Verorab

Purified inactivated rabies vaccine (Wistar rabies PM/WI 38 1503-3M strain) prepared on Vero cells.

Powder and solvent for suspension for injection in prefilled syringe.
Before reconstitution, the powder is uniform white in colour.
The solvent is a clear, colourless solution.
After reconstitution, 1 dose (0.5 mL) contains: Rabies virus*, WISTAR Rabies PM/WI38 1503-3M strain (inactivated) ≥ 2.5 IU **
*Produced in VERO cells.
**Quantity measured according to the NIH test against the international standard.
Excipient with known effect: Phenylalanine 41 micrograms.
Verorab may contain traces of polymyxin B, streptomycin and neomycin, used in the manufacturing process (see Contraindications).
Excipients/Inactive Ingredients: Powder*: Maltose, 20% human albumin solution, Basal Medium Eagle: mixture of mineral salts (including potassium), vitamins, dextrose and amino-acids (including L-Phenylalanine), Hydrochloric acid and sodium hydroxide for pH adjustment, Water for injections.
* Composition of the powder before the freeze-drying step.
Solvent: Sodium chloride, Water for injections.

Pharmacotherapeutic group: Rabies vaccines. ATC Code: J07BG.
Pharmacology: Pharmacodynamics: Mechanism of action: Protection after vaccination is provided by the induction of anti-rabies neutralising antibodies.
Clinical studies have been conducted to assess the immunogenicity of the vaccine for pre-exposure and post-exposure prophylaxis. A titre of anti-rabies neutralising antibodies ≥0.5 IU/mL is considered protective.
Pre-exposure prophylaxis: In clinical trials assessing a 3-dose regimen (D0, D7, D28 (or D21) by IM route) in adults and children, all subjects achieved an adequate immune response with anti-rabies neutralising antibody titres ≥0.5 IU/mL two weeks after the end of primary vaccination.
A ten-year follow-up in 49 subjects who received the vaccine according to a 3-dose schedule (D0,D7, D28) followed by a booster dose one year later showed the persistence of the immune response with anti-rabies neutralising antibody titres ≥0.5 IU/mL for up to 10 years in 96.9% of vaccinated subjects.
Post-exposure prophylaxis: In clinical trials assessing the 5-dose Essen regimen (D0, D3, D7, D14, D28 by IM route) and the 4-dose Zagreb regimen (2 doses at D0, then 1 dose at D7 and 1 dose at D21 by IM route) in adults and children, Verorab induced adequate titres of anti-rabies neutralising antibodies (≥ 0.5 IU/mL) in nearly all subjects at D14 and in all subjects at D28.
The administration of human rabies immunoglobulin (HRIG) or equine rabies immunoglobulin (ERIG) concomitantly with the rabies vaccine may cause slightly lower mean neutralising antibody titres due to immune interference.
The effectiveness of Verorab was evaluated in 44 adult subjects bitten by animals confirmed to be rapid. The subjects received the vaccine according to the 5-dose Essen regimen (D0, D3, D7, D14 and D28 by IM route) and immunoglobulins, where necessary. Three years after vaccination, none of the subjects had developed rabies.
Paediatric population: There are no clinically significant differences in the immunogenicity of the vaccine in the paediatric population compared to adults.
Pharmacokinetics: No pharmacokinetic studies were performed.
Toxicology: Preclinical safety data: Toxicity studies in animals (acute, subacute and chronic toxicity) do not indicate any toxic effects or target organ toxicity.

VERORAB is indicated for pre-exposure and post-exposure prophylaxis of rabies in all age groups (see Dosage & Administration and Pharmacology: Pharmacodynamics under Actions).
Verorab should be used according to official recommendations.
Pre-exposure prophylaxis should be offered to subjects at high risk of contamination by the rabies virus.
All those at permanent risk, such as the personnel of diagnostic, research or production laboratories working on the rabies virus, should be vaccinated.
Vaccination is also recommended for the following categories: chiropterologists and people regularly exposed to the bat rabies virus; exposed professionals (veterinary personnel, laboratory personnel handling equipment that is contaminated or likely to be contaminated, slaughterhouse butchers, pound personnel, naturalists, taxidermists, gamekeepers, forest rangers, slaughterhouse personnel); adults and children living in or travelling to enzootic areas.
Booster doses are determined based on the risk of exposure and on serological tests in accordance with official recommendations.

Posology: One dose consists in the administration of 0.5 mL of vaccine via the intramuscular route. The intradermal (ID) route may be used as an alternative. One intradermal dose consists of 0.1 mL of reconstituted vaccine, i.e. 1/5 of the intramuscular dose.
Pre-exposure vaccination: Three doses of VERORAB are administered by intramuscular route at days (D) D0, D7 and D28. The dose scheduled at D28 can be administered at D21. If necessary.
The doses are administered either by IM or ID route. The Intradermal route must not be used for immunocompromised individuals (see Contraindications). Intramuscular injections are preferable if antimalarial chemoprophylaxis (e.g. chloroquine) is being used concurrently or there is a possibility of an immune-compromised state (antibody response may be impaired if the intradermal method is used).
Booster doses are determined based on the risk of exposure and on serological tests in accordance with official recommendations.
VERORAB can be administered as a booster injection after primary vaccination with a cell culture rabies vaccine (a rabies vaccine prepared in VERO cells or prepared in human diploid cells (HDCV)).
Post-exposure vaccination: Post-exposure prophylaxis includes local non-specific treatment of the wound, vaccination and, where appropriate, passive immunization with rabies immunoglobulins.
Post-exposure prophylaxis should be initiated as soon as possible after suspected exposure to rabies. In all cases, proper wound care (careful washing of all bites 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 vaccine or rabies immunoglobulins, when they are indicated. Post-exposure prophylaxis should be adjusted to the exposure category, the condition of the animal (see Table 2) and the vaccination status of the patient, in accordance with official recommendations (see Table 1, WHO recommendations).
Post-exposure prophylaxis should be performed as soon as possible after exposure under medical supervision and only at a rabies centre.
If necessary, post-exposure prophylaxis can be supplemented by tetanus prophylaxis and antibiotic therapy to prevent the development of infections other than rabies. (See Tables 1 and 2.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

Post-exposure prophylaxis of non-immunised subjects: Essen regimen: The vaccine should be administered by intramuscular route at D0, D3, D7, D14 and D28 (5 injections of 0.5 ml). Or; Zagreb regimen (schedule 2-1-1): The vaccine should be administered by intramuscular route: one dose in the right deltoid and one dose in the left deltoid at D0, then one dose in the deltoid at D7 and one dose at D21 (4 injections of 0.5 mL). In young children, the vaccine should be administered in the anterolateral region of the thigh muscle. Or; The 2-site intradermal regimen (known as updated Thai Red Cross regimen, 2-2-2-0-2), which prescribes 1 injection of 0.1 mL at 2 sites on days 0, D3, D7, and D28. The Intradermal route must not be used for immunocompromised individuals (see Contraindications).
Whatever the regimen used, vaccination must not be discontinued unless the contact animal is declared free from rabies after veterinary supervision (see Table 2).R abies immunoglobulins should be administered concomitantly with the vaccine, in case of category III exposure (WHO classification, see Table 1). If possible, the vaccine should be administered contralaterally to the immunoglobulin administration sites.
Refer to the Summary of Characteristics of the rabies immunoglobulins used.
Post-exposure prophylaxis for already immunised subjects: In accordance with official recommendations, this applies to subjects who have already received pre exposure prophylaxis or post-exposure prophylaxis or who discontinued post-exposure prophylaxis after receiving at least two doses of vaccine prepared in cell culture.
Subjects who are already immunised should receive 1 dose of vaccine (0.5 mL by intramuscular route) at D0 and 1 dose on D3.
Rabies immunoglobulins are not indicated in this case.
Intradermal schedule: This vaccine is of sufficient potency to allow its safe use in the WHO recommended intradermal post-exposure regimen in countries where relevant national authorities have approved the intradermal route for rabies post-exposure treatment.
Immunocompromised subjects: Pre-exposure prophylaxis: In immunocompromised subjects, blood tests for neutralising antibodies should be performed 2 to 4 weeks following the vaccination to assess the possible need for an additional dose of the vaccine.
Post-exposure prophylaxis: In immunocompromised subjects, a complete vaccine regimen should be administered post-exposure. Rabies immunoglobulins should be administered concomitantly with the vaccine in the event of any category II or III exposure (see table 1).
Paediatric population: VERORAB can be administered to children and to adults using the same posology.
Method of administration: Precautions to be taken before handling or administering the medicinal product.
The vaccine is administered via the intramuscular route, in the anterolateral region of the thigh muscle in infants and young children and in the deltoid muscle in older children and adults.
The intradermal (ID) injection may be used as an alternative, in upper arm or forearm.
Do not inject in the buttocks region.
Do not inject via the intravascular route.
For instructions on reconstitution of the medicinal product before administration, see Contraindications

No cases of overdose were reported.

Pre-exposure vaccination: Hypersensitivity to the active substance(s) or to any of the excipients listed in Description, to polymyxin B, to streptomycin, to neomycin or to any antibiotic of the same group, to a previous administration or to any vaccine containing the same components.
Vaccination should be postponed in case of febrile or acute diseases.
The Intradermal route must not be used in the following instances: individuals receiving long term corticosteroid or other immunosuppressive therapy or chloroquine; immunocompromised individuals; individuals, particularly children, with severe wounds, especially to the head and neck or presenting late for consultation.
Post-exposure vaccination: Given the fatal outcome of the declared rabies infection, there are no contraindications to post-exposure vaccination.
The Intradermal route must not be used in the following instances: individuals receiving long term corticosteroid or other immunosuppressive therapy or chloroquine; immunocompromised individuals; individuals, particularly children, with severe wounds, especially to the head and neck or presenting late for consultation.

Special warnings: As with all vaccines, VERORAB may not protect 100% of people vaccinated.
Use with caution in people with known allergies to polymyxin B, to streptomycin, to neomycin (present as traces in the vaccine) or to any antibiotic of the same group.
Precautions for use: Injection-schedule recommendations should be followed scrupulously.
The need for serological tests (to assess seroconversion in subjects)) should be determined in accordance with official recommendations.
When the vaccine is administered to subjects with a known immunodeficiency due to an immunosuppressive illness or a concomitant immunosuppressive treatment (such as corticosteroids), a serological test should be performed to ensure that an immune response indicative of protection has been induced. In the case of post-exposure vaccination, all vaccine doses should be administered.
Rabies immunoglobulins should also be administered concomitantly with the vaccine in the event of any category II or III exposure (see Dosage & Administration).
Do not inject via the intravascular route: make sure the needle does not penetrate a blood vessel.
As with all injectable vaccines, appropriate medical treatment and supervision must be readily available in case of a rare anaphylactic reaction after vaccine administration, particularly in case of post-exposure in subjects with a known hypersensitivity to polymyxin B, to streptomycin, to neomycin or to any antibiotic of the same class.
As with all injectable vaccines, VERORAB should be administered with caution in subjects with thrombocytopenia or coagulation disorders as intramuscular injection may induce bleeding in these subjects.
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 paraesthesia. It is important that procedures are in place to avoid injury from faints.
Traceability: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Verorab contains phenylalanine, potassium and sodium: Verorab contains 41 micrograms phenylalanine per 0.5 mL dose which is equivalent to 0.68 microgram/kg for a 60 kg person. Phenylalanine may be harmful for people with phenylketonuria (PKU), a rare genetic disorder in which phenylalanine builds up because the body cannot remove it properly.
Verorab contains less than 1 mmol of potassium (39 mg) and less than 1 mmol of sodium (23 mg) per dose, that is to say essentially 'potassium-free' and 'sodium-free'.
Latex: The tip caps of the pre-filled syringes without needle contain a natural rubber latex derivative, which may cause allergic reactions in latex sensitive individuals.
Additional Precautions related to ID route: It is essential that intradermal administration of VERORAB be carried out only by medical staff trained in this technique in order to ensure that the vaccine is delivered intradermally and not subcutaneously. For the intradermal route an appropriate graduated sterile syringe with needle (insulin type) should be used. Correct intradermal injection should result in a raised papule with an "orange peel" appearance.
If the vaccine is injected too deeply into the skin, and a papule is not seen, the needle should be withdrawn and reinserted nearby.
Effects on ability to drive and use machines: Post-vaccination dizziness was frequently reported (see Section 4.8). It can temporarily affect the ability to drive or use machines.
Use in children: The potential risk of apnoea with the need for respiratory monitoring for 48-72 h must be carefully taken into account when administering the primary vaccination doses in very premature infants (born at 28 weeks' gestation or less) and particularly in those with a history of respiratory immaturity.

Pregnancy: One animal toxicity study on reproduction and development led with another inactivated rabies vaccine produced in VERO cells, did not evidence any deleterious effect on female fertility and on pre-and post-natal development.
Clinical use of rabies vaccines (inactivated "WISTAR Rabies PM/WI38 1503-3M strain") during a limited number of pregnancies did not show any malformative or fetotoxic effects to date.
Pre-exposure prophylaxis: Given the seriousness of the disease, in case of high risk contamination, vaccination should be performed during pregnancy, in compliance with the usual vaccination schedule.
Post-exposure prophylaxis: Given the seriousness of the disease, pregnancy is not a contraindication.
Lactation: This vaccine can be used during lactation.
Fertility: Verorab has not been evaluated in fertility studies.

Summary of the safety profile: Over 13,000 subjects, including approximately 1,000 children and adolescents under the age of 18, have received at least one dose of Verorab in clinical studies.
Adverse reactions were generally moderate in intensity and occurred within 3 days of vaccination. Most reactions resolved spontaneously within 1 to 3 days of their onset.
The most common adverse reactions, in all age groups (except infants/young children aged under 24 months) were headache, malaise, myalgia and pain at the injection site.
Tabulated list of adverse reactions: The adverse reactions listed below were reported during clinical studies and worldwide post-marketing surveillance. Within each system organ class, adverse reactions are ranked under headings of frequency using the following convention: Very common: ( ≥ 1/10); Common: (≥ 1/100 and < 1/10); Uncommon: ( ≥ 1/1,000 and < 1/100); Rare: (≥ 1/10,000 and < 1/1,000); Very rare: (< 1/10,000); Not known (cannot be estimated from the available data). (See Table 3.)

Click on icon to see table/diagram/image

Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorization 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 via the national reporting system.

Immunosuppressive treatments, including long-term systemic corticosteroid therapy, may interfere with the production of antibodies and lead to vaccination failure. It is therefore recommended to perform a serological test 2 to 4 weeks after vaccination (see Dosage & Administration).
Verorab may 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 must never be combined in the same syringe or injected at the same site (see Incompatibilities under Cautions for Usage).
Given that rabies immunoglobulins interfere with the development of the immune response to the rabies vaccine, the recommendations for administration of rabies immunoglobulins should be strictly followed.

Incompatibilities: Rabies immunoglobulins or any other product and the rabies vaccine must never be combined in the same syringe or injected into the same site.
This medicinal product must not be mixed with other medicinal products or other vaccines.
Special precautions for disposal and other handling: Handling instructions: Remove the cap of the vial of lyophilized powder.
Screw the plunger rod into the syringe, if provided separately.
Inject the solvent into the vial of lyophilized powder.
Shake the vial gently until homogeneous suspension of the powder is obtained.
The reconstituted vaccine should be limpid, homogeneous and free from particles.
Remove and discard the syringe that was used for vaccine reconstitution.
Use a new syringe with a new needle to withdraw the reconstituted vaccine.
Replace the needle used to withdraw the vaccine by a new needle for intramuscular or intradermal injection.
The length of the needle used for vaccine administration should be adapted to the patient.
For ID injection, using aseptic technique, a 0.1 mL dose of vaccine may be withdrawn from a vial and the remainder used for another patient provided that the vial is stored in a refrigerator between + 2°C and + 8°C. A new sterile needle and syringe must be used to withdraw and administer each dose of vaccine for each patient to avoid cross infection.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Store in a refrigerator (2°C - 8°C). Do not freeze.
Store in the original outer package, protected from light.
For storage conditions after reconstitution of the medicinal product, see Shelf life as follows.
Shelf life: 3 years.
After reconstitution, the vaccine must preferably be administered immediately.
If VERORAB is used via ID route, given that the vaccine does not contain a preservative, great care must be taken to avoid contamination of reconstituted vaccine. Vaccine may be used up to 8 hours after reconstitution provided it is maintained at 2°C to 8°C and protected from light. Unused vaccine must be discarded after 8 hours.

Vaccines, Antisera & Immunologicals

J07BG01 - rabies, inactivated, whole virus ; Belongs to the class of rabies viral vaccines.

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