Drug Class Description

Generic Name

Drug Description

Presentation

Indications

a) Pre-exposure prophylaxis (before possible risk of exposure to rabies)

b) Post-exposure treatment (after known or possible exposure to rabies) Consideration should be given to national and/or WHO guidance regarding the prevention of rabies.

Adult Dosage

Posology

The recommended single intramuscular dose is 1 ml in all age groups.

Whenever possible according to vaccine availablility, 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 treatment, even if another type of cell culture vaccine has to be used.

PRE-EXPOSURE PROPHYLAXIS

Primary immunisation

In 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 doses

The 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 TREATMENT

Post-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.

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 types of exposure (WHO 2002)

^a) Exposure to rodents, rabbits and hares seldom, if ever, requires specific anti-rabies treatment.

^b) If an apparently healthy dog or cat in or from a low-risk area is placed under observation, it may be justified to delay specific treatment.

^c) Stop treatment if animal is a cat or dog and remains healthy throughout an observation period of 10 days or if animal is euthanised and found to be negative for rabies by appropriate laboratory techniques. Except in the case of threatened or endangered species, other domestic and wild animals suspected as rabid should be euthanised and their tissues examined using appropriate laboratory techniques.

Individuals unimmunised or with uncertain immune status

Depending 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 treatment of subjects with no or uncertain immune status

Immunocompromised patients and patients with a particularly high risk of contracting rabies

For 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 Administration

The 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.

Contra Indications

Post-exposure treatment

There are no contraindications to vaccination when post-exposure treatment 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.

Pre-exposure prophylaxis

Rabipur 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 may contain polygeline, traces of neomycin, chlortetracycline, amphotericin B and chick proteins.

Vaccination should be delayed in subjects suffering from an acute febrile illness. Minor infections are not a contraindication to vaccination.

Special Precautions

As with all vaccines, appropriate medical treatment should be immediately available for use in the rare event of an anaphylactic reaction to the vaccine.

A history of allergy to eggs or a positive skin test to ovalbumin does not necessarily indicate that a subject will be allergic to Rabipur. However, subjects who have a history of a severe hypersensitivity reaction to eggs or egg products should not receive the vaccine for pre-exposure prophylaxis. Such subjects should not receive the vaccine for post-exposure treatment unless a suitable alternative vaccine is not available, in which case all injections should be administered with close monitoring and with facilities for emergency treatment.

Similarly, subjects with a history of a severe hypersensitivity reaction to any of the other ingredients in Rabipur such as polygeline (stabilizer), or to amphotericin B, chlortetracycline or neomycin (which may be present as trace residues) should not receive the vaccine for pre-exposure prophylaxis. The vaccine should not be given to such persons for post-exposure treatment unless a suitable alternative vaccine is not available, in which case precautions should be taken as above.

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 shock

After contact with animals which are suspected carriers of rabies, it is essential to observe the following procedures (according to WHO 1997):

Immediate wound treatment

In 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 administration

Prophylaxis 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.

Interactions

Patients who are immunocompromised, including those receiving immunosuppressive therapy, may not mount an adequate response to rabies vaccine. Therefore, it is recommended that serological responses should be monitored in such patients and additional doses given as necessary.

Administration of rabies immunoglobulin may be necessary for management but may attenuate the effects of concomitantly administered rabies vaccine. Therefore, it is important that rabies immunoglobulin should be administered once only for treating each at-risk exposure and with adherence to the recommended dose.

Other essential inactivated vaccines may be given at the same time as Rabipur. Different injectable inactivated vaccines should be administered into separate injection sites.

Adverse Reactions

In clinical studies the most commonly reported solicited adverse reactions were injection site pain (30 –85 %, mainly pain due to injection) or injection site induration (15 - 35 %). Most injection site reactions were not severe and resolved within 24 to 48 hours after injection. Furthermore, the following undesirable effects were observed in clinical trials and/or during the post-marketing period:

* Statistically there is no indication of increasing frequencies of primary manifestations or triggered attacks of autoimmune diseases (e.g. multiple sclerosis) after vaccination. However, in individual cases it cannot be absolutely excluded that a vaccination may trigger an episode in patients with corresponding genetic disposition. According to the current state of scientific knowledge vaccinations are not the cause of autoimmune diseases.

Manufacturer

Drug Availability

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