INFORMATION FOR HEALTH PROFESSIONALS
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QUADRACEL® is a sterile, cloudy, uniform suspension for injection.
Each vial of QUADRACEL® contains:
| 20 µg | pertussis toxoid |
| 20 µg | pertussis filamentous haemagglutinin |
| 5 µg | pertussis fimbriae 2+3 |
| 3 µg | pertussis 69kDa outer membrane protein |
| ≥30 IU (15 LfU) | diphtheria toxoid |
| ≥40 IU (5 LfU) | tetanus toxoid |
| 40 DagU | poliovirus inactivated type 1, MRC-5 (Mahoney) |
| 8 DagU | poliovirus inactivated type 2, MRC-5 (MEF1) |
| 32 DagU | poliovirus inactivated type 3, MRC-5 (Saukett) |
| 1.5 mg | aluminium phosphate |
| 0.6% v/v | phenoxyethanol |
| ≥0.02% | polysorbate 80 |
| ≤50 ng | albumin - bovine serum |
| <4 pg | polymyxin B sulfate |
| <4 pg | neomycin |
| ≤0.02% | formaldehyde |
| ≤0.1% | glutaraldehyde |
| Water for injections | to 0.5 mL |
This product does not contain thimerosal.
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), filamentous haemagglutinin (FHA), 69kDa membrane protein (pertactin or PRN) and fimbriae 2 and 3 (FIM), contained in QUADRACEL® are the same as those in TRIPACEL®, POLIACEL®, or PEDIACEL®. TRIPACEL® consists of an acellular pertussis vaccine combined with diphtheria and tetanus toxoids (DTaP), and has lesser amounts of PT and FHA, while POLIACEL® and QUADRACEL® have pertussis formulations that are similar to PEDIACEL®. QUADRACEL® contains DTaP combined with inactivated poliovirus vaccine (IPV). POLIACEL® consists of Act-HIB® reconstituted with QUADRACEL® resulting in a combination of vaccine antigens that are similar to the fully liquid PEDIACEL® at the time of administration.
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 DPT vaccines where 20,746 infants received a "hybrid" formulation of TRIPACEL® (DTaP) 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 DPT 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 DPT groups in this study.
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 1.
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, neutralizing poliovirus antibody titre levels ≥ 1:8.
Table 1: Antibody responses observed one month after a third and fourth dose with QUADRACEL®
| Antibody Response | 1 month Post-Dose 3 (7 months of age) (n = 108) |
1 month Post-Dose 4 (17 - 19 months of age) (n = 103) |
|---|---|---|
| % diphtheria antitoxin | ||
| ≥0.01 IU/mL | 99.1 | 100 |
| % tetanus antitoxin | ||
| ≥0.01 EU/mL | 100 | 100 |
| % polio ≥1:8: | ||
| Type 1 | 98.1 | 100 |
| Type 2 | 100 | 100 |
| Type 3 | 99.1 | 100 |
| GMT: | ||
| PT | 103 | 223 |
| FHA | 165 | 252 |
| FIM | 332 | 1079 |
| Pertactin | 40.5 | 160 |
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 2-4-6 months, in the two Swedish pertussis efficacy
trials (Table 2).
Table 2. Comparison of pertussis antibody GMTs obtained one month after a 3-dose primary series given at 2-4-6 months of age with TRIPACEL® in the two Swedish efficacy trials with those reported in a Canadian trial with QUADRACEL®
| Antibody to | TRIPACEL® Sweden Trial 1 (n = 178) |
TRIPACEL® * Sweden Trial 2 (n = 80) |
QUADRACEL® Canadian trial (n = 108) |
|
|---|---|---|---|---|
| PT | GMT | 49.4 | 51.6 | 103 |
| 95% CI | 44.8 - 54.4 | 44.8 - 59.5 | 90.5- 116 | |
| FHA | GMT | 34.1 | 57.0 | 165 |
| 95% CI | 30.8 - 37.8 | 49.1 - 66.2 | 148 - 184 | |
| Pertactin | GMT | 116 | 134 | 40.5 |
| 95% CI | 103 - 132 | 111 - 163 | 33.0 - 49.7 | |
| FIM | GMT | 351 | 352 | 332 |
| 95% CI | 301 - 408 | 273 - 454 | 265 - 417 | |
Note: * The TRIPACEL® used in Sweden Trial 2 was a "hybrid" formulation of the currently licensed TRIPACEL® which had higher amounts of PT and FHA and contained pertussis antigen concentrations that were similar to those for QUADRACEL®.
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.
Allergy to any component of QUADRACEL® (see components listed in DESCRIPTION) 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.
Encephalopathy not due to an identifiable cause, occurring within 7 days of a prior whole-cell or acellular DPT 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.
The following events require consideration of whether further doses of QUADRACEL® should be given:
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. QUADRACEL® should be deferred in children with a progressive, evolving, or unstable neurologic condition (including seizures) because 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 immunisation with pertussis vaccine until further observation and study have clarified the child's neurologic status. In addition, the effect of treatment, if any, can be assessed. Vaccination with QUADRACEL® may be deferred in children who have had a convulsion in the past three weeks. Immunisation with QUADRACEL® should be undertaken when the condition has been controlled or stabilized or resolved.
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.
Do not administer by intradermal or intravenous injection. Ensure that the needle does not enter a blood vessel.
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.
Intramuscular injections should be given with care in persons suffering from coagulation disorders or on anticoagulant therapy because of the risk of haemorrhage.
Vaccination should be delayed in the presence of any acute disease.
Vaccination should be postponed in the event of febrile illness. The presence of a minor infection is not a contraindication.
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.
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.
There are currently no data to support the use of QUADRACEL® in persons 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.
Before administration of QUADRACEL®, health-care providers should inform the patient, parent or guardian of the benefits and risks of immunization, 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.
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.
The vaccine must be given intramuscularly, as subcutaneous administration increases the chances of a local reaction.
If QUADRACEL® is used in persons 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.
As with any vaccine, immunisation with QUADRACEL® may not protect 100% of susceptible individuals.
Elective immunisation of persons over 6 months of age should be deferred during an outbreak of poliomyelitis because of the risk of provocation paralysis.
QUADRACEL® has not been evaluated for carcinogenicity, mutagenicity or impairment of fertility.
QUADRACEL® should not be used in adults.
QUADRACEL® should not be used in adults
QUADRACEL® should not be used in adults
See DOSAGE AND ADMINISTRATION.
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. A combination vaccine pack, POLIACEL® is provided for this purpose. 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 2000" 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.
Children receiving immunosuppressive therapy may have a reduced response to active immunisation procedures.
As with other intramuscular injections, QUADRACEL® should be given with caution to children on anticoagulant therapy.
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 3.
Table 3. Adverse event rates (%) observed within 24 and 24 to 72 hours of vaccination with QUADRACEL® according to age and number of doses.
| 1st Dose 2 months (n = 113) |
2nd Dose 4 months (n = 111) |
3rd Dose 6 months (n = 111) |
4th Dose 18 months (n = 104) |
||||||
|---|---|---|---|---|---|---|---|---|---|
| Reaction | Severity | 0-24* | 24-72* | 0-24* | 24-72* | 0-24* | 24-72* | 0-24* | 24-72* |
| redness | severe¥ any |
0 0.9 |
0 0 |
0 8.1 |
0 1.8 |
0 12.6 |
0 4.5 |
1.9 18.3 |
10.6 19.2 |
| swelling | severe¥ any |
2.7 5.3 |
0 4.5 |
0.9 3.6 |
0 1.8 |
0.9 7.2 |
0 3.6 |
4.8 13.5 |
6.7 14.4 |
| tenderness | severe any |
1.8 18.6 |
0 1.8 |
3.6 18.0 |
0 1.8 |
0 9.0 |
0 0 |
0 28.9 |
0 6.7 |
| fever | severe§ any |
0 22.1 |
0 2.7 |
0 21.1 |
0 9.4 |
0 18.0 |
0.9 4.6 |
0 24.0 |
0 10.8 |
| fussiness | severe any |
2.7 46.0 |
0.9 29.5 |
0 45.0 |
0 20.0 |
0 35.1 |
0 27.0 |
1.0 33.7 |
0 16.4 |
| crying | severe any |
1.8 31.0 |
0 6.3 |
0 28.8 |
0 18.2 |
0 23.4 |
0 17.1 |
0 19.2 |
0 10.6 |
| decreased activity | severe any |
0.9 51.3 |
0 20.5 |
0.9 27.9 |
0 16.4 |
0 21.6 |
0 9.0 |
0 16.4 |
0 4.8 |
| decreased eating | severe any |
0 34.5 |
0 17.0 |
0 20.7 |
0 18.2 |
0 16.2 |
0 19.8 |
0 20.2 |
0 15.4 |
| vomiting | severe any |
0 8.0 |
0 6.3 |
0 2.7 |
0 0.9 |
0 6.3 |
0 5.4 |
0 6.7 |
0 3.9 |
| diarrhea | severe any |
0 6.2 |
0 9.8 |
0 7.2 |
0.9 7.3 |
0 9.9 |
0 9.0 |
0 2.88 |
0.96 7.69 |
| Note: | * | interval of time in hours following vaccination |
| ¥ | redness or swelling ≥35 mm | |
| § | fever ≥40.0°C |
In a clinical trial conducted in Sweden comparing three acellular pertussis
vaccines and one whole-cell DPT 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 (DTaP), 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 multicenter trial, entire limb swelling was reported in 20 children (2%) of 1,015 children who received four consecutive doses of the same DTaP. It was found that large injection site reactions occurred more frequently after the fifth dose of DTaP 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 DTaP. In 146 recipients who received 5 doses with different DTaP vaccines, 4 (2.7%) children were reported to have such swelling. In all reports the swelling subsided spontaneously and completely, without sequelae.
The following have been reported in post-marketing experience with component acellular pertussis combination vaccines and other tetanus toxoid-, diphtheria toxoid-, acellular pertussis-, and polio-containing vaccines.
| Application Site Disorders | |
| Very Rare (<1/10,000) | the following have been reported
following administration of tetanus and/or diphtheria toxoid and/or
pertussis and/or Act-HIB®-containing vaccines: granuloma or sterile abscess at vaccination site, painless circumferential limb swelling following booster doses which resolves spontaneously, oedema of the lower extremities with cyanosis or transient purpura. |
| Body as a Whole - General Disorders: | |
| Rare (< 1/1,000 to ≥ 1/10,000) |
hypotonic/hyporesponsive episodes*, unusual high-pitched or inconsolable crying |
| Very Rare (<1/10,000) | the following have been reported following administration of tetanus
and/or diphtheria toxoid and/or pertussis and/or Act-HIB®-containing
vaccines: anaphylactic reaction |
| Central and Peripheral Nervous System Disorders: | |
| Uncommon (< 1/100 to ≥ 1/1000) |
febrile convulsions |
| Very Rare (<1/10,000) | the following have been reported
following administration of tetanus and/or diphtheria toxoid and/or
pertussis and/or Act-HIB® containing vaccines: peripheral neuropathies, demyelinating disease, encephalopathy with and without permanent intellectual and/or motor impairment, polyradiculopathies |
* hypotonic/hyporesponsive episodes (infant appears pale, hypotonic (limp) and
unresponsive) have not to date been associated with any permanent sequellae
As with any vaccine, there is the possibility that broad use of the vaccine could reveal rare adverse reactions not observed in clinical trials.
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 persons after their seventh birthday (see precautions).
Infants born prematurely whose clinical condition is satisfactory should be vaccinated according to their chronological age from birth.
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.
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 immunization 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.
Do not inject intravenously.
There are no reports of overdosage.
QUADRACEL® is supplied in packs containing one vial and packs of 5 vials.
Store at 2° to 8°C. REFRIGERATE. DO NOT FREEZE. Do not use after expiry date.
Prescription Medicine
Sanofi Pasteur Limited
Toronto,
Ontario,
Canada
Australia:
Sanofi Pasteur Pty. Ltd.
ABN 79 085 258 797
Talavera Corporate Centre - Building D
12-24 Talavera Road
Macquarie Park NSW 2113
Australia
Tel: 1800 829 468
New Zealand:
sanofi-aventis limited new zealand
Level 8, james & Wells Tower
56 Cawley St
Elelrslie
Auckland
New Zealand
Tel: 0800 727 838
Prescription Medicine
1 November 2007