Consumer medicine information

Verorab

Rabies vaccine

BRAND INFORMATION

Brand name

Verorab

Active ingredient

Rabies vaccine

Schedule

SUMMARY CMI

Verorab^®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about you or your child receiving this medicine, speak to your doctor or pharmacist.

▼ This medicine is new or being used differently. Please report side effects. See the full CMI for further details.

1. Why am I or my child receiving Verorab?

Verorab contains the active ingredient rabies virus (inactivated). Verorab is a vaccine used to help prevent rabies infection in people who have been, or are likely to be, bitten, licked, or scratched by an animal that has or is suspected to have rabies.

For more information, see Section 1. Why am I or my child receiving Verorab? in the full CMI.

2. What should I know before I or my child receives Verorab?

Do not use if you or your child has ever had an allergic reaction to Verorab or any of the ingredients listed at the end of the CMI, UNLESS bitten, licked, or scratched by an animal that is suspected to have rabies. Do not use if you or your child has a high temperature or serious illness, UNLESS bitten, licked, or scratched by an animal that is suspected to have rabies.

Talk to your doctor if you or your child has any other medical conditions or is taking any other medicines. Tell your doctor if you are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I or my child receives Verorab? in the full CMI.

3. What if I or my child is taking other medicines?

Some medicines may interfere with Verorab and affect how it works.

A list of these medicines is in Section 3. What if I or my child is taking other medicines? in the full CMI.

4. How do I or my child receive Verorab?

Verorab is given as an injection, usually into muscle in the upper arm or in the skin, by a doctor or nurse. Your doctor will decide how many injections you or your child should have and when they should have them. Carefully follow all of your doctor's directions.

More instructions can be found in Section 4. How do I or my child receive Verorab? in the full CMI.

5. What should I know after I or my child receives Verorab?

Things you should do

Keep an updated record of you or your child's vaccinations.
Keep follow-up appointments with your doctor or clinic. It is important to have follow-up doses of Verorab, and any blood tests, at the correct intervals.

Looking after your medicine

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

Keep it where children cannot reach it.
Keep it in the original pack.
Keep it in the refrigerator, between 2°C and 8°C. Do not freeze it.

For more information, see Section 5. What should I know after I or my child receives Verorab? in the full CMI.

6. Are there any side effects?

Very common side effects include feeling unwell, headache, sore muscles, pain, redness or swelling at the injection site, and in babies, irritability, inconsolable crying and drowsiness. These side effects are mild and short-lived.

Serious side effects include serious allergic reactions. Symptoms include itchy swellings, swelling of the face, lips, tongue, or other parts of the body, and rash.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

▼ This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. You can report side effects to your doctor, or directly at www.tga.gov.au/reporting-problems.

FULL CMI

Verorab^®

Active ingredient: Rabies virus (inactivated)

Consumer Medicine Information (CMI)

This leaflet provides important information about Verorab. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about you or your child receiving Verorab.

Where to find information in this leaflet:

1. Why am I or my child receiving Verorab?
2. What should I know before I or my child receives Verorab?
3. What if I or my child is taking other medicines?
4. How do I or my child receive Verorab?
5. What should I know after I or my child receives Verorab?
6. Are there any side effects?
7. Product details

1. Why am I or my child receiving Verorab?

Verorab contains the active ingredient, rabies virus (inactivated). Verorab is a vaccine used to help prevent rabies infection in people who have been, or are likely to be, bitten, licked, or scratched by an animal that has rabies. Verorab works by causing your body to produce antibodies against rabies virus.

Verorab is used to help prevent rabies infection. However, as with all vaccines, 100% protection cannot be guaranteed.

2. What should I know before I or my child receives Verorab?

Warnings

Do not receive Verorab if:

you or your child is allergic to Verorab, or any of the ingredients listed at the end of this leaflet UNLESS bitten, licked, or scratched by an animal that is suspected to have rabies.
you or your child has a high temperature or serious illness UNLESS bitten, licked, or scratched by an animal that is suspected to have rabies.

Always check the ingredients to make sure you or your child can receive this vaccine.

Check with your doctor if you or your child:

has any other medical conditions such as low immunity due to an illness or treatment with medicines such as corticosteroids, ciclosporin or cancer treatment (including radiation therapy).
experience anxiety problems, such as breathing fast, fainting, unusual skin sensations, before or after receiving needle injections.
ever had an allergic reaction to antibiotics
take any medicines for any other condition, for example antibiotics

During treatment, you or your child may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

3. What if I or my child is taking other medicines?

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

Some medicines may interfere with Verorab and affect how it works.

medicines which lower the immune system, such as corticosteroids, ciclosporin or other medicines used to treat cancer (including radiation therapy).
antirabies immunoglobulin (used to treat confirmed rabies infection).

Verorab can be administered at the same time as a typhoid fever vaccine in 2 separate injections sites.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you or your child is taking and if these affect Verorab.

4. How do I or my child receive Verorab?

How much to receive

Verorab is given as an injection, usually into muscle in the upper arm or in the skin.
Your doctor will decide how many Verorab injections are needed.

When to receive Verorab

Verorab may be given to people who are at risk of infection with rabies virus because of specific occupation (e.g., vets) or travel to areas where rabies is common. Verorab is also given to people after being bitten, licked, or scratched by an animal that is suspected to have rabies.
Your doctor will tell you how many injections you or your child should have and when they should have them. Carefully follow all of your doctor's directions.

If you forget to receive Verorab

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

If you or your child receive too much Verorab

Overdose is most unlikely because your doctor or nurse gives the injections. If you have any concerns, ask your doctor.

5. What should I know after I or my child receives Verorab?

Things you should do

Keep an updated record of you or your child's vaccinations.
Keep follow-up appointments with your doctor or clinic. It is important to have follow-up doses of Verorab, and any blood tests, at the correct intervals. This gives the vaccine the best chance of providing protection against rabies.

Tell any doctor, dentist or pharmacist you visit that you or your child have received Verorab.

Looking after your medicine

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

Keep it where children cannot reach it.
Keep it in the original pack.
Keep it in the refrigerator, between 2°C and 8°C. Do not freeze it. Freezing destroys the vaccine.

Getting rid of any unwanted medicine

If you no longer need to use this vaccine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this vaccine after the expiry date.

6. Are there any side effects?

All vaccines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effects

What to do

pain, redness, swelling, bruising or itching where the injection was given.
headache
dizziness or light-headedness
muscle ache, tenderness or weakness
painful or swollen joints
“pins and needles”, tingling sensation
nausea, vomiting or diarrhea
stomach cramps or pain
bodily discomfort, feeling unwell
flu-like symptoms
tiredness, lack of energy
chills
fever
swollen glands
breathing difficulties
inconsolable crying (in infants/ toddlers only)
inability to sleep (in infants/ toddlers only)
sudden hearing loss

Speak to your doctor if you or your child have any of these less serious side effects and they worry you.

Serious side effects

Serious side effects	What to do
Signs of allergy such as, itching or pinkish, itchy swellings on the skin (also called hives or nettle rash), swelling of the face, lips, mouth, tongue or throat which may cause difficulty in swallowing or breathing, rash.	Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you or your child feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you or your child experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems (Australia) or to Medsafe at pophealth.my.site.com/carmreportnz/s/ (New Zealand). By reporting side effects, you can help provide more information on the safety of this vaccine.

Always make sure you speak to your doctor or pharmacist before you decide to stop receiving any of your medicines.

7. Product details

This vaccine is only available with a prescription.

What Verorab contains

Each pack of Verorab contains one vial of vaccine powder and one prefilled syringe.

Vial of Vaccine Powder

Active ingredient (main ingredient)	3.25 International Units of rabies virus (inactivated) (WISTAR Rabies PM/WI 38 1503-3M strain)
Other ingredients (inactive ingredients)	Maltose 20% albumin solution Basal Medium Eagle: mixture of mineral salts, vitamins, dextrose and amino-acids including L-Phenylalanine Water for injections Hydrochloric acid and sodium hydroxide
Potential allergens	Neomycin, streptomycin and polymyxin
Excipient with known effect	Phenylalanine (4.1 micrograms)

Prefilled syringe

Ingredient

Sodium chloride 0.4%
Water for injections

Do not receive this vaccine if you or your child is allergic to any of these ingredients, UNLESS bitten, licked, or scratched by an animal that is suspected to have rabies.

What Verorab looks like

Your doctor or nurse will prepare the vaccine by mixing the vial of vaccine powder with the solution in prefilled syringe. The liquid is clear and colourless.

AUST R 371727.

Who distributes Verorab?

Distributed in Australia by:

sanofi-aventis australia pty ltd
12-24 Talavera Road
Macquarie Park NSW 2113
Freecall: 1800 818 806
Email: [email protected]

Distributed in New Zealand by:

Pharmacy Retailing (NZ) Ltd t/a Healthcare Logistics
PO Box 62027
Sylvia Park Auckland 1644
Freecall: 0800 283 684
Email: [email protected]

This leaflet was prepared in July 2024.

verorab-ccdsv11-cmiv3-17jul24

Published by MIMS October 2024

BRAND INFORMATION

Brand name

Verorab

Active ingredient

Rabies vaccine

Schedule

1 Name of Medicine

Inactivated Rabies Virus.

2 Qualitative and Quantitative Composition

Verorab is a Purified Vero Rabies Vaccine referred as PVRV.
Verorab is a sterile stable freeze-dried solution of purified and inactivated rabies virus from Wistar strain PM/WI38 1503-3M. It is cultured on Vero cell, inactivated with Beta-propiolactone and purified by ultracentrifugation.
One dose of vaccine contains 3.25 international units (IU) of rabies antigen (in vitro potency measured using G protein content by ELISA method) (corresponds to ≥ 2.5 IU by NIH test).

Excipient with known effect.

Phenylalanine 4.1 micrograms.
No adjuvant or preservative are added.
Verorab meets the World Health Organization (WHO) requirements for manufacture of biological substances.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Powder and solvent for suspension for injection.
The powder is a white homogeneous pellet.
The solvent is a clear and colorless solution.
After reconstitution, Verorab is limpid and homogeneous.

4 Clinical Particulars

4.1 Therapeutic Indications

Verorab is indicated for pre-exposure prophylaxis against rabies.
Verorab is indicated for post-exposure prophylaxis against rabies.
Verorab should be used in accordance with official local recommendations.

4.2 Dose and Method of Administration

General.

The dose and dosing schedule is identical for adults and paediatric population. The vaccine is administered by intramuscular (IM) injection, in the deltoid area for adults and children or the anterolateral area of the thigh muscle in infants and toddlers.
For dosing in immunocompromised individuals see Section 4.2, Special populations.
For further information, refer to the current Australian Immunisation Handbook.
Once the vaccine is reconstituted with 0.5 mL of solvent, one intramuscular (IM) dose consists of 0.5 mL of reconstituted vaccine and one intradermal (ID) dose consists of 0.1 mL of reconstituted vaccine per injection site.
Pre-exposure prophylaxis (PrEP). For pre-exposure prophylaxis, individuals can be vaccinated according to one of the vaccination schedules presented in Tables 1 and 2 and according to official local recommendations when available.

In addition, booster doses and/or regular serology testing of neutralising antibodies may be indicated according to official local recommendations. For further information, refer to the current Australian Immunisation Handbook.
Post-exposure prophylaxis (PEP). Post-exposure prophylaxis should be initiated as soon as possible after suspected rabies exposure. In all cases, proper wound care (thorough flushing and washing of all bite wounds and scratches with soap or detergent and copious amounts of water and/or virucidal agents) must be performed immediately or as soon as possible after exposure. It must be performed before administration of rabies vaccine or rabies immunoglobulin, when they are indicated.
The rabies vaccine administration must be performed strictly in accordance with the category of exposure, the patient immune status, and the animal status for rabies (according to official local recommendations, see Table 3 for WHO recommendations).
In addition, tetanus prophylaxis and a course of antibiotics to prevent superinfections may be required according to official local recommendations.

Post-exposure prophylaxis of non-immunised individuals or incompletely immunised individuals.

Individuals not previously immunised can be vaccinated according to one of the vaccination schedules presented in Table 4 or in accordance with the current Australian Immunisation Handbook.

For category III exposure (see Table 3), rabies immunoglobulin should be given in association with vaccine. In this case, the vaccine should be administered contra-laterally, if possible.
Vaccination should not be discontinued unless the animal is declared not rabid according to a veterinarian assessment (supervision of animal and/or laboratory analysis).

Post-exposure prophylaxis of previously immunised individuals.

According to WHO recommendation, previously immunised individuals are patients who can document previous complete PrEP (pre-exposure prophylaxis) or PEP (post-exposure prophylaxis) and patients who discontinued a PEP series after at least two doses of a cell culture or embryonated egg-based rabies vaccine.
These individuals should receive one dose of vaccine intramuscularly (vaccine dose 0.5 mL) or intradermally (vaccine dose 0.1 mL) on each of days 0 and 3. Alternatively, 4 intradermal injections (vaccine dose 0.1 mL) can be given at 4 distinct sites at D0.
Rabies immunoglobulin is not indicated for previously immunised individuals.
Official local recommendations should be followed for conditions of utilisation of these accelerated schedules. For further information, refer to the current Australian Immunisation Handbook.

Special populations.

Paediatric population. There is no dose adjustment needed for paediatric population.
Elderly. There is no dose adjustment needed for patients over the age of 65.
Immunocompromised individuals. The following recommendation should be followed for immunocompromised individuals. Also see Section 4.8.

Pre-exposure prophylaxis.

For immunocompromised individuals, conventional 3-dose regimens should be used (see Section 4.2, Pre-exposure prophylaxis (PrEP)) and serology testing of neutralising antibodies should be performed 2 to 4 weeks after the last dose, to assess the possible need for an additional dose of the vaccine.

Post-exposure prophylaxis.

For immunocompromised individuals requiring post-exposure prophylaxis, administer one of the full vaccination schedules listed in Table 4 (see Section 4.2, Post-exposure prophylaxis of non-immunised individuals or incompletely immunised individuals). Rabies immunoglobulin should be given in association with the vaccine for both categories II and III exposures (see Table 3).

Method of administration.

The vaccine is administered by the intramuscular route, in the deltoid area for adults and children or the anterolateral area of the thigh muscle in infants and toddlers.
It can also be administered by intradermal (ID) route preferably on upper arm or forearm. Do not inject in the gluteal area.
Do not inject by the intravascular route.

Instructions for preparation and administration.

1. Remove the seal of the vial of lyophilised powder.
2. Inject the solvent into the vial of lyophilised powder.
3. Gently swirl the vial until homogeneous suspension of the powder is obtained. The reconstituted vaccine should be limpid, homogeneous, and free from particles.
4. Remove and discard the syringe that was used for vaccine reconstitution and use a new syringe with a new needle to withdraw the reconstituted vaccine.
5. Replace the needle used to withdraw the reconstituted vaccine by a new needle for intramuscular or intradermal injection.
6. The length of the needle used for vaccine administration should be adapted to the patient and to the route of administration.
If Verorab is used via intramuscular route, once reconstituted, the product must be used immediately.
If Verorab is used via intradermal route, vaccine may be used up to 6 hours after reconstitution provided it is maintained at no more than 25°C and protected from light. After reconstitution, using aseptic technique, a dose of vaccine should be withdrawn from a vial. The product is for single use only and must not be reused. Discard any remaining unused contents. After use, any remaining vaccine and container must be disposed of safely, preferably by heat inactivation or incineration, according to locally agreed procedure.

4.3 Contraindications

Pre-exposure prophylaxis.

Known systemic hypersensitivity reaction to any component (i.e. as defined under Section 2 and Section 6.1) of Verorab or after previous administration of the vaccine or a vaccine containing the same components.
Vaccination must be postponed in case of febrile or acute disease.

Post-exposure prophylaxis.

Since declared rabies infection generally results in death, there are no contraindications to post-exposure vaccination.

4.4 Special Warnings and Precautions for Use

Protection.

As with any vaccine, vaccination with Verorab may not protect 100% of vaccinated individuals.
In order to reach a sufficient antibodies level of protection, recommendations for the use of Verorab must be strictly followed (see Section 4.2) as an insufficient immune response may lead to fatal cases of rabies.

Immunocompromised individuals.

In individuals with congenital or acquired immunodeficiency, the immune response to the vaccine may be inadequate. Therefore, it is recommended to monitor serologically RVNA (Rabies Virus Neutralising Antibodies) level in such individuals to ensure that an acceptable immune response has been induced. Additional doses should be given as necessary (see Section 4.2, Immunocompromised individuals).
Moreover, if post-exposure vaccination is needed, only full schedule of vaccination should be administered (see Section 4.2, Post-exposure prophylaxis of non-immunised individuals or incompletely immunised individuals). In addition, rabies immunoglobulin should be given in association with the vaccine for category II and III exposures (see Section 4.2, Immunocompromised individuals).

Administration precautions.

Before the injection of any biological, the person responsible for administration must take all precautions known for the prevention of allergic or any other reactions. As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of an anaphylactic event following administration of the vaccine.
As a precautionary measure, adrenaline (epinephrine) injection (1:1000) must be immediately available in case of unexpected anaphylactic or serious allergic reactions.
It is essential that intradermal administration of Verorab is carried out only by medical staff trained in this technique in order to ensure that the vaccine is delivered intradermally. For the intradermal route appropriate syringe and needle should be used. Do not inject by the intravascular route. Ensure that the needle does not enter a blood vessel.

Neomycin, streptomycin and polymyxin.

As each dose may contain undetectable traces of neomycin, streptomycin and polymyxin which are used during vaccine production, caution must be exercised when the vaccine is administered to subjects with hypersensitivity to those antibiotics (and other antibiotics of the same class, if appropriate).

Apnoea.

The potential risk of apnoea and the need for respiratory monitoring for 48-72 hours should be considered when administering the primary immunization series to very premature infants (born ≤ 28 weeks of gestation) and particularly for those with a previous history of respiratory immaturity.

Anxiety-related reactions.

Anxiety-related reactions, including vasovagal reactions (syncope), hyperventilation or stress-related reactions can occur following, or even before, any vaccination as a psychogenic response to the needle injection. This can be accompanied by several neurological signs such as transient visual disturbance and paresthesia. It is important that procedures are in place to avoid injury from fainting.

Traceability.

In order to improve the traceability of biological medicinal products, the name and batch number of the administered product should be clearly recorded.

Use in the elderly.

See Section 4.2, Elderly.

Paediatric use.

See Section 4.2, Paediatric population. The clinical trial program in paediatrics did not include children aged less than 28 days (see Section 5.1, Clinical trials, Paediatric population).

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Immunosuppressive treatment, including long-term systemic corticosteroid therapy, may interfere with antibody production and cause the failure of the vaccination. It is therefore advisable to perform a serological test 2 to 4 weeks after the last injection. (See Section 4.2, Immunocompromised individuals).
Verorab can be administered simultaneously with a typhoid polysaccharide Vi vaccine in two separate injection sites.
Separate injection sites and separate syringes must be used in case of concomitant administration with any other medicinal product, including rabies immunoglobulins.
As rabies immunoglobulin interferes with development of immune response to the vaccine, the recommendation of administration of rabies immunoglobulin must be strictly followed.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Verorab has not been evaluated for impairment of male or female fertility.
(Category B2)

Pre-exposure prophylaxis.

Animal reproductive studies have not been conducted with Verorab. Data on the use of this vaccine in pregnant women are limited. Verorab should be given to pregnant women only if clearly needed and following an assessment of the risks and benefit.

Post-exposure prophylaxis.

Due to the severity of the disease, pregnancy is not a contraindication.

Pre-exposure prophylaxis.

It is not known whether this vaccine is excreted in human milk. Caution must be exercised when Verorab is administered to a nursing mother.

Post-exposure prophylaxis.

Due to the severity of the disease, lactation is not a contraindication.

4.7 Effects on Ability to Drive and Use Machines

No studies on the effects on the ability to drive or use machines have been performed.

4.8 Adverse Effects (Undesirable Effects)

Adverse reaction information is derived from clinical trials and worldwide post-marketing experience.
Within each system organ class the adverse reactions are ranked under headings of frequency, using the following CIOMS frequency rating: very common ≥ 10%; common ≥ 1 and < 10%; uncommon ≥ 0.1 and < 1%; rare ≥ 0.01 and < 0.1%; very rare < 0.01%; not known (cannot be estimated from available data).

Clinical trials.

In clinical studies, more than 13,000 subjects (from 2 months through 98 years of age) received at least one dose of Verorab.
A pooled analysis has been performed on 4 randomised, controlled clinical studies sharing the same safety standards, integrating data from 1151 subjects (17 infants/toddlers younger than 24 months of age, 510 children and adolescents and 624 adults from 18 through 60 years of age). In these studies, the vaccine was given by intramuscular route (N=477) or by intradermal route (N=674). In one of the studies using intradermal route (N=599), most of the subjects received Equine Rabies Immunoglobulin (ERIG) concurrently with the first dose of Verorab.
The adverse reactions were generally of mild intensity and appeared within 3 days after vaccination. Most reactions resolved spontaneously within 1 to 3 days after onset. Most frequent systemic adverse reactions in all age groups (except infants/toddlers) were headache, malaise and myalgia. Injection site reactions (pain, erythema and swelling) were more frequent following ID injection compared to IM injection. Injection site pain was the most frequent injection site reactions for both routes of administration.
Table 5 presents the frequencies of solicited adverse reaction (recorded within 7 days) and unsolicited adverse reactions (recorded within 28 days), reported following any dose of Verorab. Injection site reaction are presented according to the route of administration (IM or ID). The systemic reactions are presented grouped.

For a comprehensive overview of vaccine safety, additional relevant adverse reactions from other studies not selected for pooled safety analysis have been included. Their frequencies are estimated based on total number of subjects included in the clinical studies, where safety of Verorab was evaluated (a total of more than 5000 subjects, including more than 1000 children younger than 18 years of age; split by age group was not available for all studies). See Table 6.

Data from post-marketing experience.

Based on spontaneous reporting, the following additional events have been reported during the commercial use of Verorab. These events have been very rarely reported, however exact incidence rate cannot be precisely calculated, their frequency is qualified as 'not known'.

Immune system disorders.

Anaphylactic reactions, angioedema.

Ear and labyrinth disorders.

Sudden sensorineural hearing loss.

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: J07BG01 Rabies, inactivated, whole virus

Mechanism of action.

Protection after vaccination is provided by the induction of rabies neutralising antibodies (RNA).

Clinical trials.

Clinical studies were conducted to assess the immunogenicity of the vaccine in both pre-exposure and post-exposure situations. A rabies neutralising antibody titre ≥ 0.5 IU/mL, considered by WHO to confer protection, was used as a proof of protective antibody level.

Pre-exposure prophylaxis.

The pre-exposure schedule, 3 doses on D0, D7 and D28 (or D21) by IM route has been assessed in several clinical studies in adult and paediatric populations.
After the vaccination series, all vaccinees reached a rabies neutralising antibody titre ≥ 0.5 IU/mL.
A ten-year follow-up in 49 patients who received the 3-injections protocol, followed by a booster dose at 1 year showed the maintenance of seroconversion up to 10 years in more than 95% of vaccinees.
The one-week pre-exposure schedule by IM route (one 0.5-mL dose at D0 and one 0.5-mL dose at D7) was assessed in Study VAJ00001 in 75 subjects (including 35 children from 2 to 17 years). At D21, 98.6% subjects reached a serum antibody titre ≥ 0.5 IU/mL.
One year later, following a simulated PEP with two 0.5-mL doses injected 3 days apart (at D0 and D3) by IM route, a high and rapid anamnestic response was demonstrated in all subjects from D7.
In 5 studies conducted with Verorab in 392 subjects (including VRV01 study with 39 subjects) in the context of a conventional 3-dose regimen assessment (at D0, D7, D21 or D28) by IM route, all subjects reached a serum antibody titre ≥ 0.5 IU/mL, at D21 or D28, after the 2 doses (at D0 and D7), just before injection of the third dose.
The one-week pre-exposure schedule by ID route (two 0.1-mL doses at D0 and two 0.1-mL doses at D7) was assessed in Study VAJ00001 in 75 subjects (including 36 children from 2 to 17 years). At D21, 97.2% subjects reached a serum antibody titre ≥ 0.5 IU/mL.
One year later, following a simulated PEP with two 0.1-mL doses injected 3 days apart (at D0 and D3) by ID route, a high and rapid anamnestic response was demonstrated in all subjects from D7, except one subject who remained seronegative at every time points despite completing all study vaccinations.
In another study conducted in 430 subjects who received one 0.1-mL dose of Verorab at D0 and one 0.1-mL dose at D7 by ID route, 99.1% subjects reached a serum antibody titre ≥ 0.5 IU/mL at D21.

Post-exposure prophylaxis.

Two post-exposure intramuscular schedules (5-dose Essen regimen [D0, D3, D7, D14 and D28] and 4-dose Zagreb regimen [2 doses on D0, then 1 dose on each D7 and D21], and immunoglobulin as appropriate) have been assessed in several clinical studies in both adult and paediatric populations. Almost all vaccinees reached a rabies neutralising antibody titre ≥ 0.5 IU/mL at D14. In Study VRV08, in which 272 subjects (adolescents and adults) were included, 100% of vaccinees reached antibody titre ≥ 0.5 IU/mL at D14.
In phase III trial RAB40, including 600 exposed subjects aged from 11 months through 50 years of age, two intradermal PEP schedules were tested: one-week 4-site regimen (4 doses on each D0, D3 and D7) with and without ERIG at D0, and Updated Thai Red Cross (TRC) regimen (2 doses on each D0, D3, D7 and D28) with ERIG at D0. Institute Pasteur Cambodia regimen (2 doses on each D0, D3 and D7) was also documented until D28 as part of TRC regimen. Almost all vaccinees reached a rabies neutralising antibody titre ≥ 0.5 IU/mL at D14.
Five years later and before the simulated PEP was received, protective level of rabies neutralising antibodies was maintained in more than 84% of subjects who received one-week 4-site regimen with or without ERIG, and in 64.1% (CI95% 55.1; 72.3) of subjects who received updated TRC regimen with ERIG. Eleven days after simulated PEP with "single-visit 4-dose" ID regimen, all the subjects had rabies neutralising antibody titre ≥ 0.5 IU/mL.
In Study VAJ00001, the simulated PEP vaccination given 1 year after a one-week (D0, D7) IM and ID PrEP vaccination, induced a high and rapid anamnestic response in all subjects from D7 (except one subject vaccinated by ID route, who remained seronegative at every time points despite completing all study vaccinations).
Effectiveness of Verorab has been evaluated in 44 adult subjects bitten by confirmed rabid animals. The subjects received the vaccine according to 5-dose Essen regimen (D0, D3, D7, D14 and D28 by IM route) and immunoglobulin as appropriate. None of these subjects developed the disease.
Effectiveness of Verorab was also confirmed in two studies that used administration schedules recommended in the past. In the first study, 106 patients received 6 IM injections on D0, D3, D7, D14, D28, and D91. In the second study, 40 patients received ID injections at the two deltoid sites on D0, D3, D7 and at 1 site on D28 and D90. All patients received immunoglobulin as appropriate. They all were bitten by confirmed rabid animals, and none of them developed the disease.

Paediatric population.

There is no clinically significant difference in immunogenicity of the vaccine in paediatric population compared to adults.
In the study VAJ00001 assessing the one-week pre-exposure schedule by ID route (two 0.1-mL doses of Verorab at D0 and two 0.1-mL doses at D7) or by IM route (one 0.5-mL dose of Verorab at D0 and one 0.5-mL dose at D7) in 71 children from 2 to 17 years of age, all children reached a serum antibody titre ≥ 0.5 IU/mL at D21.
One year later, following a simulated PEP with two doses injected 3 days apart (at D0 and D3) by IM or ID route, a high and rapid anamnestic response was demonstrated in all subjects from D7.

5.2 Pharmacokinetic Properties

No pharmacokinetic studies have been performed.

5.3 Preclinical Safety Data

Data in animals, including single dose and repeated dose studies revealed no unexpected findings and no target organ toxicity.

Genotoxicity.

No genotoxicity studies have been performed with Verorab.

Carcinogenicity.

No carcinogenicity studies have been performed with Verorab.

6 Pharmaceutical Particulars

6.1 List of Excipients

Each 0.5 mL dose of the reconstituted vaccine also contains the following excipients: maltose, 20% albumin solution, Basal Medium Eagle¹, sodium chloride, water for injections.
¹BME = Basal Medium Eagle: mixture of mineral salts, vitamins, dextrose and amino-acids including L-Phenylalanine.
Contains no antimicrobial agent.
Hydrochloric acid and/or sodium hydroxide can be used for pH adjustment. These components are only present in trace amount.
The antibiotics neomycin, streptomycin and polymyxin are used in the manufacturing process of this vaccine and may be present in trace amounts.

6.2 Incompatibilities

This vaccine must not be mixed with other medicinal products.

6.3 Shelf Life

36 months.

6.4 Special Precautions for Storage

Store in a refrigerator (2°C - 8°C). Do not freeze.
Store protected from light.

6.5 Nature and Contents of Container

Verorab is available in the following pack size:
Powder in vial (Type I glass) with a stopper (chlorobutyl) and a cap + 0.5 mL of solvent in prefilled syringe (Type I glass) with attached needle with a plunger-stopper (chlorobutyl or bromobutyl). Box of 1.

6.6 Special Precautions for Disposal

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

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