Posology
A single injection of one (0.5 mL) dose is recommended in all indicated age groups.
REPEVAX may be administered from the age of three years onwards. The use of REPEVAX in children aged 3 to 5 years is based upon studies in which REPEVAX was given as the fourth dose (first booster) of diphtheria, tetanus, pertussis and poliomyelitis vaccines.
REPEVAX is a vaccine containing low-dose diphtheria toxoid plus tetanus toxoid in combination with pertussis and polio antigens for booster vaccinations. When administering the vaccine, indications and dosing intervals according to the official recommendations should be considered for all antigens contained in the vaccine.
Individuals with an incomplete, or no history of a primary series of diphtheria and tetanus toxoids or polio vaccine should not be vaccinated with REPEVAX.
REPEVAX is not precluded in persons with an incomplete, or no history of previous pertussis vaccination. However, a booster response will only be elicited in individuals who have been previously primed by vaccination or by natural infection.
There are currently no data upon which to base a recommendation for the optimal interval for administering subsequent booster doses with REPEVAX.
Repeat vaccination against diphtheria, tetanus, pertussis and/or poliomyelitis should be performed at intervals according to official recommendations.
REPEVAX can be used in the management of tetanus prone injuries with or without concomitant administration of Tetanus Immunoglobulin according to official recommendations.
Paediatric Population
REPEVAX should not be used in children under 3 years of age.
Children from the age of 3 years onwards and adolescents should receive the same dosage as adults.
Method of Administration
A single injection of one dose (0.5 mL) of REPEVAX should be administered intramuscularly. The preferred site is into the deltoid muscle.
Do not administer REPEVAX intravascularly. After insertion of the needle, aspirate to ensure that the needle has not entered a blood vessel.
REPEVAX 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
Pregnancy
The effect of REPEVAX on embryo-foetal development has not been assessed. No teratogenic effect of vaccines containing diphtheria or tetanus toxoids, or inactivated poliovirus has been observed following use in pregnant women. Data on the use of vaccines containing acellular pertussis antigens inLimited post-marketing information is available on the safety of administering REPEVAX to pregnant women are not available.
The use of this combined vaccine is not recommended during pregnancy.
Breastfeeding
It is not known whether the active substances included in REPEVAX are excreted in human milk. The effect on breast-fed infants of the administration of REPEVAX to their mothers has not been studied.
The risks and benefits of vaccination should be assessed before making the decision to immunize a nursing woman.
The effect of administration of REPEVAX during lactation has not been assessed. Nevertheless, as REPEVAX contains toxoids or inactivated antigens, no risk to the breastfed infant should be expected. The benefits versus the risk of administering REPEVAX to breastfeeding women should be evaluated by the health-care providers.
Fertility
REPEVAX has not been evaluated in fertility studies.
Clinical Trials
In clinical trials REPEVAX was given to a total of 1,384 children, 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. They all resolved without sequelae.
Adverse reactions are ranked under headings of frequency using the following convention:
Very common (³1/10)
Common (³1/100 to <1/10)
Uncommon (³1/1,000 to <1/100)
Rare (³1/10,000 to <1/1,000)
Very Rare (<1/10,000), including individual cases
Not Known cannot be estimated from the available data
Children
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 REPEVAX at 5 to 6 years of age.
The rates of general symptoms after the first day but within 10 days after vaccination were low; only fever (³38.0°C) and fatigue were reported in >10% of subjects. Transient severe swelling of the injected upper arm was reported in <1% of subjects.
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 REPEVAX at 3 to 5 years of age.
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Adverse Events
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Children 3 to 5 years (150 Persons)[*]
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Children 5 to 6 years (240 Persons)[†]
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Gastrointestinal Disorders
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Diarrhoea
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Common
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Uncommon
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|
Vomiting
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Nausea
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NRNot Reported
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Skin and Subcutaneous System Disorders
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Rash
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Common
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Not Reported
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Musculoskeletal and Connective Tissue Disorders
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Arthralgia/joint swelling
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Common
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Not Reported
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General Disorders and Administration Site Conditions
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Fatigue
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Very Common
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Fever[‡]
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Very Common
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Common
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Irritability
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NRNot Reported
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Arthralgia/joint swelling
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Common
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NR
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Injection site reactions
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|
pain
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Very Common
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swelling
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erythema
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Very Common
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Common
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dermatitis
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Common
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NRNot Reported
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pruritus
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NRCommon
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Common
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bruising
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Common
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NRNot Reported
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Skin and Subcutaneous System Disorders
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|
Rash
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Common
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NR
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NR: Not Reported
Adolescents (11 years of age and older) and Adults
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, erythema and swelling occurred in less than 1.2%. Most of the reported adverse reactions occurred within 24 hours after the vaccination.
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Adverse Events
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Adolescents and Adults (994 Persons)
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Nervous System Disorders
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Headache
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Very Common
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Gastrointestinal Disorders
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Nausea
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Very Common
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Vomiting
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Common
|
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Diarrhoea
|
|
Musculoskeletal and Connective Tissue Disorders
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|
Arthralgia/joint swelling
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Very Common
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Myalgia
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General Disorders and Administration Site Conditions
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Asthenia
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Very Common
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Chills
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Fever≥38.0°C
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Common
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Injection site reactions
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|
pain
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Very Common
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swelling
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erythema
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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 REPEVAX showed that there was more injection-site swelling and 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.
Data from Post-Marketing Experience
The following additional adverse events have been spontaneously reported during the post-marketing use of REPEVAX worldwide. Because these 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.
Blood and Lymphatic Disorders
Lymphadenopathy
Immune System Disorders
Anaphylactic reactions, such as urticaria, face oedema and dyspnea
Nervous System Disorders
Convulsions, vasovagal syncope, Guillain-Barré syndrome, facial palsy, myelitis, brachial neuritis, transient paresthesia / hypoesthesia of vaccinated limb, dizziness.
Musculoskeletal and Connective Tissue Disorders
Pain in vaccinated limb
General Disorders and Administrative Site Conditions
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 REPEVAX. 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 4th and 5th doses.
Malaise, pallor, injection site induration
[*] AEs observed within 7 days following vaccination
[†] AEs observed within 24 hours following vaccination
[‡] Fever was measured as temperature ≥38°C in the group “children 5 to 6 years” and measured as temperature ≥37.5°C in the groups “Children 3 to 5 years”
NR: Not Reported
Adolescents (11 years of age and older) and Adults
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, erythema and swelling occurred in less than 1.2%. Most of the reported adverse reactions occurred within 24 hours after the vaccination.
|
Adverse Events
|
Adolescents and Adults (994 Persons)
|
|
Nervous System Disorders
|
|
Headache
|
Very Common
|
|
Gastrointestinal Disorders
|
|
Nausea
|
Very Common
|
|
Vomiting
|
Common
|
|
Diarrhoea
|
|
Musculoskeletal and Connective Tissue Disorders
|
|
Arthralgia/joint swelling
|
Very Common
|
|
Myalgia
|
|
General Disorders and Administration Site Conditions
|
|
Asthenia
|
Very Common
|
|
Chills
|
|
Fever≥38.0°C
|
Common
|
|
Injection site reactions
|
|
pain
|
Very Common
|
|
swelling
|
|
erythema
|
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 REPEVAX showed that there was more injection-site swelling and 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.
Data from Post-Marketing Experience
The following additional adverse events have been spontaneously reported during the post-marketing use of REPEVAX worldwide. Because these 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.
Blood and Lymphatic Disorders
Lymphadenopathy
Immune System Disorders
Anaphylactic reactions, such as urticaria, face oedema and dyspnea
Nervous System Disorders
Convulsions, vasovagal syncope, Guillain-Barré syndrome, facial palsy, myelitis, brachial neuritis, transient paresthesia / hypoesthesia of vaccinated limb, dizziness.
Musculoskeletal and Connective Tissue Disorders
Pain in vaccinated limb
General Disorders and Administrative Site Conditions
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 REPEVAX. 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 4th and 5th doses.
Malaise, pallor, injection site induration
5.1 Pharmacodynamic Properties
Pharmacotherapeutic Group: Vaccine against diphtheria, tetanus, pertussis and 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 REPEVAX are shown in the table below. The use of REPEVAX in children aged 3 to 5 years is based upon studies in which REPEVAX was given as the fourth dose (first booster) of diphtheria, tetanus, pertussis and poliomyelitis vaccines.
Table 1: Immune Responses 4 Weeks after Vaccination
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|
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³0.1 IU/mL
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92.8%
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99.4%
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100%
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|
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³0.1 IU/mL§
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100%
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99.5%
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100%
|
|
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³5 EU/mL**
³5 EU/mL**
³5 EU/mL**
³5 EU/mL**
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99.7%
99.9%
99.6%
99.8%
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91.2%
99.1%
100%
99.5%
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99.3%
99.3%
100%
100%
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|
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³1:8 Dilution
³1:8 Dilution
³1:8 Dilution
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99.9%
100%
100%
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100%
100%
100%
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100%
100%
100%
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* 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 REPEVAX 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 REPEVAX had elicited protective immune responses.
In a subsequent study, robust immune responses were observed following a single dose of REPEVAX 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.
Serology follow-up studies were conducted in children adolescents and adults immunized with a single booster dose of REPEVAX.
At the 5-year follow-up time point, seroprotective antibody levels (≥0.01IU/ml) were maintained in 100% of participants of all age groups, for tetanus, and in 96-100% of the children and adolescent and >79% of the adults, for diphtheria.
For poliovirus, the seroprotective levels (≥1:8 dilution) for each type (1, 2 and 3) were maintained for 95-100% of the children, adolescents and adults at the 5-year follow-up time point.
GMTs for all pertussis antigens at 5 years remained several fold higher than pre-immunization levels, indicating a sustained long-term immune response for all age groups.
0.5 mL of suspension in pre-filled syringe (type I glass) with a plunger stopper (chlorobromobutyl, or bromobutyl or chlorobutyl elastomer), without attached needle, with a tip-cap (chlorobromobutyl elastomer) - pack size of 1, 10 or 20.
0.5 mL of suspension in pre-filled syringe (type I glass) with a plunger stopper (chlorobromobutyl, or bromobutyl or chlorobutyl elastomer), without attached needle, with a tip-cap (chlorobromobutyl elastomer) and 1 or 2 separate needles - pack size of 1 or 10.
0.5 mL of suspension in pre-filled syringe (type I glass) with a plunger stopper (chlorobromobutyl elastomer) with attached needle and needle guard (elastomer) - pack size of 1, 10 or 20.
0.5 mL of suspension in pre-filled syringe (type I glass) with a 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 REPEVAX are latex-free.
Not all pack sizes may be marketed.
