VERORAB Powder and Solvent for Injectable Suspension in Pre-filled Syringe. Inactivated Rabies Vaccine

2. What you need to know before you or your child use Verorab

Do not use Verorab:

Pre-exposure prophylaxis:

• If you or your child are allergic to the active substance or to any of the other components of this vaccine, including those listed in section 6.
• If you or your child developed an allergic reaction during a previous injection with this vaccine or with any vaccine of the same composition.
• If you or your child have a fever or if you have an acute illness (in this case, it is preferable to postpone vaccination).

Post-exposure prophylaxis:

• Given the fatal outcome of declared rabies infection, there are no contraindications for post-exposure vaccination.

Warnings and precautions

• As with all vaccines, Verorab may not protect 100% of vaccinated individuals.
• Verorab should not be administered intravascularly; ensure that the needle does not penetrate a blood vessel.
• Use with caution if you or your child are allergic to polymyxin B, streptomycin, or neomycin (present in small amounts in the vaccine) or to any antibiotic of the same class.
• As with all injectable vaccines, adequate medical treatment and supervision should be readily available in the rare case of an anaphylactic reaction after vaccine administration.
• The need for serological tests (to evaluate seroconversion in individuals) should be determined according to official local recommendations.
• When the vaccine is administered to individuals with known immunodeficiency due to an immunosuppressive disease or concomitant immunosuppressive treatment, serological tests should be performed 2 to 4 weeks after vaccination to ensure that a protective immune response was obtained. In the case of post-exposure vaccination, a complete vaccination schedule should be administered. Rabies immunoglobulin should also be administered concomitantly with the vaccine in case of any category II or III exposure, see “3. How to use Verorab”.
• Verorab should be administered with caution in individuals with decreased platelet counts (thrombocytopenia) or coagulation disorders, as intramuscular injection may induce bleeding.
• Consult your doctor, pharmacist, or nurse before starting to use Verorab if you or your child have had any allergic reaction to latex. It may cause severe allergic reactions because it contains a derivative of natural rubber latex (latex rubber) in the stopper at the end of the pre-filled syringe without a needle.

Consult your doctor, pharmacist, or nurse before using Verorab.

Children and adolescents

Not applicable

Using Verorab with other medicines

Immunosuppressive treatments, including long-term systemic corticosteroid treatment, may interfere with antibody production and may cause vaccine failure. Therefore, it is recommended to perform a serological test 2 to 4 weeks after vaccination; see “Warnings and precautions”.

Verorab can be administered concomitantly with a Vi polysaccharide typhoid vaccine during the same vaccination visit, using two different injection sites.

Rabies immunoglobulins or any other product and the rabies vaccine should never be combined in the same syringe or injected in the same site.

As rabies immunoglobulin interferes with the development of the immune response to the vaccine, official recommendations regarding the administration of rabies immunoglobulin should be strictly followed.

Tell your doctor or pharmacist if you or your child are using, have recently used, or might use any other medicines.

Verorab with food and drink

Not applicable

Pregnancy, breastfeeding, and fertility

Consult your doctor or pharmacist before receiving this vaccine if you are pregnant, think you may be pregnant, or are planning to become pregnant or are breastfeeding.

Data on the use of Verorab in pregnant women is limited.

It is not known whether Verorab is excreted in breast milk, but no risk has been identified or is expected for breastfed infants.

Given the severity of the disease, Verorab can be administered during pregnancy or breastfeeding after evaluation of the risks and benefits by your doctor.

Driving and using machines

Dizziness has been frequently reported after vaccination. It may temporarily affect the ability to drive and use machines.

Verorab contains phenylalanine, potassium, and sodium

Verorab contains 4.1 micrograms of phenylalanine per 0.5 ml dose, which is equivalent to 0.068 micrograms/kg for a 60 kg person. Phenylalanine may be harmful to people with phenylketonuria (PKU), a rare genetic disorder in which phenylalanine accumulates because the body cannot eliminate it properly.

Verorab contains less than 1 mmol of potassium (39 mg) and less than 1 mmol of sodium (23 mg) per dose, i.e., it is essentially “potassium-free” and “sodium-free”.

3. How to use Verorab

Follow exactly the administration instructions of this vaccine as indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

The recommended dose is 0.5 ml of reconstituted vaccine by intramuscular (IM) route or 0.1 ml of reconstituted vaccine by intradermal (ID) route at each injection site.

• Pre-exposure prophylaxis

For primary pre-exposure immunization, immunocompetent individuals can be vaccinated according to the vaccination schedules presented in Table 1 and according to official recommendations that apply in the national scope in case they are available:

Table 1: Pre-exposure Vaccination Schedules

a - This regimen should not be used in immunocompromised individuals (see section "Immunocompromised individuals").

b - One injection in each arm (for adults and children) or in each anterolateral thigh (for infants and young children).

Booster doses are determined based on exposure risk and serological tests to detect the presence of rabies virus neutralizing antibodies (≥ 0.5 IU/ml). A booster dose consists of a 0.5 ml dose administered by intramuscular route or a 0.1 ml dose administered by intradermal route, according to WHO recommendations.

• Post-exposure prophylaxis

Post-exposure prophylaxis should be initiated as soon as possible after suspected exposure to rabies. In all cases, proper wound care (thorough washing of all bites and scratches with soap or detergent and large amounts of water and/or virucidal agents) should be performed immediately or as soon as possible after exposure. It should be done before the administration of vaccines or rabies immunoglobulins, when indicated.

Table 2: WHO Guide for Post-exposure Prophylaxis Depending on Exposure Severity (to be adapted to official local recommendations)

(a) If the animal is a dog or cat that appears healthy and is under veterinary supervision, treatment can be delayed.

(b) This observation period applies only to dogs and cats. With the exception of endangered or threatened species, other domestic and wild animals suspected of having rabies should be humanely killed and their tissues examined for the presence of the rabies virus using appropriate laboratory techniques.

(c) Bites suffered especially on the head, neck, face, hands, and genitals are category III exposures due to the rich innervation of these parts of the body.

Post-exposure prophylaxis of non-immunized individuals

Non-immunized individuals can be vaccinated according to one of the vaccination regimens by intramuscular (IM) route or intradermal (ID) route presented in Table 3.

In all cases, consult official local recommendations if available.

Table 3: Post-exposure Prophylaxis of Non-immunized Individuals

(a) one injection IM in the anterolateral region of each thigh (in infants and young children) or in each deltoid (in older children and adults).

(b) to be injected in 2 separate locations, contralateral if possible.

(c) to be injected in 4 separate locations.

Regardless of the regimen used, vaccination should not be interrupted unless the contact animal is declared free of rabies.

Rabies immunoglobulins should be administered concomitantly with the vaccine in case of category III exposure (WHO classification, see Table 1). If possible, each dose of the vaccine should be administered in a separate body location from the locations where the immunoglobulin was administered.

Post-exposure prophylaxis of previously immunized individuals

According to official recommendations, this applies to individuals who have already received pre-exposure or post-exposure prophylaxis or who interrupted post-exposure prophylaxis after receiving at least two doses of cell culture vaccine.

Individuals who have already been immunized should receive 1 dose of the vaccine (0.5 ml by intramuscular route or 0.1 ml by intradermal route) on D0 and 1 dose on D3.

Alternatively, 4 intradermal injections of 0.1 ml can be administered in 4 separate body locations on D0. Rabies immunoglobulins are not indicated in this case.

Immunocompromised individuals

Pre-exposure prophylaxis

A 3-dose regimen (listed in the "Pre-exposure prophylaxis" section) should be used and serological tests for neutralizing antibodies should be performed 2 to 4 weeks after the last dose to evaluate the possible need for an additional dose of the vaccine.

Post-exposure prophylaxis

A complete post-exposure vaccination schedule should be administered. Rabies immunoglobulin should be administered concomitantly with the vaccine in case of any category II or III exposure (see Table 2).

Use in children

Children should receive the same dose as adults.

Method of administration

• Intramuscular (IM)

The vaccine is administered in the anterolateral region of the thigh in infants and young children and in the deltoid muscle in older children and adults.

If the Zagreb regimen is used, one dose should be administered in each deltoid muscle (left and right) in adults on D0, then one dose on D7 and D21.

• Intradermal (ID)

The vaccine should be administered preferably in the upper arm or forearm.

Verorab should not be injected in the gluteal region.

The vaccine should not be injected intravascularly.

If you or your child use more Verorab than you should

Not applicable.

If you or your child forget to use Verorab

Not applicable.

If you or your child stop using Verorab

Not applicable.

If you have any further questions on the use of this vaccine, ask your doctor, pharmacist, or nurse.

4. Possible Adverse Effects

Like all medicines, this vaccine can cause adverse effects, although not all people suffer from them.

Severe Allergic Reactions

Severe allergic reactions (anaphylactic reactions) can always occur, even if they are very rare. Consult your doctor or healthcare professional immediately or go to the emergency center of the nearest hospital immediately if you or your child experience an anaphylactic reaction.

The signs or symptoms of an anaphylactic reaction, if they occur, usually occur shortly after the injection, and may include rash, itching, difficulty breathing, shortness of breath, and swelling of the face, lips, throat, or tongue.

Other Adverse Effects

Most adverse effects appeared within 3 days following vaccination and resolved spontaneously within 1 to 3 days after onset. Adverse effects were reported with the following frequencies:

Very common: may affect more than 1 in 10 people

• General discomfort,
• Headache (cephalalgia),
• Muscle pain (myalgia),
• Pain at the injection site,
• Redness (erythema) at the injection site,
• Swelling at the injection site,
• Only in babies: irritability, inconsolable crying, and somnolence.

Common: may affect up to 1 in 10 people

• Fever,
• Enlargement of the lymph nodes (lymphadenopathy),
• Allergic reactions, such as skin rash and itching,
• Pseudoinfluenza symptoms,
• Itching (pruritus) at the injection site,
• Induration at the injection site,
• Only in babies: difficulty sleeping.

Uncommon: may affect up to 1 in 100 people

• Decreased appetite,
• Nausea,
• Stomach pain (abdominal pain),
• Diarrhea,
• Vomiting,
• Chills,
• Fatigue, unusual weakness (asthenia),
• Dizziness,
• Joint pain (arthralgia),
• Bruising at the injection site (ecchymosis).

Rare: may affect up to 1 in 1,000 people

• Difficulty breathing.

Frequency not known: frequency cannot be estimated from available data

• Swelling of the face, lips, mouth, tongue, or throat, which may cause difficulty swallowing or breathing,
• Sudden loss/decrease in hearing.

Reporting Adverse Effects

If you or your child experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Verorab

Keep this medicine out of sight and reach of children.

Do not use this vaccine after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Store in a refrigerator (between 2°C and 8°C). Do not freeze.

Store in the original packaging, protected from light.

Medicines should not be thrown away through drains or into the trash. Ask your pharmacist how to dispose of packaging and medicines that are no longer needed. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Verorab

• The active ingredient is:

After reconstitution with 0.5 ml of solvent, 1 vial contains:

Rabies virus(a), WISTAR Rabies PM/WI38 1503-3M strain (inactivated) …… 3.25 UI(b)

(a) Produced in Vero cells

(b) Quantity measured according to the ELISA test in accordance with the international standard

• The other ingredients are:

Powder: maltose, 20% human albumin solution, Basal Eagle Medium (mineral salt mixture including potassium, vitamins, dextrose, and amino acids, including L-phenylalanine), water for injectable preparations, hydrochloric acid, and sodium hydroxide.

Solvent: sodium chloride, water for injectable preparations.

Verorab may contain traces of polymyxin B, streptomycin, and neomycin, used in the manufacturing process (see "Warnings and Precautions").

Appearance of Verorab and Package Contents

Verorab, powder and solvent for injectable suspension in a pre-filled syringe (powder vial + 0.5 mL solvent in a pre-filled syringe with or without a needle - Boxes of 1 or 10).

Marketing Authorization Holder and Manufacturer:

The marketing authorization holder is:

Sanofi Winthrop Industrie

82 avenue Raspail

94250 Gentilly

France

The manufacturer is:

Sanofi Winthrop Industrie - 1541 avenue Marcel Mérieux - 69280 Marcy l’Etoile - France

Sanofi Winthrop Industrie - Voie de l’Institut – Parc Industriel d’Incarville B.P 101 - 27100 Val de Reuil - France

Sanofi-Aventis Zrt. Bdg. DC5 - Campona Utca 1. Budapest XXII – 1225 Budapest - Hungary

Local Representative

Sanofi-aventis, S.A.

C/ Rosselló i Porcel, 21

08016 Barcelona

Spain

Tel: +34 93 485 94 00

This vaccine is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) with the following denominations:

• Austria, Belgium, Denmark, Spain, Finland, Ireland, Italy, Norway, Netherlands, Sweden, United Kingdom (Northern Ireland): Verorab.
• France: Vaccin Rabique Pasteur

Date of the last revision of this prospectus:04/2024

Other Sources of Information

Detailed information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

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This information is intended only for healthcare professionals:

The instructions for injection must be followed scrupulously:

Handling instructions:

• Remove the cap from the vial of lyophilized powder.
• Screw the plunger into the syringe, if provided separately.

• For syringes without a needle: Connect the reconstitution needle to the syringe

• Inject 0.5 ml of solvent into the vial of lyophilized powder.
• Gently shake the vial until a homogeneous suspension of the powder is obtained.
• The reconstituted vaccine must be clear, homogeneous, and free of particles.
• For syringes with a fixed needle
• • Remove and discard the syringe used for reconstitution of the vaccine.
  • Use a new syringe with a new needle to extract the reconstituted vaccine.
• For syringes without a needle
• • Extract the suspension using a syringe

• Replace the needle used to withdraw the vaccine with a new needle for intramuscular or intradermal injection.
• The length of the needle used for vaccine administration should be adapted to the patient.

If Verorab is administered by intramuscularroute, the vaccine must be used immediately after reconstitution.

If Verorab is administered by intradermalroute, the vaccine can be used up to 6 hours after reconstitution, provided it is stored at a temperature below 25°C and protected from light. After reconstitution with 0.5 ml of solvent, using aseptic techniques, each dose of 0.1 ml should be taken from the vial. The remainder can be used for another patient. Before each extraction, gently shake the vial to obtain a homogeneous suspension. A new sterile needle and a new sterile syringe should be used to extract and administer each dose of vaccine to each patient to avoid cross-infection. The reconstituted vaccine that is not used should be discarded after 6 hours.

Unused medicine and materials that have come into contact with it should be disposed of in accordance with local regulations.

This medicine is subject to medical prescription.