4.1. Therapeutic indications

REPEVAX (Tdap-IPV) is indicated for:

Active immunization against diphtheria, tetanus, pertussis and poliomyelitis in persons from 3 years of age as a booster following primary immunization.

Passive protection against pertussis in early infancy following maternal immunization during pregnancy (see sections 4.2, 4.6 and 5.1).

REPEVAX should be used in accordance with official recommendations.

4.2. Posology and method of administration

Posology

A single injection of one (0.5 mL) dose is recommended in all indicated age groups.

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).

REPEVAX can be used in the management of tetanus prone injuries with or without concomitant administration of Tetanus Immunoglobulin according to official recommendations.

REPEVAX may be administered to pregnant women during the second or third trimester to provide passive protection of infants against pertussis (see sections 4.1, 4.6 and 5.1).

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.

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.

4.3. Contraindications

• REPEVAX 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)

- to any residual substances carried over from manufacture (formaldehyde, glutaraldehyde, streptomycin, neomycin, polymyxin B and bovine serum albumin), which may be present in undetectable trace amounts.

• REPEVAX 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 REPEVAX 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

REPEVAX should not be used for primary immunization.

Regarding the interval between a booster dose of REPEVAX and preceding booster doses of diphtheria and/or tetanus containing vaccines, the official recommendations should generally be followed. Clinical data in adults have demonstrated that there was no clinically relevant difference in rates of adverse reactions associated with administration of REPEVAX 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 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 occurred within 6 weeks of receipt of prior vaccine containing tetanus toxoid, the decision to give any vaccine containing tetanus toxoid, including REPEVAX 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 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 REPEVAX 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 REPEVAX. 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).

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.

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Excipients with known effects

REPEVAX contains 1.01 milligram of alcohol (ethanol) in each 0.5 mL dose. The small amount of alcohol in this medicine will not have any noticeable effects.

4.5. Interaction with other medicinal products and other forms of interaction

REPEVAX 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.

REPEVAX may be administered concomitantly with a dose of hepatitis B vaccine.

Based on the results of concomitant use clinical studies, REPEVAX can be administered with human papilloma virus vaccine (HPV) and/or Meningococcal Polysaccharide (Serogroups A, C, Y, and W) (MenACYW) conjugate vaccines (either all three vaccines concomitantly or in pairs) (see section 4.8) according to local recommendations.

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 REPEVAX 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.

4.6. Fertility, pregnancy and lactation

Pregnancy

REPEVAX can be used during the second or third trimester of pregnancy in accordance with official recommendations (see section 4.2).

Safety data from 4 randomized controlled trials (310 pregnancy outcomes), 1 prospective observational study (546 pregnancy outcomes), 5 retrospective observational studies (124, 810 pregnancy outcomes), and from passive surveillance of women who received REPEVAX or ADACEL (Tdap ; containing the same amounts of tetanus, diphtheria and pertussis antigens as REPEVAX) during the second or third 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 REPEVAX during any trimester would harm the fetus.

Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/fetal development, parturition or postnatal development.

For information on immune responses to vaccination during pregnancy and its effectiveness at preventing pertussis in infants, see section 5.1.

Breastfeeding

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.

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. REPEVAX 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 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.

The safety analysis of concomitant use of either REPEVAX or ADACEL administered with MenACYW (Menactra or MenQuadfi) and/or HPV (Gardasil or Gardasil 9) vaccines included 5 122 healthy male and female subjects aged 10 to 17 years from 6 clinical trials.

The overall safety profile of REPEVAX or ADACEL was similar when all three vaccines were administered concomitantly compared to coadministered pairs (ADACEL and Menactra or REPEVAX/ADACEL and Gardasil/Gardasil 9). The safety profile of coadministered REPEVAX and Gardasil/Gardasil 9 was similar to Gardasil/Gardasil 9 administered alone.

In clinical studies, injection site reactions (pain, erythema, swelling, and bruising), as well as headache, malaise, and myalgia were observed more frequently when all three vaccines were administered together or in pairs, compared to when they were administered alone. Overall, the differences observed in injection site reactions were < 10%, while the differences in headache, malaise, and myalgia ranged from < 10% to < 28%. The difference in fever rates across clinical studies was < 2%.

The majority of 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 REPEVAX 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

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 REPEVAX; 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 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 population

The 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.

- 150 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 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. 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 or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Not applicable.