Rabipur

PACKAGE LEAFLET: INFORMATION FOR THE USER

Rabipur

Powder and solvent for injectable solution in pre-filled syringe
Rabies virus (inactivated, Flury LEP strain)
Please read all of this leaflet carefully before you or your child are given Rabipur, as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This vaccine has been prescribed for you or your child personally. Do not give it to others.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

1. What Rabipur is and what it is used for
2. What you need to know before you or your child are vaccinated with Rabipur
3. How to use Rabipur
4. Possible side effects
5. How to store Rabipur
6. Contents of the pack and other information

1 WHAT RABIPUR IS AND WHAT IT IS USED FOR
What Rabipur is
Rabipur is a vaccine containing inactivated rabies virus. After administration of the vaccine, the immune system (the body's natural defence system) produces antibodies against the rabies virus. These antibodies protect against infections or diseases caused by the rabies virus. None of the components of the vaccine can cause rabies.

What Rabipur is used for
Rabipur can be used in individuals of all ages.
Rabipur can be used to prevent rabies:

• before possible exposure to the rabies virus (pre-exposure prophylaxis), or
• after suspected or confirmed exposure to the rabies virus (post-exposure prophylaxis).

Rabies is an infection that can be transmitted when a person is bitten, scratched, or even licked by an infected animal, particularly if the skin is broken. Contact with animal traps that have been licked or bitten by infected animals may also cause infection in humans.

2. WHAT YOU SHOULD KNOW BEFORE YOU OR YOUR CHILD RECEIVE

RABIPUR
You or your child must not receive Rabipur before a possible risk of exposure to the rabies virus if:

• You have a history of severe allergic reaction to the active substance or to any of the other components of the vaccine listed in section 6.
• You have an acute illness requiring treatment.

Due to the severity of rabies infection, Rabipur may be administered to anyone who has been exposed to rabies, including pregnant women.
Severe allergic reactions (hypersensitivity)
If you or your child are known to be at risk of a severe allergic reaction to the vaccine or to any of its components, you may receive a different rabies vaccine that does not contain these components. If an alternative vaccine is not available, your doctor or nurse will assess with you the risks of vaccination versus the risk of rabies virus infection before you or your child receive the vaccine.
Warnings and precautions
If you have an acute illness requiring treatment, vaccination is generally postponed until at least two weeks after recovery. A minor infection does not require postponement of vaccination, but you should consult your doctor or nurse first.
Inform your doctor or nurse before you or your child receive Rabipur for post-exposure prophylaxis if:

• You have a severe allergy to eggs or egg-derived products (for symptoms, see section 4 of this leaflet). Rabipur contains traces of chicken proteins originating from the manufacturing process.
• You have a severe allergy to the antibiotics neomycin, chlorotetracycline, or amphotericin B. These antibiotics may be present in very small amounts in the vaccine.
• You have a severe allergy to polygelin. Fainting may occur after, or even before, any needle injection; therefore, inform your doctor or nurse if you have fainted following previous injections.

Very rare but serious neurological conditions have been reported after vaccination with Rabipur. See section 4. Anti-inflammatory medicines (steroids), often used to treat these conditions, may interfere with the effectiveness of the vaccine (see below Other medicines and Rabipur). Your doctor or nurse will decide how to proceed in such cases.
As with all vaccines, Rabipur may not fully protect all vaccinated individuals.
The vaccine must not be injected into the buttocks, under the skin, or into a blood vessel.
Other medicines and Rabipur
Inform your doctor or nurse if you or your child are taking or have recently taken or might take any other medicines, including those not requiring a prescription. Unless otherwise instructed by your doctor, you or your child should continue taking all prescribed medicines as usual.
If you or your child have a weakened immune system or are already taking medicines that reduce immunity to infections, Rabipur may still be administered; however, the protection provided by the vaccine may not be as effective as in others. In such cases, your doctor may decide to perform blood tests after vaccination to check whether sufficient antibodies against the virus have been produced. If necessary, you or your child will receive additional doses of the vaccine (see section 3 of this leaflet).
Rabipur can be administered at the same time as other inactivated vaccines. Each type of vaccine will be given at a different injection site.
You or your child may also need to receive rabies antibodies (known as "anti-rabies immunoglobulins") if you have not completed the full course of rabies vaccination and if infection with the virus is highly likely. In such cases, the anti-rabies immunoglobulins (which are administered only once, usually with the first vaccine dose) and the vaccine will be given at different sites on the body.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, you should still receive the rabies vaccine if you have had, or are likely to have had, contact with the virus. You may also receive Rabipur during pregnancy or while breastfeeding, and before exposure to the virus, if the risk of contact with the virus is considered substantial. In such cases, your doctor will discuss with you the risks of vaccination and of rabies virus infection and advise you on the best timing for Rabipur vaccination.
Driving and using machines
Some of the adverse effects described in section 4 of this leaflet may affect your ability to drive or operate machinery.
Rabipur contains:
Less than 23 mg of sodium per dose and is therefore essentially "sodium-free".

3. HOW TO USE RABIPUR

Rabipur will be administered to you or your child by a doctor or a nurse trained in administering vaccines. Treatment necessary for managing severe allergic reactions that may occur after vaccination must be readily available (see section 4 of this leaflet). The vaccine must be administered to you or your child in a hospital or medical office equipped with the necessary equipment to manage such reactions.
Instructions for reconstitution of the vaccine for healthcare professionals are provided at the end of this leaflet.
The recommended dose for adults and children of any age is one millilitre (1.0 ml) per injection.
Your doctor will determine the number of doses you or your child need, depending on whether Rabipur is administered before or after potential exposure to the virus.
The vaccine is administered by intramuscular injection (usually into the upper arm; in young children, into the thigh muscle).

If you or your child have never been vaccinated against rabies:

• initially, three doses are required. The first dose is administered at the first visit, the second dose is given 7 days later, and the third dose is administered 21 or 28 days after the first dose
• if you are an adult between 18 and 65 years of age who requires rapid protection, Rabipur may also be administered as a total of three doses within 7 days. The first dose is administered at the first visit, the second dose is given 3 days later, and the third dose is administered 4 days after the second dose.
• alternatively, if you have a normal immune response, Rabipur may be administered as two doses within 7 days. The first dose is administered at the first visit and the second dose is given 7 days later.

If you or your child miss a scheduled injection appointment, you should arrange to receive the missed dose as soon as possible.
The need for booster doses depends on the risk of exposure to the rabies virus. Your doctor will consult official recommendations on rabies vaccination and advise you when a booster dose is required.
If you are at continuous high risk of infection, your doctor may also recommend regular blood tests to measure the level of rabies antibodies in your blood, so that booster doses can be administered as soon as necessary. Experience shows that booster doses are usually required every 2–5 years.

AFTER SUSPECTED OR CONFIRMED EXPOSURE TO THE VIRUS

Previously vaccinated individuals
If you or your child have already been vaccinated against rabies and have received booster doses, and have been exposed to a rabid or suspected rabid animal, normally two additional doses of vaccine (1.0 ml each) are required. The first dose should be administered as soon as possible after exposure, and the second dose is given 3 days later.

Previously unvaccinated individuals
If you or your child have never been vaccinated before or have received an inadequate primary immunization, you will be administered 4 or 5 doses (1.0 ml each), according to one of the following schedules:

• If a 4-dose schedule is used, the first two doses are administered as soon as possible after exposure (Day 0), followed by single doses on Day 7 and Day 21 after the first dose
• For healthy individuals with a known good immune response, an alternative 4-dose schedule may be used, administering the first dose as soon as possible after exposure (Day 0) and subsequent doses on Days 3, 7, and 14 after the first dose
• If a 5-dose schedule is used, the first dose is administered as soon as possible after exposure (Day 0), and subsequent doses are given on Days 3, 7, 14, and 28 after the first dose.

After any possible exposure to the rabies virus, your doctor will assess the risk of infection based on the type of contact you or your child had. For example, if you were bitten or scratched by an animal that might carry the virus or had contact with bats, your risk of rabies infection is significantly higher than for someone who was licked but has no skin lesions.

Individuals with compromised immune systems (poor immunity to infections)
If you or your child are at higher risk of rabies infection because your immune system is not functioning properly, you will need five or six doses (1.0 ml each) of anti-rabies vaccine after contact with a rabid or suspected rabid animal. Vaccination should be administered in combination with local wound treatment and administration of anti-rabies immunoglobulins.
If six doses are administered, the first two doses are given as soon as possible after exposure, followed by single doses on Days 3, 7, 14, and 28 after the first dose.
If five doses are administered, the first dose is given as soon as possible after exposure, and the remaining doses are administered on Days 3, 7, 14, and 28 after the first dose.
You or your child may also need blood tests to determine the level of antibodies against the rabies virus in the blood, so that additional vaccine doses can be administered if necessary. Your doctor will explain what needs to be done and will advise you when to undergo further tests or receive additional doses.

4. POSSIBLE ADVERSE REACTIONS

Like all medicines, this medicine can cause adverse reactions, although not everybody experiences them.
Following vaccination with Rabipur, severe allergic reactions affecting the entire body may occur, sometimes associated with shock (dangerously low blood pressure).* Appropriate medical treatment and supervision must always be readily available in case of a rare severe allergic reaction to the vaccine. If this occurs, seek immediate medical advice.

The most commonly reported adverse reactions with Rabipur are pain at the injection site, mainly injection-related pain, or hardening of the skin at the injection site. These reactions are very common (occur in more than 1 in 10 people). Most injection site reactions were not serious and resolved within 24–48 hours after injection.

Other adverse reactions include:
Very common (may affect more than 1 in 10 people)
Headache
Dizziness
Skin rash
General discomfort
Fatigue
Weakness
Fever

Common (may affect up to 1 in 10 people)
Swollen glands
Reduced appetite
Nausea
Vomiting
Diarrhoea
Pain/discomfort in the abdomen
Hives
Muscle pain
Joint pain

Rare (may affect up to 1 in 1,000 people)
Allergic reactions
Tingling or sensation of tingling
Sweating
Chills

Very rare (may affect up to 1 in 10,000 people)
Inflammation of the brain (CNS), disorders affecting the peripheral nerves which may cause weakness, inability to move, or loss of sensation in certain parts of the body*
Fainting, instability with dizziness*
Severe allergic reaction causing swelling of the face or throat*
* Description of adverse reactions reported spontaneously

Additional adverse reactions in children
The frequency, type, and severity of adverse reactions in children are expected to follow the same pattern as observed in adults.

Reporting of adverse reactions
If you or your child experience any adverse reaction, including those not listed in this leaflet, tell your doctor or nurse. You may also report adverse reactions directly via the national reporting system at: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse .
By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. HOW TO STORE RABIPUR

Keep this vaccine out of the sight and reach of children.
Store protected from light in a refrigerator (2 °C - 8 °C). Do not freeze.
Keep the vial and syringe in the outer packaging to protect the medicine from light.
Do not use this vaccine after the expiry date stated on the outer packaging. The expiry date refers to the last day of that month. Do not dispose of any medicine via wastewater. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. PACK CONTENTS AND OTHER INFORMATION

What Rabipur contains
The active substance contained in the vaccine is rabies virus (inactivated, Flury LEP strain)  2.5 IU produced
on purified chicken embryo cells (PCEC).
The other components are: tromethamine, sodium chloride, disodium edetate, potassium-L-glutamate, polygeline,
sucrose and water for injections.
Residual amounts of chicken proteins (e.g. ovalbumin), human serum albumin, neomycin, chlortetracycline,
and amphotericin B are present.

Description of the appearance of Rabipur and contents of the pack
Rabipur is a white lyophilized powder to be reconstituted with a clear, colourless solvent. The reconstituted vaccine
is from clear to slightly opalescent and from colourless to slightly pink.
Rabipur is supplied in packs containing:

• 1 vial of powder,
• 1 pre-filled single-use syringe or sterile diluent with white stopper with tamper-evident seal or sterile diluent with transparent screw cap,
• and 2 identical needles (25 gauge, 25 mm), one for reconstitution and one for injection.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder:
Bavarian Nordic A/S
Philip Heymans Alle 3
2900 Hellerup
Denmark

Manufacturer:
Bavarian Nordic A/S
Hejreskovvej 10A
3490 Kvistgaard
Denmark
or
GSK Vaccines GmbH
Emil-von-Behring-Str. 76
35041 Marburg
Germany

This medicinal product is authorized in the Member States of the European Economic Area under the following
name:
Austria, Belgium, Croatia, Denmark, France, Germany, Italy, Luxembourg, Norway, Poland, Portugal,
Netherlands, Spain, Sweden, Hungary: Rabipur

Other sources of information
The following information is intended for healthcare professionals only:
There are two types of pre-filled syringes which differ by the type of cap.
Both types of syringes are equipped with a safety device that facilitates handling and administration of the injection. In addition, the safety device reduces the diameter of the opening of the syringe barrel and simultaneously widens the finger flange with ergonomic wings. This prevents the piston seal from being accidentally removed from the syringe.
Before preparing Rabipur for administration, identify the pre-filled syringe in the pack (either with white stopper with tamper-evident seal or with transparent screw cap) and follow the instructions for the corresponding pre-filled syringe provided in the pack.

Instructions for use of the Rabipur single-use pre-filled syringe:

Pre-filled syringe with white stopper with tamper-evident seal:

Step 1: Hold the syringe (E) in one hand with the cap facing upwards. Be sure to hold the syringe by the white ribbed gripping ring (D).
Step 2: Hold the cap (A) with the other hand and firmly rock it back and forth to break the connection at the gripping ring (D). Do not twist or rotate the cap.
Step 3: Lift to remove the cap (A) and the grey closure cap (B). Take care not to touch the sterile tip of the syringe (C).

Needle application (these instructions apply to both needles provided):

Step 1: Twist to remove the cap (H) from one of the two identical needles. This needle will be used for reconstitution. Do not remove the plastic needle cover (G).
Step 2: Firmly hold the syringe (E) in one hand by the white ribbed gripping ring (D). With the other hand, insert this needle (F) and rotate clockwise until it locks in place. Once the needle is secured, remove the plastic needle cover (G). The syringe is now ready for use.

Prefilled syringe with transparent screw cap:

Step 1: Hold the syringe with one hand
with the cap pointing upwards. Make sure to
hold the syringe by the transparent, ribbed
holding ring (D). Unscrew the cap (A)
by turning it counterclockwise.
Needle attachment (these instructions apply to both needles provided):

Step 1: Twist to remove the cap (H) from
one of the two identical needles. This needle will be used
for reconstitution. Do not remove the plastic needle cover (G).
Step 2: Firmly grasp the syringe (E)

holding it by the transparent, ribbed
holding ring (D). With the other hand, insert this
needle (F) and rotate clockwise until slight resistance
is felt. Once the needle is secured, remove the plastic
needle cover (G).
The syringe is now ready for use.
Instructions for reconstituting Rabipur using the prefilled syringe:
The vaccine should be inspected visually before and after reconstitution for the presence of any extraneous particulate
matter and/or changes in physical appearance. The vaccine must not be used if any change in appearance has occurred.
The reconstituted vaccine should be clear to slightly opalescent and colourless to slightly pink.
The powder for solution must be reconstituted using the provided solvent for solution and shaken carefully before
injection. The reconstituted vaccine must be used immediately.
The vaccine vial is under negative pressure. After reconstituting the vaccine, it is recommended to unscrew the
syringe from the needle to release the negative pressure. The vaccine can then be easily withdrawn from the
vial. Excessive pressure should be avoided, as over-pressurization may cause difficulties in withdrawing the
correct amount of vaccine.
The needle will not reach the bottom of the vial; therefore, please invert the vial and withdraw the needle until it is
close to the stopper. This will allow withdrawal of the entire vaccine solution from the vial.
Once reconstitution of the vaccine is complete, remove the cap from the second needle (as shown in
Step 1 for needles) and replace the reconstitution needle with the second needle for administration.
Do not use the same needle for both reconstitution and administration.