י'צידמ___םושירה לעב םש

םיטרפ

לע

םי/יונישה

םי/שקובמה קרפ

ןולעב טסקט

יחכונ טסקט

שדח

Special warning

and precautions

for use

קט תפסות טס

Syncope (fainting) has been reported

following vaccination with

ADACEL

-POLIO.

Procedures shouls be in place to prevent

falling injury and manage syncopal reactions

Post Market

Adverse Drug

Reactions

קט תפסות טס

Gastrointestinal Disorders:

Abdominal pain

ובש ,ןולעה

םינמוסמ

םייונישה

םישקובמה

בוהצב

רבעוה

ראודב

ינורטקלא

.......ךיראתב

27.03.2014

...........

page

1.

NAME OF THE MEDICINAL PRODUCT

ADACEL®-POLIO, suspension for injection in a pre-filled syringe

Diphtheria (reduced antigen content), Tetanus, Pertussis (acellular, component) and

Poliomyelitis (inactivated) Vaccine (adsorbed)

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

1 dose (0.5 mL) contains:

Diphtheria toxoid adsorbed Not less than 2 IU*

Tetanus toxoid adsorbed

Pertussis antigens adsorbed:

Pertussis toxoid adsorbed 2.5 micrograms

Filamentous haemagglutinin adsorbed

5 micrograms

Fimbriae types 2 + 3 adsorbed

5 micrograms

Pertactin adsorbed

3 micrograms

Poliomyelitis virus type 1** (inactivated)

40 D antigen units

Poliomyelitis virus type 2** (inactivated)

8 D antigen units

Poliomyelitis virus type 3** (inactivated)

32 D antigen units Adsorbed on

aluminum phosphate

1.5 mg (0.33 mg Al)

* or the equivalent antigen quantity, determined by suitable immunochemical

method

For a full list of excipients, see section 6.1

3.

PHARMACEUTICAL FORM

Suspension for injection in a pre-filled syringe. ADACEL®-POLIO appears as a

cloudy whitish suspension.

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

ADACEL

-POLIO

is indicated for

active

immunization against diphtheria,

tetanus,

pertussis and poliomyelitis in persons from

the age of four

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

always

confer

immunity.

Human

Immunodeficiency

Virus

(HIV)-infected

persons,

both

asymptomatic

symptomatic, should be immunized against tetanus, diphtheria and pertussis

according to standard schedules.

The use of ADACEL®-POLIO should be determined on the basis of official

recommendations.

4.2 Posology and method of administration

page

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

tetanus

prophylaxis

routine

wound

management shown in Table 1.

Table 1: NACI Recommended Use of Immunizing Agents in Wound

Management (1)

History of Tetanus

Immunization

Clean, minor

wounds

All other wounds

Td

TIG†

(Human

)

Td*

TIG†

(Human)

Uncertain or <3 doses

of an immunization

series‡

3 doses received in an

immunization series‡

No&

No**

No††

* Adult-type tetanus and diphtheria toxoid.

† Tetanus immune globulin, given at a separate site from the Td.

‡ Primary immunization is at least 3 doses at age appropriate

intervals. & Yes, if >10 years since last booster.

** Yes, if >5 years since last booster.

†† Yes, if persons are known to have a significant humoral immune deficiency

state (e.g., HIV, agammaglobulinemia) since immune response to tetanus

toxoid may be suboptimal.

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

Inspect for extraneous particulate matter and/or discolouration before use. If these

conditions exist, the product should be discarded.

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.

page

Needles should not be recapped but should be disposed of according to

biohazard waste guidelines.

Before injection, the skin over the site to be injected should be cleansed with a

suitable germicide.

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.

4.3 Contraindications

ADACEL POLIO should not be administered to persons with known hypersensitivity

- to diphtheria, tetanus, pertussis or poliomyelitis vaccines

- to any other component of the vaccine (see Section 6.1)

residual

substances

carried

over

from

manufacture

(formaldehyde,

glutaraldehyde, streptomycin, neomycin, polymyxin B and bovine serum albumin),

which may be present in undetectable trace amounts.

ADACEL POLIO should not be administered to persons who experienced an

encephalopathy of unknown origin within 7 days of previous immunization with a

pertussis-containing vaccine.

As with other vaccines, administration of ADACEL POLIO should be postponed in

persons suffering from an acute severe febrile illness. The presence of a minor

infection (e.g., mild upper respiratory infection) is not a contraindication.

4.4 Special warnings and precautions for use

ADACEL

-POLIO should not be administered into the gluteal area; intradermal or

subcutaneous routes should not be used (in exceptional cases the subcutaneous route

may be considered, see section 4.4).

Precautions to be taken before handling or administering the medicinal product

For instructions on handling of the medicinal product before administration, see section

6.6.

ADACEL

-POLIO should not be used for primary immunization.

Regarding the interval between a booster dose of ADACEL

-POLIO and preceding

booster

doses

diphtheria

and/or

tetanus

containing

vaccines,

official

recommendations

should

generally

followed.

Clinical

data

adults

have

demonstrated that there was no clinically relevant difference in rates of adverse

reactions associated with administration of ADACEL

-POLIO as early as 4 weeks,

compared to at least 5 years after a preceding dose of tetanus and diphtheria-

containing vaccine.

Prior to immunization

Vaccination should be preceded by a review of the person's medical history (in

particular previous vaccinations and possible adverse events). In persons who have a

history of serious or severe reaction within 48 hours of a previous injection with a

vaccine containing similar components, administration of ADACEL

-POLIO vaccine

must be carefully considered.

As with all injectable vaccines, appropriate medical treatment and supervision should

be readily available for immediate use in case of a rare anaphylactic reaction following

the administration of the vaccine.

If Guillain-Barré syndrome occurred within 6 weeks of receipt of prior vaccine

containing tetanus toxoid, the decision to give any vaccine containing tetanus toxoid,

page

including ADACEL

-POLIO should be based on careful consideration of the potential

benefits and possible risks.

ADACEL

-POLIO

should not be administered to individuals with a progressive or

unstable neurological disorder, uncontrolled epilepsy or progressive encephalopathy

until a treatment regimen has been established and the condition has stabilized.

The rates and severity of adverse events in recipients of tetanus toxoid antigen are

influenced by the number of prior doses and level of pre-existing antitoxins.

The immunogenicity of the vaccine could be reduced by immunosuppressive treatment

or immunodeficiency. It is recommended to postpone the vaccination until the end of

such disease or treatment if practical. Nevertheless, vaccination of HIV infected

persons or persons with chronic immunodeficiency, such as AIDS, is recommended

even if the antibody response might be limited.

Administration precautions

Do not administer by intravascular or intradermal injection.

Intramuscular injections should be given with care in patients on anticoagulant therapy

or suffering from coagulation disorders because of the risk of haemorrhage. In these

situations and following official recommendations the administration of ADACEL

POLIO by deep subcutaneous injection may be considered, although there is a risk of

increased local reactions.

Syncope (fainting) can occur following, or even before, administration of injectable

vaccines, including ADACEL

-POLIO. Procedures should be in place to prevent falling

injury and manage syncopal reactions.

Other considerations

As with any vaccine, a protective immune response may not be elicited in all vaccines

(see section 5.1).

Limited data indicate that maternal antibodies may reduce the magnitude of the

immune response to some vaccines in infants born to women vaccinated with

ADACEL®-POLIO during pregnancy.

A persistent nodule at the site of injection may occur with all adsorbed vaccines,

particularly if administered into the superficial layers of the subcutaneous tissue.

4.5 Interaction with other medicinal products and other forms of interaction

ADACEL

-POLIO may be administered concomitantly with a dose of inactivated

influenza vaccine, based on the results of a clinical trial conducted in persons 60 years

of age and older.

ADACEL

-POLIO may be administered concomitantly with a dose of hepatitis B

vaccine.

ADACEL

-POLIO may be administered concurrently with a dose of recombinant

Human Papillomavirus vaccine with no significant interference with antibody response

to any of the components of either vaccine. However, a trend of lower anti-HPV GMTs

was observed in the concomitant group. The clinical significance of this observation is

not known. This is based on the results from a clinical trial in which ADACEL

-POLIO

was administered concomitantly with the first dose of Gardasil (see section 4.8).

Separate limbs must be used for the site of injection. Interaction studies have not been

carried out with other vaccines, biological products or therapeutic medications.

However, in accordance with commonly accepted immunization guidelines, since

ADACEL

-POLIO is an inactivated product it may be administered concomitantly with

other vaccines or immunoglobulins at separate injection sites.

In the case of immunosuppressive therapy please refer to Section 4.4.

page

4.6 Fertility, pregnancy and lactation

Pregnancy

No teratogenic effect of vaccines containing diphtheria or tetanus toxoids, or

inactivated poliovirus has been observed following use in pregnant women.

Safety

data

from

randomized

controlled

trials

(310

pregnancy

outcomes),

prospective

observational

studies

(2670

pregnancy

outcomes),

retrospective

observational studies (81,701 pregnancy outcomes), and from passive surveillance of

women who received ADACEL

-POLIO or ADACEL (Tdap component of ADACEL

POLIO; containing the same amounts of diphtheria, tetanus and pertussis antigens)

during the 2

or 3

trimester have shown no vaccine-related adverse effect on

pregnancy or on the health of the fetus/newborn child. As with other inactivated

vaccines, it is not expected that vaccination with ADACEL

-POLIO during any trimester

would harm the fetus. The benefits versus the risks of administering ADACEL

-POLIO

during pregnancy should be evaluated.

Animal studies do not indicate direct or indirect harmful effects with respect to

pregnancy, embryonal/fetal development, parturition or postnatal development.

Limited clinical data have shown there is interference with the immune response to

other antigens (i.e. diphtheria, tetanus, polio, pneumococcal, meningococcal) in infants

born to women vaccinated with ADACEL®-POLIO during pregnancy. However, in most

of the cases, the antibody concentrations remain above the thresholds established as

protective. The clinical relevance of this observation is unknown.

Breastfeeding

The effect of administration of ADACEL

-POLIO during lactation has not been

assessed.

Nevertheless,

ADACEL

-POLIO

contains

toxoids

inactivated

antigens, no risk to the breastfed infant should be expected. The benefits versus the

risk of administering ADACEL

-POLIO to breastfeeding women should be evaluated

by the health-care providers.

Fertility

ADACEL

-POLIO has not been evaluated in fertility studies.

4.7 Effects on ability to drive and use machines

No studies on the effects on the ability to drive or use machines have been

performed. ADACEL

-POLIO has no or negligible influence on the ability to drive and

use machines.

4.8 Undesirable effects

Summary of the safety profile

In clinical trials ADACEL POLIO was given to a total of 1,384 persons including 390

children 3 through 6 years of age and 994 adolescent and adults. Most commonly

reported reactions following vaccination included local reactions at the injection site

(pain, redness and swelling). These signs and symptoms usually were mild in intensity

and occurred within 48 hours following vaccination (Adverse Events have been

observed within 24 hours and 7 days following vaccination in children 3 through 6

years). They all resolved without sequelae.

There was a trend for higher rates of local and systemic 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 post-immunization), such as injection site pain,

page

erythema and swelling occurred in less than 1.2%. Most of the reported adverse

reactions occurred within 24 hours after the vaccination.

In a clinical trial of 843 healthy adolescent males and females 11-17 years of age,

administration of the first dose of Gardasil concomitantly with ADACEL POLIO showed

that

there

more

injection-site

swelling

headache

reported

following

concomitant administration. The differences observed were < 10% and in the majority

of subjects, the adverse events were reported as mild to moderate in intensity.

Tabulated list of adverse reactions

Adverse reactions are ranked under headings of frequency using the following

convention:

Very common

Common

Uncommon

Rare

Very rare

Not known

(≥1/10)

(≥1/100 to <1/10)

(≥1/1,000 to <1/100)

(≥1/10,000 to <1/1,000)

(<1/10,000), including individual cases

cannot be estimated from the available data

Table 1 presents adverse reactions observed in clinical trials and also includes

additional adverse events which have been spontaneously reported during the post-

marketing use of ADACEL POLIO worldwide. Adverse events in children were

collected from clinical trials conducted in 3 to 5 years of age and 5 to 6 years of age.

The highest frequency from either study is presented. Because post-marketing

adverse events are reported voluntarily from a population of uncertain size, it is not

always possible to reliably estimate their frequency or establish a causal relationship

to vaccine exposure. Therefore, the frequency category “Not known” is assigned to

these adverse events.

Table 1: Adverse events from clinical trials and worldwide post marketing

experience

System Organ Class

Frequency

Children 3 through 6 years

Adolescents and

Adults

Blood and lymphatic

system disorders

Not known

Lymphadenopathy*

Immune system

disorders

Not known

Anaphylactic reactions, such as urticaria, face oedema and

dyspnea*

Nervous system

disorders

Very

common

Headache

Common

Headache

Not known

Convulsions, Vasovagal Syncope, Guillain Barré syndrome,

Facial Palsy, Myelitis, Brachial Neuritis, Transient

paresthesia/hypoesthesia of vaccinated limb, Dizziness*

Gastrointestinal

disorders

Very

common

Diarrhoea

Nausea

Common

Vomiting, Nausea

Diarrhoea, Vomiting

Not known

Abdominal pain

Skin and

subcutaneous system

disorders

Common

Rash

page

Musculoskeletal and

connective tissue

disorders

Very

common

Arthralgia/joint swelling,

Myalgia

Common

Arthralgia/joint swelling

Not known

Pain in vaccinated limb*

General disorders and

administration site

conditions

Very

common

Fatigue/Asthenia, Fever†

Fatigue/Asthenia, Chills

Injection site pain, Injection site swelling, Injection site

erythema

Common

Irritability, Injection site dermatitis,

Injection site bruising, Injection site

pruritus

Fever†

Not known

Malaise

, Pallor*, Extensive limb swelling‡, Injection site

induration*

* Post marketing adverse events

† Fever was measured as temperature ≥37.5°C in Children groups and measured as

temperature ≥38°C in Adolescents and Adults group

‡ See section c)

§ was observed at a frequency of very common in adolescents and adults, in studies

with ADACEL (Tdap component of ADACEL

-POLIO; containing the same amounts

of diphtheria, tetanus and pertussis antigens)

Description of selected adverse reactions

Extensive limb swelling which may extend from the injection site beyond one or both

joints and is frequently associated with erythema, and sometimes with blisters has

been reported following administration of ADACEL

-POLIO. The majority of these

reactions appeared within 48 hours of vaccination and spontaneously resolved over

an average of 4 days without sequelae.

The risk appears to be dependent on the number of prior doses of d/DTaP vaccine,

with a greater risk following the 4

and 5

doses.

Paediatric population

The safety profile of ADACEL

-POLIO in 390 children 3 to 6 years of age as presented

in Table 1 is derived from two clinical studies:

- In a clinical study, 240 children were primed at 3, 5 and 12 months of age with a

DTaP vaccine with no additional dose in the second year of life. These children

received ADACEL

-POLIO at 5 to 6 years of age.

- One hundred and fifty children primed at 2, 3, and 4 months of age with a DTwP

vaccine (with no additional dose in the second year of life) received ADACEL

-POLIO

at 3 to 5 years of age.

In both studies the rates of most systemic adverse events within 7 to 10 days following

vaccination were less than 10%. Only fever (≥37.5°C) and fatigue were reported in

more than 10 % of subjects 3 to 6 years of age. In addition, irritability was reported in

more than 10% of subjects 3 to 5 years of age. (See Table 1).

Transient severe swelling of the injected upper arm was reported in <1% of children

aged 5 to 6 years.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is

important. It allows continued monitoring of the benefit/risk balance of the medicinal

product.Any suspected adverse events should be reported to the Ministry of Health

(www.health.gov.il) according to the National Regulation by using an online form

https://sideeffects.health.gov.il

page

4.9 Overdose

Not applicable.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic

Group:

Vaccine

against

diphtheria,

tetanus,

pertussis

poliomyelitis

ATC Code: J07CA02

Clinical trials

The immune responses of adults, adolescents and children 3 to 6 years of age one-

month after vaccination with ADACEL POLIO are shown in the table below. 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.

Table 2: Immune responses 4

weeks after vaccination Antigen

Criteria

Adults and

Adolescents*

(n = 994)

Children 5-6

years old†

(n = 240)

Children 3-5

years old‡

(n = 148)

Diphtheria

≥0.1 IU/mL

92.8%

99.4%

100%

Tetanus

≥0.1 IU/mL§

100%

99.5%

100%

Pertussis

Pertussis Toxoid

Filamentous Haemagglutinin

Pertactin

Fimbriae Types 2 and 3

≥5 EU/mL**

≥5 EU/mL**

≥5 EU/mL**

≥5 EU/mL**

99.7%

99.9%

99.6%

99.8%

91.2%

99.1%

100%

99.5%

99.3%

99.3%

100%

100%

Polio 1

Polio 2

Polio 3

≥1:8 Dilution

≥1:8 Dilution

≥1:8 Dilution

99.9%

100%

100%

100%

100%

100%

100%

100%

100%

* From the age of 10 years onwards

† Primed with DTaP at 3 and 5 months with a booster at 12 months of age

‡ Primed with DTwP at 2, 3 and 4 months of age

§ Measured by ELISA

** EU = ELISA units: Antibody levels of >5 EU/mL were postulated as possible

surrogate markers for protection against pertussis by Storsaeter J. et al, Vaccine

1998;16:1907-16.

The safety and immunogenicity of ADACEL

-POLIO in adults and adolescents was

shown to be comparable to that observed with a single booster dose of Td adsorbed

or Td Polio adsorbed vaccines containing a similar amount of tetanus and diphtheria

toxoids and inactivated poliovirus types 1, 2 and 3.

The lower response to diphtheria toxoid in adults probably reflected the inclusion of

some participants with an uncertain or incomplete immunization history.

Serological correlates for protection against pertussis have not been established. On

comparison with data from the Sweden I pertussis efficacy trials conducted between

1992 and 1996, where primary immunization with Sanofi Pasteur Limited's acellular

pertussis infant DTaP formulation confirmed a protective efficacy of 85% against

pertussis disease, it is considered that ADACEL

-POLIO had elicited protective

immune responses.

In a subsequent study, robust immune responses were observed following a single

dose of ADACEL

-POLIO in UK children 3.5 to 4.0 years of age previously primed with

either an acellular pertussis combination vaccine (DTaP-IPV-Hib) or whole cell

pertussis combination vaccine (DTwP//Hib) and OPV.

page

Antibody persistence

Pivotal studies conducted with ADACEL provide serology follow-up data at 3, 5 and 10

years, in individuals previously immunized with a single booster dose of ADACEL.

Persistence of seroprotection to diphtheria and tetanus, and seropositivity to pertussis

is summarised in Table 3.

Table

3:

Persistence

of

Seroprotection/Seropositivity

Rates

in

Children,

Adolescents and Adults at 3-, 5- and 10- years following a dose of ADACEL (Tdap

component of ADACEL

®

-POLIO) (PPI Population

1

)

Children (4-

6 years)

Adolescents

(11-17 years)

Adults

(18-64 years)

Time point

5 years

3

years

5 years

10 years

3 years

5 years

10 years

Antibody

N=128-150

N=300

N=204-

N=28-39

N=292

N=237-

N=120-

Diphtheria

(SN, IU/mL)

≥ 0.1

86.0

97.0

95.1

94.9

81.2

81.1

84.6

≥ 0.01

100.0

100.0

100.0

100.0

95.2

93.7

99.3

Tetanus

(ELISA,

IU/mL)

≥ 0.1

97.3

100.0

100.0

100.0

99.0

97.1

100.0

Pertussis

(ELISA,

IU/mL)

Sero-

positivity

PT

63.3

97.3

85.4

82.1

94.2

89.1

85.8

FHA

97.3

100.0

99.5

100.0

99.3

100.0

100.0

PRN

95.3

99.7

98.5

100.0

98.6

97.1

99.3

FIM

98.7

98.3

99.5

100.0

93.5

99.6

98.5

N = number of subjects with available data; SN: seroneutralisation; ELISA: Enzyme

Linked Immunoassay

Eligible subjects for whom immunogenicity data was available for at least one antigen

at the specified time-point.

Age at which subjects received a dose of ADACEL

Percentage of subjects with antibodies ≥ 4 EU/mL for PT, FHA and PRN, and ≥ 17

EU/mL for FIM for the 3 year follow-up; ≥ 4 EU/mL for PT, FIM and PRN, and ≥ 3

EU/mL for FHA for the 5-year and 10-year follow-up

serology

follow-up

studies

conducted

with

ADACEL

-POLIO,

seroprotective

antibody levels (≥1:8 dilution) for each poliovirus (type1, 2 and 3) were maintained in

95% to 100% of the children, adolescents and adults at the 5-year follow-up time point,

and in 100% of the adolescents at the 10-year follow-up time point.

Immunogenicity following repeat vaccination

The immunogenicity of ADACEL following repeat vaccination 10 years after a previous

dose

ADACEL

ADACEL

-POLIO,

been

evaluated. One month

post-

vaccination ≥ 98.5% of study participants achieved seroprotective antibody levels (≥

0.1 IU/ml) for diphtheria and tetanus, and ≥ 84% achieved booster responses to the

pertussis antigens. (A pertussis booster response was defined as a post-vaccination

antibody concentration ≥ 4 times the LLOQ if the pre-vaccination level was < LLOQ; ≥

4 times the pre-vaccination level if that was ≥ LLOQ but < 4 times LLOQ; or ≥ 2 times

the pre-vaccination level if that was ≥ 4 times the LLOQ).

Based on the serology follow-up and repeat vaccination data, ADACEL

-POLIO can

be used instead of a dT vaccine or dT-IPV vaccine to boost immunity to pertussis in

addition diphtheria, tetanus and polio.

Immunogenicity in naïve subjects

page

After administration of one dose of ADACEL

-POLIO to 330 adults ≥40 years of age

that had not received any diphtheria- and tetanus-containing vaccine in the past 20

years:

≥95.8% of adults were seropositive (≥ 5 IU/mL) for antibodies to all vaccine-containing

pertussis antigens,

82.4% and 92.7% were seroprotected against diphtheria at a threshold ≥0.1 and

≥0.01 IU/mL, respectively,

98.5% and 99.7% were seroprotected against tetanus at a threshold ≥0.1 and ≥0.01

IU/mL, respectively,

and ≥98.8% were seroprotected against polio (types 1, 2 and 3) at a threshold ≥1:8

dilution.

After administration of two additional doses of diphtheria- tetanus- and polio-containing

vaccine to 316 subjects, one and six months after the first dose, the seroprotection

rates against diphtheria were 94.6% and 100% (≥0.1 and ≥ 0.01 IU/mL, respectively),

against tetanus 100% (≥0.1 IU/mL), and against polio (types 1, 2 and 3) 100% (≥1:8

dilution) (see Table 4).

Table 4: Serological immune status (seroprotection/seroresponse rates and

GMC/GMT) before vaccination and after each dose of a 3 dose-vaccination

schedule including ADACEL

®

-POLIO (Dose 1) followed by 2 doses of REVAXIS

®

1 and 6 months later (Dose 2 and 3) in subjects vaccinated according to protocol

(FAS)

Antigen

Criteria

Pre-vaccination

Post-dose 1

ADACEL

®

-

POLIO

Post-dose 2

REVAXIS

®

Post-dose 3

REVAXIS

®

N=330

N=330

N=325

N=316

Diphtheria

0.059

0.813

1.373

1.489

(SN, IU/mL)

95%CI

[0.046; 0.077]

[0.624; 1.059]

[1.100; 1.715]

[1.262; 1.757]

≥0.1

44.5%

82.4%

90.5%

94.6%

95%CI

[39.1; 50.1]

[77.9; 86.4]

[86.7; 93.4]

[91.5; 96.8]

≥0.01

72.4%

92.7%

96.0%

100%

95%CI

[67.3; 77.2]

[89.4; 95.3]

[93.3; 97.9]

[98.8; 100]

Tetanus

0.48

6.82

7.60

5.46

(ELISA, IU/mL)

95%CI

[0.39;0.60]

[5.92;7.87]

[6.77;8.52]

[5.01;5.96]

≥0.1

81.2%

98.5%

100%

100%

95%CI

[76.6; 85.3]

[96.5; 99.5]

[98.9; 100]

[98.8; 100]

≥0.01

92.4%

99.7%

100%

100%

95%CI

[89.0; 95.0]

[98.3; 100]

[98.9; 100]

[98.8; 100]

Poliomyelitis (SN, 1/dil)

Type 1

162.6

2869.0

2320.2

1601.9

95%CI

[133.6; 198.0]

[2432.9; 3383.4]

[2010.9; 2677.0]

[1425.4;

1800.3]

≥8

93.3%

99.4%

100%

100%

95%CI

[90.1; 95.8]

[97.8; 99.9]

[98.9; 100]

[98.8; 100]

Type 2

164.5

3829.7

3256.0

2107.2

95%CI

[137.6;196.8]

[3258.5;4501.1]

[2818.2;3761.7]

[1855.7;2392.8]

≥8

95.5%

100%

100%

100%

page

95%CI

[92.6; 97.4]

[98.9; 100]

[98.9; 100]

[98.8; 100]

Type 3

69.0

5011.4

3615.6

2125.8

95%CI

[56.9; 83.6]

[4177.4; 6012.0]

[3100.5; 4216.4]

[1875.5;

2409.6]

≥8

89.1%

98.8%

99.7%

100%

95%CI

[85.2; 92.2]

[96.9; 99.7]

[98.3; 100]

[98.8; 100]

Pertussis (ELISA, EU/mL)

PT

41.3

95%CI

[6.8; 8.7]

[36.7; 46.5]

≥5

96.3%

95%CI

[93.6; 98.1]

FHA

28.5

186.7

95%CI

[25.5; 31.8]

[169.6; 205.6]

≥5

100%

95%CI

[98.9; 100]

PRN

328.6

95%CI

[6.7; 8.9]

[273.0; 395.6]

≥5

99.4%

95%CI

[97.8; 99.9]

FIM2&3

149.6

95%CI

[5.2; 7.1]

[123.6; 181.0]

≥5

95.8%

95%CI

[93.0; 97.7]

GMC: Geometric mean of antibody concentrations; GMT: Geometric mean of

antibody titres; CI: Confidence Interval; SN: seroneutralisation; ELISA: Enzyme

Linked Immunoassay; dil: dilution

FAS: Full Analysis Set – includes all subjects who received the study vaccine dose

and for whom the post-vaccination immunogenicity evaluation was available.

5.2 Pharmacokinetic properties

Evaluation of pharmacokinetic properties is not required for vaccines.

5.3 Preclinical safety data

Non-clinical data revealed no special hazard for humans based on conventional

studies of repeated doses toxicity.

6. Pharmaceutical particulars

6.1 List of excipients

Phenoxyethanol, Aluminum phosphate, Polysorbate 80, Water for injections

Manufacturing Process Residuals:

The final product may contain trace amount of formaldehyde, glutaraldehyde,

streptomycin, neomycin, polymyxin B, bovine serum albumin (trace).

6.2 Incompatibilities

In the absence of compatibility studies,

ADACEL

-POLIO

must not be mixed with

other medicinal products.

page

6.3 Shelf life

The expiry date of the product is indicated on the packaging materials.6.4 Special

precautions for storage

Store in a refrigerator at 2°C to 8°C.

Do not freeze. Discard the vaccine if it has been frozen.

Keep the container in the outer carton in order to protect from light.

6.5 Nature and contents of container

suspension

pre-filled

syringe

(glass)

with

plunger

stopper

(chlorobromobutyl or bromobutyl or chlorobutyl elastomer), without attached needle,

with

tip-cap

(chlorobromobutyl

elastomer

synthetic

isoprene-bromobutyl

elastomer) - pack size of 1, 10 or 20.

suspension

pre-filled

syringe

(glass)

with

plunger

stopper

(chlorobromobutyl or bromobutyl or chlorobutyl elastomer), without attached needle,

with a tip-cap (chlorobromobutyl elastomer or synthetic isoprene-bromobutyl elastomer

) and 1 or 2 separate needles - pack size of 1 or 10.

suspension

pre-filled

syringe

(glass)

with

plunger

stopper

(chlorobromobutyl or bromobutyl or chlorobutyl elastomer) with attached needle and

needle guard (translucent polypropylene rigid safeshield and polyisoprene) - pack size

of 1, 10 or 20.

The stoppers, plunger stoppers and caps for all presentations of ADACEL

-POLIO are

latex-free.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Instructions for use

Parenteral products should be inspected visually for extraneous particulate matter

and/or discoloration prior to administration. In the event of either being observed,

discard the medicinal product.

The normal appearance of the vaccine is a uniform cloudy, white suspension which

may sediment during storage. Shake the prefilled syringe well to uniformly distribute

the suspension before administering the vaccine.

For needle free syringes, the needle should be pushed firmly on to the end of the

prefilled syringe and rotated through 90 degrees.

Disposal

Any unused medicinal product or waste material should be disposed of in accordance

with local requirements.

Needles should not be recapped.

7. LICENSE HOLDER:

Medici Medical Ltd., 3 Hamachshev St. Netanya

8. MANUFACTURER:

Sanofi Pasteur

14 Espace Henry

Vallee, 69007 LYON-

FRANCE

9. MARKETING AUTHORISATION NUMBER

142-60-31938-00

Approved in: February 2015

Revised in: August 2020