Rabipur^® (Lyophilisate) Instructions for Use

Marketing Authorization Holder

Chiron Behring Vaccines, Private Ltd. (India)

Manufactured By

Chiron Behring Vaccines, Private Ltd. (India)

Solvent Manufacturer

SOVEREIGN PHARMA, Private Limited (India)

ATC Code

J07BG01 (Rabies virus inactivated whole)

Active Substance

Rabies vaccine for human use prepared in cell cultures (Ph.Eur.)

Dosage Form

Rabipur^®

Lyophilizate for preparation of solution for intramuscular administration not less than 2.5 IU/1 dose: fl. 1 pc. in set with solvent and Luer-syringe tubes with Luer attachments with separate needles

Dosage Form, Packaging, and Composition

Lyophilisate for preparation of solution for intramuscular administration in the form of a hygroscopic porous mass of white color.

	1 dose (1 ml)
Inactivated rabies virus strain Flury LEP*	Not less than 2.5 IU

Excipients: trometamol, sodium chloride, EDTA (tritriplex III), potassium L-glutamate, polygeline (polygelin), sucrose; the vaccine does not contain preservatives.

Solvent water for injections (1 ml).

1 dose – glass vials (1) in a set with solvent (amp. 1 pc.) and sterile syringe tubes with Luer attachments with separate needles (1 pc.) – cardboard packs.

* grown on chicken embryo cell culture, inactivated, purified, lyophilized.

Clinical-Pharmacological Group

Vaccine for the prevention of rabies

Pharmacotherapeutic Group

MIBP-vaccine

Pharmacological Action

Vaccine for active immunization against rabies. Pre-exposure and post-exposure immunization are distinguished.

Pre-exposure immunization is carried out routinely for persons at risk of infection with the rabies virus. Post-exposure immunization is carried out after contact with animals with confirmed or suspected rabies.

Indications

Pre-exposure immunization for persons at risk of infection with the rabies virus

Veterinarians;
Veterinary students;
Hunters;
Forestry workers;
Slaughterhouse workers;
Laboratory personnel working with the rabies virus or infected material;
In cases of planned visits to regions endemic for rabies.

Post-exposure immunization

After contact with animals with confirmed or suspected rabies.

ICD codes

Open the list of ICD codes

ICD-10 code	Indication
Z24.2	Need for immunization against rabies

ICD-11 code	Indication
QC01.2	Need for immunization against rabies

Dosage Regimen

The method of application and dosage regimen for a specific drug depend on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly adhere to the compliance of the dosage form of a specific drug with the indications for use and dosage regimen.

A single dose for immunization is 1 ml.

Pre-exposure immunization

Immunization according to the scheme: 1 ml of immunizing dose on days 0, 7, and 21 or 28.

Revaccination

For persons with a constant risk of infection, it is recommended to monitor the level of specific antibodies in the blood every 6 months.
For persons with frequently occurring risk of infection, it is recommended to monitor the level of antibodies in the blood every two years.

If the level of antibodies in the blood falls below 0.5 IU/ml, a single revaccination with one immunizing dose is carried out.

It is necessary to take into account the fact that immunization with the Rabipur^® vaccine provides a pronounced immune response and a protective level of specific antibodies circulating for a long time.

In cases where serological testing is not possible, the first revaccination is recommended one year after the immunization course. Subsequent revaccinations are carried out every five years with one immunizing dose.

Post-exposure vaccination

Vaccination should be started as early as possible.

Table 1. Appropriate post-exposure immunization regimens depending on the contact category

Contact Category	Nature of contact (contact with an animal with confirmed or suspected rabies, contact during animal autopsy)	Vaccination Schedule
I	Touching or feeding animals in the absence of skin and mucous membrane licking. The patient’s skin is intact before and after contact.	Vaccination is not required. In doubtful cases, vaccination according to the scheme is recommended: 1.0 ml of Rabipur^® on days 0, 3, 7, 14, 30, and 90.
II	Licking of intact skin; abrasions, scratches, superficial non-bleeding bites of the trunk, upper and lower extremities (except for bites of dangerous localization: head, face, neck, hand, fingers of hands and feet), inflicted by domestic and farm animals.	In case of a bite by a domestic or known animal, immediate treatment is prescribed according to the scheme: 1.0 ml of Rabipur^® on days 0, 3, 7, 14, 30, and 90. In case of a bite by an unknown or rabies-suspected animal, immediate combined treatment (active and passive immunization) is prescribed according to the scheme: anti-rabies immunoglobulin on day 0 and Rabipur^® 1.0 ml on days 0, 3, 7, 14, 30, and 90. If the observed domestic animal remains healthy for 10 days, treatment is stopped*. In other cases, treatment should be continued. If the absence of rabies in the animal is laboratory proven, then treatment is stopped.
III	Any licking of mucous membranes, any bites of the head, face, neck, hand, fingers of hands and feet, genitals: single or multiple deep, bleeding lacerated wounds inflicted by domestic or farm animals. Any licking and damage inflicted by wild carnivores, bats and rodents.	Immediate combined treatment (active and passive immunization) according to the scheme: anti-rabies immunoglobulin on day 0 and Rabipur^® 1.0 ml on days 0, 3, 7, 14, 30, and 90. If the observed domestic animal remains healthy for 10 days, treatment is stopped*. In other cases, treatment should be continued. If the absence of rabies in the animal is laboratory proven, then treatment is stopped.

* – the patient should be warned that immunization is incomplete. In case of subsequent contact with a rabies-suspected animal, a full course of vaccination is necessary.

If it is necessary to conduct a combined course of anti-rabies treatment, anti-rabies immunoglobulin is administered first and, no more than 30 minutes later, the Rabipur^® vaccine is administered. Heterologous anti-rabies immunoglobulin is prescribed at a dose of 40 IU per 1 kg of body weight, and homologous anti-rabies immunoglobulin – at a dose of 20 IU per 1 kg of body weight. It is not allowed to exceed or reduce the dose, as well as to administer it repeatedly due to the danger of reducing the effectiveness of vaccination. If anti-rabies immunoglobulin is not available at the time of the first injection, its administration should be carried out no later than 3 days after the bite for anti-rabies immunoglobulin from horse serum (heterologous), and no later than 7 days after the bite for anti-rabies immunoglobulin from human serum (homologous).

To decide on the tactics of providing anti-rabies care to persons with a history of a completed full course of anti-rabies vaccination, it is recommended to determine the level of anti-rabies antibodies in the blood. The protective level of antibodies is 0.5 IU/ml.

Depending on the time elapsed since the course of anti-rabies vaccination, the schemes indicated in Table 2 should be followed.

Table 2. Vaccination schemes for persons previously immunized after a bite

Interval after vaccination course	Vaccination Schedule
Less than 1 year (provided that a full course of immunization was received)	Vaccination on days 0, 3, 7 with 1.0 ml of Rabipur^®
More than 1 year	Full immunization according to the post-exposure prophylaxis scheme (according to the type of injury)

For persons with immunodeficiency conditions receiving post-exposure anti-rabies treatment, it is recommended to monitor the protective level of antibodies in the blood 14 days after the end of the vaccination course. Depending on the detected level of protective antibodies, additional vaccine administration may be necessary. If the antibody level is below the protective level (0.5 IU/ml), an additional three-time administration of the vaccine according to the scheme 0, 7, 21 or 28 days is necessary.

Method of administration

The Rabipur^® vaccine can be used for vaccination of all age groups.

Reconstituted vaccine: a clear or slightly opalescent liquid, colorless or light yellow in color.

The lyophilisate must be dissolved in the water for injection supplied in the package immediately before use. Before administration, the solution must be gently shaken. The dissolved vaccine must not be stored and must be used immediately after preparation of the solution.

Rabipur^® must be administered intramuscularly into the deltoid muscle, or into the anterolateral surface of the thigh in young children (up to 18 months). The vaccine must not be administered into the gluteal muscle.

Adverse Reactions

When evaluating the side effects of the drug, the following data on their frequency, obtained by the manufacturer, were used: very common (≥10%), common (from 1% to 10%), uncommon (from 0.1% to 1%), rare (from 0.01% to 0.1%), very rare (< 0.01%, including isolated cases).

Based on data obtained during clinical trials and results of clinical use of the vaccine, the following information on the frequency of occurring adverse events was presented

Local reactions at the injection site and general reactions: very common – pain at the injection site, induration at the injection site, fever, fatigue; common – erythema at the injection site; very rare – tremor.

From the nervous system very common – headache; very rare – paresthesia, radicular lesions, polyneuropathy including Guillain-Barré syndrome, paralysis, optic neuritis.

From the musculoskeletal system very common – myalgia; very rare – arthritis.

Other very common – gastrointestinal dysfunction, very rare – dizziness, increased sweating, lymphadenopathy, hypersensitivity.

A statistically significant increase in the frequency of primary manifestations of autoimmune diseases (for example, multiple sclerosis) after vaccination has not been noted. However, in individual cases this cannot be completely excluded, vaccination may cause symptoms of autoimmune diseases in patients with a genetic predisposition.

Contraindications

Pre-exposure immunization

Acute infectious diseases or exacerbation of chronic diseases (vaccinations are carried out no earlier than 2 weeks after recovery);
Allergic reactions to antibiotics (neomycin, chlortetracycline and amphotericin B) and components included in the Rabipur^® vaccine;
Complications, including systemic allergic reactions, that developed after previous administration of the Rabipur^® vaccine;
Pregnancy.

Post-exposure immunization

Since rabies disease leads to death, there are no contraindications for post-exposure immunization.

Pregnancy and lactation are not contraindications for post-exposure immunization.

Use in Pregnancy and Lactation

Pregnancy and lactation are not contraindications for post-exposure immunization. No cases of harm attributed to the use of this vaccine in pregnant women have been recorded.

Information on the penetration of the Rabipur^® vaccine into breast milk is not available.

Pediatric Use

Special Precautions

For post-exposure vaccination of persons with clinical symptoms such as rash, swelling of the lips and/or epiglottis, laryngo- or bronchospasm, arterial hypotension or shock, in case of previously observed serious allergic reactions to vaccine components (including polygeline), incl. to antibiotics used in the vaccine production process (amphotericin B, chlortetracycline, neomycin), another anti-rabies vaccine should be used. Vaccination should be carried out only under careful clinical supervision in a room equipped with anti-shock therapy means.

Under no circumstances should the vaccine be administered intravenously! Accidental entry of the vaccine into a blood vessel may be accompanied by a severe reaction, up to shock. In such cases, emergency measures should be taken immediately to prevent such a reaction. Mixing the vaccine and anti-rabies immunoglobulin in the same syringe is unacceptable.

Measures for emergency wound treatment (local treatment)

For persons who have been in contact with rabies-suspected animals, the following measures are mandatory: as soon as possible after a bite or injury, all wounds and injuries should be immediately washed with plenty of water using soap or another detergent for several minutes (up to 15 min). Then the edges of the wound should be treated with 70% ethyl alcohol or 5% alcohol solution of iodine.

If possible, stitches should not be applied to the wounds. Stitching is indicated exclusively in the following cases

For extensive wounds: several guiding skin sutures after preliminary wound treatment;
Application of skin sutures to facial wounds;
Suturing bleeding vessels to stop external bleeding. If there are indications for the use of anti-rabies immunoglobulin, it is used immediately before suturing. The recommended dose of immunoglobulin should be administered as deep as possible into the wound and adjacent areas. The remaining immunoglobulin should be administered intramuscularly at a site different from the vaccine administration site, preferably into the gluteal muscle.

If necessary, tetanus prophylaxis should be carried out.

Overdose

Data on overdose of the Rabipur^® vaccine have not been provided.

Drug Interactions

During the course of post-exposure vaccination, it is recommended to refrain from simultaneous use of immunosuppressive drugs and antimalarial drugs.

In patients receiving immunosuppressive therapy, as well as in persons with primary or secondary immunodeficiencies, vaccination may not be effective enough to produce the necessary immune response.

Anti-rabies immunoglobulin should be used in strictly established quantities. The dose should not be exceeded or reduced, nor should it be administered repeatedly due to the danger of reducing the effectiveness of simultaneous vaccination.

During the course of post-exposure immunization, simultaneous use of tetanus toxoid and anti-tetanus serum is allowed. After the end of rabies vaccination, vaccination against other infectious diseases is allowed no earlier than after 2 months. Pre-exposure immunization is carried out no earlier than 1 month after vaccination against another infectious disease.

Storage Conditions

The vaccine should be stored out of the reach of children, protected from light, at a temperature from 2°C (35.6°F) to 8°C (46.4°F); do not freeze.

Shelf Life

Shelf life – 4 years. Do not use after the expiration date printed on the package.

Dispensing Status

Dispensed only to medical and preventive institutions.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.

Medical Disclaimer