- 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 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 recommended single intramuscular dose is 1 ml in all age groups.Whenever possible according to vaccine availability, it is recommended that one type of cell culture vaccine should be used throughout the course of pre- or post-exposure immunisation. However, adherence to the recommended schedules is of critical importance for post-exposure prophylaxis, even if another type of cell culture vaccine has to be used.
Primary immunisationIn previously unvaccinated persons, an initial course of pre-exposure prophylaxis consists of three doses (each of 1 ml) administered on days 0, 7 and 21 or 28.
Booster dosesThe need of intermittent serological testing for the presence of antibody ≥ 0.5 IU/ml (as assessed by the Rapid Focus-Fluorescent inhibition Test) and the administration of booster doses should be assessed in accordance with official recommendations.The following provides general guidance:• Testing for neutralising antibodies at 6-month intervals is usually recommended if the risk of exposure is high (e. g. Laboratory staff working with rabies virus). • In persons who are considered to be at continuing risk of exposure to rabies (e. g. veterinarians and their assistants, wildlife workers, hunters), a serological test should usually be performed at least every 2 years, with shorter intervals if appropriate to the perceived degree of risk.• In above mentioned cases, a booster dose should be given should the antibody titre fall below 0.5 IU/ml. • Alternatively, booster doses may be given at official recommended intervals without prior serological testing, according to the perceived risk. Experience shows that reinforcing doses are generally required every 2-5 years.Rabipur may be used for booster vaccination after prior immunisation with human diploid cell rabies vaccine.
POST-EXPOSURE PROPHYLAXISPost-exposure immunisation should begin as soon as possible after exposure and should be accompanied by local measures to the site of inoculation so as to reduce the risk of infection. Official guidance should be sought regarding the appropriate concomitant measures that should be taken to prevent establishment of infection (see also section 4.4).
Previously fully immunised individuals:For WHO exposure categories II and III, and in category I cases where there is uncertainty regarding the correct classification of exposure (see Table 1 below), two doses (each of 1 ml) should be administered, one each on days 0 and 3. On a case by case basis, schedule A (see Table 2 below) may be applied if the last dose of vaccine was given more than two years previously.Table 1: Immunisation schedules appropriate to different type of contact, exposure and recommended post-exposure prophylaxis (WHO 2004)
|Category||Type of contact with a suspect or confirmed rabid domestic or wilda) animal, or animal unavailable for testing||Type of exposure||Recommended post-exposure prophylaxis|
|I||Touching or feeding of animals Licks on intact skin Touching of inoculated animal lure with intact skin||None||None, if reliable case history is available. In case of unreliable case history, treat according to schedule A (see Table 2).|
|II||Nibbling of uncovered skin Minor scratches or abrasions without bleeding Touching of inoculated animal lure with skin damaged||Minor||Administer vaccine immediately b) Stop treatment if animal remains healthy throughout an observation period of 10 daysc) or if animal is proven to be negative for rabies by reliable laboratory using appropriate diagnostic techniques In case of uncertainty and/or exposure in a high-risk area, administer active and passive treatment as in schedule B (see Table 2).|
|III||Single or multiple transdermal bites or scratches, licks on broken skin Contamination of mucous membrane with saliva (i. e. licks) Exposure to batsd) Touching of inoculated animal lure with mucous membrane or fresh skin wound||Severe||Administer rabies immunoglobulin and vaccine immediately b) as in schedule B (see Table 2). Stop treatment if animal remains healthy throughout an observation period of 10 daysc) or if animal is proven to be negative for rabies by reliable laboratory using appropriate diagnostic techniques|
Individuals unimmunised or with uncertain immune statusDepending on the WHO category as in Table 1, treatment according to schedules A or B (see Table 2 below) may be required for previously unimmunised persons and for those who have received fewer than 3 doses of vaccine or who have received a vaccine of doubtful potency.Table 2: Post-exposure prophylaxis of subjects with no or uncertain immune status
|Schedule A Active immunisation after exposure is required||Schedule B Active and passive immunisation after exposure are required|
|One injection of Rabipur i.m. on days: 0, 3, 7, 14, 28 (5-doses schedule) Or One dose of Rabipur is given into the right deltoid muscle and one dose into the left deltoid muscle on day 0, and one dose is applied into the deltoid muscle on days 7 and 21 (2-1-1 regimen). In small children the vaccine is to be given into the thighs.||Give Rabipur as in schedule A + l × 20 IU/kg body weight human rabies immunoglobulin* concomitantly with the first dose of Rabipur. If HRIG is not available at the time of the first vaccination it must be administered not later than 7 days after the first vaccination.|
Immunocompromised patients and patients with a particularly high risk of contracting rabiesFor immunocompromised patients, those with multiple wounds and/or wounds on the head or other highly innervated areas, and those for whom there is a delay before initiation of treatment, it is recommended that:- The days 0, 3, 7, 14 and 28 immunisation regimen should be used for these cases- Two doses of vaccine may be given on day 0. That is, a single dose of 1 ml vaccine should be injected into the right deltoid and another single dose into the left deltoid muscle. In small children, one dose should be given into the anterolateral region of each thigh.Severely immunosuppressed patients may not develop an immunologic response after rabies vaccination. Therefore, prompt and appropriate wound care after an exposure is an essential step in preventing death. In addition, rabies immune globulin should be administered in all immunosuppressed patients experiencing Category II and Category III wounds.In immunocompromised patients, the neutralising antibody titre should be measured 14 days after the first injection. Patients with a titre that is less than 0.5 IU/ml should be given another two doses of vaccine simultaneously and as soon as possible. Further checks on the antibody titre should be made and further doses of vaccine should be administered as necessary.In all cases, the immunisation schedule must be followed exactly as recommended, even if the patient does not present for treatment until a considerable time has elapsed since exposure.
Method of AdministrationThe vaccine should be given by intramuscular injection into the deltoid muscle, or into the anterolateral region of the thigh in small children.It must not be given by intra-gluteal injection.
Do not administer by intravascular injection (see Section 4.4).
Post-exposure prophylaxisThere are no contraindications to vaccination when post-exposure prophylaxis is indicated. However, subjects considered to be at risk of a severe hypersensitivity reaction should receive an alternative rabies vaccine if a suitable product is available (see also section 4.4 regarding previous hypersensitivity reactions).
Pre-exposure prophylaxisRabipur should not be administered to subjects with a history of a severe hypersensitivity reaction to any of the ingredients in the vaccine. Note that the vaccine contains polygeline and residues of chicken proteins, and may contain traces of neomycin, chlortetracycline and amphotericin B (see also section 4.4).Vaccination should be delayed in subjects suffering from an acute febrile illness. Minor infections are not a contraindication to vaccination.
Do not administer by intravascular injection.If the vaccine is inadvertently administered into a blood vessel there is a risk of severe adverse reactions, including shockAfter contact with animals which are suspected carriers of rabies, it is essential to observe the following procedures (according to WHO 1997):Immediate wound treatmentIn order to remove rabies virus, immediately cleanse wound with soap and flush thoroughly with water. Then treat with alcohol (70%) or iodine solution. Where possible, bite injuries should not be closed with a suture, or only sutured to secure apposition.Tetanus vaccination and rabies immunoglobulin administrationProphylaxis against tetanus should be implemented when necessary.In cases of indicated passive immunisation, as much of the recommended dose of human rabies immunoglobulin (HRIG) as anatomically feasible should be applied as deeply as possible in and around the wound. Any remaining HRIG should be injected intramuscularly at a site distant from the vaccination site, preferably intragluteally. For detailed information plesase refer to the SmPC and/or package insert of HRIG.
|Standard system organ class||Frequency||Adverse reactions|
|General disorders and administration site condition||Very common > 1/10||Injection site pain, injection site reaction, injection site induration, injection site swelling|
|Common > 1/100, < 1/10||Asthenia, malaise, fever, chills, fatigue, influenza like illness, injection site erythema|
|Uncommon >1/1000, <1/100||Dizziness|
|Cardiac disorders||Rare > 1/10.000, < 1/1.000||Circulatory reactions (such as palpitations or hot flush)|
|Blood and lymphatic system disorders||Common > 1/100, < 1/10||Lymphadenopathy|
|Ear and labyrinth disorders||Very rare < 1/10.000||Vertigo|
|Eye disorders||Rare > 1/10.000, < 1/1.000||Visual disturbance|
|Nervous system disorders*||Common > 1/100, < 1/10||Headache|
|Rare > 1/10.000, < 1/1.000||Paraesthesia|
|Very rare < 1/10.000||Nervous system disorders (such as paresis or Guillain-Barré-Syndrome)|
|Skin disorders||Common > 1/100, < 1/10||Rash|
|Immune system disorders||Very rare < 1/10.000||Allergic reactions (such as anaphylaxis, bronchospasm, oedema, urticaria or pruritus), Serum-sickness like symptoms|
|Musculosceletal and connective tissue disorders||Common > 1/100, < 1/10||Myalgia, arthralgia|
|Gastrointestinal disorders||Common > 1/100, < 1/10||Gastrointestinal disorder (such as nausea or abdominal pain)|
Pre-exposure ProphylaxisIn clinical trials with previously unimmunised subjects, almost all subjects achieve a protective antibody titre (≥ 0.5 IU/ml) by day 28 of a primary series of three injections of Rabipur when given according to the recommended schedule by the intramuscular route.As antibody titres slowly decrease, booster doses are required to maintain antibody levels above 0.5 IU/ml. However, persistence of protective antibody titres for 2 years after immunisation with Rabipur without additional booster has been found to be 100 % in clinical trials.In clinical trials, a booster dose of Rabipur elicited a 10-fold or higher increase in Geometric Mean Titres (GMTs) by day 30. It has also been demonstrated that individuals who had previously been immunised with Human Diploid Cell Vaccine (HDCV) developed a rapid anamnestic response when boosted with Rabipur. Persistence of antibody titres has been shown for 14 years in a limited number (n = 28) of subjects tested.Nevertheless, the need for and timing of boosting should be assessed on a case by case basis, taking into account official guidance (see also section 4.2).
Post-exposure ProphylaxisIn clinical studies, Rabipur elicited neutralising antibodies (≥ 0.5 IU/ml) in 98% of patients within 14 days and in 99-100% of patients by day 28 38, when administered according to the WHO-recommended schedule of five intramuscular injections of 1 ml, one each on days 0, 3, 7, 14 and 28.Concomitant administration of either Human Rabies Immunoglobulin (HRIG) or Equine Rabies Immunoglobulin (ERIG) with the first dose of rabies vaccine caused a slight decrease in GMTs. However, this was not considered to be clinically relevant.
Powder:Trometamol Sodium chloride Disodium edetate Potassium-L-glutamate Polygeline Sucrose
Solvent:Water for injections
Not all pack sizes may be marketed.
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