Data Sheet

TRIPLE ANTIGEN™

Diphtheria, Tetanus and Pertussis Vaccine (Adsorbed)

Description

Triple Antigen™ is a vaccine composed of a mixture of Diphtheria toxoid, Tetanus toxoid and killed organisms of strains of Bordetella pertussis.

Each 0.5 mL dose of Triple Antigen™ has a potency of not less than 30 International Units (IU) of purified diphtheria toxoid, not less than 60 IU of purified tetanus toxoid, with not more than 20,000 million organisms of Bordetella pertussis (inactivated) with an estimated potency of not less than 4 IU.

The vaccine also contains thiomersal 0.01% w/v as a preservative, aluminium phosphate as an adjuvant, sodium phosphate and sodium chloride in an aqueous solution.

Pharmacology

Following intramuscular administration, Triple Antigen™ stimulates production of antibodies which protect against the diseases caused by each of the three infective organisms. Effective protection requires the administration of three consecutive injections of Triple Antigen™, preferably at 4 to 8 week intervals. Longer intervals do not appear to impair the final immune response.

Clinical Trials

In a clinical study conducted in Australia (1993-1994), 600 children received the first dose of a primary immunisation course of Triple Antigen™ at age 2 months, and 200 children completed the course at 4 and 6 months of age.

The following table shows the geometric mean titres for antibodies before and after vaccination. The protective antibody level for diphtheria and tetanus is considered to be 0.01 IU/mL; protective levels for the pertussis antibodies are not known. Protective antibody levels for diphtheria and tetanus were present in all the children evaluated for immunogenicity following the course of injections. Some children showed protective antibody levels prior to vaccination.

Indications

Triple Antigen™ is indicated for active immunisation against diphtheria, tetanus and pertussis for children and infants over 2 months of age.

Contraindications

Hypersensitivity to any components of Triple Antigen™, or an immediate severe allergic or anaphylactic reaction to a previous dose of a whole cell or acellular Diphtheria, Tetanus and Pertussis (DTP) vaccine.

Encephalopathy not due to an identifiable cause, occurring within 7 days of a previous injection of a pertussis-containing vaccine, and characterised by a severe acute neurological illness with prolonged seizures and/or unconsciousness and/or focal neurological signs, but not a simple febrile convulsion.

Precautions

DO NOT administer by any route other than by deep intramuscular injection. Injections given subcutaneously are believed to increase the risk of local reactions.

Vaccination with Triple Antigen™ should be deferred in the presence of any major acute illness, including high fever. A minor febrile illness is not usually a reason to defer vaccination.

Triple Antigen™ should be deferred in children with active or progressive neurological disease, including those who have had a convulsion in the past 3 weeks. Administration of the pertussis component may coincide with the onset of overt manifestations of such disorders and result in confusion about causation. It is prudent to defer vaccination with a pertussis-containing vaccine until further observation and study have clarified the child's neurological status. Vaccination with Triple Antigen™ should be undertaken when the condition has been controlled or stabilised or resolved. If there is doubt in individual cases, it may be appropriate to obtain specialist medical advice.

Caution, on an individual basis, should be exercised in children with a history of allergy. Such a history is generally not considered to be a contraindication to childhood immunisation but care should be taken to ensure that the child is not allergic to any component of the vaccine (See CONTRAINDICATIONS).

As with other injectable vaccines, appropriate medical treatment and supervision should always be available in case of anaphylactic reactions. Adrenalin should always be readily available whenever the injection is given.

Immunisation with Triple Antigen™ should be replaced by immunisation with a combined diphtheria and tetanus vaccine (ie CDT™ Vaccine) in:

(a) children in whom the pertussis component is contraindicated;

(b) children who have already suffered a bacteriologically confirmed attack of pertussis.

An accurate and detailed history must be sought about a child's reaction to a previous dose of Triple Antigen™ or any other vaccine. The following post vaccination events require consideration of whether further doses of Triple Antigen™ should be given:

• Fever of 40.5°C or greater within 48 hours, not due to another identifiable cause;
• Hypotonic hyporesponsive episodes within 48 hours;
• Inconsolable crying for 3 hours or longer occurring within 3 days
• Convulsions, with or without fever, within 3 days
• Severe local reaction within 48 hours of vaccination (characterised by extensive circumferential swelling and redness). This reaction is sometimes followed later by a sterile abscess and may be due to inadvertent subcutaneous rather than intramuscular injection.

Clinical data with further doses of Triple Antigen™ or other pertussis-containing vaccines in such patients are inadequate. Immunisation should be completed with a combined diphtheria and tetanus vaccine (ie CDT™ Vaccine). However, the Australian National Health and Medical Research Council recommends completion of the primary course of vaccination, under close medical supervision, as there is no evidence that these reactions increase the risk of neurological sequelae.

Triple Antigen™ may not induce protective antibody levels for up to four weeks following completion of the primary vaccination course, and may not result in a positive antibody response in all individuals given the vaccine. Individuals remain at risk prior to the development of a protective immune response. In immunosuppressed patients, the antibody responses may be diminished.

Use in Pregnancy

Not relevant.

Use in Lactation

Not relevant.

Adverse Reactions

Clinical trial data

In the clinical trial, the frequency of adverse reactions in the first 36 hours is shown in the following table.

One incident of hypotonic hyporesponsive episode (HHE) was reported in this study.

Post-marketing data

A variety of adverse reactions have been reported with clinical use of Triple Antigen™. The reactions are summarised below and categorised by frequency according to the following definitions. Very common: ≥ 1/10; common: <1/10 and ≥1/100; uncommon: <1/100 and ≥1/1000, rare: <1/1000 and ≥1/10,000 and very rare: <1/10,000.

Mild to moderate local and systemic effects occur commonly. More severe reactions occur rarely.

Local Reactions

Very common: Redness, Swelling, Tenderness, Nodule formation

Rare: Abscess formation, Extensive circumferential swelling

Systemic Reactions

Very common: Fever ≥38°C, Irritability, Abnormal crying (Crying more than usual), Malaise, Vomiting

Uncommon: High pitched persistent crying, Constant inconsolable crying

Rare: Convulsions, Hypotonic hyporesponsive episodes, Pallor

Very Rare: Encephalopathy, Anaphylaxis

Encephalopathy is a very rare sequel of pertussis immunisation. A causal relationship has not been established.

Hypotonic hyporesponsive episodes may occur within 48 hours after the vaccination. HHE is a collapse or shock-like state characterised by the child becoming pale, limp and unresponsive. Shallow respiration and cyanosis are frequently observed. The episode may last from a few minutes to 36 hours. Resuscitation is rarely required. Follow up of children with HHE shows no long-term neurological or other sequelae.

Drowsiness, apnoea and cyanosis, rash, urticaria and oedema have been described in spontaneous post-marketing reports, however, causal relationships have not been established.

If a severe local or systemic reaction occurs, consideration should be given to administration of further doses of Triple Antigen™ (see Contraindications and Precautions). CDT™ Vaccine should be substituted to complete the course.

Dosage and Administration

The dose of Triple Antigen™ is 0.5 mL given by deep intramuscular injection into the lateral aspect of the thigh or deltoid muscle. Alternate limbs should be used for each injection. DO NOT administer by any route other than by deep intramuscular injection.

Containers of Triple Antigen™ should be shaken vigorously immediately before opening and the vaccine should be injected as soon as possible after the syringe is filled.

Injection technique may contribute to the severity of local reactions, including abscess formation at the injection site, as a result of the antigen seeding the needle track. The following precautions have been suggested:

1. When withdrawing the antigen into the syringe avoid any residue on the outer surface of the needle.
2. Administer by deep intramuscular injection.
3. Inject slowly so as to allow the injected material to disperse instead of coming up the needle track.

For routine immunisation of children, injections of Triple Antigen™ should be given at 2, 4 and 6 months of age with a booster dose at 18 months of age.

If for any reason the schedule is delayed, the first three doses should be administered with an interval of 4 to 8 weeks between doses and a booster dose given one year later.

If, at any age, the primary course is interrupted, it should be resumed but not repeated, allowing appropriate time intervals between the remaining doses.

Each child who is immunised should receive a permanent personal immunisation record, which is updated at the time of each injection. The records of the person administering the vaccine should include the name of the vaccine, the date given, the dose, the name of the manufacturer and the lot number.

If Triple Antigen™ is administered at the same time as other vaccines, separate syringes and different sites must be used.

Administration of paracetamol (15 mg/kg per dose) at the time of the injection and 3-4 hourly afterwards up to a maximum of 6 doses in 24 hours may reduce both the local and systemic side effects of the vaccine.

Overdosage

No information is available.

Presentation

Triple Antigen™ is issued in 0.5 mL containers.

Storage

Triple Antigen™ should be protected from light and stored at 2° to 8°C. Do not freeze.

Medicine Classification

Prescription Medicine.

Name and Address

Distributed by:

CSL (New Zealand) Limited
Level 4, Building 10
Central Park
666 Great South Road
Auckland
NEW ZEALAND

Telephone: 09 579 8105

Manufactured by:

CSL Limited ACN 051 588 348
45 Poplar Road
Parkville 3052 VICTORIA AUSTRALIA

Date of Preparation

25 June 1999

Triple Antigen™ and CDT™ Vaccine are trademarks of CSL Limited.