- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
PosologyA single injection of one (0.5 mL) dose is recommended in all indicated age groups.REPEVAX is a vaccine containing low-dose diphtheria toxoid plus tetanus toxoid in combination with pertussis and polio antigens for booster vaccinations.In adolescents and adults with an unknown or incomplete diphtheria or tetanus vaccination status against diphtheria or tetanus, one dose of REPEVAX can be administered as part of a vaccination series to protect against pertussis and poliomyelitis and in most cases also against tetanus and diphtheria. One additional dose of a diphtheria- and tetanus- (dT) containing vaccine can be administered one month later followed by a 3rd dose of a diphtheria or dT containing vaccine 6 months after the first dose to optimize protection against disease (see section 5.1). The number and schedule of doses should be determined according to local recommendations.REPEVAX can be used for repeat vaccination to boost immunity to diphtheria, tetanus and pertussis at 5 to 10 year intervals (see section 5.1). Repeat vaccination should be performed 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 PopulationREPEVAX 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 administrationA single injection of one dose (0.5 mL) of REPEVAX should be administered intramuscularly. The preferred site is into the deltoid muscle. 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 productFor instructions on handling of the medicinal product before administration, see section 6.6.
Prior to immunizationVaccination 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 REPEVAX 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 or brachial neuritis has occurred following receipt of prior vaccine containing tetanus toxoid, the decision to give any vaccine containing tetanus toxoid should be based on careful consideration of the potential benefits and possible risks.REPEVAX 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 precautionsDo 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 REPEVAX by deep subcutaneous injection may be considered, although there is a risk of increased local reactions.Syncope (fainting) can occur in association with administration of injectable vaccines, including REPEVAX. Procedures should be in place to prevent falling injury and manage syncopal reactions.
Other considerationsAs with any vaccine, a protective immune response may not be elicited in all vaccinees (see section 5.1). 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.
PregnancyThe 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. Available data on exposures during pregnancy do not indicate any adverse foetal or maternal outcomes attributable to REPEVAX. The administration of REPEVAX to a pregnant woman should be on the basis of official recommendations or on an individual assessment of the benefits versus the risks.
BreastfeedingThe 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.
FertilityREPEVAX has not been evaluated in fertility studies.
Summary of the safety profileIn clinical trials REPEVAX 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, 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 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.
Tabulated list of adverse reactionsAdverse 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|
|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|
|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|
|Musculoskeletal and connective tissue disorders||Very common||Arthralgia/joint swelling, Myalgia|
|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*|
Description of selected adverse reactionsExtensive 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.
Paediatric populationThe safety profile of REPEVAX 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 REPEVAX 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 REPEVAX 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 reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Medicines and Healthcare products Regulatory Agency (MHRA), Yellow Card Scheme at www.mhra.gov.uk/yellowcard.
Clinical trialsThe 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 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)|
|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%|
Antibody persistencePivotal studies conducted with COVAXiS (Tdap component of REPEVAX; containing the same amounts of diphtheria, tetanus and pertussis antigens) provide serology follow-up data at 3, 5 and 10 years, in individuals previously immunized with a single booster dose of COVAXiS. 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 COVAXiS (Tdap component of REPEVAX) (PPI Population1)
|Children (4-6 years)2||Adolescents (11-17 years)2||Adults (18-64 years)2|
|Time point||5 years||3 years||5 years||10 years||3 years||5 years||10 years|
|Diphtheria (SN, IU/mL)||≥ 0.1||86.0||97.0||95.1||94.9||81.2||81.1||84.6|
|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-positivity3||63.3||97.3||85.4||82.1||94.2||89.1||85.8|
Immunogenicity following repeat vaccinationThe immunogenicity of COVAXiS (Tdap component of REPEVAX) following repeat vaccination 10 years after a previous dose of COVAXiS or REPEVAX, has 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, REPEVAX 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 subjectsAfter administration of one dose of REPEVAX 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 REPEVAX® (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 REPEVAX®||Post-dose 2 REVAXIS®||Post-dose 3 REVAXIS®|
|Diphtheria (SN, IU/mL)||GMC||0.059||0.813||1.373||1.489|
|95%CI||[0.046; 0.077]||[0.624; 1.059]||[1.100; 1.715]||[1.262; 1.757]|
|95%CI||[39.1; 50.1]||[77.9; 86.4]||[86.7; 93.4]||[91.5; 96.8]|
|95%CI||[67.3; 77.2]||[89.4; 95.3]||[93.3; 97.9]||[98.8; 100]|
|Tetanus (ELISA, IU/mL)||GMC||0.48||6.82||7.60||5.46|
|95%CI||[76.6; 85.3]||[96.5; 99.5]||[98.9; 100]||[98.8; 100]|
|95%CI||[89.0; 95.0]||[98.3; 100]||[98.9; 100]||[98.8; 100]|
|Poliomyelitis (SN, 1/dil)|
|95%CI||[133.6; 198.0]||[2432.9; 3383.4]||[2010.9; 2677.0]||[1425.4; 1800.3]|
|95%CI||[90.1; 95.8]||[97.8; 99.9]||[98.9; 100]||[98.8; 100]|
|95%CI||[92.6; 97.4]||[98.9; 100]||[98.9; 100]||[98.8; 100]|
|95%CI||[56.9; 83.6]||[4177.4; 6012.0]||[3100.5; 4216.4]||[1875.5; 2409.6]|
|95%CI||[85.2; 92.2]||[96.9; 99.7]||[98.3; 100]||[98.8; 100]|
|Pertussis (ELISA, EU/mL)|
|95%CI||[6.8; 8.7]||[36.7; 46.5]|
|95%CI||[25.5; 31.8]||[169.6; 205.6]|
|95%CI||[6.7; 8.9]||[273.0; 395.6]|
|95%CI||[5.2; 7.1]||[123.6; 181.0]|
Instructions for useParenteral 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.
DisposalAny unused medicinal product or waste material should be disposed of in accordance with local requirements. Needles should not be recapped.
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