QUINTANRIX powder+suspension for injection suspension medication leaflet

Quintanrix powder and suspension for suspension for injection

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

After reconstitution, 1 dose (0.5 ml) contains:

Diphtheria toxoid1 not less than 30 International Units

Tetanus toxoid1 not less than 60 International Units

Inactivated Bordetella pertussis 2 not less than 4 International Units

Hepatitis B surface antigen (rDNA) 2, 3 10 micrograms

Haemophilus influenzae type b polysaccharide(polyribosylribitol phosphate) 2 2.5 microgramsconjugated to tetanus toxoid as a carrier 5-10 micrograms1 adsorbed on aluminium hydroxide, hydrated Total: 0.26 milligrams Al3+2adsorbed on aluminium phosphate Total: 0.40 milligrams Al3+3 produced in Saccharomyces cerevisae cells by recombinant DNA technology

For excipients, see section 6.1.

Powder and suspension for suspension for injection

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

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

Quintanrix is indicated for primary immunisation of infants (during the first year of life) againstdiphtheria, tetanus, pertussis, hepatitis B and invasive disease caused by Haemophilus influenzaetype 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.

The primary vaccination schedule consists of three doses of 0.5 ml to be administered at intervals ofat 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 inclinical trials: 2-4-6 months, 3-4-5 months and 6-10-14 weeks. The 3-5-12 month schedule was notevaluated.

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 tohepatitis B virus carrying mothers. This may require separate administration of hepatitis B vaccineand should follow official recommendations.

Booster vaccination:

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

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

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

Hypersensitivity to the active substances or to any of the excipients.

Quintanrix is contra-indicated if the child has experienced an encephalopathy of unknown aetiology,occurring within 7 days following previous vaccination with pertussis containing vaccine. In thesecircumstances 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 sufferingfrom acute severe febrile illness. The presence of a minor infection, such as a cold, is not acontraindication for vaccination.

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

As with all injectable vaccines, appropriate medical treatment and supervision should always bereadily available in case of a rare anaphylactic event following the administration of the vaccine. Forthis 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 givesubsequent 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.

* Collapse or shock-like state (hypotonic-hyporesponsive episode) within 48 hours.

* Persistent crying lasting ≥ 3 hours, occurring within 48 hours.

* Convulsions with or without fever, occurring within 3 days.

There may be circumstances, such as a high incidence of pertussis, when the potential benefitsoutweigh possible risks.

Quintanrix should be administered with caution to subjects with thrombocytopenia or a bleedingdisorder since bleeding may occur following an intramuscular administration to these subjects. Afine needle can be used for the vaccination and firm pressure applied to the site (without rubbing) forat 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 ashepatitis A, hepatitis C and hepatitis E virus.

The HIB component of the vaccine does not protect against diseases due to capsular serotypes otherthan 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 offebrile convulsions should be closely followed up as such adverse events may occur within 2 to 3days post vaccination.

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

Since the capsular polysaccharide antigen is excreted in the urine a positive urine antigen test can beobserved 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 consideredwhen administering immunisation series to very premature infants (born ≤ 28 weeks of gestation) andparticularly 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 ordelayed.

In paediatric vaccination it is often practice to co-administer different injectable vaccines at separateinjection 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 patientsreceiving immunosuppressive therapy or patients with immunodeficiency.

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

Not relevant.

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

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

Adverse reactions are listed below.

Frequencies are reported as:

Very common: (>1/10)

Common: (>1/100, <1/10)

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

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

Very rare: (<1/10,000) including isolated reports

Psychiatric disorders:very common: irritability

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

Respiratory, thoracic and mediastinal disordersrare: bronchitis, coughing

Gastrointestinal disorders:very common: loss of appetiterare: 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)

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

Adverse reactions reported after booster vaccination are listed below.

Psychiatric disordersvery common: irritability

Nervous system disorders:very common: 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 rarelyfollowing vaccination with DTP, hepatitis B and HIB containing vaccines.

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

This medicinal product contains thiomersal (an organomercuric compound) as a preservative andtherefore 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)

No case of overdose has been reported.

The immune response after a three-dose primary vaccination course was evaluated in five trials: 297infants 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 differentstudies 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 percentageof infants with anti-PRP titres ≥ 0.15 µg/ml was > 99% and the percentage with anti-HBs titres ≥ 10mIU/ml was 97.3%. More than 99% of subjects were considered to have responded to the pertussiscomponent of the vaccine, which was defined as the appearance of antibodies in initiallyseronegative subjects (i.e. subjects with pre-vaccination titres < 15 ELU/ml) or a post-vaccinationtitre 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 theexception 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 dueto the small sample size:

2, 4, 6 months schedule 3, 4, 5 months schedule 6, 10, 14 weeks schedule

N = 672 N = 107 N = 9798.9% 95.3% 92.8%

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 showedthat, for 63 infants primed according to a 6, 10, 14 week schedule, > 80% still had antibodies todiphtheria, tetanus, HBs and PRP at levels considered to be protective. Forty-one percent hadantibodies to pertussis. Data from clinical trials show that Quintanrix, when given as a booster dosein the second year of life, induces a greater than 10-fold increase in mean antibody titre with respectto prebooster levels for all vaccine components.

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

Not applicable.

No preclinical safety testing with the vaccine has been conducted.

Lyophilised HIB component:

Liquid DTPw-HBV component:

Thiomersal

Sodium chloride

Water for injections.

For adjuvants, see section 2.

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

3 years.

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

Store in a refrigerator (2°C - 8°C)

Do not freeze.

Store in the original package in order to protect from light.

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.

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 whitesuspension and should be inspected visually for any foreign particulate matter and/or abnormalphysical appearance. Any unused vaccine or waste material should be disposed of in accordance withlocal requirements.

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

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

GlaxoSmithKline Biologicals s.a.

Rue de l'Institut 89

B-1330 Rixensart, Belgium

EU/1/04/301/001

EU/1/04/301/002

17/02/2005