- 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.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 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. 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 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 precautionsIntramuscular 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.
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. Limited post-marketing information is available on the safety of administering REPEVAX to pregnant women.The use of this combined vaccine is not recommended during pregnancy.
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.
a. Summary of the safety profileIn 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. 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.
b. Tabulated list of adverse reactionsAdverse reactions are ranked under headings of frequency using the following convention:
|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|
|Not known||cannot be estimated from the available data|
|System Organ Class||Frequency||Children 3 to 6 years (390 Persons)*||Adolescents and Adults (994 Persons)|
|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||Nausea|
|Common||Diarrhoea, Vomiting, Nausea||Diarrhoea, Vomiting|
|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, Irritability||Fatigue/Asthenia, Chills|
|Not known||Malaise, Pallor |
|Injection site reactions||Very common||Pain, Swelling, Erythema|
|Common||Dermatitis, Bruising Pruritus|
|Not known||Extensive limb swelling §, Injection site induration |
|*||AEs observed within 24 h and 7 days following vaccination|
|||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)|
c. 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.
d. 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 Table1).Transient severe swelling of the injected upper arm was reported in <1% of children aged 5 to 6 years.
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%|
|*||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.|
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.
Sanofi Pasteur MSD Limited
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