Consumer medicine information

Rabipur

Rabies vaccine

BRAND INFORMATION

Brand name

Rabipur

Active ingredient

Rabies vaccine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Rabipur.

What is in this leaflet

This leaflet answers some common questions about RABIPUR (Inactivated Rabies Virus Vaccine).

It does not contain all the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines, including vaccines, have risks and benefits. Your doctor has weighed the risks of you or your child having RABIPUR against the benefits they expect it will have.

If you have any concerns about this vaccine, ask your doctor, nurse or pharmacist.

Keep this leaflet. You may need to read it again.

What RABIPUR is used for

RABIPUR is a vaccine used to help prevent rabies infection in people who either:

  • have been; or
  • are at risk of being bitten, licked or scratched by an animal infected with rabies virus.

Rabies is a very serious infection. The rabies virus attacks the nerves and the brain. Rabies infection can be fatal if not treated as early as possible.

How it works

RABIPUR works by encouraging your body to protect itself against rabies. The body makes substances called antibodies that fight the rabies virus.

If the rabies virus gets into someone who has been vaccinated against rabies, the antibodies kill the virus before it can cause damage.

After vaccination your body takes several weeks to develop enough antibodies to successfully fight rabies.

For vaccination against rabies you need a course of 3 to 5 injections.

After this course, most people produce enough antibodies against rabies. However, as with all vaccines, RABIPUR may not fully protect all people who are vaccinated.

For people at risk, further booster injections of rabies vaccine may be needed every few years to ensure enough antibodies are present.

The vaccine will not give you or your child rabies.

The chance of a severe reaction from RABIPUR is very small, but the risks from not being vaccinated against rabies may be very serious.

Before you are given RABIPUR

When you or your child must not be given RABIPUR

Do NOT have RABIPUR if you have:

  • an allergy to RABIPUR or any of the ingredients listed at the end of this leaflet;
  • a severe allergy to chicken eggs; or
  • an acute infection or are suffering from any illness or fever. The presence of a minor infection, such as a cold, should not require postponement of the vaccination.

Untreated rabies infection can be fatal. Therefore, even if you may be allergic to an ingredient of this vaccine and you have been bitten or scratched by an animal which has/is thought to have rabies, it is essential to have the rabies vaccine. Your doctor will be able to manage any allergic reaction you may have.

Do not have RABIPUR after the expiry date printed on the pack.

Do not have RABIPUR if the packaging is torn or shows signs of tampering.

If you are not sure whether you or your child should have RABIPUR, talk to your doctor or pharmacist.

Before you or your child are given RABIPUR

Tell your doctor if you have, or have had, any medical conditions, especially the following:

  • low immunity due to an illness OR treatment with medicines such as corticosteroids, cyclosporin or cancer treatment (including radiation therapy);
  • a severe allergy to chicken eggs;
  • an allergy to antibiotics, particularly neomycin, chlortetracycline or amphotericin B (amphotericin).
  • fainting, feeling faint or other stress-related reactions can occur as a response to any needle injection. Tell your doctor or nurse if you have experienced this kind of reaction previously.

Tell your doctor if you are pregnant or intend to become pregnant. Your doctor will discuss the possible risks and benefits of having RABIPUR during pregnancy.

Tell your doctor if you are breast-feeding Your doctor will discuss the possible risks and benefits of having RABIPUR during breastfeeding.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you buy without a prescription from your pharmacy, supermarket or health food shop.

RABIPUR and some medicines may interfere with each other. These include:

  • medicines that lower the body's immunity, such as corticosteroids, cyclosporin or other medicines used to treat cancer (including radiation therapy).

These medicines may be affected by RABIPUR or may affect how well it works. You may need different amounts of these medicines, or you may need to take different medicines. Your doctor or pharmacist will advise you.

How RABIPUR is given

A doctor or nurse gives RABIPUR as an injection (usually into muscle in your upper arm).

RABIPUR should not be injected directly into the skin or a vein.

How much is given

Each injection of rabies vaccine is 1.0 mL.

Your doctor will decide how many injections of RABIPUR you will need.

When it is given

"Post exposure"
RABIPUR may be given to people after they have been exposed to rabies infection.

Vaccinated individuals
If you have been fully vaccinated against rabies and/or have received boosters, the usual course is 2 injections.

Unvaccinated individuals
If you have not been vaccinated before or have not received a full vaccination, the usual course is 4 to 5 injections, given at intervals over 3 or 4 weeks.

Compromised immune system
The usual course is 5 or 6 injections.

"Pre-exposure"
RABIPUR may be given in advance to people at risk of being infected with rabies.

The usual course is 3 injections given at intervals over 3 - 4 weeks.

Booster Injections
After two to five years, depending on the circumstances, a booster injection may be needed. Further boosters may be needed every few years.

Your doctor will tell you how many injections you should have and when you should have them.

Follow carefully all your doctor's directions.

If you miss a dose

If you miss a dose, talk to your doctor and arrange another visit as soon as possible.

Overdose

Overdose is most unlikely because your doctor or nurse gives the injections.

If you have any concerns, ask your doctor

After having RABIPUR

Things you or your child must do

Keep an updated record of your vaccinations.

Keep follow-up appointments with your doctor or clinic.

It is important to have your follow-up doses of RABIPUR, and any blood tests, at the correct intervals. This gives the vaccine the best chance of providing protection against rabies and allows the antibody level to be measured.

Side effects

Tell your doctor or pharmacist as soon as possible if you or your child do not feel well after having RABIPUR.

Ask your doctor or pharmacist to answer any questions you may have.

RABIPUR may have unwanted side effects. All medicines, including vaccines can have side effects. Sometimes they are serious, most of the time they are not. You or your child may need medical treatment if you get some of the side effects.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • any effects at the injection site such as redness, swelling or pain
  • headache
  • fever
  • tiredness
  • generally feeling unwell
  • flu-like symptoms
  • chills
  • increased sweating
  • swollen glands in the neck, groin or armpit
  • muscle ache, weakness, joint pain
  • nausea or vomiting
  • stomach cramps or pain
  • rash

These are common side effects of RABIPUR. Mostly these are mild and short-lived.

Tell your doctor immediately if you notice any of the following:

  • fast or irregular heartbeat or hot flushes
  • problems with vision
  • tingling or numbness of the hands or feet
  • dizziness or light-headedness, feeling faint or fainting
  • weakness that restricts movement
  • inability to move or loss of feeling in some parts of the body

If any of the following happen, tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

  • signs of allergy, such as itchy pink rash, itchy swellings on the skin (also called hives or nettle rash)
  • swelling of the face, lips, tongue or other parts of the body such as limbs
  • difficulty breathing
  • blue discolouration of the tongue or lips
  • headache and high-temperatures associated with hallucinations, confusion, paralysis of part or all of the body, disturbances of behaviour, speech and eye movements, stiff neck and sensitivity to light.

These are very serious side effects. You or your child may need urgent medical attention or hospitalisation.

All of these side effects are very rare.

This is not a complete list of side effects. Tell your doctor or pharmacist if you notice anything related to RABIPUR that makes you or your child feel unwell.

Storing RABIPUR

RABIPUR is usually stored in the doctor's surgery or clinic, or at the pharmacy. However, if you need to store RABIPUR:

  • Keep it where children cannot reach it.
  • Keep RABIPUR in the original pack until it is time for it to be given.
  • Keep it in the refrigerator, between 2°C and 8°C. Do not freeze RABIPUR.
    Freezing can lower the effectiveness of the vaccine.

Product description

What RABIPUR looks like

Each pack of RABIPUR contains

  • one vial of vaccine powder
  • one pre-filled syringe of sterile water for injections

Your doctor will inject the sterile water into the vial to make the liquid for your injection. This liquid is clear and colourless.

Ingredients

Vaccine

Active ingredients:

  • Not less than 2.5 International Units of inactivated Rabies virus (Flury LEP strain)

Other ingredients:

  • Trometamol
  • Sodium chloride
  • Disodium edetate
  • Monopotassium glutamate
  • Polygeline
  • Sucrose
  • Possible trace amounts: neomycin, chlortetracycline, amphotericin B (amphotericin).

Diluent

  • Water for Injections

The manufacture of this product includes exposure to bovine derived materials. No evidence exists that any case of vCJD (considered to be the human form of bovine spongiform encephalitis) has resulted from the administration of any vaccine product.

Contains no antimicrobial agent. Product is for single use in one patient only. Discard any residue.

Sponsor

RABIPUR is sponsored in Australia by:

Seqirus Pty Ltd
ABN: 26 160 735 035
63 Poplar Road
Parkville VIC 3052
Australia
Telephone: 1800 642 865
www.seqirus.com.au

RABIPUR is sponsored in New Zealand by:

Seqirus (NZ) Ltd
PO Box 62 590
Greenlane,Auckland
1546
New Zealand
Telephone: 0800 502 757

Date of preparation

7 June 2021

Trade marks are owned or licensed to Bavarian Nordic A/S.

Published by MIMS August 2021

BRAND INFORMATION

Brand name

Rabipur

Active ingredient

Rabies vaccine

Schedule

S4

 

1 Name of Medicine

Inactivated Rabies Virus Vaccine.

2 Qualitative and Quantitative Composition

Rabipur is an inactivated rabies virus vaccine, derived from the fixed virus strain, Flury LEP. The virus is propagated in a Purified Chick Embryo Cell (PCEC) culture, inactivated using β-propiolactone and purified via centrifugation.
Each 1.0 mL dose of the reconstituted vaccine contains no less than 2.5 IU of inactivated rabies virus, in accordance with the World Health Organization requirements.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Powder and diluent for injection.
The reconstituted vaccine is clear to slightly opalescent and colourless to slightly pink.

4 Clinical Particulars

4.1 Therapeutic Indications

For active immunisation against rabies virus, including:
a) pre-exposure immunisation;
b) post-exposure treatment following exposure to rabies virus.

4.2 Dose and Method of Administration

Recommended dosages, as outlined below, are the same for children, adolescents and adults.

Dosage.

Pre-exposure prophylaxis.

Primary immunisation.

In previously unvaccinated persons, an initial course of pre-exposure prophylaxis consists of three doses (each of 1.0 mL) administered on days 0, 7 and 21 or 28.

Booster doses.

In persons with ongoing risk of exposure to rabies virus, the following general guidance is provided:
Testing for neutralising antibodies by the Rapid Focus-Fluorescent Inhibition Test (RFFIT) at 6 month intervals is usually recommended if the risk of exposure to rabies virus 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, in persons with ongoing risk of rabies exposure, booster doses may be offered every 2 to 5 years without serological testing.
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.

Immediate wound treatment.

In order to remove as much of the rabies virus as possible, immediately cleanse the wound with soap and flush thoroughly with water. Then treat with alcohol (70%) or an iodine tincture. Where possible, bite injuries should not be closed with a suture, or only sutured to secure apposition. Prophylaxis against tetanus should be administered when necessary.
In cases where passive immunisation is also indicated, as much of the recommended dose of HRIG as is 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 site of vaccine administration (preferably intragluteally).

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), two doses (each of 1.0 mL) should be administered on both day 0 and day 3. On a case by case basis, schedule A (see Table 2) may be applied if the last dose of vaccine was given more than two years previously.

Individuals non-immunised or with uncertain immune status.

Depending on the WHO category as in Table 1, treatment according to schedules A or B (see Table 2) may be required for previously non-immunised persons and for those who have received fewer than 3 doses of vaccine or who have received a vaccine of doubtful potency.

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 1.0 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 exposure is an essential step in preventing death. In addition, rabies immunoglobulin should be administered in all immunosuppressed patients experiencing category II and category III wounds.
For 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 as soon as possible. Further checks on the antibody titre should be made and further doses of vaccine should be administered as necessary. In such instances, specialist advice should be sought. Additional information can be obtained from the current Australian Immunisation Handbook.

Method of administration.

Reconstitution. The vaccine should be visually inspected both before and after reconstitution for any foreign particulate matter and/or change in physical appearance. The vaccine must not be used if any change in the appearance of the vaccine has taken place.
The powder for solution should be reconstituted by addition of the diluent supplied using a sterile syringe supplied. The reconstituted vaccine is clear to slightly opalescent and colourless to slightly pink. The reconstituted vaccine must be carefully agitated prior to injection and should be used immediately with any unused vaccine or waste material suitably disposed.
The vial of vaccine contains negative pressure. After reconstitution of the vaccine, it is recommended to unscrew the syringe from the needle to eliminate the negative pressure. After that, the vaccine can be easily withdrawn from the vial. It is not recommended to induce excess pressure, since over-pressurization will create the problems in withdrawing the proper amount of the vaccine.
Administration. The vaccine must be given by intramuscular injection into the deltoid muscle, or into the anterolateral region of the thigh in small children. The vaccine must not be given by intragluteal injection.
Product is for single use in one patient only.
Instructions for use and handling.

Administration of Rabipur presented in a pre-filled syringe.

See Figure 1.
Step 1: With one hand, hold the syringe (E) with the cap pointing upward. Be sure to hold the syringe by the white textured holding ring (D).
Step 2: With the other hand, grasp the cap (A) and firmly rock it back and forth to break its connection to the holding ring (D). Do not twist or turn the cap.
Step 3: Lift up to remove the cap (A) and the attached grey tip cap (B). Be careful not to touch the sterile syringe tip (C).

Instructions for attaching needle.

To attach a reconstitution needle, firmly hold the syringe (E) with one hand by the white textured holding ring (D). With your other hand, insert needle and twist clockwise until it locks into place. Once needle is locked, remove its plastic cover.
The syringe (E) is now ready for use.
After completing the reconstitution of the vaccine, replace the reconstitution needle with an administration needle.

4.3 Contraindications

a) Pre-exposure immunisation.

Rabipur is contraindicated in subjects with a known severe hypersensitivity to any of the components of the vaccine, including chicken eggs, chicken protein, bovine gelatin, neomycin, chlortetracycline and amphotericin B (amphotericin).
Vaccination should be delayed in subjects suffering from an acute febrile illness. Minor infections are not a contraindication to vaccination.

b) Post-exposure treatment.

In view of the fatal outcome of clinically manifest rabies, any suspicion of infection should always lead to treatment. Subjects that have a severe hypersensitivity to components of the vaccine 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 available.

4.4 Special Warnings and Precautions for Use

For intramuscular injection only.
Serious systemic anaphylactic reactions, including cases of anaphylactic shock, have been reported in temporal association with Rabipur.
Serious neurological events, such as encephalitis, Guillain-Barré syndrome, meningitis, multiple sclerosis, myelitis, paresis and retrobulbar neuritis have been reported (< 1:100,000) in temporal association with Rabipur.
If complications arise following any of the series of injections in the schedule, do not continue with further vaccine doses until the cause of the complications have been clarified.
As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of a rare anaphylactic event following the administration of the vaccine.
In patients with known hypersensitivity to constituents of the vaccine receiving postexposure treatment, appropriate remedial facilities for treating anaphylactic shock should always be available during immunisation, or alternatively another equivalent modern cell culture rabies vaccine should be used.
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.
Patients who are immunocompromised, including those receiving immunosuppressive therapy or high dose corticosteroids, 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.
Anxiety-related reactions, including vasovagal reactions (syncope), hyperventilation or stress-related reactions, may occur in association with vaccination as a psychogenic response to the needle injection (see Section 4.8 Adverse Effects (Undesirable Effects)). It is important that procedures are in place to avoid injury from fainting.
Rabipur may contain residual amounts of the antibiotics neomycin, chlortetracycline and amphotericin B (amphotericin).
Do not inject intravascularly. Unintentional intravascular injection may result in systemic reactions, including shock.
Rabies vaccine must not be given by intra-gluteal injection or subcutaneously, as the induction of an adequate immune response may be less reliable. Do not administer the vaccine intradermally.
The vaccine must not be mixed in the same syringe with other medicinal products. If rabies immunoglobulin is indicated in addition to Rabipur vaccine, then it must be administered at an anatomical site distant to the vaccination (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Adherence to treatment guidelines, as outlined below, are of utmost importance in order to minimise risk of rabies disease. However, in very few cases development of rabies disease despite correct treatment has been reported. Direct inoculation of the rabies virus into nerve endings has been discussed as an explanation for these rare cases.
As with other vaccines, a protective immune response may not be achieved in all patients who receive the vaccine.

Use in the elderly.

See Section 4.2 Dose and Method of Administration.

Paediatric use.

See Section 4.2 Dose and Method of Administration.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Other vaccines, which are deemed clinically essential, may be given at the same time as Rabipur. Different injectable vaccines should be administered into separate injection sites. Do not mix vaccines within the same syringe.
For patients receiving immunosuppressive therapy, or with congenital or acquired immunodeficiency, the response to the vaccination may be reduced or absent. Therefore, it is recommended that serological responses should be monitored in such subjects, and additional doses administered as necessary (see Section 4.2 Dose and Method of Administration, Immunocompromised patients and patients with a particularly high risk of contracting rabies). Specialist advice should be sought. Additional information can be obtained from the current Australian Immunisation Handbook.
Immunosuppressive therapy during postexposure treatment should be avoided.
Antirabies immunoglobulins may attenuate the effects of concomitantly administered rabies vaccine. All of the rabies immunoglobulin, or as much as anatomically possible (but avoiding possible compartment syndrome), should be administered into or around the wound site or sites. The remaining immunoglobulin, if any, should be injected intramuscularly at a site distant from the site of vaccine administration to avoid possible interference with simultaneously administered rabies vaccine. Additional information can be obtained from the anti-rabies immunoglobulin product information.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No reproductive toxicity studies have been performed with Rabipur.
(Category B2)
Animal embryofetal development studies have not been conducted with the vaccine. It is not known whether the vaccine can cause foetal harm when administered to a pregnant woman or can effect reproductive capacity. For pre-exposure vaccination, Rabipur should not be given to a pregnant woman, unless benefits outweigh potential risks and vaccination is clearly needed, as might occur in high risk situations.
Pregnancy is never a contraindication to postexposure rabies vaccination. In postexposure situations the vaccine should be given as recommended.
No cases of harm attributable to use of this vaccine during pregnancy have been observed in mothers or children.
 It is not known whether Rabipur is excreted in human milk. Caution should be exercised when the vaccine is administered to a nursing mother.
It is advisable to carefully weigh expected benefits against potential risks prior to prophylactic administration of Rabipur during lactation.

4.7 Effects on Ability to Drive and Use Machines

No studies have been carried out with Rabipur to assess the effect on the ability to drive or use machines.

4.8 Adverse Effects (Undesirable Effects)

As with all vaccines and as outlined below, Rabipur administration may cause unintended reactions. However, not all events occurring after vaccination are causally related to the vaccine. For any unexpected effects while taking Rabipur, contact your physician or pharmacist.

Adverse drug reaction overview.

In very rare cases, neurological and neuroparalytical events and cases of hypersensitivity have been reported in temporal association with administration of Rabipur.
The most commonly occurring adverse reactions are injection site reactions, such as injection site erythema, induration and pain; flu-like symptoms, such as asthenia, fatigue, fever, headache, myalgia and malaise; arthralgia, dizziness, lymphadenopathy, nausea and rash.
A patient's risk of acquiring rabies must be carefully considered before deciding to discontinue vaccination.

Clinical trials experience.

As clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared to rates in the clinical trials of another vaccine and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to vaccine use and for approximating rates.
In a comparative trial in normal volunteers, Dreesen et al (Vaccine, 1989; 7:397-400) described their experience with Rabipur compared to a human diploid cell culture rabies vaccine (HDCV). Nineteen subjects received Rabipur and 20 received HDCV. The most commonly reported adverse reaction was pain at the injection site, reported in 45% of the HDCV group and 34% of the Rabipur group. Localised lymphadenopathy was reported in about 15% of each group. The most common systemic reactions were malaise (15% Rabipur group versus 25% HDCV group), headache (10% Rabipur group versus 20% HDCV group), and dizziness (15% Rabipur group versus 10% HDCV group).
In a recent study in the USA, 83 subjects received Rabipur and 82 received HDCV. Again, the most common adverse reaction was pain at the injection site in 80% in the HDCV group and 84% in the Rabipur group. The most common systemic reactions were headache (52% Rabipur group versus 45% HDCV group), myalgia (53% Rabipur group versus 38% HDCV group) and malaise (20% Rabipur group versus 17% HDCV group). None of the adverse events were serious, almost all adverse events were of mild or moderate intensity.

Other common adverse events reported in clinical trials.

The data from clinical trials described in Table 3 reflect exposure to Rabipur in 1,307 subjects, including 355 subjects in pre-exposure vaccination settings and 952 patients who received Rabipur for postexposure prophylaxis. Rabipur was studied primarily in single blind, randomised controlled trials. The population studied was mainly Caucasian and Asian, ranging from healthy infants to healthy adults with an equal gender distribution. Patients only received intramuscular administration of Rabipur.

Post-marketing adverse drug reactions.

Those adverse reactions identified during postapproval use of Rabipur can be found in Table 4. As these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccine exposure. Decisions to include these reactions in labelling are typically based on one or more of the following factors: 1) seriousness of the reaction; 2) frequency of reporting; or 3) strength of causal connection to vaccine exposure, or a combination of these factors.
Once initiated, rabies prophylaxis should not be interrupted or discontinued because of local or mild systemic adverse reactions to rabies vaccine. Usually such reactions can be successfully managed with anti-inflammatory and antipyretic agents.
In postmarketing experience to November 2004 (a period in which approximately 33 million doses have been distributed) 47 deaths due to rabies were reported in persons who had been received postexposure treatment with Rabipur. In all but three cases WHO recommendations for postexposure treatment had not been followed. The other three cases involved severe exposures such as facial bites.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

ATC code: J07B G01.

Mechanism of action.

Injection of the vaccine induces production of an antibody titre that markedly exceeds 0.5 IU/mL of serum, the threshold considered to provide adequate protection. As the antibody concentration slowly falls, booster doses are required to maintain antibody levels above the acceptable level of 0.5 IU/mL.

Clinical trials.

Pre-exposure immunisation.

The immunogenicity of Rabipur has been demonstrated in clinical trials conducted in Europe, North America and Asia. When administered according to the recommended immunisation schedule (days 0, 7, 21 or 28), 100% of subjects attained an adequate titre of 0.5 IU/mL by day 28 or earlier. Persistence of antibody titres ≥ 0.5 IU/mL for up to 2 years after immunisation with Rabipur has been measured in clinical trials.
Table 5 details the serum antibody titres of subjects, vaccinated according to the pre-exposure vaccination dosage regimen with either Rabipur or human diploid cell rabies vaccine (HDCV). These data demonstrate that Rabipur causes production of antibodies, with geometric mean titres (GMT) greater than 0.5 IU/mL by day 28. The study also demonstrated no statistically significant difference in GMT following vaccination with either type of vaccine.
In other studies, long-term antibody titres following pre-exposure vaccination with Rabipur were evaluated in 36 patients. The study showed that 2 years postvaccination, the antibody GMTs remained above 0.5 IU/mL for 64% of recipients vaccinated. Antibody titre data is provided in Table 6.

Postexposure immunisation.

Clinical studies in patients exposed to rabies virus have demonstrated that Rabipur, when used in the recommended postexposure World Health Organization (WHO) schedule of 5 x 1.0 mL intramuscular injections (on days 0, 3, 7, 14, 28), provided protective titres of neutralising antibodies (> 0.5 IU/mL) in 98% of patients within 14 days and in 100% of patients by day 30. Similar results were obtained in several studies with healthy volunteers who had been given the WHO recommended postexposure regimen ("simulated" postexposure immunisation). Table 7 details the proportion of subjects who developed a protective antibody titre (≥ 0.5 IU/mL) following vaccination in accordance with the postexposure regimen.
One study followed cohorts of patients presenting with bites from laboratory proven rabid animals for one year. No case of rabies was observed in this patient population. Some patients received passive immunisation with human rabies immunoglobulin (HRIG) 20 - 30 IU/kg bodyweight, or equine rabies immune globulin (ERIG) 40 IU/kg bodyweight, at the time of the first vaccine dose. Analysis of the data concluded that the addition of either HRIG or ERIG caused a slight decrease in GMTs when compared to subjects not receiving the immunoglobulin; this slight decrease was deemed neither clinically relevant nor statistically significant.

Booster immunisation.

The ability of Rabipur to boost antibody titres in previously immunised subjects has been examined through clinical studies. Data from one study demonstrated that after one booster dose, a 10-fold or higher increase in GMTs on day 30 were observed in subjects previously vaccinated with HDCV. A significant increase was observed among all vaccinees with antibody titres of > 0.5 IU/mL at baseline on day 0. Table 8 details the GMTs for this trial.
Data from an additional booster vaccination study demonstrated that individuals known to have been previously immunised with a PCEC vaccine or human diploid cell vaccine (HDCV), developed a rapid anamnestic response when boosted with Rabipur. A booster response was observed on day 7 for all individuals. One Rabipur intramuscular booster dose resulted in a significant increase in antibody titres in all subjects, regardless of whether they had received Rabipur or HDCV as the primary vaccine. More than one year after primary immunisation, one or two IM doses of Rabipur induced a 10-fold or higher increase in GMTs by day 7. On day 21 postbooster, the GMTs of subjects that received two booster doses of vaccine were higher than those that received one booster dose of vaccine (Table 9).

5.2 Pharmacokinetic Properties

Not applicable.

5.3 Preclinical Safety Data

Genotoxicity.

No genotoxicity studies have been performed with Rabipur.

Carcinogenicity.

No carcinogenicity studies have been performed with Rabipur.

6 Pharmaceutical Particulars

6.1 List of Excipients

Each 1.0 mL dose of the reconstituted vaccine also contains the following excipients: trometamol, sodium chloride, disodium edetate, monopotassium glutamate, polygeline, sucrose, water for injections.
The quantities of each excipient (excluding water for injection) will vary dependent on virus concentration in the harvested material.
Contains no antimicrobial agent.
The antibiotics neomycin, chlortetracycline and amphotericin B (amphotericin) are used in the manufacturing process of this vaccine and may be present in trace amounts.
The manufacture of this product includes exposure to bovine derived materials. No evidence exists that any case of vCJD (considered to be the human form of bovine spongiform encephalitis) has resulted from the administration of any vaccine product.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store vaccine and diluent at 2°C - 8°C (in a refrigerator). Do not freeze.

6.5 Nature and Contents of Container

Rabipur is available in the following pack sizes:
5 single dose lyophilised vaccine vials (type 1 glass) with a stopper (chlorobutyl or bromobutyl) with 5 single dose disposable pre-filled syringes (type 1 glass) with a plunger-stopper (bromobutyl) containing diluent (1.0 mL), without needle and with a tip-cap (bromobutyl).
1 single dose lyophilised vaccine vial (type 1 glass) with a stopper (chlorobutyl or bromobutyl), with 1 single dose disposable pre-filled syringe (type 1 glass) with a plunger-stopper (bromobutyl) containing diluent (1.0 mL), without needle and with a tip-cap (bromobutyl).
Not all pack sizes and presentations may be marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

No data available.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription only medicine.

Summary Table of Changes