Consumer medicine information

Quadracel

Diphtheria toxoid; Tetanus toxoid; Pertussis vaccine; Poliomyelitis vaccine (inactivated)

BRAND INFORMATION

Brand name

Quadracel

Active ingredient

Diphtheria toxoid; Tetanus toxoid; Pertussis vaccine; Poliomyelitis vaccine (inactivated)

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Quadracel.

What is in this leaflet

This leaflet answers some common questions about QUADRACEL.

It does not contain all the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines, including vaccines, have risks and benefits. Your doctor has weighed the risks of your child having QUADRACEL against the benefits they expect it will have.

If you have any concerns about this vaccine, ask your doctor, nurse or pharmacist.

Keep this leaflet. You may need to read it again.

What QUADRACEL is used for

QUADRACEL is a vaccine used to help prevent whooping cough, tetanus, diphtheria and polio.

This vaccine is for use in children up to 6 years of age, and is used in infants from the age of 2 months who are at the greatest risk from these diseases.

Polio, whooping cough, tetanus and diphtheria cause significant sickness and sometimes death in unvaccinated infants, children, and adults.

How it works

QUADRACEL works by causing the body to produce its own protection against whooping cough, tetanus, diphtheria, and polio. It does this by making substances called antibodies in the blood, which fight the bacteria and toxins that cause these diseases. If a vaccinated person comes into contact with these bacteria and toxins, the body is usually ready to destroy them.

It usually takes several weeks after vaccination to develop protection against these diseases.

Protection requires 3 doses of this vaccine or this vaccine used alternately with other vaccines protecting against the same diseases. A booster dose may be required between 15 months of age and six years.

Most children will produce enough antibodies against these diseases. However, as with all vaccines, 100% protection cannot be guaranteed.

The vaccine will not give your child any of these diseases.

The chance of a severe reaction from QUADRACEL is very small, but the risks from not being vaccinated against these diseases may be very serious.

Before you are given QUADRACEL

When your child must not be given it

Do not give QUADRACEL to a child who has:

  • an allergy to QUADRACEL or any of the ingredients listed at the end of this leaflet.
  • had an anaphylactic or other allergic reaction to a previous dose of this vaccine or another vaccine designed to protect against whooping cough, tetanus, diphtheria, polio, or Haemophilus influenzae type b.
  • had a serious nervous system disorder within 7 days after a previous whooping cough vaccine
  • progressive nervous system disorder such as infant spasm, uncontrolled epilepsy. The vaccination may be considered only after a treatment has been established and the condition is stabilised.
  • an illness with febrile or acute infection. The vaccination shall be postponed until after the child has recovered.

Symptoms of an allergic reaction may include:

  • shortness of breath, wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • skin rash, itching or hives

Do not use QUADRACEL after the expiry date printed on the pack.

Do not use QUADRACEL if the packaging is torn or shows signs of tampering.

If you are not sure whether your child should have QUADRACEL, talk to your doctor or pharmacist.

Before your child is given it

Tell your doctor if your child has reacted to previous vaccination with any of the following:

  • life-threatening allergic reaction
  • shock-like state or being unresponsive for a long period of time
  • convulsions with or without high temperature
  • high temperature (greater than 40.5°C)
  • persistent crying lasting for more than 3 hours

Tell your doctor if your child has or has had any medical conditions, especially the following:

  • lowered immunity due to diseases (such as HIV/AIDS or cancer) or medicines (such as medicines used to treat cancer including radiation therapy)
  • a higher risk of convulsion than the general population
  • a bleeding disorder or taking blood-thinning medicines

Tell your doctor if your child has allergies to:

  • any other medicines
  • any other substances, such as foods, preservatives or dyes

Having other vaccines

Tell your doctor if your child has had any vaccines in the last 4 weeks. Your doctor will advise you if QUADRACEL is to be given with another vaccine as a separate injection.

How QUADRACEL is given

For infants under the age of 12 months, QUADRACEL is given as an injection into the upper thigh muscle. In older children who have started walking, the vaccine is usually injected into the upper arm muscle.

QUADRACEL should not be injected directly into the veins.

How much is given and when it is given

The primary immunisation schedule is one 0.5mL dose given at 2, 4 and 6 months of age. A booster dose may be given at 15 months to 6 years of age.

If your child misses a dose

If your child misses a dose, talk to your doctor and arrange another visit as soon as possible.

After having QUADRACEL

Things you must do

Keep an updated record of your child's vaccinations.

Keep follow-up appointments with your doctor or clinic. It is important your child has follow-up doses of QUADRACEL at the appropriate times to make sure the vaccine has the best chance of providing protection against whooping cough, tetanus, diphtheria, and polio.

Side effects

Tell your doctor or pharmacist as soon as possible if your child does not feel well after having QUADRACEL. QUADRACEL may have unwanted side effects in a few people. All medicines, including vaccines, can have side effects. Sometimes they are serious, most of the time they are not. Your child may need medical treatment if you get some of the side effects.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • local reaction around the injection site such as redness, tenderness, pain or discomfort, or swelling
  • flushing or redness of the skin
  • fussiness
  • decreased activity
  • decreased eating
  • crying or screaming
  • fever
  • vomiting
  • diarrhoea
  • sleepiness

These are the more common side effects of QUADRACEL. Mostly these are mild and short-lived.

If any of the following happen, tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

  • abscess at the injection site
  • sudden signs of allergic reactions such as rash, itching or hives on the skin, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or trouble breathing
  • convulsions with or without high temperature
  • the child becomes pale, limp and unresponsive
  • pale skin or bluish appearance to finger nails or lips
  • unusual muscle slackness
  • nervous system disorders that may result in headache and fever, progressing to hallucinations, confusion, paralysis of part or all the body, disturbances of behaviour, speech and eye movements, stiff neck and sensitivity to light.

These are very serious side effects. Your child may need urgent medical attention or hospitalisation.

All of these side effects are very rare.

Very rarely children may experience swelling of the whole arm after the booster (4th) dose. This reaction occurs very rarely in association with all vaccines with similar active ingredients to QUADRACEL. It is a short-lived reaction, which resolves spontaneously without any permanent damage.

Other side effects not listed above may occur in some patients. Tell your doctor or pharmacist if you notice anything that is making your child feel unwell.

Do not be alarmed by this list of possible side effects.

Your child may not experience any of them.

After using QUADRACEL

Storage

QUADRACEL is usually stored in the doctor's surgery or clinic, or at the pharmacy. However, if you need to store QUADRACEL:

  • Keep it where children cannot reach it.
  • Keep QUADRACEL in the original pack until it is time for it to be given.
  • Keep it in the refrigerator, between 2°C and 8°C. Do not freeze QUADRACEL.

Freezing destroys the vaccine.

Product description

What it looks like

QUADRACEL is a sterile, uniform, white to off-white suspension for injection.

Ingredients

Active ingredients:

  • 20 microgram pertussis toxoid
  • 20 microgram pertussis filamentous haemagglutinin
  • 5 microgram pertussis fimbriae Types 2+3
  • 3 microgram pertussis pertactin
  • at least 30 IU (15 LF) diphtheria toxoid
  • at least 40 IU (5 LF) tetanus toxoid
  • 40 D-antigen Units Poliovirus inactivated type 1
  • 8 D-antigen Units Poliovirus inactivated type 2
  • 32 D-antigen Units Poliovirus inactivated type 3

Other ingredients:

  • aluminium phosphate
  • phenoxyethanol
  • polysorbate 80
  • albumin - bovine serum
  • polymyxin B sulfate
  • neomycin
  • formaldehyde
  • glutaral
  • water for injections

QUADRACEL does not contain thiomersal, lactose, sucrose, gluten, tartrazine or any other azo dyes.

The manufacture of this product includes exposure to bovine materials. No evidence exists that any case of vCJD (considered to be the human form of bovine spongiform encephalopathy) has resulted from the administration of any vaccine product.

Manufacturer

Sanofi Pasteur Limited
Toronto, Ontario, Canada

Distributor

Australia:

sanofi-aventis australia pty ltd
Talavera Corporate Centre - Building D
12 - 24 Talavera Road
Macquarie Park NSW 2113
Australia
Tel: 1800 829 468

New Zealand:

sanofi-aventis new zealand limited
Level 8, James & Wells Tower
56 Cawley St
Ellerslie
Auckland
New Zealand
Tel: 0800 727 838

Aust R number

Aust R 91355

Date of preparation

16 June 2020

quad-ccdsv4-cmiv2-16jun20

Published by MIMS August 2020

BRAND INFORMATION

Brand name

Quadracel

Active ingredient

Diphtheria toxoid; Tetanus toxoid; Pertussis vaccine; Poliomyelitis vaccine (inactivated)

Schedule

S4

 

1 Name of Medicine

Pertussis vaccine acellular and diphtheria and tetanus toxoids (adsorbed) combined with inactivated poliovirus types 1, 2 and 3 (MRC-5 cell).

2 Qualitative and Quantitative Composition

Each vial of Quadracel contains:
Diphtheria toxoid ≥ 30 IU (15 Lf);
Tetanus toxoid ≥ 40 IU (5 Lf);
Pertussis toxoid (PT) 20 microgram;
Pertussis filamentous haemagglutinin (FHA) 20 microgram;
Pertactin (PRN) 3 microgram;
Pertussis fimbriae 2 + 3 (FIM) 5 microgram;
Poliovirus inactivated type 1, MRC-5 (Mahoney) 40 D-antigen units;
Poliovirus inactivated type 2, MRC-5 (MEF-1) 8 D-antigen units;
Poliovirus inactivated type 3, MRC-5 (Saukett) 32 D-antigen units;
Absorbed on 1.5 mg aluminium phosphate (0.33 mg aluminium).
This product does not contain thiomersal.
The manufacture of this product includes exposure to bovine materials. No evidence exists that any case of variant Creutzfeldt-Jakob disease (vCJD) (considered to be the human form of bovine spongiform encephalopathy) has resulted from the administration of any vaccine product.
Diphtheria toxoid is a cell free preparation of diphtheria toxin detoxified with formaldehyde.
Tetanus toxoid is prepared by detoxification of tetanus toxin with formaldehyde.
Inactivated poliovirus (diploid cell origin) - IPV (sometimes referred to as e-IPV), is an enhanced formaldehyde inactivated product, which has a higher potency than the original IPV. The three poliovirus types are propagated in MRC-5 cells.
The 5 component pertussis antigens, pertussis toxoid (PT), pertussis filamentous haemagglutinin (FHA), pertactin (PRN) and pertussis fimbriae types 2 + 3 (FIM), contained in Quadracel are the same as those in Tripacel or Pediacel. Tripacel consists of an acellular pertussis vaccine combined with diphtheria and tetanus toxoids (DTPa), and has lesser amounts of PT and FHA, while Quadracel has pertussis formulations that are similar to Pediacel. Quadracel contains DTPa combined with inactivated poliovirus vaccine (IPV).
This product contains residual neomycin and polymyxin B sulfate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Quadracel is a sterile, uniform, cloudy white to off-white suspension for injection.

4 Clinical Particulars

4.1 Therapeutic Indications

Quadracel is indicated for primary immunisation of children from the age of 2 months to 12 months against diphtheria, tetanus, whooping cough and poliomyelitis.
Quadracel is also indicated for the fourth dose for children from 15 months to six years of age who have been immunised previously with three doses of diphtheria, tetanus, pertussis and polio vaccines.

4.2 Dose and Method of Administration

Dose.

For primary immunisation of infants the following routine Quadracel immunisation schedule is recommended: one 0.5 mL dose administered intramuscularly at 2, 4 and 6 months of age.
A fourth dose of Quadracel may be administered as a booster dose for children from 15 months to 6 years of age who have been immunised previously with up to three doses of diphtheria, tetanus, pertussis and polio vaccines.
The vaccine should not be administered to individuals after their seventh birthday (see Section 4.4 Special Warnings and Precautions for Use).
Infants born prematurely whose clinical condition is satisfactory should be vaccinated according to their chronological age from birth.

Administration.

Inspect for extraneous particulate matter and/or discolouration before use. If these conditions exist, the product should not be administered.
Shake the vial well to distribute uniformly the suspension before withdrawing each dose. When administering a dose from a stoppered vial, do not remove either the stopper or the metal seal holding it in place. Once the vial has been opened, any of its contents not used immediately should be discarded. Aseptic technique must be used for withdrawal of the dose. Before injection, the skin over the site should be cleansed with a suitable germicide.
Administer the vaccine intramuscularly. The anterolateral thigh is the preferred site for vaccination in infants and children under 12 months of age. The deltoid region is an alternative site for vaccination in older children (those who have commenced walking). If any other vaccines are administered during the same visit, they must be given at separate sites and with separate syringes.
Do not inject intravenously. After insertion of the needle, ensure that the needle has not entered a blood vessel.
Needles should not be recapped and should be disposed of properly.
Product is for single use in one patient only. Discard any residue.
The parent or guardian of the child should be given a card recording the details of the immunisation. In addition, it is essential that the physician or nurse record the immunisation history in the permanent medical record of each patient. This permanent office record should contain the name of the vaccine, date given, dose, manufacturer and lot number.

4.3 Contraindications

Allergy to any component of Quadracel (components listed, see Section 2 Qualitative and Quantitative Composition; Section 6.1 List of Excipients) or an anaphylactic or other allergic reaction to a previous dose of DTP, Tripacel, IPV or to a previous dose of this vaccine are contraindications to vaccination.
Vaccination should be postponed in cases of acute or febrile disease.
Encephalopathy not due to an identifiable cause, occurring within 7 days of a prior whole cell or acellular DTP immunisation 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) is a contraindication to vaccination.
Progressive neurological disorder, including infantile spasms, uncontrolled epilepsy, progressive encephalopathy. Pertussis vaccine should not be administered to individuals with such conditions until a treatment regimen has been established and the condition has stabilised.

4.4 Special Warnings and Precautions for Use

Prior history of severe adverse events following pertussis vaccination.

If any of the following events occur within the specified period after administration of a whole cell pertussis vaccine or a vaccine containing an acellular pertussis component, the decision to administer Quadracel should be based on careful consideration of potential benefits and possible risks. The following events require consideration of whether further doses of Quadracel should be given.
Temperature of ≥ 40.5°C within 48 hours of a dose of Quadracel, not due to another identifiable cause.
Hypotonic/ hyporesponsive episodes within 48 hours. A hypotonic/ hyporesponsive episode is one in which the child becomes pale, limp and unresponsive, lasting from 10 minutes to 36 hours. Shallow respiration and cyanosis are frequently observed. However, resuscitation is rarely required.
Persistent crying lasting ≥ 3 hours within 48 hours.
Convulsions with or without fever within 3 days.
Clinical data in such patients are inadequate. The Australian National Health and Medical Research Council recommends completion of the primary course of vaccination as in its view there is no evidence that these reactions increase the risk of neurological sequelae.
When immunisation with pertussis vaccine is contraindicated, immunisation against diphtheria, tetanus, poliomyelitis and invasive Hib disease may be continued with adsorbed diphtheria and tetanus vaccine and inactivated poliovirus vaccine at separate sites and with separate syringes. The use of fractional doses in an attempt to reduce the severity of adverse reactions cannot be recommended because there is insufficient evidence on the safety or efficacy of such smaller doses.
When pertussis infections are occurring in the community the benefits of pertussis vaccine greatly outweigh any risk of vaccination.
Elective immunisation of individuals over 6 months of age should be deferred during an outbreak of poliomyelitis because of the risk of provocation paralysis.

Hypersensitivity.

Bovine serum albumin, formaldehyde and glutaraldehyde have been used in the manufacturing process of this product and residual trace amounts may be present in the final product. Therefore, a hypersensitivity reaction may occur.
Neomycin and polymyxin B sulphate have been used in the manufacturing process of this product. As each dose may contain residual trace amounts of neomycin and polymyxin B, caution must be exercised when the vaccine is administered to individuals with hypersensitivity to these antibiotics (and other antibiotics of the same class).
The rates and severity of adverse events in recipients of tetanus toxoid are influenced by the number of prior doses and level of pre-existing antitoxins.

Protection.

As with any vaccine, immunisation with Quadracel may not protect 100% of susceptible individuals.
As with other injectable vaccines, appropriate medical treatment and supervision should always be available in case of anaphylactic reactions. Adrenaline should always be readily available whenever the injection is given.

Neurological adverse events.

A review by the US Institute of Medicine (IOM) found evidence for a causal relation between tetanus toxoid and both brachial neuritis and Guillain-Barré syndrome (GBS). If GBS occurred within 6 weeks of receipt of prior vaccine containing tetanus toxoid, the decision to give Quadracel or any vaccine containing tetanus toxoid should be based on careful consideration of the potential benefits and possible risks.
For infants or children at higher risk for seizures than the general population, an appropriate antipyretic may be administered (in the dosage recommended in its prescribing information) at the time of vaccination with a vaccine containing an acellular pertussis component (including Quadracel) and for the following 24 hours, to reduce the possibility of post-vaccination fever.
Parents of infants and children with a personal or family history of convulsions should be informed of their children's increased risk of seizures following administration of any vaccine causing a febrile reaction. A family history of convulsions in parents and siblings is not a contraindication to pertussis vaccination. Paracetamol prophylaxis is particularly recommended for a child with a personal history of convulsions.

Administration route-related precautions.

Do not administer by intradermal or intravenous injection. Ensure that the needle does not enter a blood vessel.
The vaccine must be given intramuscularly, as subcutaneous administration increases the chances of a local reaction.
Intramuscular injections should be given with care in individuals suffering from coagulation disorders or on anticoagulant therapy because of the risk of haemorrhage.
Quadracel should not be administered into the buttocks due to the varying amount of fatty tissue in this region, nor by the intradermal route, since these methods of administration may induce a weaker immune response.
Use a separate sterile needle and syringe, or a sterile disposable unit, for each individual patient to prevent disease transmission.

Use in individuals with altered immune status.

There are currently no data to support the use of Quadracel in individuals with an immunodeficiency. However, it is generally advised that HIV-infected individuals, both asymptomatic and symptomatic, should be immunised against diphtheria, pertussis, tetanus, poliomyelitis and invasive Hib disease according to standard schedules.
If Quadracel is used in individuals with malignancies, receiving immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs, who are otherwise immunocompromised, including HIV-infected individuals, or on corticosteroid therapy, the expected immune response may not be obtained.
The immunogenicity of Quadracel could be reduced by immunosuppressive treatment. In such cases it is recommended to postpone the vaccination until the end of the immunosuppression. Nevertheless, vaccination of individuals with chronic immunodeficiency such as HIV infection is recommended even if the antibody response may be limited.

Use in the elderly.

Quadracel should not be used in adults.

Paediatric use.

Quadracel should not be administered to children after their seventh birthday or to adults because the quantity of diphtheria toxoid and pertussis antigens may provoke enhanced local reactions, fever and malaise.
The potential risk of apnoea and the need for respiratory monitoring for 48-72 hours should be considered when administering the primary immunisation series to very premature infants (born ≤ 28 weeks of gestation) and particularly for those with a previous history of respiratory immaturity. As the benefit of vaccination is high in this group of infants, vaccination should not be withheld or delayed.
Before administration of Quadracel, health-care providers should inform the patient, parent or guardian of the benefits and risks of immunisation, inquire about the recent health status of the patient and comply with any local requirements regarding information to be provided to the patient before immunisation and the importance of completing the immunisation series.
It is extremely important when a child returns for the next dose in the series that the patient, parent or guardian should be questioned concerning any symptoms and/or signs of an adverse reaction after the previous dose of vaccine.

Effects on laboratory tests.

Interference of Quadracel with laboratory tests has not been studied.

4.5 Interactions with Other Medicines and Other Forms of Interactions

When both vaccines are indicated, Quadracel may be used to reconstitute Act-HIB (Haemophilus influenzae type b polysaccharide conjugated to tetanus protein) for simultaneous administration of all 5 antigens in a single injection. Quadracel must not be mixed in the same syringe with any other vaccines.
There are currently no data regarding the concomitant administration of Quadracel with MMR or hepatitis B vaccine. The Australian Immunisation Handbook accepts that inactivated vaccines can be given during the same visit at separate sites with separate syringes. MMR and hepatitis B vaccine may be administered simultaneously with Quadracel for children who are the recommended age to receive them.
Immunosuppressive treatments may interfere with the development of the expected immune response.
As with other intramuscular injections, Quadracel should be given with caution to children on anticoagulant therapy.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Quadracel has not been evaluated for the effects on fertility.
(Category B2)
Not applicable. Quadracel should not be used in adults.
Not applicable. Quadracel should not be used in adults.

4.7 Effects on Ability to Drive and Use Machines

Not applicable - for paediatric use only.

4.8 Adverse Effects (Undesirable Effects)

Clinical trials experience.

The most frequent reactions observed with Quadracel include redness and tenderness at the injection site, irritability and slight fever. These symptoms usually occur within the first 24 hours after vaccination and may continue for 24-48 hours. The rates of adverse events observed in children who received Quadracel at 2, 4, 6 and 18 months of age during a clinical trial with the vaccine in Canada are shown in Table 1.
In a clinical trial conducted in Sweden comparing three acellular pertussis vaccines and one whole cell DTP vaccine, 20,745 infants received a "hybrid" formulation of Tripacel which contained the same amounts of pertussis antigens as in Quadracel at 2, 4 and 6 or 3, 5 and 12 months of age. Rates of adverse events were less than or comparable to the rates in the other acellular pertussis vaccine and whole cell DTP groups in this study. The rates of reports of fever > 40.5°C and seizures or suspected seizures were significantly higher following whole cell DTP than following acellular pertussis vaccines. Rates of hypotonic/ hyporesponsive episodes were comparable, with 29 reports following administration of Tripacel. No deaths or cases of encephalitis/ acute encephalopathy, invasive bacterial infection, infantile spasms or anaphylactic reactions were reported within 48 hours of vaccination.
There are currently no clinical data to support administration of a fifth dose with Quadracel. In a study conducted by the U.S. National Institutes of Health (NIH), thirteen different formulations of acellular pertussis vaccines combined with diphtheria and tetanus toxoids (DTPa), including Tripacel (containing less PT and FHA than Quadracel), were evaluated for safety and immunogenicity when administered at 2, 4, 6 and 18 months, and 4 - 6 years of age. In an analysis of fourth and fifth dose follow-up studies from this multicentre trial, entire limb swelling was reported in 20 children (2%) of 1,015 children who received four consecutive doses of the same DTPa. It was found that large injection site reactions occurred more frequently after the fifth dose of DTPa than after the previous fourth dose. No reports were received of entire limb swelling in 121 children who received a fifth dose of the same DTPa. In 146 recipients who received 5 doses with different DTPa vaccines, 4 (2.7%) children were reported to have such swelling. In all reports the swelling subsided spontaneously and completely, without sequelae.

Data from postmarketing experience.

The following have been reported in postmarketing experience with component acellular pertussis combination vaccines and other tetanus toxoid, diphtheria toxoid, acellular pertussis and polio containing vaccines (see Table 2).
As with any vaccine, there is the possibility that broad use of the vaccine could reveal rare adverse reactions not observed in clinical trials.
The following additional adverse events have been spontaneously reported during the postmarketing use of Quadracel worldwide. Because these 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.

Immune system disorders.

Anaphylactic reaction, hypersensitivity and allergic reactions (such as rash, urticaria, dyspnoea).

Psychiatric disorders.

Screaming.

Nervous system disorders.

Somnolence, convulsion, febrile convulsion, hypotonic-hyporesponsive episode, hypotonia.

Cardiac disorders.

Cyanosis.

Vascular disorders.

Pallor.

General disorders and administration site conditions.

Injection site reactions (including inflammation, mass, abscess and sterile abscess), oedema.
Listlessness.
Large injection site reactions (> 50 mm), including limb swelling which may extend from the injection site beyond one or both joints have been reported in children following Quadracel administration. 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. The risk appears to be dependent on the number of prior doses of d/DTPa vaccine, with a greater risk following the 4th and 5th doses.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.9 Overdose

There are no reports of overdosage.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Bacterial and Viral Vaccines, Combined, ATC code: J07CA02.

Clinical trials.

Studies of protective efficacy of Tripacel against pertussis.

A randomised controlled double blind efficacy study was conducted in Sweden (Trial 1) where 2,551 infants received the regular formulation of Tripacel (containing lower concentrations of PT and FHA than Quadracel) and 2,539 received a control vaccine containing diphtheria and tetanus toxoids at 2, 4 and 6 months of age. Tripacel was shown to have an absolute vaccine efficacy of 85% (95% CI: 81%- 89%) against pertussis disease (defined as at least 21 days of paroxysmal cough with culture, serologic or epidemiologic confirmation of infection with Bordetella pertussis). The incidence of local and systemic reactions after administration of Tripacel was comparable to the diphtheria tetanus vaccine (DT) control group.
A second randomised, double blind controlled efficacy trial (Trial 2) was carried out in Sweden with 82,892 infants comparing 3 acellular pertussis and one European whole cell DTP vaccines where 20,746 infants received a "hybrid" formulation of Tripacel (DTPa) which contained the same concentration of pertussis antigens as Quadracel, at 2, 4 and 6 (n = 2,552) or 3, 5 and 12 (n = 18,194) months of age. The "hybrid" Tripacel and the European whole cell DTP vaccine had similar and high efficacy against culture confirmed pertussis irrespective of duration. The other acellular pertussis combination vaccines were less effective. Rates of adverse events were less than or comparable to the rates observed in the other acellular pertussis and European whole cell DTP groups in this study.

Immunogenicity of Quadracel.

In a clinical trial conducted in Canada, infants received either Pediacel (n = 339), Penta (Act-HIB reconstituted with a whole cell pertussis DTP-IPV vaccine) (n = 112), Poliacel (Quadracel used to reconstitute Act-HIB) (n = 335), or Quadracel and Act-HIB, given at separate sites at the same visit (n = 113) at 2, 4 and 6 months of age. Of the 899 children enrolled, 798 received a fourth dose of the same vaccine at 18-20 months of age. Serologic responses are shown in Table 3.
The following antibody levels are considered to be protective: diphtheria, diphtheria antitoxin levels ≥ 0.01 IU/mL; tetanus, tetanus antitoxin levels ≥ 0.01 IU/mL; and poliomyelitis, neutralising poliovirus antibody titre levels ≥ 1:8.
The pertussis antibody responses observed with Quadracel were comparable to those observed following administration of the two different formulations of Tripacel (component pertussis vaccine combined with diphtheria and tetanus toxoids adsorbed), given at 2, 4 and 6 months, in the two Swedish pertussis efficacy trials (Table 4).

5.2 Pharmacokinetic Properties

No pharmacokinetic studies have been performed.

5.3 Preclinical Safety Data

Genotoxicity.

Quadracel has not been evaluated for the genotoxic potential.

Carcinogenicity.

Quadracel has not been evaluated for the carcinogenic potential.

6 Pharmaceutical Particulars

6.1 List of Excipients

Aluminium phosphate, phenoxyethanol, polysorbate 80, bovine serum albumin, polymyxin B sulfate, neomycin, formaldehyde, glutaral, water for injections.

6.2 Incompatibilities

Clinical studies have demonstrated that Quadracel may be used to reconstitute freeze dried Act-HIB.
The vaccine must not be mixed with other vaccines or medicinal products (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store at 2° to 8°C. Refrigerate. Do not freeze. Do not use after expiry date.

6.5 Nature and Contents of Container

Quadracel is supplied in packs containing one vial and in packs containing 5 vials.

6.6 Special Precautions for Disposal

After use, any remaining vaccine and container must be disposed of safely according to locally agreed procedures.

6.7 Physicochemical Properties

No data available.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes