- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
PosologyThe 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 (25U) 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 (25U) 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 doseA 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 (25U/0.5 mL) presentation.
Method of administrationVAQTA 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 productFor instructions on preparation of the medicinal product before administration, see section 6.6.
Known or presumed exposure to HAV/Travel to endemic areas
Use with immune globulinFor 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 vaccinesHepatitis 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.
PregnancyIt 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-feedingIt 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.
FertilityVAQTA Paediatric has not been evaluated in fertility studies.Animal reproduction studies have not been conducted with VAQTA Paediatric.
Summary of the safety profile
Children 12 months through 23 months of ageIn 5 combined clinical trials, 4,374 children 12 through 23 months of age received one or two 25U 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 StudyIn 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 reactionsThe 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|
|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|
|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|
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|
|Nervous system disorders||Common||Headache|
|Not Known||Guillain-Barré syndrome1|
|Ear and labyrinth disorders||Rare||Ear pain|
|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|
|Musculoskeletal, connective tissue disorders||Uncommon||Arm pain (in the injected limb), Arthralgia, Myalgia|
|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|
Description of selected adverse reactionsAs with all vaccines, allergic reactions, in rare cases leading to shock, may occur (see section 4.4).
Reporting of suspected adverse reactionsReporting 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.
Mechanism of actionHepatitis A vaccine elicits circulating neutralising antibodies to Hepatitis A virus sufficient to confer protection against the virus.
Clinical efficacy and safetyEfficacy 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 (≥2 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 (≥2 years of age) and adolescents. To date, no cases of clinically confirmed hepatitis A disease ≥50 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 ageIn 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 AIn a concomitant use study, children received VAQTA Paediatric (25U) at approximately 12 months and approximately 18 months of age with or without other paediatric vaccines. After each dose of VAQTA Paediatric (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 approximately 12 months of age does not affect the immune response to VAQTA Paediatric.
Antibody persistenceIn studies of healthy children (≥2 years of age) and adolescents who received an initial 25U dose of VAQTA Paediatric at Day 0 and a subsequent 25U 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 studyIn 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.
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