Quintanrix - summary of medicine characteristics

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

For excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Powder and suspension for suspension for injection

The liquid diphtheria, tetanus, pertussis (whole cell), hepatitis B (DTPw-HBV) component is a turbid white suspension.

The lyophilised Haemophilus influenzae type b (HIB) component is a white powder.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Quintanrix is indicated for primary immunisation of infants (during the first year of life) against diphtheria, tetanus, pertussis, hepatitis B and invasive disease caused by Haemophilus influenzae type b and for booster immunisation of young children during the second year of life.

The use of Quintanrix should be determined on the basis of official recommendations.

4.2 Posology and method of administration

Posology

Primary vaccination:

The primary vaccination schedule consists of three doses of 0.5 ml to be administered at intervals of at least 4 weeks within the first six months of life in accordance with local official recommendations. The first dose can be administered at 6 weeks of age. The following schedules have been studied in clinical trials: 2–4–6 months, 3–4–5 months and 6–10–14 weeks. The 3–5–12 month schedule was not evaluated.

Quintanrix can be given to children who have received hepatitis B vaccine at birth.

The immunoprophylactic measures for hepatitis B should not be modified for children born to hepatitis B virus carrying mothers. This may require separate administration of hepatitis B vaccine and should follow official recommendations.

Booster vaccination:

After the completion of the primary series, a booster should be administered preferably before the end of the second year of life. Booster administration should be in accordance with official recommendations.

Quintanrix may be used to boost responses to DTP, HBV and HIB antigens if its composition is in accordance with official recommendations for boosting. The booster dose s at least 6 months after the last primary dose.

Method of administration

Quintanrix is for deep intramuscular injection, preferably in the anterolateral thig­h.

4.3 Contraindications

Hypersensitivity to the active substances or to any of the excipi

Quintanrix is contra-indicated if the child has experienced an ecephalopathy of unknown aetiology, occurring within 7 days following previous vaccination with pertussis containing vaccine. In these circumstances the vaccination course should be continued with diphtheria, tetanus, hepatitis B and HIB vaccines.

As with other vaccines, the administration of Quintanrix should be postponed in subjects suffering from acute severe febrile illness. The presence of a minor infection, such as a cold, is not a contraindication for vaccination.

4.4 Special warnings and special precautions for use

Vaccination should be preceded by a review of the medical history (especially with regard to previous vaccination and possible occurrence of undesirable events).

As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of a rare anaphylactic event following the administration of the vaccine. For this reason, the vaccinee should remain under medical supervision for at least 30 minutes.

If any of the following events occur in temporal relation to receipt of Quintanrix, the decision to give subsequent doses of a vaccine containing the pertussis component should be carefully considered:

• • Temperature of > 40.0 °C within 48 hours, not due to another identifiable cause.

ck-like state (hypotonic-hyporesponsive episode) within 48 hours.

ig lasting >  3 hours, occurring within 48 hours.

ns with or without fever, occurring within 3 days.

cumstances, such as a high incidence of pertussis, when the potential benefits

Quintanrix should be administered with caution to subjects with thrombocytopenia or a bleeding disorder since bleeding may occur following an intramuscular administration to these subjects. A fine needle can be used for the vaccination and firm pressure applied to the site (without rubbing) for at least two minutes following administration.

Quintanrix should under no circumstances be administered intravascularly.

The vaccine will not prevent infection caused by other pathogens known to infect the liver such as hepatitis A, hepatitis C and hepatitis E virus.

The HIB component of the vaccine does not protect against diseases due to capsular serotypes other than type b of Haemophilus influenzae or against meningitis caused by other organisms.

A history of febrile convulsions, a family history of convulsions or Sudden Infant Death Syndrome (SIDS) do not constitute a contraindication for the use of Quintanrix. Vaccinees with a history of febrile convulsions should be closely followed up as such adverse events may occur within 2 to 3 days post vaccination.

HIV infection is not considered as a contraindication. The expected immunological response may not be obtained after vaccination of immunosuppressed patients.

Since the capsular polysaccharide antigen is excreted in the urine a positive urine antigen test can be observed within 1–2 weeks following vaccination. Other tests should be performed in order to confirm HIB infection during this period.

Antipyretic treatment should be initiated according to local treatment guidelines.

The potential risk of apnoea and the need for respiratory monitoring for 48–72h should be considered when administering 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 the vaccination is high in this group of infants, vaccination should not be withheld or delayed.

4.5 Interaction with other medicinal products and other forms of interaction

In paediatric vaccination it is often practice to co-administer different injectable vaccines at separate injection sites, during the same session.

Limited data show that there is no interference with the response to Measles-Mumps-Rubella (MMR) and OPV antigens. Although no data are available on the immune response to the Bacille-Calmette-Guérin (BCG) antigen, no interference is expected.

As with other vaccines it may be expected that an adequate response may not be achieved in patients receiving immunosuppressive therapy or patients with immunodeficiency.

• 4.6 Pregnancy and lactation

As Quintanrix is not intended for use in adults, information on the safety of the vaccine when used during pregnancy or lactation is not available.

4.7 Effects on ability to drive and use machines

Not relevan

4.8 Undesirable effects

Quintanrix was administered to approximately 1,340 healthy infants from 6 weeks of age as a primary vaccination course in several clinical trials.

In these trials, the most common reactions occurring after vaccine administration were pain at the site of injection, fever (axillary >  37.5°C; rectal >  38°C) and irritability, which were associated with about 50% of the doses administered.

Adverse reactions are listed below.

Frequencies are reported as:

(>1/10)

(>1/100, <1/10)

(>1/1,000, <1/100)

(>1/10,000, <1/1,000)

(<1/10,000) including isolated reports

Psychiatric disorders:

very common: irritability

Nervous system disorders: very common: drowsiness rare: collapse or shock-like state (hypotonic-hyporesponsiveness episode), convulsions

Respiratory, thoracic and mediastinal disorders

rare: bronchitis, coughing

Gastrointestinal disorders: very common: loss of appetite rare: vomiting

General disorders and administration site conditions: very common: pain, redness and swelling, fever (axillary.5°C; rectal >  38°C) common: induration, fever (axillary > 39°C; rectal > 39.5°C)

Quintanrix was administered as a booster to 435 i other vaccines, the booster dose is potentially ass events such as fever and local reactions.

Adverse reactions reported after booster vaccination are listed below.

Nervous system disorders: very common: drowsiness

Psychiatric disorders very common: irritability

Gastrointestinal disorders: very common: loss of appetite

General disorders

inistration site conditions:

very common: pain, redness and swelling, fever (axillary >  37.5°C; rectal >  38°C) common: fever (axillary > 39°C; rectal > 39.5°C) uncommon: induration

Allergic reactions, including anaphylactoid reactions and urticaria, have been reported very rarely following vaccination with DTP, hepatitis B and HIB containing vaccines.

During post marketing surveillance studies with other hepatitis B containing vaccines, serum sickness like disease and thrombocytopenia have been reported very rarely.

This medicinal product contains thiomersal (an organomercuric compound) as a preservative and therefore it is possible that sensitisation reactions may occur (see section 4.3).

Apnoea in very premature infants (< 28 weeks of gestation) (see section 4.4)

4.9 Overdose

No case of overdose has been reported.

5. PHARMACOLOGICAL PROPERTIES

Pharmaco-therapeutic group: Bacterial and viral vaccines combined,

5.1 Pharmacodynamic properties

The immune response after a three-dose primary vaccination course was evaluated in five trials: 297 infants were evaluated after vaccination at 6, 10 and 14 weeks of age, 685 after vaccination at 2, 4, and 6 months of age and 107 after vaccination at 3, 4 and 5 months of age. Results from different studies show that, overall, 95.5% and 99.9% of subjects had anti-diphtheria and anti-tetanus titres > 0.1 IU/ml one month after completion of the primary vaccination course. At this time, the percentage of infants with anti-PRP titres > 0.15 ^g/ml was > 99% and the percentage with anti-HBs titres > 10 mIU/ml was 97.3%. More than 99% of subjects were considered to have responded to the pertussis component of the vaccine, which was defined as the appearance of antibodies in initially seronegative subjects (i.e. subjects with pre-vaccination titres < 15 ELU/ml) or a post-vaccination titre at least equal to pre-vaccination levels in subjects initially seropositive due to maternally-derived antibodies.

Seroprotection and vaccine response rates were similar for the three schedules used, with the exception of anti-HBs. The seroprotection rates for anti-HBs (> 10 mlU/ml) observed with the 6, 10, 14 week schedule was lower as shown in the table below, but is unlikely to be clinically relevant due to the small sample size:

Limited information exists on the persistence of the immune response after primary vaccination with Quintanrix as well as on the immunogenicity of booster doses. Results from one pilot study showed that, for 63 infants primed according to a 6, 10, 14 week schedule, > 80% still had antibodies to diphtheria, tetanus, HBs and PRP at levels considered to be protective. Forty-one percent had antibodies to pertussis. Data from clinical trials show that Quintanrix, when given as a booster dose in the second year of life, induces a greater than 10-fold increase in mean antibody titre with respect to prebooster levels for all vaccine components.

It can be expected that hepatitis D will also be prevented by immunisation with Quintanrix as hepatitis D (caused by the delta agent) does not occur in the absence of hepatitis B infection.

5.2 Pharmacokinetic properties

Not applicable.

5.3 Preclinical safety data

No preclinical safety testing with the vaccine has been conducted.

6. PHARMACEUTICAL PARTICULARS6.1 List of excipients

Lyophilised HIB component :

Lactose

Liquid DTPw-HBV component :

Thiomersal

Sodium chloride Water for injections.

For adjuvants, see section 2.

6.2 Incompatibilities

In the absence of compatibility studies, the reconstituted Quintanrix vaccine must not be mixed with

other medicinal products.

6.3 Shelf life

3 years.

After reconstitution, it is recommended to inject the vaccine promptly. However the stability has been demonstrated for 8 hours at 25°C after reconstitution.

6.4 Special precautions for storage

Store in a refrigerator (2°C – 8°C)

Do not freeze.

Store in the original package in order to

6.5 Nature and contents of cont

Powder in a vial (type I glass) for 1 dose with a stopper (rubber butyl).

0.5 ml of suspension in a vial (type I glass) for 1 dose with a stopper (rubber butyl) in the following pack sizes:

• – pack size of 1 vial of powder plus 1 vial of suspension

• – pack size of 100 vials of powder plus 100 vials of suspension

Not all pack sizes may be marketed.

6.6 Instructions for use and handling

Upon storage, a white deposit and clear supernatant may be observed for the DTPw-HBV component. This does not constitute a sign of deterioration.

The DTPw-HBV component should be well shaken in order to obtain a homogeneous turbid white suspension and should be inspected visually for any foreign particulate matter and/or abnormal physical appearance. Any unused vaccine or waste material should be disposed of in accordance with local requirements.

The vaccine is reconstituted by withdrawing the contents of the vial containing the DTPw-HBV component by means of a syringe and by adding it to the vial containing the HIB powder. After the addition of the DTPw-HBV component to the HIB powder, the mixture should be well shaken until the powder is completely dissolved. The reconstituted vaccine is a homogeneous turbid white suspension.

Remove and discard the needle used for reconstitution and replace it with a second needle to administer the vaccine. After reconstitution, the vaccine should be injected promptly.

7. MARKETING AUTHORISATION HOLDER

GlaxoSmithKline Biologicals s.a.

Rue de l'Institut 89

B-1330 Rixensart, Belgium

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/04/301/001

EU/1/04/301/002

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION17/02/200510. DATE OF REVISION OF THE TEXT