Quintanrix (diphtheria toxoid / tetanus toxoid /...) – Summary of product characteristics - J07CA10

1. NAME OF THE MEDICINAL PRODUCT

Quintanrix powder and suspension for suspension for injection

Diphtheria, tetanus, pertussis (whole cell), hepatitis B (rDNA) and Haemophilus type b conjugate vaccine (adsorbed)

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

3 produced in Saccharomyces cerevisae cells by recombinant DNA technology

3. PHARMACEUTICAL FORM

Powder and suspension for suspension for injection

Quintanrix is indicated for primary immunisation of infants (during the first year of life) against

4.2 Posology and method of administration

diphtheria, tetanus, pertussis, hepatitis B and invasive disease caused by Haemophilus influenzae The useMedicinalof Quintanrix should be determined on the basis of official recommendations.

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.

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.

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.

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 otherauthorisedorganisms.

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 locallongertreatment 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

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.

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.

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 ≥ 37.5°C; rectal ≥ 38°C) common: induration, fever (axillary > 39°C; rectal > 39.5°C)

longer

Quintanrix was administered as a booster to 435 infantsno in the second year of life. As shown with

other vaccines, the booster dose is potentially associated with an increased incidence of minor adverse

events such as fever and localProductreactions.

Adverse reactions reported after booster vaccination are listed below.

Gastrointestinal disorders: very Medicinalcommon: loss of appetite

General disorders and administration 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).

5. PHARMACOLOGICAL PROPERTIES

Pharmaco-therapeutic group: Bacterial and viral vaccines combined, ATC code JO7CA10

5.1 Pharmacodynamic properties

of infants with anti-PRP titres ≥ 0.15 µg/ml was > 99% and the percentageauthorisedwith anti-HBs titres ≥ 10 mIU/ml was 97.3%. More than 99% of subjects were considered to have responded to the pertussis

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

seronegative subjects (i.e. subjects with pre-vaccination longertitres < 15 ELU/ml) or a post-vaccination titre at least equal to pre-vaccination levels in subjects initially seropositive due to maternally- derived antibodies.

component of the vaccine, which was defined as the appearance of antibodies in initially

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:

in the second year of life, inducesProducta greater than 10-fold increase in mean antibody titre with respect

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

antibodiesMedicinalto pertussis. Data from clinical trials show that Quintanrix, when given as a booster dose

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.

1. NAME OF THE MEDICINAL PRODUCT

Quintanrix powder and suspension for suspension for injection, multidose

Diphtheria, tetanus, pertussis (whole cell), hepatitis B (rDNA) and Haemophilus type b conjugate vaccine (adsorbed)

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

3 produced in Saccharomyces cerevisae cells by recombinant DNA technology This is a multidose container. See section 6.5 for the number of doses per vial.

3.PHARMACEUTICAL FORM

Powder and suspension for suspension for injectionno

Quintanrix is indicated for primaryProductimmunisation 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 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.

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

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.

Quintanrix was administered as a booster to 435 infants in the second year of life. As shown with other vaccines, the booster dose is potentially associated with an increased incidence of minor adverse events such as fever and local reactions.

Adverse reactions reported after booster vaccination are listed below.

very Medicinalcommon: drowsiness Gastrointestinal disorders:

very common: loss of appetite

General disorders and administration 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

5. PHARMACOLOGICAL PROPERTIES

Pharmaco-therapeutic group: Bacterial and viral vaccines combined, ATC code JO7CA10

5.1 Pharmacodynamic properties

infants were evaluated after vaccination at 6, 10 and 14 weeks of age, 685 after vaccination at 2, 4,

The immune response after a three-dose primary vaccination course wasauthorisedevaluated in five trials: 297

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 µg/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

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 onProductthe 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.

In the absence of compatibility studies, the reconstituted Quintanrix vaccine must not be mixed with other medicinal products.

6.3 Shelf life

3 years.

Do not freeze.

Store in the original packageProductin order to protect from light. in the following pack sizes:

6.5 Nature and contents of container

Powder in a vial (type I glass) for 2 doses with a stopper (rubber butyl).

1 ml of suspension in a vial (type I glass) for 2 doses with a stopper (rubber butyl)

– packMedicinalsize of 1 vial of powder plus 1 vial of suspension

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

Powder in a vial (type I glass) for 10 doses with a stopper (rubber butyl).

5 ml of suspension in a vial (type I glass) for 10 doses with a stopper (rubber butyl) in a pack size of 50 vials of powder plus 50 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.