Product Summary File - WHO

1 CompositionOne vial of powder and solvent for solution for injection for one immunisation dose (1 ml) contains: inactivated rabies virus (strain flury LEP), potency > system: primary chicken fibroblast cell culturesOther ingredients:TRIS-(hydroxymethyl-)aminome thane, sodium chloride, EDTA (Titriplex III), potassium-L-glutamate, polygeline, saccharose, water for injectionsPresentation and contents by weight, volume or number of itemsPowder and solvent for solution for injectionAfter dissolution of the white lyophilisate (powder), a clear colourless solution find enclosed our full range of pack/container sizes. Please note that some itemslisted may not be available in all contains: One vial of lyophilisate for one immunisation dose (1 ml) One ampoule containing 1 ml water for injectionsPack contains: One vial of lyophilisate for one immunisation dose (1 ml) One ampoule containing 1 ml water for injections One disposable syringePack contains: Five vials, each with lyophilisate for one immunisation dose (5 x 1 ml) Five ampoules, each containing 1 ml water for injections Five disposable syringesPack contains: 30 vials, each with lyophilisate for 1 immunisation dose (30 x 1 ml)Pack contains: 30 ampoules, each containing 1 ml water for injectionsDisposable syringes are provided or indication categoryVaccinesName and address of the holder of the marketing authorisationNovartis Vaccines and Diagnostics GmbH & Co.

2 KGPO Box 1630D-35006 MarburgGermanyIndicationsActive immunisation against ) Pre-exposure immunisation (preventative, priorto exposure):Immunisation priorto possible infection with rabies, particularly for vets, veterinarymedicine students, animal keepers, hunters, forestry workers, animal handlers, butchers,personnel in rabies research laboratories etc., or prior to visits to areas in which rabiesis endemic (rabies infected areas).b) Post-exposure treatment (afterexposure):Treatment aftercontact with animals which are rabid or suspected to be rabid, orafter contact with an inoculated rabies further details, see enclosed ) Immunisation priorto exposureIt is advisable to avoid pre-exposure (prophylactic) immunisation in individuals withacute disorders requiring complications arise after vaccination, this should be considered a contraindicationfor further administration of the same vaccine, until the causes of the complicationshave been individuals with known allergy to one of the constituents of Rabipur, use of thisvaccine is ) Treatment afterexposureIn view of the fact that rabies is a fatal disease, there are no contraindications toimmunisation after suspected exposure (see section "Special precautions for use").

3 Pregnancy and breast-feedingNo cases of harm attributable to use of this vaccine during pregnancy have been observedto date in mothers or is not known whether Rabipur passes into breast G26 00479 (17984A)1 Date of revision of the package leafletSeptember 2006 Additional InformationThis vaccine conforms to the World Health Organisation (WHO) requirements andcontains no antibody concentration achieved by the immunisation falls gradually; boosterdoses are therefore required to maintain immunisations and all immunoglobulins administered should be entered by thedoctor, with the name of the preparation (proprietary name) and Lot. No., in the inter-national immunisation record. Optimal immunity will only be conferred if the full im-munisation schedule is Active substance: Inactivated rabies virusPackage leafletExposurecategoryIIIIIIC ontact with a rabid orsuspected rabid*wild or domestic animal Touching/feedinganimals, but clearly nocontact with their saliva;patient's skinundamaged prior to andduring contact Animal has nibbled orlicked exposed skin ofthe patient Contact with saliva Superficial, non-bleeding, scratchesmade by the animal,with the exception ofscratches on the head,neck, shoulder region,arms and hands(see exposure grade III) All bites Bleeding scratches All scratches on thehead, neck, shoulderregion, arms, and hands Contact of patient'smucous membrane withanimal saliva(e.)

4 G. licking, spray)Contact with aninoculated animalcarcass Touching inoculated carcass; skin intact Touching inoculatedcarcass; skin damaged Contact ofinoculated carcasswith mucousmembrane or freshskin woundTreatment scheduleNo treatment cases of uncertainty,immunisation to beadministered as perschedule B (Table 2)Immediate treatment asspecified in schedule cases of uncertainty, simultaneous administra-tion of vaccine and immu-noglobulin (active andpassive immunisation) should be administedas specified in schedule C(Table 2).If the animal proves to behealthy after examination,it is advisable to continuetreatment as in schedule patient's immunityagainst immediate simul-taneous administration ofvaccine and immunoglo-bulin (active and passiveimmunisation) as specifiedin schedule C (Table 2).If the animal proves to behealthy after examination,it is advisable to continuetreatment as in schedule patient s immunityagainst of exposureSchedule AImmunisation prior toexposureOne injection of on days: 0, 7, and 21 or 28 Schedule BImmunisation after exposureOne injection of Rabipur days: 0, 3, 7, 14, 28 (5-dose schedule)orOne dose of Rabipur to begiven into the right deltoidmuscle and one dose into theleft deltoid muscle on day 0;and one dose to be appliedinto the deltoid muscle ondays 7 and 21 (2-1-1 regimen).

5 In small children the vaccine isto be given into the CSimultaneous prophylaxisafter exposureGive Rabipur as in schedule B + 1 x 20 IU/kg BW human rabiesimmunoglobulin** or 40 IU/kgBW equine rabies immuno-globulin simultaneously withthe first dose of no rabies immunoglobulinis available at the time of thefirst vaccination, it must beadministered no later than 7days after the first vaccination.*Persons who have received less than three immunisation doses, or a vaccine ofdoubtful potency or origin** Observe manufacturer s instructions!(Based on the 1997 WHO guidelines)* All animals exhibiting abnormal behaviour in an area which has been officially decla-red as rabies endemic area must be considered potentially rabid. The corpses of rabidanimals can also transmit :Where indicated, prophylactic immune treatment should be given as soon aspossible!

6 Table 2: Pre-exposure immunisation and post-exposure treatment of indivi-duals with no or inadequate* immunityTable 1: Appropriate rabies treatment based on different categories of 10:07 Seite 1 (Schwarz/Process Black Bogen) Product Summary FileRabipurNovartis Vaccines and Diagnostics GmbH & Co. KG, GermanyAs an alternative to the above mentioned 5-dose schedule, the World Health Organi-sation (WHO) also recommends the abbreviated 2-1-1 regimen as being effective:Two doses on day 0 (one dose given into the right and one dose into the left deltoidmuscle [upper-arm muscle] or, in small children, one dose each into the anterolateralregion of the right and left thigh), and one dose each on days 7 and 21 (see also Table2, schedule B/C).In all injuries caused by rabid animals or animals suspected to be rabid, or aftercontact between the saliva of these animals and the mucous membranes or damagedskin of the patient (see Table 1), the 5-dose schedule or 2-1-1 schedule along withadditional passive immunisation are required (see Table 2, schedule C).

7 20 IU/kgbodyweight (BW) of human rabies immunoglobulin or 40 IU/kg of equine rabiesimmunoglobulin are to be given once at the time of the first vaccination. As much ofthe rabies immunoglobulin preparation as is anatomically feasible should be appliedas deeply as possible in and around the wound. Any remaining rabies immunoglobu-lin should be administered intramuscularly (preferablyintragluteally) at a site distantfrom the site of the vaccine injection. If rabies immunoglobulin is not available at the time of the first vaccination it mustbe administered no later than 7 days after the first vaccination since later administrationwould result in interference with antibody immunoglobulin should only be administered at the recommended recommended immunoglobulin dose should neither be increased, nor decreased,nor should rabies immunoglobulin administration be repeated (for further detailsrefer to the manufacturer's information).

8 The immunisation schedule must be followed exactly, even if considerable timehas elapsed since subjects at particularly high risk of contracting rabies infection (e. g. with multiplewounds, particularly on the head or other markedly innervated parts of the body), orfor those who have delayed initiation of treatment, the patient must be vaccinatedon each of the days 0, 3, 7, 14, 28. Additionally the initial immunisation dose shouldbe doubled: a single dose of vaccine should be given by injection as soon as possibleafter exposure into the right deltoid and another single dose into the left deltoidmuscle, or in small children, a single dose given into the anterolateral region of theright thigh with another single dose given into the left Previously fully immunised individuals:Patients who have previously received a complete course of primary immunisation(pre- or post-exposure) should receive two doses of Rabipur; one on each of days 0and 3, respectively.

9 This is independent of the interval to the last immunisation. Noadministration of rabies immunoglobulin is Immunocompromised individuals:Patients receiving immunosuppressive therapy, or who have congenital or acquiredimmunodeficiency, should be vaccinated once on each of the days 0, 3, 7, 14, 28. Inaddition, the initial immunisation dose (day 0) should be doubled with a single doseof vaccine being administered as soon as possible after exposure into each of the rightand left deltoid muscles (upper-arm muscle) or, in small children, into the anterolateralregion of each of the right and left immunocompromised patients (with impaired defence system) are treated afterexposure to rabies, it is advisable that the antibody titre be measured 14 days afterthe first dose. If a titre of at least IU/ml, which is considered adequate to conferprotection, is not present, a dose of vaccine should be immediately administered intoeach upper-arm (or into each thigh in the case of small children).

10 Depending on theimmunisation status of these patients, additional doses may be necessary to achieveappropriate antibody titres in serum (for information on immunoglobulin adminis-tration see Section x "Unimmunised or incompletely immunised individuals)".Method and duration of administrationThe lyophilisate should be reconstituted immediately using the diluent supplied, andcarefully agitated prior to injection. The reconstituted vaccine should be used must be given by intramuscular injection into the deltoid muscle (upper-armmuscle), or into the anterolateral region of the thigh in small children. The vaccine mustnot be given by intragluteal (in the gluteal muscle) vaccine must not be administered by intravascular (in a blood vessel) injection! Undesirable effectsIf you develop side effects, especially side effects which are not mentioned in thispackage leaflet, please inform your doctor or reactions at the injection site, such as pain, redness, swelling or induration arepossible.