SmithKline Beecham International - Pharmaceuticals
[CPI Pack Insert]
Permitted in sport
Use: Active immunisation against diphtheria, tetanus and pertussis
Contraindications: Acute severe febrile illness; IV admin.
Precautions: Previous reaction to DTPw (see MIMS Annual); immunodeficiency
Adverse Reactions: Inj. site redness, swelling, pain; fever; loss of appetite; GI upset; drowsiness; restlessness; sleep disturbances
Infanrix (Injection) Rx
Diphtheria toxoid; Tetanus toxoid; Pertussis vaccine; Diphtheria toxoid 25 Lf, tetanus toxoid 10 Lf, purified Bordetella pertussis antigens (pertussis toxoid 25 mcg, filamentous haemagglutinin 25 mcg, 69 kDA outer membrane protein 8 mcg) per 0.5 mL; aluminium hydroxide (adsorbant),
2-phenoxyethanol; sterile susp; single dose prefilled syringe; Gluten free.
Pack(s): 0.5 mL .Fields[1]: $40.24
Dose: 0.5 mL IMI. Primary course: 3 doses at 2, 4 and 6 months, then 4th dose at 18 months, 5th dose at 4-5 years
Composition
Active.
Diphtheria toxoid, tetanus toxoid and three purified antigens of Bordetella pertussis (pertussis toxoid (PT), filamentous haemagglutinin (FHA) and 69 kilodalton (kDa) outer membrane protein (OMP)).
Inactive.
Aluminium hydroxide, sodium chloride; 2-phenoxyethanol as preservative.
Description
Infanrix DTPa vaccine is a sterile suspension which contains diphtheria toxoid, tetanus toxoid and three purified antigens of Bordetella pertussis adsorbed onto aluminium hydroxide. The diphtheria and tetanus toxins are obtained from cultures of Corynebacterium diphtheriae and Clostridium tetani and are then detoxified and purified. The acellular pertussis vaccine components (PT, FHA and 69 kDa OMP) are extracted from phase I Bordetella pertussis, and are then purified and stabilised.
Each 0.5 mL dose of Infanrix contains not less than diphtheria toxoid 25 Lf, tetanus toxoid 10 Lf, PT 25 microgram, FHA 25 microgram and 69 kDa OMP 8 microgram. The diphtheria toxoid, tetanus toxoid and acellular pertussis vaccine (DTPa) components are adsorbed on aluminium 0.5 mg in the form of aluminium hydroxide, and suspended in isotonic sodium chloride.
Infanrix meets the World Health Organization requirements for biological substances and for diphtheria and tetanus vaccines. No substances of human origin are used in its manufacture.
Actions
Infanrix (DTPa vaccine) induces antibodies against all vaccine components.
Clinical trials.
Primary immunisation protective efficacy studies.
In a randomised, double blind, controlled clinical study conducted in Italy, the efficacy of a primary vaccination course of Infanrix against pertussis was assessed. Pertussis was defined as illness with paroxysmal cough of greater than or equal to 21 days, and confirmation of B. pertussis infection by culture or serology. Infants were administered three vaccine doses at two, four and six months of age, and followed for an average of 17 months. Of 4,481 infants receiving three doses of Infanrix, 37 confirmed cases of pertussis were reported. Of 1,470 infants in the control group receiving three doses of diphtheria and tetanus antigens only, 74 confirmed cases of pertussis were reported. Infanrix vaccine efficacy was calculated to be 83.9% with a two sided 95% confidence interval of 75.8 to 89.4%. Blood samples were collected from a 10% subset of children. Response to diphtheria and tetanus antigens (antibody titre > 0.1 IU/mL dose) was recorded in 96.6 and 99.8% respectively of this subset (> 0.01 IU/mL is considered the minimum protective level).
A prospective blinded household contact study conducted in Germany assessed the vaccine efficacy of a primary course of Infanrix against typical pertussis (defined by World Health Organization as spasmodic cough of greater than or equal to 21 days, with confirmation of B. pertussis infection by culture or serology) up until the time of booster dosing. Of the 360 evaluable secondary contacts in households where there was an index case of typical pertussis, 173 were unvaccinated, 112 received Infanrix and 75 received a whole cell DTP vaccine. Of the 173 unvaccinated contacts, 96 developed typical pertussis, compared with seven of the 112 contacts vaccinated with Infanrix. The vaccine efficacy for Infanrix was calculated at 88.7% with a two sided 95% confidence interval of 76.6 to 94.6%. Protection did not wane until at least the time recommended for booster vaccination.
Primary immunisation immunogenicity studies.
The immunogenicity of primary vaccination schedules of Infanrix have been evaluated in over 1,700 infants administered the vaccine at either two, four and six months (n = 417) or three, four and five months of age (n = 1,302). For the two, four, six month schedule, over 99% of vaccinees displayed antibody titres greater than or equal to 0.1 IU/mL for diphtheria and tetanus one month after the third dose. The pre- and postvaccination geometric mean antibody titre (GMT) values for the three pertussis antigens are provided in Table 1. Please refer to table 1.
The overall response rates observed with Infanrix for the diphtheria, tetanus and three pertussis antigens were equal or superior to those obtained after immunisation with a whole cell DTP (DTPw) vaccine.
Infanrix booster dosing (following primary diphtheria tetanus pertussis whole cell vaccination.
The response to Infanrix booster doses after a primary DTPw vaccination course has been assessed in 559 children administered doses at 15 to 20 months (n = 400) or at three to seven years of age (n = 159). Similar booster responses following the fourth at 15 to 20 months of age or fifth vaccine dose at three to seven years of age were observed for each of the vaccine antigens studied. Following the fourth vaccine dose, diphtheria and tetanus antibodies one month after vaccination were demonstrated in 94.0 and 99.3% of vaccinees respectively, compared to antibody responses of 99.4 and 98.1% respectively following the fifth vaccine dose. All vaccinees had antibody titres of greater than or equal to 0.1 IU/mL against diphtheria and tetanus. The pre- and postvaccination GMT values for the three pertussis antigens following a fourth or fifth vaccine dose are provided in Table 2. Overall the booster response following Infanrix was equal or superior to that obtained following DTPw booster vaccination. Please refer to table 2.
Infanrix booster dosing following primary Infanrix vaccination.
The response to Infanrix booster doses after a primary DTPa vaccination course has been assessed in over 520 children administered a fourth dose between 15 and 24 months of age. No data are available on the use of Infanrix as a fifth dose following primary and first booster (fourth dose) vaccination using DTPa, as the children studied had not yet reached an age to receive the final dose. A booster response to the diphtheria and tetanus antigens occurred in 97 and 100% of vaccinees respectively, one month after vaccination. All vaccinees had antibody titres of greater than or equal to 0.1 IU/mL against diphtheria and tetanus, and 98% displayed antibody titres greater than or equal to 1 IU/mL for both antigens. The pre- and postvaccination GMT values for the three pertussis components are provided in Table 3. Please refer to table 3.
Indications
Active primary immunisation against diphtheria, tetanus and pertussis when commenced between 2 and 12 months of age.Fourth and fifth dose for children from 15 months of age up to and including 6 years of age who have been immunised previously with three or four doses of diphtheria, tetanus and pertussis (whole cell or acellular) vaccine.
Contraindications
Known hypersensitivity to any components of the vaccine. As with other vaccines, the administration of Infanrix should be postponed in subjects suffering from acute severe febrile illness. The presence of a minor infection, however, is not a contraindication.
Precautions
Infanrix should under no circumstances be administered intravenously. It is good clinical practice for immunisation to be preceded by a review of the medical history (especially with regard to previous immunisation and possible occurrence of undesirable events) and a clinical examination.
If any of the following events have occurred in temporal relation to receipt of DTPw, the decision to give subsequent doses of Infanrix, containing the pertussis component, should be carefully considered; however, no data currently exist on use of DTPa vaccines in these children. There may be circumstances, such as a high incidence of pertussis, when the potential benefits outweigh possible risks, particularly since these events are not associated with permanent sequelae.
Temperature of greater than or equal to 40.5 deg. C within 48 hours, not due to another identifiable cause.
Collapse or shock-like state (hypotonic-hyporesponsive episode) within 48 hours.
Persistent, inconsolable crying lasting three hours or more, occurring within 48 hours.
Convulsions with or without fever, occurring within three days.
Acute encephalopathy has been reported rarely (estimated rate 0 to 10.5 cases per million vaccinations) following whole cell DTP vaccination; however a causal relationship has not been established. No such cases have been reported to date with acellular DTP vaccines.
As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of anaphylactic reactions following the administration of the vaccine.
Infanrix should be administered with caution to subjects with thrombocytopenia or a bleeding disorder since bleeding may occur following an intramuscular administration to these subjects.
HIV infection is not considered a contraindication for diphtheria, tetanus and pertussis (whole cell or acellular) immunisation. However in patients with immunodeficiency or in patients receiving immunosuppressive therapy, an adequate immunological response may not be achieved. No data currently exist on the use of Infanrix in these patients.
Adverse Reactions
Clinical trial experience.
During controlled clinical studies, diary cards and a checklist were used to monitor signs and symptoms in all vaccinees following each administered dose of Infanrix. Table 4 summarises pooled data from all studies for solicited symptoms reported within 48 hours of vaccination as a percentage of doses administered. Onset of the majority of local and general symptoms occurred within 48 hours of vaccination. A causal relationship between these events and vaccination has not been established. Please refer to table 4.
Redness and swelling > 10 cm diameter has been reported after the Infanrix booster dose. This resolved spontaneously. As with other vaccines such as diphtheria and tetanus and DTP, swelling of the entire thigh has occasionally been observed.
Comparative trials between Infanrix and a DTPw vaccine have been conducted for primary immunisation or as a booster after Infanrix or DTPw primary immunisation. The overall frequency of symptoms following the administration of Infanrix was lower than that following DTPw vaccine, reaching statistical significance for most calculated symptom parameters. Table 5 summarises the results of individual comparative studies for solicited symptoms reported within 48 hours of vaccination as a percentage of doses administered. A causal relationship between these events and vaccination has not been established. Please refer to table 5.
Other unsolicited events reported in clinical trials for Infanrix primary vaccination or booster doses after Infanrix or DTPw primary courses are listed below. It should be noted, however, that causality has not necessarily been established for these events.
The events are listed within body systems and categorised by frequency according to the following definitions. Common: < 1/10 and greater than or equal to 1/100 patients; uncommon: < 1/100 and greater than or equal to 1/1,000 patients; rare: < 1/1,000 patients.
The following events were reported in clinical trials with Infanrix primary immunisation (total of 11,406 documented doses).
Dermatological.
Common: dermatitis.
Nervous system.
Common: nervousness, somnolence.
Respiratory.
Common: coughing, rhinitis, bronchitis, other respiratory tract infection.
Special senses.
Common: otitis media.
The following events were reported in clinical trials with Infanrix booster following Infanrix primary immunisation (total of 2,363 documented doses).
Body as a whole.
Common: viral infection.
Local.
Common: injection site reaction.
Respiratory.
Common: coughing, pharyngitis, bronchitis, other upper respiratory tract infection, rhinitis, respiratory disorder.
Special senses.
Common: otitis media.
The following events were reported in clinical trials with Infanrix booster following DTPw primary immunisation (total of 606 documented doses).
Respiratory.
Common: coughing, pharyngitis, bronchitis, upper respiratory tract infection.
Special senses.
Common: otitis media.
Postmarketing experience with Infanrix is currently limited.
Interactions
Infanrix was administered simultaneously with other paediatric vaccines (e.g. Haemophilus influenzae type B and oral polio) in some studies during the clinical trial program, however immune responses to the other vaccines were not assessed.
Different injectable vaccines should always be administered at different injection sites.
Infanrix must not be mixed with other vaccines.
Dosage and Administration
All parenteral drug and vaccine products should be inspected visually for any particulate matter or discolouration prior to administration. Before use of Infanrix, the vaccine should be well shaken to obtain a homogeneous turbid suspension. Discard the vaccine if it appears otherwise.
Dosage.
Each dose consists of a 0.5 mL ready to use sterile suspension.
Administration.
Infanrix is administered by intramuscular injection. The vaccine should never be administered intravenously.Infanrix should be injected intramuscularly in the lateral aspect of the thigh or the deltoid region of the arm. The recommended dose (0.5 mL) of vaccine must be administered.
Immunisation schedule.
The primary immunisation course consists of three doses at two, four and six months of age, with a fourth dose at 18 months of age and a fifth dose at four to five years of age, before school entry.
Infanrix can also be used as the fourth and/or fifth dose for children 18 months of age and four to five years of age, who have previously been immunised with three or four doses of diphtheria, tetanus and pertussis (whole cell or acellular) vaccine.
Presentation
Single dose prefilled syringe, 0.5 mL: 1's.
Storage
Store at 2 to 8 deg. C. Do not freeze. Discard if vaccine has been frozen. Shelf life: 24 months. Upon storage a white deposit and clear supernatant can be observed. The expiry date of the vaccine is indicated on the label and packaging.
Poisons Schedule
S4.