Sanofi Pasteur MSD Limited

Act-HIB

powder and solvent for solution for injection.

Haemophilus influenzae type b conjugate vaccine.

Each 0.5 ml dose of reconstituted vaccine contains:

Active Substance

Excipient

The lyophilised vaccine is reconstituted with 0.5 millilitre solvent contained in the syringe supplied.

For a full list of excipients, see section 6.1

Powder and solvent for solution for injection.

White powder in a vial and colourless solvent in a syringe.

Act-HIB is indicated for active immunisation against invasive diseases caused by Haemophilus influenzae type b in infants from 2 months of age.

Posology

Infants from 2 months of age:

Three doses each of 0.5 millilitre separated by intervals of at least 4 weeks according to national vaccination policies.

The vaccine would normally be administered at the same time as diphtheria, tetanus, pertussis and polio vaccination. In such cases, Act-HIB may be reconstituted with a single dose of Tetravac (diphtheria, tetanus, acellular pertussis and inactivated poliomyelitis vaccine, adsorbed) and administered as a single injection.

Conjugate vaccine from the same manufacturer should be used for the whole primary course.

Children 12 months and over:

A single dose of 0.5 millilitre, which may be administered simultaneously with measles, mumps and rubella vaccine but at a different site.

Booster dose:

After completion of a 3 dose primary series in infancy an additional booster dose of Hib conjugate vaccine may be administered in accordance with official guidance.

Adults and the elderly:

Not recommended.

Method of administration

Act-HIB should be administered by intramuscular or deep subcutaneous injection.

The recommended injection sites are the anterolateral aspect of the thigh in infants and the deltoid region in children.

See section 6.6 for instructions for preparation

• Hypersensitivity to the active substance or to any of the excipients (in particular the tetanus protein)

• Hypersensitivity following a previous injection of this vaccine or a vaccine containing the same substances

• Vaccination must be postponed in subjects with febrile or acute disease.

The vaccine should only be administered in circumstances where appropriate facilities, including epinephrine (adrenaline), are available for management of acute anaphylactoid reactions.

Prior to the onset of the protective effects of the vaccine, cases of Haemophilus influenzae type b disease may occur in the week after vaccination.

Immunisation with this product does not substitute for routine tetanus immunisation.

If this product is used in persons with malignancies or those receiving immunosuppressive therapy or who are otherwise immuno-compromised the expected immune response may not be obtained. It is therefore recommended to wait for the end of the treatment for the vaccination or to make sure that the subject is well protected. However, the vaccination of subjects with chronic immunosupression, such as HIV infection, asplenia or sickle cell disease, is recommended even though there is a risk of suboptimal immune response.

As with any vaccine, this product may not protect 100% of individuals receiving the vaccine.

Immunisation does not protect against serogroups of Haemophilus influenzae other than type b or against meningitis caused by meningococci or other organisms

Prior to administration of any dose of Act-HIB, the parent or guardian of the recipient must be asked about the personal history of the recipient, family history, and recent health status, including immunization history, current health status and any adverse event after previous immunizations

Prior to injection of any vaccine, all known precautions should be taken to prevent adverse reactions. This includes a review of the patient's history with respect to possible hypersensitivity to the vaccine or similar vaccines.

Patients with rare hereditary problems of fructose intolerance should not receive this vaccine.

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

Special care should be taken to ensure that the vaccine is not inadvertently administered intravenously

As with all injectable vaccines, the vaccine must be administered with caution to subjects with thrombocytopenia or a bleeding disorder, since bleeding may occur following intramuscular injection to these subjects.

Act-HIB may be administered concomitantly with other recommended vaccines: diphtheria, tetanus, pertussis and poliomyelitis, at the same site if combined or at two different sites.

Act-HIB may be administered concomitantly with measles, mumps and rubella vaccine, or with hepatitis B vaccine, at two different sites.

Except in the case of immunosuppressive therapy (see section 4.4), no significant clinical interaction with other treatments or biological products has been documented.

Not applicable.

This vaccine is not intended for administration to women of child-bearing age.

No studies on the effects on the ability to drive and use machines have been performed.

In line with childhood immunisation schedules, WHO (World Health Organisation) and ACIP (Advisory Committee on Immunisation Practices) recommendations, Act-HIB is rarely administered alone, but often given in association or combination with other concomitant vaccines, such as diphtheria-tetanus-pertussis (whole cell or acellular) containing vaccines. Therefore the safety profile of Act-HIB will reflect this concomitant use.

Adverse events presented in this section are listed using MedDRA terminology (system organ classes and terms). Within each system organ class, the adverse events are ranked under headings of frequency, most frequent reactions first, using the following convention:

Very common (1/10), Common (1/100, <1/10), Uncommon (1/1000, <1/100), Rare (1/10000, <1/1000), Very rare (<1/10000), including isolated reports.

The safety data presented below are divided into two subsections: safety data from clinical studies, and safety data from post-marketing surveillance.

Safety data from clinical studies

During clinical studies with an active monitoring of adverse events, more than 7000 healthy infants and young children less than 2 years of age were involved and received Act-HIB, almost always in conjunction with whole cell or acellular DTP vaccines.

In controlled studies, when Act-HIB was administered in conjunction with DTP vaccines, the rate and type of subsequent systemic reactions were not different from those seen with DTP administered alone.

Adverse events, possibly related, observed during clinical studies in more than 1/100 patients after immunisation (i.e. 'common' or 'very common') are presented in this section, categorised by frequency. They usually occur soon after the administration of the vaccine (within 6-24 hours), are transient, and have a mild to moderate intensity. No increase in the incidence or severity of these events was seen with subsequent doses of the primary vaccination series.

The most common reactions occurring after Act-HIB administration were local reactions at the injection site, fever and irritability.

Psychiatric disorders

Very common: irritability

Uncommon to common: crying (uncontrollable or abnormal)

Gastrointestinal disorders

Common: vomiting

General disorders and administration site conditions

Common to very common: injection site reactions such as pain, erythema, swelling and/or inflammation, induration

Common: pyrexia (fever) (above 39°C: uncommon)

Safety data from post-marketing surveillance

Act-HIB post-marketing surveillance is based on extensive experience. Since the product launch, several million doses have been administered worldwide.

Adverse events reported in clinical studies are also observed in post-marketing surveillance.

The following additional adverse events were reported during the commercial use of Act-HIB with frequencies of less than 1/10000 (very rare). This computation is based on the number of adverse event reports per estimated number of vaccinated patients.

Immune system disorders

Hypersensitivity reactions

Nervous system disorders

Headache

Convulsions (with or without fever), seizures

Cases of hypotonia have been reported (in almost all cases this has occurred when a pertussis-containing vaccine has been administered at the same time)

Skin and subcutaneous tissue disorders

Urticaria, rash, pruritis, erythema multiforme,

Face oedema, laryngeal oedema (suggestive of a possible hypersensitivity reaction):

Exceptional

General disorders and administration site conditions

Oedema of lower limbs: Oedematous reaction affecting one or both lower limbs may occur following vaccination with Haemophilus influenzae type b containing vaccines. If this reaction occurs, it does so mainly after primary injections and is observed within the first few hours following vaccination. Associated symptoms may include cyanosis, redness, transient purpura and severe crying. All events resolve spontaneously without sequelae within 24 hours.

Additional information on special populations:

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

Not applicable.

Pharmacotherapeutic group: Bacterial vaccine, ATC code: J07AG01

Act-HIB provides immunity against Haemophilus influenzae type b invasive infections. In humans, the capsular polysaccharide (polyribosyl ribitol phosphate: PRP) induces an anti-PRP serological response. However, as for all polysaccharide antigens, the nature of the immune response is thymo-independent, characterised by the absence of a booster effect after repeated injections and by a low immunogenicity in infants. The covalent bond of the Haemophilus influenzae type b capsular polysaccharide to the tetanus protein enables the polysaccharide conjugate to behave like a thymodependent antigen inducing a specific anti-PRP serological response in infants with the induction of specific IgG and the set-up of an immune memory. The study of the functional activity of the PRP-specific antibodies, induced by the Haemophilus influenzae type b conjugate vaccine in infants and children, demonstrated their bactericidal activity and their opsonising activity.

The immunogenicity studies in infants vaccinated from 2 months of age demonstrated that almost all the children had a PRP antibody titre 0.15 µg/ml, and approximately 90% had a titre 1 µg/ml after the 3^rd dose. In the infants before 6 months of age who received three doses of Haemophilus influenzae type b conjugate vaccine, a booster injection administered 8 to 12 months later induced a very significant increase in the mean titre of the PRP antibodies.

Not applicable.

Data in animals including single dose, repeated dose and local tolerance studies revealed no unexpected findings and no target organ toxicity.

Lyophilised Vaccine

Sucrose

Trometamol

Solvent

Sodium chloride

Water for injections

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

3 years.

After reconstitution, use within one hour, if stored between 2- 8 °C.

Store in a refrigerator (2°C to 8°C).

Do not freeze.

The vaccine is supplied in single dose cartons containing:

Lyophilised vaccine in a single dose 3ml vial (Type 1 glass) with stopper (chlorobutyl rubber), aluminium seal and flip-off cap (polypropylene).

Solvent for reconstitution (0.5ml) in prefilled syringe (type I glass), with a plunger-stopper (halobutyl), attached needle and needle-shield (natural rubber or polyisoprene)

The vaccine should be reconstituted with the diluent provided or with TETRAVAC (Diphtheria, Tetanus, Acellular Pertusis and Inactivated Poliomyelitis Vaccine, Adsorbed).

Shake and examine the appearance of the solution obtained. The normal appearance of the reconstituted vaccine is a colourless solution.

The vaccine should be inspected visually for extraneous particulate matter and /or discolouration prior to administration. In the event of either being observed, discard the vaccine.

Shake well immediately before use. Use the vaccine within one hour of reconstitution.

Any unused product or waste material should be disposed of safely in accordance with local requirements.

Sanofi Pasteur MSD Limited

Block A, Second Floor,

Cookstown Court,

Old Belgard Road

Tallaght

Dublin 24

PA 544/11/1

Date of first Authorisation: 31st August 1992

Date of last renewal: 5^th February 2006

April 2011