4.1. Therapeutic indications

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.

4.2. Posology and method of administration

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.

4.3. Contraindications

History of hypersensitivity to the active substances, to any of the excipients listed in section 6.1, to neomycin or to formaldehyde (which may be present as trace residues, see sections 2 and 4.4).

Vaccination should be delayed in subjects with current severe febrile infections.

4.4. Special warnings and precautions for use

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 using the single dose vial since the vial stopper contains 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.

4.5. Interaction with other medicinal products and other forms of interaction

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.

4.6. Fertility, pregnancy and lactation

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.

4.7. Effects on ability to drive and use machines

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.

4.8. Undesirable effects

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 (≥2 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

System Organ Class

Frequency

Adverse Reactions

Blood and lymphatic system disorders

Not Known

Thrombocytopenia1

Immune system disorders

Rare

Multiple allergies

Metabolism and nutrition disorders

Uncommon

Decreased appetite, Anorexia

Rare

Dehydration

Psychiatric disorders

Uncommon

Insomnia, Restlessness

Rare

Agitation, Nervousness, Phobia, Screaming, Sleep disorder

Nervous system disorders

Uncommon

Somnolence, Crying, Lethargy, Hypersomnia, Poor quality sleep

Rare

Dizziness, Headache, Ataxia

Not Known

Guillain-Barré syndrome1

Eye disorders

Rare

Eyelid margin crusting

Respiratory, thoracic and mediastinal disorders

Uncommon

Rhinorrhea, Cough, Nasal congestion

Rare

Respiratory tract congestion, Sneezing, Asthma, Allergic rhinitis, Oropharyngeal pain

Gastrointestinal disorders

Common

Diarrhoea

Uncommon

Vomiting

Rare

Flatulence, Abdominal distension, Upper abdominal pain, Faeces discolored, Frequent bowel movements, Nausea, Stomach discomfort, Constipation, Eructation, Infantile spitting up

Skin and subcutaneous tissue disorders

Uncommon

Rash, Dermatitis diaper

Rare

Urticaria, Cold sweat, Eczema, Generalized erythema, Papular rash, Blister, Erythema, Generalized rash, Heat rash, Hyperhidrosis, Skin warm

Musculoskeletal, connective tissue disorders

Rare

Synovitis

General disorders and administrative site conditions

Very Common

Injection-site pain/ tenderness, Injection-site erythema

Common

Injection-site swelling, Fever, Irritability, Injection-site warmth, Injection-site bruising

Uncommon

Injection-site hematoma, Injection-site nodule, Malaise, Injection-site rash,

Rare

Pain, Injection-site haemorrhage, Injection-site pruritus, Discomfort, Fatigue, Gait disturbance, Injection-site discoloration, Injection-site papule, Injection-site urticaria, Feeling hot

1 Spontaneous reporting after use of marketed vaccine

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

System Organ Class

Frequency

Adverse Events

Blood and lymphatic system disorders

Not Known

Thrombocytopenia1

Metabolism and nutrition disorders

Rare

Anorexia

Psychiatric disorders

Uncommon

Irritability

Rare

Nervousness

Nervous system disorders

Common

Headache

Uncommon

Dizziness

Rare

Somnolence, Paraesthesia

Not Known

Guillain-Barré syndrome1

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 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

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 the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

There are no data with regard to overdose.