Hexavac - summary of medicine characteristics

Summary of medicine characteristics - Hexavac

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 0.5 ml adjuvanted dose contains:

Active substances:

Purified diphtheria toxoid................................

Purified tetanus toxoid.....................................

Purified pertussis toxoid..................................

Purified pertussis filamentous haemagglutinin Hepatitis B surface antigen .........................

Inactivated type 1 poliovirus (Mahoney).........

Inactivated type 2 poliovirus (MEF 1)............

equal to or greater than 20 IU* ( equal to or greater than 40 I 25 micrograms 25 micrograms 5.0 micrograms D antigenA: 40 t D antigenA: 8 ui

Inactivated type 3 poliovirus (Saukett)...................................D antigenA: 32 units'

Haemophilus influenzae type b polysaccharide (polyribosylribitol phosphate) 12 micrograms conjugated to tetanus toxoid (24 micrograms)

Adjuvanted on aluminium hydroxide (0.3 mg)

As lower confidence limit (p = 0.95).

Surface antigen of hepatitis B virus produced from recombinant strain 2150–2–3 of the yeast Saccharomyces cerevisiae.

Quantity of antigen in the final bulk pr , according to W.H.O. (TRS 673, 1992)

Or equivalent antigenic quantity dete by a suitable immunochemical method

For excipients, see 6.1

4.1

Suspension for inj HEXAVAC is a s

3. PHARMACEUTIC

PARTICULARS

peutic indications

syringe aque white suspension

ombined vaccine is indicated for primary and booster vaccination of children against diphtheria, s, pertussis, hepatitis B caused by all known subtypes of viruses, poliomyelitis and invasive infections caused by Haemophilus influenzae type b.

4.2 Posology and method of administration

Primary vaccination :

The primary vaccination schedule consists of two or three doses of 0.5 ml administered within the first year of life according to official recommendations. There should be an interval of at least 1 month between doses : such as 2 , 3, 4 months; 2, 4, 6 months; 3, 5 months.

Booster :

After a primary vaccination with 2 doses of HEXAVAC (i.e. 3, 5 months), a booster dose must be given between 11 and 13 months of age; after a primary vaccination with 3 doses of Hexavac (e.g. 2, 3, 4 months; 2, 4, 6 months), a booster dose must be given between 12 and 18 months of age, according to official recommendations.

HEXAVAC can be used for the booster dose provided the toddler has received a full primary vaccination course of each of the antigens contained in HEXAVAC regardless of whether they were administered as monovalent or combination vaccines produced by Sanofi Pasteur MSD.

Method of administration

fter previous

HEXAVAC should be administered intramuscularly into the quadriceps or deltoid preferably alternating sites for subsequent injections.

This vaccine should not be used in newborns, adolescents or adults.

4.3 Contraindications

Known hypersensitivity to any component of the vaccine or severe re administration of the vaccine.

ne containing pertussis

Encephalopathy within 7 days of administration of a previous dose of a antigens (whole cell or acellular pertussis vaccines).

with vaccine not containing a

In these circumstances the vaccination course should be con pertussis component.

se.

Vaccination should be postponed in the case of fever or a

4.4 Special warnings and special precautions f

This vaccine should not be used in newborns, a

ents or adults.

Infants born of hepatitis B virus surface anti

used as the birth dose or positive mothers.

Immune Globulin (HBIG) and He hepatitis B vaccination series. Th hepatitis B vaccination series i HBIG or infants born of mo

(HBsAg)-positive mothers should receive Hepatitis B accine (Recombinant) at birth and should complete the

quent administration of HEXAVAC for completion of the ts who were born of HBsAg-positive mothers and received unknown status has not been studied. HEXAVAC should not be

uent doses during the first year of life for children born to HbsAg-

HEXAVAC should be administered with caution to subjects with thrombocytopenia or a bleeding disorder since bleeding may occur following an intramuscular administration to these subjects.

HEXAVAC uld under no circumstances be administered intravascularly. The intradermal or subcutaneous routes must not be used either.

f the following events are known to have occurred in temporal relation to receipt of the ine, the decision to give further doses of pertussis-containing vaccines should be carefully considered:

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

Collapse or shock-like state (hypotonic-hyporesponsiveness episode) within 48 hours of vaccination.

Persistent, inconsolable crying lasting > 3 hours, occurring within 48 hours of vaccination.

Convulsions with or without fever, occurring within 3 days of vaccination.

Antipyretic treatment should be initiated according to local guidelines.

As with all injectable vaccines, appropriate medical treatment and supervision should be readily available for immediate use in case of a rare anaphylactic reaction following the administration of vaccine.

In subjects who have a history of a severe reaction within 48 hours of a previous injection with a vaccine containing similar components, the course of vaccination should be carefully considered.

Because of the long incubation period of hepatitis B, it is possible for unrecognised hepatitis B

infection to be present at the time of immunisation. The vaccine may not prevent hepatitis B infection in such cases.

HEXAVAC will not prevent hepatitis infection caused by other agents such as hepatitis A, hepatiti and hepatitis E or by other liver pathogens.

HEXAVAC does not protect against invasive diseases due to serotypes other than influenzae type b or against meningitis of other origins.

hilus

As each dose may contain undetectable traces of neomycin, streptomycin and should be exercised when the vaccine is administered to antibiotics.

xin B, caution tivity to these

The immunogenicity of HEXAVAC could be reduced by immunosuppressive treatment or immunodeficiency. In such cases it is recommended to postpone the vaccination until the end of the disease or treatment. Nevertheless, vaccination of subjects with chronic immunodeficiency such as HIV infection is recommended even if the antibody response might be limited.

There are currently no sufficient data available re

immunogenicity of the concomitant

administration of HEXAVAC with PREVENAR (pneumococcal polysaccharide conjugated vaccine, adsorbed). However when HEXAVAC was co-administered with PREVENAR (pneumococcal polysaccharide conjugated vaccine, adsorbed) in clinical studies, the rate of febrile reactions was higher compared to that occurring following the administration of hexavalent vaccines alone. These reactions were mostly moderate (less than or equal to 39° C) and transient.

HEXAVAC must not be mixed administered drugs.

4.5 Interaction with ot

same syringe with other vaccines or other parenterally

dicinal products and other forms of interaction

Except in the case for use), no signi documented.

munosuppressive therapy (see 4.4 Special warnings and special precautions clinical interaction with other treatments or biological products has been

There a with Me

ta in regards to the efficacy and safety of concomitant administration of HEXAVAC umps and Rubella Virus Vaccine, live.

There are currently no sufficient data available regarding immunogenicity of the concomitant administration of HEXAVAC with PREVENAR (pneumococcal polysaccharide conjugated vaccine, adsorbed).

4.6 Pregnancy and lactation

Not applicable

4.7 Effects on ability to drive and use machines

Not applicable

4.8 Undesirable effects

• Potential undesirable effects

4.9 Overdose

Not applicable.

5. PHARMACOLOGICAL PROPERTIES5.1 Pharmacodynamic propertiesTC code : J07CA

Pharmacotherapeutic group: Bacterial and viral vaccines, co

The diphtheria and tetanus toxoids are prepared from the toxins of cultures of Corynebacterium diphtheriae and Clostridium tetani by formaldehyde detoxification followed by purification. The surface antigen of hepatitis B virus is produ culture of a recombinant strain of yeast cells (Saccharomyces cerevisiae).

The poliomyelitis vaccine is obtained from the ropagation of poliomyelitis viruses types 1, 2 and 3 on Vero cells, purified, then inactivated by formaldehyde.

The acellular pertussis compo extracted from Bordetella per detoxified separately with glut

has been shown that This vaccine contai

Haemophilus infl serological re toxoid mak

and whi

nents (pertussis toxin: PT and filamentous haemagglutinin: FHA) are rtussis cultures then separately purified. The pertussis toxin (PT) is taraldehyde to create the toxoid (PTxd). The FHA is not detoxified. It FHA play a major role in protection against pertussis.

purified capsular polysaccharide (polyribosyl ribitol phosphate: PRP) of type b conjugated to tetanus toxoid. When administered alone PRP induces a

e, but it is weakly immunogenic in infants. The covalent binding of PRP to tetanus

-cell dependent antigen which induces a specific IgG anti-PRP response in infants its immune memory.

This vaccine induces specific humoral antibodies against HBsAg (anti-HBs) and against diphtheria and tetanus toxoids (anti-D and anti-T). Development of anti-HBs titre equal to or greater than 10 mIU/ml and of anti-D and anti-T equal to or greater than 0.01 IU/ml measured 1–2 months after the third injection correlates with protection against hepatitis B infection and against diphtheria and tetanus respectively.

Immune response after primary vaccination

In the pivotal clinical study, all infants (100 %) developed a seroprotective antibody level (equal to or greater than 0.01 IU/ml) to both diphtheria and tetanus antigens one month after completion of the primary series. For pertussis, 91.8 % and 90.5 % of infants achieved a four-fold rise in PT and FHA antibody titres respectively. The 4-fold increase in post immunisation titres is considered a sign of seroconversion of which the clinical significance is unknown in the absence of a serological correlate of protection. Protective levels of anti-HBs (equal to or greater than 10 mIU/ml) were achieved in

96.6 % of infants ; the geometric mean titres (GMTs) were diminished compared to the control group. Anti-poliovirus titres above the threshold of 5 (reciprocal of dilution in seroneutralisation) against poliovirus types 1, 2 and 3 were developed in 100 % of infants and these were considered protected against poliomyelitis. After primary vaccination, 93.7 % of infants had an anti-PRP titre equal to or greater than 0.15 gg/ml; the GMTs were diminished compared to the control group (2.06 gg/ml versus 3.69 gg/ml).

Immune response after booster injection

In the pivotal clinical study where toddlers received HEXAVAC as a booster dose after having been primed with HEXAVAC, antibody titres equal to or greater than 0.1 IU/ml were achieved by all toddlers to tetanus and by 98.8 % to diphtheria. A mean 7.4 and 4.3-fold rise in antibody titres and FHA respectively was achieved and all toddlers developed protective antibody titres poliovirus types 1, 2 and 3. Just before the booster injection anti-PRP GMTs were 0.40 gg/

0.64 gg/ml for HEXAVAC and for the control group respectively. After booster, GMTs in 16.7 gg/ml and 23.0 gg/ml in each group respectively, indicating a strong anamnestic respo

. Anti-

PRP titres equal to or greater than 0.15 gg/ml and equal to or greater than 1 gg/ml 100 % and 96.6 % of toddlers respectively. Following the booster dose, 96.6 % anti-HBs titres equal to or greater than 10 mIU/ml. A mean 20.5-fold rise in anti

observed after the booster dose. Other trials gave similar or higher results. S long term persistence studies are ongoing and will provide additional in

chieved in developed es to HBs was

duration of protection.

After a 3, 5, 12 months schedule, immune responses were com protection and of the same magnitude as those reported previous combination vaccines during the second year of life

5.2 Pharmacokinetic properties

nce and antibody n in regards to the

ible with the sought clinical EXAVAC or other licensed

Evaluation of pharmacokinetic properties is not required for vaccines.

5.3 Preclinical safety dataPreclinical data including singl unexpected findings and no target6. PHARMACEUTICAted dose and localTICULARS

6.3 Shelf life

6.4 Special precautions for storage

Store at 2 °C – 8 °C (in a refrigerator). Do not freeze.

6.5 Nature and contents of container

0.5 ml of suspension in pre-filled syringe (type I glass) with a plunger stopper (chlorobromobutyl) without needle – pack of 1, 10, 25 and 50.

0.5 ml of suspension in pre-filled syringe (type I glass) with a plunger stopper (chlorobromobutyl), with 1 or 2 separate needles – pack of 1 and 10.

Not all pack sizes may be marketed.

6.6 Instructions for use and handling

Before use, the vaccine should be well shaken in order to obtain a homogeneous slightly op suspension.

For needle free syringes, the needle should be pushed firmly on to the end of the rotated through 90 degrees.

syringe and

EU/1/00/147/001– 012

October 23rd, 2000

Sanofi Pasteur MSD SNC 8, rue Jonas Salk F-69007 Lyon

10. DATE OF RE