1. NAME OF THE MEDICINAL PRODUCT FSME-IMMUN 0.5 ml Baxter Suspension for injection in pre-filled syringe Tick-Borne Encephalitis (TBE) Vaccine (Inactivated) Summary of Product Characteristics 2. QUALITATIVE AND QUANTITATIVE COMPOSITION One dose (0.5 ml) contains: Tick-Borne Encephalitis Virus 1,2 ( strain Neudörfl) 1 adsorbed on aluminium oxide, hydrated (0.35 milligrams Al 3+ ) 2 produced in chick embryo fibroblast cells (CEF cells) 2.4 micrograms For excipients, see 6.1. 3. PHARMACEUTICAL FORM Suspension for injection in a pre-filled syringe After shaking the vaccine is an off-white, opaque suspension. 4. CLINICAL PARTICULARS 4.1 Indications FSME-IMMUN 0.5 ml Baxter is indicated for the active (prophylactic) immunization of persons of at least 16 years of age against tick-borne encephalitis (TBE). FSME-IMMUN 0.5 ml Baxter is to be given on the basis of official recommendations regarding the need for and timing of vaccination against TBE. 4.2 Posology and method of administration Posology Persons of at least 16 years of age The primary vaccination schedule for persons of at least 16 years of age consists of three doses of FSME-IMMUN 0.5 ml Baxter. 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 the spring, the first and second doses should preferably be given in the winter months. The third vaccination should be given 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). 1/6
Booster doses in subjects under 60 years The first booster dose should be given no more than 3 years after the third dose (see section 5.1.). Sequential booster doses may be given at 3 to 5 year intervals if the subject is likely to continue to be exposed to a risk of infection. Elderly persons (above the age of 60) and persons 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. 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). In general, in individuals over 60 years of age the booster intervals should not exceed three years. 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). 4.3 Contraindications Hypersensitivity to the active component, one 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. 4.4 Special warnings and special precautions for use 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 FSME-IMMUN 0.5 ml Baxter. Nevertheless, such persons should only be vaccinated under appropriate supervision and facilities for emergency management of hypersensitivity reactions should be available. 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 FSME-IMMUN 0.5 ml Baxter 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 FSME- IMMUN 0.5 ml Baxter cannot be expected to prevent the onset of a clinically apparent TBE infection. As with all vaccines, FSME-IMMUN 0.5 ml Baxter may not completely protect all vaccinees against the infection that it is intended to prevent. 2/6
Tick bites may transmit infections other than TBE, including certain pathogens (such as some bacteria of the genus Borrelia) that can sometimes cause a clinical picture that resembles tick-borne encephalitis. 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. 4.5 Interactions with other medicinal products and other forms of interaction No interaction studies with other vaccines or medicinal products have been performed. The administration of other vaccines at the same time as FSME-IMMUN 0.5 ml Baxter 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. 4.6 Pregnancy and lactation Relevant human data on use during pregnancy and adequate animal reproduction studies are not available. It is not known whether FSME-IMMUN 0.5 ml Baxter enters breast milk. Therefore, FSME-IMMUN 0.5 ml Baxter 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 riskbenefit-relationship. 4.7 Effects on the ability to drive and to use machines FSME-IMMUN 0.5 ml Baxter 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. 4.8 Undesirable effects In a controlled safety study in adults aged 16 to 65 (2977 after the first vaccination and 2950 after the second vaccination), the following undesirable effects were observed: Blood and lymphatic system disorders: Uncommon (>1/1000; <1/100): lymphadenopathy Gastrointestinal disorders: Common (>1/100; <1/10): nausea Uncommon (>1/1000; <1/100): vomiting General disorders and administration site conditions: Very common (>1/10): injection site pain, injection site tenderness Common (>1/100; <1/10): fatigue, malaise Uncommon (>1/1000; <1/100): injection site swelling, injection site erythema, injection site induration, pyrexia Musculosceletal and connective tissue disorders: Common (>1/100; <1/10): myalgia, arthralgia Nervous system disorders: Common (>1/100; <1/10): headache The following additional undesirable effects were reported under the spontaneous reporting system: Eye disorders: Very rare (<1/10000): visual disturbance, as for instance vision blurred and photophobia, eye pain 3/6
General disorders and administration site conditions: Very rare (<1/10000): rigors, gait abnormal Nervous system disorders: Very rare (<1/10000): meningism, dizziness, neuritis Skin and subcutaneous tissue disorders: Very rare (<1/10000): erythema, pruritus, urticaria As with all vaccinations, an aggravation of autoimmune diseases (e.g., multiple sclerosis or iridocyclitis) cannot be ruled out after the administration of FSME-IMMUN 0.5 ml Baxter; an adequate weighing of benefits and risks is therefore required. In very rare cases (<1/10000) a temporal relationship between TBE vaccination and the development of encephalitis cannot be ruled out.. 4.9 Overdose There is no experience of overdose. 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. 5. PHARMACOLOGICAL PROPERTIES 5.1 Pharmacodynamic properties 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. In three clinical studies with FSME-IMMUN 0.5 ml Baxter, seroconversion was defined as a baseline ELISA value of < 63 VIE U/ml rising to > 126 VIE U/ml after vaccination. By these criteria, Table 1 shows that seroconversion was observed in > 88 % of vaccinees (N=480) 3 to 5 weeks after the 2 nd dose. Seroconversion after the 3 rd dose increased to 96-100%. Therefore completion of the primary vaccination schedule of three doses is necessary to achieve protective antibody levels in almost all recipients. Table 1: Seroconversion as determined by ELISA N Seroconversion rate after 2 nd vaccination N Seroconversion rate after 3 rd vaccination Study 1 280 88.6% 243 97.1% Study 2 68 88.2% 59 96.6% Study 3 132 97.0% 118 100.0%- Currently, results from a follow-up study that investigated the persistence of anti-tbe antibody 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. 5.2 Pharmacokinetic properties 4/6
Not applicable 5.3 Preclinical safety data Animal studies performed have shown no indication of a safety risk for humans. 6. PHARMACEUTICAL PARTICULARS 6.1 Excipients Human albumin, sodium chloride, disodium phosphate-dihydrate, potassium dihydrogenphosphate, water for injection. 6.2 Incompatibilities In the absence of incompatibility studies, FSME-IMMUN 0.5 ml Baxter must not be mixed with other medicinal products. 6.3 Shelf life 30 months. 6.4 Special storage requirements Store in a refrigerator (+2 to +8 C). Keep container in outer carton. Do not freeze. 6.5 Nature and contents of container Pack containing: 0.5 ml of suspension in pre-filled syringe (type I glass) with a plunger stopper (halogen butyl isoprene rubber), with no additional needles included. Packs of 1, 10, 20 and 100. Not all pack sizes may be marketed. 6.6 Instructions for use/handling The vaccine should reach room temperature before administration. Shake well prior to administration to thoroughly mix the vaccine suspension. After shaking, FSME-IMMUN 0.5 ml Baxter 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 FSME-IMMUN 0.5 ml Baxter 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. 5/6
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. 7. MARKETING AUTHORISATION HOLDER Baxter Vaccine AG, A-1221 Vienna, Industriestrasse 67, Austria 8. MARKETING AUTHORISATION NUMBER PL 19901/001 9. DATE OF AUTHORISATION 30 December 2003 10. DATE OF REVISION OF THE TEXT 23 February 2006 6/6