TicoVac 0.5 ml Suspension for injection in a prefilled syringe

Tick-Borne Encephalitis Vaccine (whole Virus inactivated)

One dose (0.5 ml) contains:

Tick-Borne Encephalitis Virus^1,2 (strain Neudörfl) 2.4 micrograms

¹ adsorbed on aluminium hydroxide, hydrated (0.35 milligrams Al³⁺)

² produced in chick embryo fibroblast cells (CEF cells)

For a full list of excipients, see section 6.1.

Suspension for injection in a pre-filled syringe

After shaking the vaccine is an off-white, opalescent suspension.

TicoVac 0.5 ml is indicated for the active (prophylactic) immunization of persons of at least 16 years of age against tick-borne encephalitis (TBE).

TicoVac 0.5 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 the age of 16 onwards and consists of three doses of TicoVac 0.5 ml.

The first dose should be given on an elected date and the second dose should be given between 1 and 3 months later.

If there is a need to achieve an immune response rapidly, the second dose may be given two weeks after the first dose. The third dose should be given between 5 and 12 months after the second vaccination.

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.

Extending the interval between the three doses may leave subjects with inadequate protection against infection in the interim period (see sections 4.4 and 5.1).

Booster doses

Persons from 16 to 60 years of age

The first booster dose should be given no more than 3 years after the third dose (see section 5.1.).

Sequential booster doses should be given following official recommendations, but not less than 3 years after the last booster dose. Based on local epidemiology and experience, intervals of 3 up to 5 years for sequential boosters have been officially recommended.

Persons above 60 years of age

In general, in individuals over 60 years of age the booster intervals should not exceed three years.

Persons with an impaired immune system (including those undergoing immunosuppressive therapy) and elderly persons (above the age of 60)

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. A third dose should be given as scheduled and the need for subsequent booster doses may then be assessed by serological tests at intervals (see sections 4.4 and 5.1).

Method of administration

The vaccine should be given by intramuscular injection into the upper arm (deltoid muscle). Care must be taken to avoid accidental intravascular administration (see section 4.4).

Hypersensitivity to the active substance, any of the excipients, or production residues (formaldehyde, neomycin, gentamicin, protamine sulfate).

Severe hypersensitivity to egg and chick proteins (anaphylactic reaction after oral ingestion of egg protein).

TBE vaccination should be postponed if the person is suffering from an acute febrile infection.

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 0.5 ml. Nevertheless, such persons should only be vaccinated under appropriate supervision and facilities for emergency management of hypersensitivity reactions should be available.

The container of this medicinal product contains latex rubber which may cause severe allergic reactions in persons allergic to latex.

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.

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 0.5 ml might have an adverse effect on the course of the auto-immune disease.

Caution is required when considering the need for vaccination in persons with pre-existing cerebral disorders.

In case of a tick bite before or within 2 weeks after receiving the first dose, a single administration of TicoVac 0.5 ml cannot be expected to prevent the onset of a clinically apparent TBE infection.

As with all vaccines, TicoVac 0.5 ml may not completely protect all vaccinees against the infection that it is intended to prevent.

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 infection 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 0.5 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.

A protective immune response may not be elicited in persons undergoing immunosuppressive therapy or persons with an impaired immune system. In such cases antibody concentrations should be determined in order to assess the response and the need for sequential doses.

Relevant human data on use during pregnancy and adequate animal reproduction studies are not available. It is not known whether TicoVac 0.5 ml enters breast milk.

Therefore, TicoVac 0.5 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 0.5 ml is unlikely to affect a person's ability to drive and use machines. It should be taken into account, however, that impaired vision or dizziness may occur.

The following undesirable effects were observed in clinical safety studies in adults aged 16 years and older (3512 after the first vaccination, 3477 after the second vaccination, and 3277 after the third vaccination). The ADRs listed in this Section are given according to the recommended frequency convention:

Very common: 1/10

Common: 1/100 and <1/10

Uncommon: 1/1,000 and <1/100

Rare: 1/10,000 to <1/1,000

Very rare: <1/10,000

Not known: Cannot be estimated from the available data

* Undesirable effects under this frequency category are derived from a spontaneous reporting system and thus, there is no valid estimate of incidence rates.

No case of overdose has been reported. However, due to the presentation of the vaccine, accidental overdose in terms of volume is unlikely. If doses are administered closer together than recommended or more doses than requested are applied, undesirable effects may be expected.

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 TBE vaccine has been determined during a continuous surveillance as performed among the total Austrian population since 1984. In this surveillance a protection rate of above 90% after the second vaccination, and above 97% after completion of the primary vaccination schedule (3 doses) was calculated.

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 regular vaccination i.e before completion of the basic vaccination scheme by the third vaccination, but it is significantly lower in those with a record of irregular vaccination ..

In clinical studies with TicoVac 0.5 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 one time point after the second and one time point after the third vaccination in the conventional and the rapid immunization schedule are presented in table 1 and 2.

Table 1: Conventional immunization schedule, pooled seropositivity rates 1 as determined by ELISA and NT in subjects aged 16-65 years

¹– evaluated 21 days after each dose

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

Table 2: Rapid 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 rate as determined by ELISA and NT in both age groups 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.

Results from a follow-up study that investigated the persistence of anti TBE antibodies support the need for the first booster vaccination no later than three years after primary immunization. Further investigations into the optimal timing of booster doses are ongoing.

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, TicoVac 0.5 ml 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.

0.5 ml of suspension in pre-filled syringe (type I glass) with a plunger stopper (chlorobutyl isoprene rubber), with needle attached. Pack sizes of 1, 10, 20 and 100. Not all pack sizes may be marketed.

The vaccine should reach room temperature before administration. Shake well prior to administration to thoroughly mix the vaccine suspension. After shaking, TicoVac 0.5 ml is an off-white, opaque homogenous 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.

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

Remove needle guard as follows:

1. Hold syringe at the lower part of the needle guard fixed onto the glass recipient.

2. Use the other hand to take the upper part of the needle guard between thumb and forefinger and twist to break the seal (tamper evident).

3. Remove the detached part of the needle guard from the needle by a vertical movement.

Following the removal of the needle guard TicoVac 0.5 ml must be used immediately.

To avoid loss of sterility and/or clogging of the needle, it should not be left without protection for prolonged periods of time. Therefore, the needle guard should only be removed after shaking and immediately prior to use.

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.

Baxter AG, Industriestrasse 67, A-1221 Vienna, Austria

PL 19901/001

19.07.1996/18.07.2006

May 2009