VAQTA Paediatric is indicated for active pre-exposure prophylaxis against disease caused by hepatitis A virus. VAQTA Paediatric is recommended for healthy individuals from 12 months of age to 17 years of age who are at risk of contracting or spreading infection or who are at risk of life-threatening disease if infected (e.g., hepatitis C with diagnosed liver disease).

The use of VAQTA Paediatric should be based on official recommendations.

For optimal antibody response, primary immunisation should be given at least 2, preferably 4, weeks prior to expected exposure to hepatitis A virus.

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

Posology

The vaccination series consists of one primary dose and one booster dose given according to the following schedule:

Primary dose:

Children and adolescents aged 12 months to 17 years of age should receive a single 0.5 mL (25 U) dose of vaccine at an elected date.

Safety and effectiveness in infants <12 months of age have not been established.

Booster dose:

Individuals who received a primary dose at 12 months to 17 years of age should receive a booster dose of 0.5 mL (25 U) 6 to 18 months after the first dose.

Hepatitis A virus (HAV) antibodies persist for at least 10 years after the second dose (i.e. booster). Based on mathematic modeling duration of antibody persistence is predicted for at least 25 years (see section 5.1).

Interchangeability of the booster dose

A booster dose of VAQTA Paediatric may be given at 6 to 12 months following the initial dose of other inactivated hepatitis A vaccines as shown by data for adults, 18 to 83 years of age; no such data are available for VAQTA (25 U/0.5 mL) presentation.

Method of administration

VAQTA Paediatric should be injected INTRAMUSCULARLY. The deltoid muscle is the preferred site for injection. The anterolateral thigh region may be used in infants if the deltoid muscle is not sufficiently developed. The vaccine should not be administered subcutaneously or intradermally since administration by these routes may result in a less than optimal antibody response.

For individuals with bleeding disorders who are at risk of haemorrhage following intramuscular injection (e.g., haemophiliacs) other measures can be taken such as intramuscular administration of the vaccine after anti- haemophilia or other similar therapy, or applying pressure. This vaccine may be administered subcutaneously to these subjects.

Precautions to be taken before handling or administering the medicinal product For instructions on preparation of the medicinal product before administration, see section 6.6.

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Individuals who develop symptoms suggestive of hypersensitivity after an injection of VAQTA Paediatric should not receive further injections of the vaccine. This vaccine may contain traces of neomycin and formaldehyde which are used during the manufacturing process (see sections 2 and 4.3).

VAQTA Paediatric must not be administered into a blood vessel.

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.

Qualitative testing for antibodies to hepatitis A prior to immunisation should be considered based on the probability of previous hepatitis A virus infection in patients who grew up 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 becomes detectable.

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

As with any vaccine, adequate treatment provisions, including epinephrine (adrenaline), should be available for immediate use should an anaphylactic or anaphylactoid reaction occur.

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

Excipient(s) with known effect:

This medicinal product contains less than 1mmol (23mg) sodium per dose and is considered to be essentially sodium free.

If VAQTA Paediatric is used in individuals with malignancies or those receiving immunosuppressive therapy or who are otherwise immunocompromised, the expected immune response may not be obtained.

Known or presumed exposure to HAV/Travel to endemic areas Use with immune globulin

For individuals requiring either post-exposure prophylaxis or combined immediate and longer term protection (e.g., travelers departing on short notice to endemic areas), in countries where IG is available VAQTA Paediatric may be administered concomitantly with IG using separate sites and syringes. Although the antibody titre obtained is likely to be lower than when the vaccine is given alone. The clinical relevance of this observation has not been established.

Use with other vaccines

Hepatitis A response has been shown to be similar when VAQTA Paediatric was given alone or concomitantly with measles, mumps, rubella, varicella, pneumococcal 7-valent conjugate, inactivated polio, diphtheria toxoid, tetanus toxoid, acellular pertussis, or Haemophilus influenzae b vaccine. Responses to measles, mumps, rubella, varicella, pneumococcal 7-valent conjugate, inactivated polio, diphtheria toxoid, tetanus toxoid, acellular pertussis, and Haemophilus influenzae b vaccine were not affected by concomitant administration with VAQTA Paediatric. Studies in adults 18 to 54 years of age have shown that VAQTA may be administered concomitantly with yellow fever and polysaccharide typhoid vaccines.

VAQTA Paediatric must not be mixed with other vaccines in the same syringe. When concurrent administration is necessary, different injection sites and separate syringes must be used for each vaccine.

Pregnancy

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.

Breast-feeding

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.

Fertility

VAQTA Paediatric has not been evaluated in fertility studies.

Animal reproduction studies have not been conducted with VAQTA Paediatric.

No studies on the effects on the ability to drive and use machines have been performed. However, VAQTA Paediatric is expected to have no or negligible influence on the ability to drive and use machines.

4.3      Summary of the safety profile

Children 12 months through 23 months of age

In 5 combined clinical trials, 4,374 children 12 through 23 months of age received one or two 25 U doses of VAQTA Paediatric. Out of the 4,374 children who received VAQTA Paediatric, 3,885 (88.8%) children received 2 doses of VAQTA Paediatric and 1,250 (28.6%) children received VAQTA Paediatric concomitantly with other vaccines. Children were followed for elevated temperature and injection-site adverse reactions during a 5-day period postvaccination and systemic adverse events including fever during a 14-day period postvaccination.

In three of the five protocols which specifically prompted for injection-site erythema, pain/tenderness, and swelling daily for Day 1 through Day 5 postvaccination, the most frequently reported injection-site adverse reaction after any dose of VAQTA Paediatric was injection-site pain/tenderness.

The most common systemic adverse events among recipients of VAQTA Paediatric alone were fever and irritability. The data from the five protocols were combined as similar methods for collecting systemic adverse events were used.

Children/adolescents (2 years through 17 years of age)

In clinical trials with 2,595 healthy children (22 years of age) and adolescents who received one or more doses of hepatitis A vaccine, subjects were followed for elevated temperature and local reactions during a 5-day period postvaccination and systemic adverse events including fever during a 14-day period postvaccination. Injection-site reactions, generally mild and transient, were the most frequently reported adverse events.

Adverse reactions reported as vaccine related are listed below in decreasing order of frequency within each system organ classification.

Post-marketing Safety Study

In a post-marketing safety study, a total of 12,523 individuals 2 through 17 years of age received 1 or 2 doses of VAQTA Paediatric. There was no serious, vaccine-related, adverse event identified. There was no non-serious, vaccine-related, adverse event resulting in outpatient visits.

Tabulated summary of adverse reactions

The tables below present adverse reactions reported as vaccine related observed in clinical trials, and in a post-authorisation safety study and adverse reactions spontaneously reported after use of the marketed vaccine.

Adverse reactions are ranked under headings of frequency using the following convention:

[Very Common ( 1/10); Common ( 1/100 to <1/10); Uncommon ( 1/1,000 to

<1/100); Rare ( 1/10,000 to <1/1,000); Very Rare (<1/10,000); Not Known (cannot be estimated from the available data)].

Children 12 months through 23 months of age

¹ Spontaneous reporting after use of marketed vaccine

Children/adolescents (2 years through 17 years of age)

¹ Spontaneous reporting after use of marketed vaccine

Description of selected adverse reactions

As with all vaccines, allergic reactions, in rare cases leading to shock, may occur (see section 4.4).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via:

To report any side effect(s):

· Saudi Arabia:

The National Pharmacovigilance Centre (NPC):

SFDA Call Center: 19999

E-mail: npc.drug@sfda.gov.sa

Website: https://ade.sfda.gov.sa

· Other GCC States:

Please contact the relevant competent authority.

There are no data with regard to overdose.

Pharmacotherapeutic group: viral vaccines, hepatitis A, inactivated, whole virus ATC code: J07BC02

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 virus is grown, harvested, highly purified, formalin inactivated, and then adsorbed onto amorphous aluminium hydroxyphosphate sulfate.

Mechanism of action

Hepatitis A vaccine elicits circulating neutralising antibodies to Hepatitis A virus sufficient to confer protection against the virus.

Clinical efficacy and safety

Efficacy of VAQTA Paediatric: The Monroe Clinical Study

Clinical studies showed that the seroconversion rate in children approximately 12 months of age was 96% within 6 weeks after the recommended primary dose and that the seroconversion rate was 97% in children (22 years of age) and adolescents within 4 weeks after the recommended primary dose. The onset of seroconversion following a single dose of VAQTA Paediatric was shown to parallel the onset of protection against clinical hepatitis A disease. Protective efficacy has been demonstrated after a single dose of VAQTA Paediatric in 1,037 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 pre-exposure protective efficacy of a single dose of VAQTA Paediatric was observed to be 100% beginning 2 weeks after vaccination. 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, since the trial ended, there has been no case of hepatitis A disease in any vaccinee.

Persistence of immunologic memory was demonstrated with an anamnestic antibody response to a booster dose given 6 to 18 months after the primary dose in children (22 years of age) and adolescents. To date, no cases of clinically confirmed hepatitis A disease 250 days after vaccination have occurred in these vaccinees from the Monroe Efficacy Study monitored for up to 9 years.

Immunogenicity studies in children 12 through 23 months of age

In three combined clinical studies that assessed immunogenicity, 1,022 initially seronegative subjects received 2 doses of VAQTA Paediatric alone or concomitantly with other vaccines (combined diphtheria toxoid-tetanus toxoid- acellular pertussis and/or Haemophilus influenzae b and/or combined measles- mumps-rubella-varicella and/or combined measles-mumps-rubella and/or varicella and/or pneumococcal 7-valent conjugate vaccine). Seroconversion was achieved in 99.9% of initially seronegative subjects. No significant differences were observed when vaccines were given individually or concomitantly.

Use in children with maternal antibody to hepatitis A

In a concomitant use study, children received VAQTA Paediatric (25 U) at approximately 12 months and approximately 18 months of age with or without other paediatric vaccines. After each dose of VAQTA Paediatric (25 U), 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 approximately 12 months of age does not affect the immune response to VAQTA Paediatric.

Antibody persistence

In studies of healthy children (22 years of age) and adolescents who received an initial 25 U dose of VAQTA Paediatric at Day 0 and a subsequent 25 U dose 6 to 18 months later, the hepatitis A antibody response to date has been shown to persist for at least 10 years. The geometric mean titres (GMTs) tend to decline over time. The 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 based on mathematical modeling at least 99% of subjects will remain seropositive (≥10 mlU 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.

Post-marketing safety study

In a post-marketing safety study, conducted at a large health maintenance organisation in the United States, a total of 12,523 individuals 2 through 17 years of age received 1 or 2 doses of VAQTA Paediatric. Safety was monitored by reviewing medical records that tracked emergency room and outpatient visits, hospitalisations and deaths. There was no serious, vaccine- related, adverse event identified among the 12,523 individuals in this study. There was no nonserious, vaccine-related, adverse event resulting in outpatient visits. There was no vaccine-related, adverse event identified that had not been reported in earlier clinical trials with VAQTA Paediatric.

Evaluation of pharmacokinetic properties is not required for vaccines.

No preclinical safety testing was performed using the vaccine.

Sodium borate Sodium chloride Water for injections

For adjuvant and for information regarding residual components in trace quantities, see sections 2, 4.3 and 4.4.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

Store in a refrigerator (2°C - 8°C).

DO NOT FREEZE since freezing destroys potency.

0.5 mL suspension in a pre-filled syringe (type I glass) with plunger-stopper (chlorobutyl isoprene blend or bromobutyl).

0.5 mL suspension in a pre-filled syringe (type I glass) with plunger-stopper (chlorobutyl isoprene blend or bromobutyl), without needle, with a tip-cap (chlorobutyl isoprene blend or bromobutyl isoprene blend), with 0, 1 or 2 separate needles.

0.5 mL suspension in a vial (glass), grey rubber stopper (chlorobutyl isoprene blend).

Pack sizes: Pack of 1 syringe or 1 vial.

Not all pack sizes and presentations may be marketed.

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

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

Shake well immediately before use. Thorough agitation is necessary to maintain suspension of the vaccine. For syringe without attached needle, hold the syringe barrel and attach the needle by twisting in clockwise direction until the needle fits securely on the syringe.

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

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