VAQTA Paediatric

Hepatitis A Vaccine, Purified Inactivated, for Paediatrics and Adolescents

Each 0.5ml dose contains:

Strain CR 326F Hepatitis A virus, inactivated……………..25U

Adsorbed onto approximately 0.225 mg of aluminium provided as amorphous aluminium hydroxyphosphate sulphate

For excipients, see section 6.1

VAQTA Paediatric is a sterile suspension for intramuscular use.

VAQTA Paediatric is indicated for active pre-exposure prophylaxis of children and adolescents 12 months of age up to and including 17 years of age, against disease caused by hepatitis A virus.

Posology

Children and adolescents aged 12 months to 17 years of age should receive a single 0.5 millilitre (25U) dose of vaccine at an elected date and a second (booster) dose of 0.5 millilitre (25U) 6 to 18 months after the first dose.

The vaccine should not be used in children under 12 months old since safety and immunogenicity have not been evaluated in this age group.

A single dose of VAQTA Paediatric may also be given at 6 to 12 months following the administration of a single (first) dose of another inactivated hepatitis A vaccine in order to complete the vaccination series.

In studies of healthy children and adolescents who received two doses (25U) of VAQTA Paediatric at 0 and 6 to 18 months, the hepatitis A antibody response has been shown to persist for at least 10 years.

It is not yet established whether booster doses are needed after completion of a two-dose vaccination course (see section 5.1).

The International Consensus Group on Hepatitis A Virus Immunity does not currently recommend the administration of further booster doses to immunocompetent individuals who have completed the initial two-dose vaccination course.

Method of administration

VAQTA Paediatric should be injected INTRAMUSCULARLY in the deltoid region. The vaccine should not be administered subcutaneously or intradermally since administration by these routes may result in a less than optimal antibody response.

VAQTA Paediatric must not be administered intravenously.

VAQTA Paediatric should not be administered to subjects with known hypersensitivity to any component of the vaccine, to subjects who showed signs of hypersensitivity after a previous dose of the vaccine or to subjects who are hypersensitive to neomycin or formaldehyde.

As with other vaccines, administration of VAQTA Paediatric should be postponed in subjects suffering from an acute severe febrile illness. The presence of a minor infection, however, is not a contra-indication for vaccination.

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.

Use caution when vaccinating latex-sensitive individuals since the syringe plunger stopper and tip cap contain dry natural latex rubber that may cause allergic reactions.

Testing for antibodies to hepatitis A prior to a decision on immunisation should be performed in patients born in areas of high endemicity and/or with a history of jaundice.

VAQTA Paediatric does not cause immediate protection against hepatitis A, and there may be a period of 2 to 4 weeks before antibody induction occurs.

Because of the long incubation period (approximately 20 to 50 days) for hepatitis A, it is possible for unrecognised hepatitis A infection to be present at the time the vaccine is given. The vaccine may not prevent hepatitis A in such individuals.

VAQTA Paediatric will not prevent hepatitis caused by infectious agents other than hepatitis A virus.

In subjects with an impaired immune system, adequate anti-HAV antibody titres may not be obtained. If the immunosuppression is due to medical treatment, vaccination should be delayed if possible until the completion of therapy and immune system recovery.

The vaccine has been evaluated in human immunodeficiency virus (HIV) infected adults. There are no data on the use of VAQTA Paediatric in HIV infected subjects.

As with any vaccine, vaccination with VAQTA Paediatric may not result in a protective response in all susceptible vaccinees.

As no studies have been performed with VAQTA Paediatric in subjects with liver disease, caution is advised if administering the vaccine in these subjects.

VAQTA Paediatric must not be mixed with other vaccines or medicinal products in the same syringe.

VAQTA Paediatric may be given concomitantly with measles, mumps, rubella, varicella, pneumococcal 7-valent conjugate and inactivated polio vaccines. (see Section 5.1 Pharmacodynamic properties).

VAQTA Paediatric may be administered concomitantly with immunoglobulin using separate syringes and separate limbs for the injections when combined intermediate and longer-term protection is desirable.

In a clinical study conducted in healthy adults seropositivity rates for hepatitis A when VAQTA, yellow fever and polysaccharide typhoid vaccines were administered concomitantly were generally similar to when VAQTA was given alone. Also antibody response rates for yellow fever and typhoid vaccines were equivalent when administered with and without VAQTA.

Immunogenicity data are insufficient to support concomitant administration of VAQTA with DTaP (Diphtheria, Tetanus and acellular Pertussis) vaccine.

Other interaction studies have not been performed. However, interactions with other vaccines are not anticipated when vaccines are administered at different injection sites.

Animal reproduction studies have not been conducted with VAQTA Paediatric. It is not known whether VAQTA Paediatric can cause foetal harm when administered to a pregnant woman or can affect reproduction capacity. VAQTA Paediatric is not recommended in pregnancy unless there is a high risk of hepatitis A infection, and the attending physician judges that the possible benefits of vaccination outweigh the risks to the foetus.

It is not known whether VAQTA Paediatric is excreted in human milk, and the effect on breastfed infants following administration of VAQTA Paediatric to mothers has not been studied. Hence, VAQTA Paediatric should be used with caution in women who are breastfeeding.

There are no specific data. However, asthenia/fatigue and headache have been reported following administration of VAQTA Paediatric.

Clinical Studies

Children and adolescents from 12 months to 17 years of age

In combined clinical trials involving 706 healthy children 12 months to 23 months of age and 2595 healthy children (2 years of age) and adolescents who received one or more 25U doses of hepatitis A vaccine with or without other paediatric vaccines, subjects were followed for elevated temperature and local reactions during a 5-day period post vaccination and systemic adverse experiences including fever during a 14 day period post vaccination. Of the 706 children, 241 received VAQTA without other paediatric vaccines for both doses and 309 received VAQTA without other paediatric vaccines for one of the two doses. Fever and injection-site reactions, generally mild and transient were the most frequently reported adverse experiences. Adverse experiences reported as vaccine related for the two age groups (12 months to 23 months and 2 to 17 years of age) are listed below in decreasing order of frequency within each system organ classification.

[Very common: (>1/10), Common: (>1/100, <1/10), Uncommon: (>1/1000, <1/100 and Rare: ( 1/10,000, <1/1000)]

Children aged 12 months up to and including 23 months of age

Metabolism and nutrition disorders:

Uncommon:anorexia.

Psychiatric disorders:

Common: irritability.

Uncommon: crying; nervousness; insomnia; agitation.

Nervous system disorders:

Uncommon: somnolence;dizziness; hypersomnia; loss of balance.

Respiratory, thoracic and mediastinal disorders:

Uncommon: rhinorrhea; cough; respiratory congestion.

Gastrointestinal disorders:

Uncommon: diarrhea; vomiting; eructation; flatulence; abdominal distension.

Skin and subcutaneous tissue disorders:

Common: rash.

Uncommon: miliaria rubra; sweating; clammy skin; eczema.

General disorders and administrative site conditions:

Common: fever, injection-site pain/tenderness/soreness, swelling, erythema, and warmth.

Uncommon: gait abnormality; injection-site ecchymosis; malaise.

In more recent clinical trials involving 2424 healthy children 12 through 23 months of age who received one or two doses of VAQTA 6 months apart with or without other vaccines, the incidence of adverse experiences appeared to be consistent with that reported in the prior trials with the exception of the following adverse experiences which were reported very commonly: injection-site pain/tenderness/soreness, injection-site erythema, and injection-site swelling.

Children/Adolescents (2 years up to and including 17 years of age)

Metabolism and nutrition disorders:

Rare: anorexia.

Psychiatric disorders:

Uncommon: irritability.

Rare: nervousness.

Nervous system disorders:

Common: headache.

Uncommon: dizziness.

Rare: somnolence; paraesthesia.

Ear and labyrinth disorders:

Rare: ear pain.

Vascular disorders:

Rare: flushing.

Respiratory, thoracic and mediastinal disorders:

Rare: nasal congestion; cough; rhinorrhea.

Gastrointestinal disorders:

Uncommon: abdominal pain; vomiting; diarrhoea; nausea.

Skin and subcutaneous tissue disorders:

Uncommon: rash; pruritus.

Rare: urticaria; sweating.

Musculoskeletal, connective tissue and bone disorders:

Uncommon: arm pain (in the injected limb); arthralgia; myalgia.

Rare: stiffness.

General disorders and administrative site conditions:

Very common: injection-site pain and tenderness.

Common: injection-site warmth, erythema and swelling; fever; injection-site ecchymosis.

Uncommon: asthenia/fatigue; injection-site pruritus and pain/soreness.

Rare: injection-site induration; flu-like illness; chest pain; pain; warm sensation; injection-site scab; stiffness/tightness and stinging.

Additional complaints not reported in infants, children and adolescents have been reported in clinical trials involving adult subjects.

Should anaphylactic reactions occur see section 4.4 Special Warnings and Precautions for Use.

Marketed experience

As with other vaccines, single cases of central or peripheral affections of the nervous system including Guillain-Barré Syndrome and haematologic autoimmune diseases like thrombocytopenia have been reported.

Post-marketing Safety Study

In a post-marketing safety study, a total of 42,110 individuals > 2 years of age received 1 or 2 doses of VAQTA. There were no vaccine related serious adverse reactions in the 30 days after vaccination.

There are no data with regard to overdose, however overdose is unlikely given the presentation of the product in single dose vials or syringes.

VAQTA Paediatric is derived from hepatitis A virus that has been cultured in human MRC-5 diploid fibroblasts. It contains inactivated virus of a strain which was originally derived by further serial passage of a proven attenuated strain.

The onset of seroconversion following a single dose of VAQTA Paediatric was shown to parallel the onset of protection against clinical hepatitis A disease. A very high degree of protection has been demonstrated after a single dose of VAQTA Paediatric in 1037 children and adolescents 2 to 16 years of age in a US community with recurrent outbreaks of hepatitis A (The Monroe Efficacy Study). Seroconversion was achieved in more than 99% of vaccine recipients within 4 weeks of the vaccination. The protective efficacy of a single dose of VAQTA Paediatric was observed to be 100%. A booster dose was administered to most vaccinees 6, 12 or 18 months after the primary dose. The effectiveness of VAQTA Paediatric for use in this community has been demonstrated by the fact that after 9 years, no cases of hepatitis A disease 16 days after vaccination have occurred in the vaccinees.

Clinical studies showed seropositivity rates of more than 96% in children and adolescents within 4-6 weeks after the recommended primary dose. In children (2 years of age) and adolescents seropositivity has been shown to persist up to 18 months after a single 25U dose. Persistence of immunologic memory has been demonstrated by eliciting an anamnestic antibody response to a second (booster) of 25U given 6 to 18 months after the primary dose to children (> 2 years of age) and adolescents.

In studies of healthy children and adolescents who received two doses (25U) of VAQTA Paediatric at 0 and 6 to 18 months, the hepatitis A antibody response has been shown to persist for at least 10 years. The geometric mean antibody titres (GMTs) declined over the first 5 to 6 years, but appeared to plateau through 10 years.

Data available from long-term studies up to 10 years on the persistence of HAV antibodies after 2 doses of VAQTA in healthy, immunocompetent subjects up to 41 years of age allows prediction that at least 99% of subjects will remain seropositive (>10 mIU anti-HAV/ml) at least 25 years after vaccination.

Based on this analysis, an additional vaccination following complete primary immunisation with 2 doses appears to be unnecessary. However, decisions regarding additional vaccination should be based on risk-benefit for the individual.

Use With Other Vaccines

Hepatitis A response has been shown to be similar when VAQTA was given alone or concomitantly with measles, mumps, rubella, varicella, pneumococcal 7-valent conjugate or inactivated polio vaccine. Responses to measles, mumps, rubella, varicella, pneumococcal 7-valent conjugate and inactivated polio were not affected by concomitant administration with VAQTA. Immunogenicity data are insufficient to support concomitant administration of VAQTA with DTaP.

Use in Children With Maternal Antibody to Hepatitis A

In a concomitant use study, children received VAQTA (25U) at 12 months and 18 months of age with or without other paediatric vaccines. After each dose of VAQTA (25U), the hepatitis A antibody titres were comparable between children who were initially seropositive to hepatitis A and children who were initially seronegative to hepatitis A. These data suggest that maternal antibody to hepatitis A in children 12 months of age does not affect the immune response to VAQTA.

Not applicable

None stated.

Sodium borate

Sodium chloride

Water for injections

For adjuvant see section 2.0 Qualitative and Quantitative Composition

Neomycin and formaldehyde are used in the manufacturing process

Do not mix in the same syringe with other vaccines/drugs.

36 months when stored between +2°C and +8°C.

Expiry date has been printed on the package (month followed by year) and is applicable only if the vaccine has been stored between +2°C and +8°C. Potency of this vaccine is not significantly affected after exposure to temperatures up to 28°C for up to 3 months. However this is NOT a storage recommendation and if kept longer than three months at this temperature it should not be used.

Store in a refrigerator (2°C - 8°C).

DO NOT FREEZE since freezing destroys potency.

Single dose (0.5ml, approx 25U) vials and prefilled syringes, with or without an attached needle. Up to two needles may be included in the pack containing the syringe without an attached needle.

Available as a single unit pack.

Not all pack sizes and presentations may be marketed.

The vaccine should be used as supplied; no reconstitution is necessary.

Shake well immediately before withdrawal and use. Thorough agitation is necessary to maintain suspension of the vaccine.

Parenteral drug products should be inspected visually for extraneous particulate matter and discoloration prior to administration. After thorough agitation, VAQTA Paediatric is a slightly opaque white suspension.

It is important to use a separate sterile syringe and needle for each individual to prevent transmission of infections from one person to another.

Sanofi Pasteur MSD Limited

Mallards Reach

Bridge Avenue

Maidenhead

Berkshire

SL6 1QP

PL 6745/0064

15^th August 1996

February 2011

POM