ADACEL SUSPENSION FOR INJECTION IN PRE-FILLED SYRINGE DIPHTHERIA TETANUS PERTUSSIS VACCINE - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

ADACEL, suspension for injection in pre-filled syringe.

Diphtheria, Tetanus, Pertussis (acellular component) Vaccine (adsorbed, reduced antigen(s) content)

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

1 dose (0.5 mL) contains:

Diphtheria Toxoid

Tetanus Toxoid

Pertussis Antigens

Pertussis Toxoid

Filamentous Haemagglutinin

Pertactin

Fimbriae Types 2 and 3

Adsorbed on aluminium phosphate

Not less than 2 IU* (2 Lf)

Not less than 20 IU* (5 Lf)

2.5 micrograms

5 micrograms

3 micrograms

5 micrograms

1.5 mg (0.33 mg Al3+)

* As lower confidence limit (p = 0.95) of activity measured according to the assay described in the European Pharmacopoeia.

This vaccine may contain traces of formaldehyde and glutaraldehyde which are used during the manufacturing process (see sections 4.3 and 4.4).

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Suspension for injection in pre-filled syringe.

ADACEL appears as a cloudy white suspension.

4.1 Therapeutic indications

ADACEL (Tdap) is indicated for:

Active immunization against tetanus, diphtheria and pertussis in persons from 4 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).

ADACEL 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.

Individuals with an incomplete, or no history of a primary series of diphtheria and tetanus toxoids should not be vaccinated with ADACEL.

ADACEL 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.

ADACEL can be used for repeat vaccination to boost immunity to diphtheria, tetanus and pertussis at 5 to 10 year intervals (see section 5.1).

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

ADACEL 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 ADACEL should be administered intramuscularly. The preferred site is into the deltoid muscle.

ADACELshould 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

ADACEL should not be administered to person with known hypersensitivity

– to diphtheria, tetanus or pertussis vaccines

– to any other component of the vaccine (see section 6.1)

– to any residual substances carried over from manufacture (formaldehyde and glutaraldehyde), which may be present in undetectable trace amounts.

ADACEL 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 should be postponed in persons suffering from an acute severe febrile illness. The presence of a minor infection is not a contraindication

4.4 Special warnings and precautions for use

ADACEL should not be used for primary immunization.

Regarding the interval between a booster dose of ADACEL and preceding booster doses of diphtheria and/or tetanus containing vaccines, the official recommendations should generally be followed.

Clinical data have demonstrated that there was no clinically relevant difference in rates of adverse reactions associated with administration of a tetanus-, diphtheria- and pertussis-containing booster vaccine 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 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 ADACEL should be based on careful consideration of the potential benefits and possible risks.

ADACEL should not be administered to persons with progressive neurological disorder, uncontrolled epilepsy or progressive encephalopathy until a treatment regimen has been established and the condition has stabilized.

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 administration of ADACEL 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. Procedures should be in place to prevent falling injury and manage syncopal reactions.

The tip caps of the prefilled syringes contain a natural rubber latex derivative, which may cause allergic reactions in latex sensitive individuals.

Other considerations

As with any vaccine, vaccination with ADACEL may not protect 100% of susceptible individuals.

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.

4.5 Interaction with other medicinal products and other forms of interaction

Based on the results of concomitant use clinical studies, ADACEL can be administered concomitantly with any of the following vaccines: inactivated Influenza vaccine, Hepatitis B vaccine, Inactivated or Oral Poliomyelitis vaccine and recombinant Human Papillomavirus vaccine (See section 4.8) according to local recommendations.

Separate limbs must be used for the site of injection of concomitant parenteral vaccines. 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 is an inactivated product itmay be administered concomitantly with other vaccines or immunoglobulins at a separate injection site.

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

4.6 Fertility, pregnancy and lactation

Pregnancy

ADACEL 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 ADACEL or REPEVAX (Tdap-IPV; containing the same amounts of tetanus, diphtheria and pertussis antigens as ADACEL) 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 ADACEL 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.

Breast-feeding

It is not known whether the active substances included in ADACEL are excreted in human milk but antibodies to the vaccine antigens have been found to be transferred to the suckling offspring of rabbits. Two animal developmental studies conducted in rabbits have not shown any harmful effects of maternal antibodies induced by the vaccine on offspring postnatal development.

However, the effect on breast-fed infants of the administration of ADACELto their mothers has not been studied. As ADACEL is inactivated, any risk to the infant is unlikely. The risks and benefits of vaccination should be assessed before making the decision to immunize a nursing woman.

Fertility

ADACEL 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 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 was given to a total of 4,546 persons, including 298 children (4 to 6 years), 1,313 adolescents (11 to 17 years) and 2,935 adults (18 to 64 years). Most commonly reported reactions following vaccination included local reactions at the injection site (pain, redness and swelling) that occurred in 21% – 78% of the vaccinees, headache and tiredness that occurred in 16% –44% of vaccinees. These signs and symptoms usually were mild in intensity and occurred within 48 hours following vaccination. They all resolved without sequelae.

Safety analysis was conducted in 1,042 healthy adolescent males and females aged 10 to 17 years during a clinical trial. They received quadrivalent human papillomavirus types 6/11/16/18 vaccine (Gardasil) concurrently with a dose of ADACEL and a dose of quadrivalent meningococcal conjugate vaccine serogroup A, C, Y and W135. The safety profiles were similar in both concomitant and nonconcomitant groups. Higher frequencies of swelling at the Gardasil injection site, bruising and pain at ADACEL injection sites were observed in the concomitant administration group. The differences observed between concomitant and non-concomitant groups were less than 7% and in a 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:

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 worldwide. 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 trials and worldwide post-marketing experience

Post-marketing Adverse Events

Description of selected adverse reactions

General Disorders and Administration Site Conditions:

Large injection site reactions (>50 mm), including extensive limb swelling from the injection site beyond one or both joints occur after administration of ADACEL in adolescents and adults. These reactions usually start within 24 – 72 hours after vaccination, may be associated with erythema, warmth, tenderness or pain at the injection site and resolve spontaneously within 3 – 5 days.

Paediatric population

The safety profile of ADACEL as presented in Table 1 includes data from a clinical trial in 298 children 4 to 6 years of age who had previously received a total of 4 doses, including primary immunization, with DTaP-IPV combined with Hib, at approximately 2, 4, 6 and 18 months of age. In this clinical study, the most common adverse events reported within 14 days post-vaccination were pain at the injection site (in 39.6 % of subjects) and tiredness (in 31.5 % of subjects).

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.

United Kingdom

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.

5 PHARMACOLOGICAL PROPERTIES

6   PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Phenoxyethanol

Water for injections

6.2 Incompati­bilities

In the absence of compatibility studies, ADACEL must not be mixed with other medicinal products.

6.3 Shelf life

3 years.

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 syringe in the outer carton in order to protect from light.

Stability data indicate that the vaccine components are stable at temperatures up to 25°C for 72 hours. At the end of this period, ADACEL should be used or discarded. These data are intended to guide healthcare professionals in case of temporary temperature excursion only.

6.5 Nature and contents of container

0.5 mL of suspension in pre-filled syringe (glass) with a plunger stopper (bromobutyl elastomer), without

needle, with a tip-cap (rubber compound) – pack size of 1 or 10.

0.5 mL of suspension in pre-filled syringe (glass) with a plunger stopper (bromobutyl elastomer), with a

tip-cap (rubber compound) and 1 or 2 separate needles – pack size of 1 or 10.

The tip caps of the prefilled syringes contain a natural rubber latex derivative.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Instructions for use

Parenteral products should be inspected visually for extraneous particulate matter and/or discolouration 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 pre-filled 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 pre-filled 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.