TicoVac Junior 0.25 ml Suspension for injection in a pre-filled syringe

TicoVac Junior 0.25 ml is indicated for the active (prophylactic) immunization of children aged from 1 year to 15 years against tick-borne encephalitis (TBE).

TicoVac Junior 0.25 ml is to be given on the basis of official recommendations regarding the need for, and timing of, vaccination against TBE.

Posology

Primary vaccination schedule

The primary vaccination schedule is the same for all persons from 1 year to 15 years of age and consists of three doses of TicoVac Junior 0.25 ml.

The first and second dose should be given at a 1 to 3 month interval.

If there is a need to achieve an immune response rapidly, the second dose may be given two weeks after the first dose. After the first two doses a sufficient protection for the ongoing tick season is to be expected (see section 5.1).

The third dose should be given 5 to 12 months after the second vaccination. After the third dose protection is expected to last for at least 3 years.

To achieve immunity before the beginning of the seasonal tick activity, which is in spring, the first and second doses should preferably be given in the winter months. The vaccination schedule should ideally be completed with the third vaccination within the same tick season or at the least before the start of the following tick season.

Booster doses

The first booster dose should be given 3 years after the third dose (see section 5.1).

Sequential booster doses should be given every 5 years after the last booster dose.

Extending the interval between any of the doses (primary vaccination schedule and booster doses) may leave subjects with inadequate protection against infection (see section 5.1).

However, in the case of an interrupted vaccination schedule of at least two previous vaccinations, a single catch-up dose is sufficient to continue the vaccination schedule (see section 5.1).

No data regarding catch-up dose in children less than 6 years of age are available (see section 5.1).

Children with an impaired immune system (including those undergoing immunosuppressive therapy)

There are no specific clinical data on which to base dose recommendations. However, consideration may be given to determining the antibody concentration at four weeks after the second dose and administering an additional dose if there is no evidence of seroconversion at this time. The same applies to any of the following doses.

Method of administration

The vaccine should be given by intramuscular injection into the upper arm (deltoid muscle).

In children up to 18 months of age, or dependent on a child's development and nutrition status, the vaccine is administered into the thigh muscle (vastus lateralis muscle).

In exceptional cases only (in subjects with a bleeding disorder or in subjects receiving prophylactic anticoagulation), the vaccine may be administered subcutaneously (see sections 4.4 and 4.8).

Care must be taken to avoid accidental intravascular administration (see section 4.4).

Hypersensitivity to the active substance, any of the excipients listed in section 6.1, or production residues (formaldehyde, neomycin, gentamycin, protamine sulfate). Cross allergies with aminoglycosides other than neomycin and gentamycin should be considered.

Severe hypersensitivity to egg and chick proteins (anaphylactic reaction after oral ingestion of egg protein) may cause severe allergic reactions in sensitized individuals (see also section 4.4).

TBE vaccination should be postponed if the person is suffering from a moderate or severe acute illness (with or without fever).

As with all vaccines that are administered by injection, appropriate emergency treatment and supervision should always be readily available in case of a rare anaphylactic event following the administration of the vaccine.

Non-severe allergy to egg protein does not usually constitute a contraindication to vaccination with TicoVac Junior 0.25 ml. Nevertheless, such persons should only be vaccinated under appropriate supervision and facilities for emergency management of hypersensitivity reactions should be available.

The levels of potassium and sodium are at less than 1 mmol per dose, i.e., essentially “ potassium and sodium-free” .

Intravascular administration must be avoided as this might lead to severe reactions, including hypersensitivity reactions with shock.

The recommended route of administration is intramuscular. However, this may not be appropriate in subjects with a bleeding disorder or subjects receiving prophylactic anticoagulation. Limited data in healthy adults suggest comparable immune response for subcutaneous booster vaccinations when compared to intramuscular booster vaccinations. However, subcutaneous administration might lead to an increased risk for local adverse reactions. No data are available for children/adolescents. Furthermore, no data are available for primary immunisation via the subcutaneous route.

Fever may occur in children after the first immunization in particular in the very young (see section 4.8). In general, the fever subsides within 24 hours. Fever rates reported after the second vaccination are generally lower as compared to the fever rates after the first vaccination. In children with a history of fever convulsions or high fever following vaccinations, antipyretic prophylaxis or treatment may be considered.

A protective immune response may not be elicited in persons undergoing immunosuppressive therapy.

Whenever serological testing is considered necessary in order to determine the need for sequential doses, assays should be performed in an experienced, qualified laboratory. This is because cross reactivity with pre-existing antibodies due to natural exposure or previous vaccination against other flaviviruses (e.g. Japanese encephalitis, Yellow fever, Dengue virus) may give false positive results.

In case of a known or suspected auto-immune disease in the intended recipient, the risk of TBE infection must be weighed against the risk that TicoVac Junior 0.25 ml might have an adverse effect on the course of the auto-immune disease.

Caution is required when considering the need for vaccination in children with pre-existing cerebral disorders such as active demyelinating disorders or poorly controlled epilepsy.

There is no data concerning post exposure prophylaxis with TicoVac Junior 0.25 ml.

As with all vaccines, TicoVac Junior 0.25 ml may not completely protect all vaccinees against the infection that it is intended to prevent. For details on product administration in persons with impaired immune system and persons undergoing immunosuppressive therapy please see section 4.2.

Tick bites may transmit infections other than TBE, including certain pathogens that can sometimes cause a clinical picture that resembles tick-borne encephalitis. TBE vaccines do not provide protection against Borrelia infection. Therefore, the appearance of clinical signs and symptoms of possible TBE infections in a vaccinee should be thoroughly investigated for the possibility of alternative causes.

No interaction studies with other vaccines or medicinal products have been performed. The administration of other vaccines at the same time as TicoVac Junior 0.25 ml should be performed only in accordance with official recommendations. If other injectable vaccines are to be given at the same time, administrations should be into separate sites and, preferably, into separate limbs.

Pregnancy

There are no data from the use of TicoVac Junior 0.25 ml in pregnant women.

Breast-feeding

It is unknown whether TicoVac Junior 0.25 ml is excreted in human milk.

Therefore, TicoVac Junior 0.25 ml should only be administered during pregnancy and to breastfeeding women when it is considered urgent to achieve protection against TBE infection and after careful consideration of the risk-benefit relationship.

TicoVac Junior 0.25 ml is unlikely to affect a child's motor skills (e.g., when playing in the street or cycling) or a person's ability to drive and use machines. It should be taken into account, however, that impaired vision or dizziness may occur.

The calculated frequencies are based on a pooled analysis of adverse reactions reported after the 1^st vaccination (3088 subjects) from 8 clinical studies conducted with TicoVac Junior 0.25 ml (1.2 µ g) in subjects aged 1-15 years of age. Rates of systemic adverse reactions observed after the 2^nd and 3^rd vaccination were lower than after the 1^st vaccination. Comparable rates of injection site reactions are observed after the first, second and third vaccination.

The following other undesirable effects listed in this Section are given according to the recommended frequency convention:

Adverse Reactions from clinical trials

¹ Frequency is estimated based on data from children aged 1-5 years

² A subject may have experienced more than 1 event.

³ Fevers occurred more frequently in younger than in older children (i.e., Very common to Common, respectively). Fever rates after the second and third vaccinations are generally lower than after the first vaccination.

⁴ Frequency is estimated based on data from children aged 6 - 15 years.

Fever was measured rectally in children up to at least 3 years of age and orally in children 3 years of age and older. The analysis includes any fever temporally associated with vaccination whether or not causally related.

Fever is age dependent and is decreasing with the number of vaccinations.

In a safety study and dose finding studies the fever rates observed after the first vaccination were as follows:

1 to 2 year olds (n=262): mild fever (38-39° C) in 27.9%; moderate fever (39.1-40.0° C) in 3.4%; no severe fever (>40° C). 3 to 15 year olds (n=2519): mild fever in 6.8%; moderate fever in 0.6%; no severe fever (>40° C).

Fever rates reported after the second vaccination are generally lower as compared to the fever rates after the first vaccination: 15.6% (41/263) in 1 to 2 year old children and 1.9% (49/2522) in 3 to 15 year old children.

Adverse reactions from post-marketing surveillance

The following additional adverse reactions have been reported in post-marketing experience.

* The upper limit of the 95% confidence interval of the event frequency is calculated with 3/n, with n representing the number of subjects included in all clinical trials with TicoVac Junior 0.25 ml. Therefore, the calculated frequency “ rare” represents the theoretical maximum frequency for these events

In a small comparative study on the immune response after intramuscular and subcutaneous administration of FSME-IMMUN in healthy adults, the subcutaneous route led to a higher local reactogenicity profile, particularly in women. No data are available in children.

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.

There are reports of children receiving the adult formulation. It is conceivable that the risk of adverse reactions is increased in such cases.

Pharmacotherapeutic group: encephalitis vaccines, ATC Code: J07 BA01

The pharmacodynamic effect of the product consists of the induction of a sufficiently high concentration of anti-TBE antibody to provide protection against the TBE virus.

The protection rate of the previous generation and current TBE vaccine has been determined during a continuous surveillance as performed among the total Austrian population since 1984. In this surveillance a protection rate in children of above 98% after completion of the primary vaccination schedule (3 doses) was calculated for the period 1994 to 2003. Based on a follow up surveillance performed among the total Austrian population for the years 2000 to 2006, a protection rate of 99% was calculated with no statistically significant difference between age groups in regularly vaccinated persons.

The protection rate is at least as high after the first two vaccinations, following the conventional and rapid vaccination i.e., before completion of the basic vaccination scheme by the third vaccination.

In those with a record of irregular vaccination protection rate is significantly lower.

In clinical studies with TicoVac Junior 0.25 ml, seropositivity was defined as an ELISA value >126 VIE U/ml or NT titers ≥ 10. Pooled seropositivity rates determined by ELISA and NT at 21 days after the second and third vaccination in the conventional schedule are presented in Table 1 and Table 2.

Table 1.

Conventional immunization schedule, pooled seropositivity rates ¹ as determined by ELISA and NT

Table 2.

Conventional immunization schedule, pooled seropositivity rates ¹ as determined by ELISA and NT

¹ - evaluated 21 days after each dose

² - seropositivity cut-off: ELISA >126 VIE U/ml; NT ≥ 1:10

The highest seropositivity rates as determined by ELISA and NT were achieved upon administration of the third dose. Therefore, completion of the primary vaccination schedule of three doses is necessary to achieve protective antibody levels in almost all recipients.

5 months after the second vaccination more than 97% of children aged 1-5 years and more than 93% of children aged 6-15 years showed seropositive TBE antibody levels in both ELISA and NT.

Results from a follow-up study that investigated the persistence of TBE antibodies support the need for the first booster vaccination no later than three years after primary immunization. An analysis on seropersistence up to 58 months after the first booster showed high seropositivity rates in NT for all age subgroups: 96.6% in children aged 1-2 years, 100% in children aged 3-6 years and 98.1% in those aged 7-15 years, supporting a 5-year booster interval from the first booster onwards.

TicoVac vaccination induces statistically equivalent titers of TBE virus neutralizing antibodies against European, Siberian and Far Eastern TBE virus strains. In a published clinical study considerable cross-neutralising antibodies were also induced against Omsk Hemorrhagic Fever Virus, however titers were lower than against the TBE virus subtypes.

A study on the persistence of immune memory in individuals from the age of 6 years and older whose vaccination intervals were longer than recommended (≤ 12 years) showed that a single catch-up vaccination with TicoVac was able to elicit an anamnestic antibody response in 99% of children as measured by ELISA. No data are available on antibody response as measured by NT.

Not applicable.

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology.

Human albumin

Sodium chloride

Disodium phosphate-dihydrate

Potassium dihydrogenphosphate

Water for Injections

Sucrose

Aluminium hydroxide, hydrated.

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

30 months.

Store in a refrigerator (2 ° C - 8 ° C). Keep the syringe in the outer carton in order to protect from light.

Do not freeze.

0.25 ml of suspension for injection in pre-filled syringe (type I glass) with a plunger stopper (halogenobutyl rubber). Pack sizes of 1 and 10 are available. The pack may include no needles or 1 separate needle per syringe. Needles are sterile and for single use only. Not all pack sizes may be marketed.

Each pre-filled syringe is packed in a blister. The opening in the blister seal is intended and allows for the equilibration of moisture during the recommended warm-up prior to the administration of the vaccine. Open the blister by removing the lid to take out the syringe. Do not press the syringe through the blister.

For subcutaneous administration, see section 6.6.

The vaccine should reach room temperature before administration. Shake well prior to administration to thoroughly mix the vaccine suspension. After shaking, TicoVac Junior 0.25 ml is an off-white, opalescent, homogeneous suspension. The vaccine should be inspected visually for any foreign particulate matter and/or variation in physical appearance prior to administration. In the event of either being observed, discard the vaccine.

After removing the syringe cap, attach the needle immediately and remove the needle shield prior to administration. Once the needle is attached, the vaccine must be administered immediately. In the exceptional cases of subcutaneous administration, an appropriate needle should be used.

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

The administration of the vaccine should be documented by the physician, and the lot number recorded. A detachable documentation label is attached to each preloaded syringe.