Antirabies vaccine

APPLICATION INSTRUCTIONS
For cultural concentrated purified inactivated freez-dried antirabies vaccine and for antirabies immunoglobulin

Cultural concentrated purified inactivated freez-dried antirabies vaccine (KOKAV) is produced from rabies virus Vnukovo-32 strain that has been grown on primary Syrian hamster kidney cell culture, inactivated with ultraviolet rays and formaldehyde, concentrated and purified with: ultrafiltration with further purification in porous silica, or with ultracentrifugation, or with ion exchange chromatography. The vaccine is stabilized with gelatose and sucrose. The vaccine looks like white hygroscopic porous mass, after re-dissolving it is slightly opalescent colourless solution. Each dose (1.0 ml) contains no less than 2.5 IU.

Immunological properties: The vaccine induces immunity against rabies.

Prescription: Therapeutic and prophylactic immunization.

Administration: Ampoule contents should be dissolved in 1.0 ml of water for injections during no longer than 5 minutes. Dissolved vaccine should be injected slowly and intramuscularly into the deltoid muscle for adults, and into the upper part of haunch for children under 5 years old. Do not inject the vaccine into the buttock. The product must not be administered in case of broken ampoule, illegible labelling, changing of coloration and transparency afrter dissolving, expired shelf life, and incorrect storage. The aseptic measures must be applied while open and administer the vaccine.

Storage term for dissolved vaccine must be no longer than 5 minutes.

A patient should be under medical supervision during 30 minutes since he vaccinated. Vaccination stations should be supplied by antishock remedies. All data about type and series of preparations being used for vaccination as well as the schedule of vaccination and post-vaccination reactions should be fixed in special personal sertificate.

Antirabies treatment consists of d-bridement and antirabies vaccine administration, or simultaneous administration of antirabies immunoglobulin (AIg) and antirabies vaccine (KOKAV).

D-tritment

D-tritment is extremily important and should be conducted immediately or as soon as possible in case of bite or injury. Bite wound should be washed by detergent solution. Wound adges should be cleansed by 70% alcohol or by 5% iodine solution. In case of indications, administer antirabies immunoglobulin (AIg) just before suturing (see Antirabies immunoglobulin (AIg) dosage).

It is needed to avoid suturing as far as possible. Suturing is indicated in the following cases only:

Vast wound – several cuticular sutures;

Cosmetic indications – suturing of face wounds;

Suturing of blood vessels to stop bleeding.

Therapeutic immunization should be started immediately after d-tritment.

Therapeutic immunization

Indications: Contact with or bite by rabid, suspected for rabies or unknown animals.

Contra-indications: Do not exist

Therapeutic immunization scheme: Detailed scheme is placed at the end of the document.

In case of combined treatment both with the vaccine and the immunoglobulin, in accordance with the scheme (p.3) both preparations should be administered simultaneously (first AIg, next KOKAV) and injected into the different locations.

Administer AIg as soon as possible after contact with rabid, suspected for rabies or unknown animals (see Scheme for therapeutic immunization). It must be administered no late than 3 days after the contact. Do not administer AIg after administration of KOKAV.

Antirabies immunoglobulin (AIg) dosage: Heterologous (equine) immunoglobuline dosage is 40 IU per kg of body weight. Homologous (human) immunoglobulon dosage is 20 IU per kg of body weight.

As much as possible AIg should be infiltrated into the tissue around wonder and into the wonder. In case of impossibility to inject the whole dose into wonder due to anatomical peculiarities (finger ends etc.), the rest of the dose should be injected intramascularly (upper part of haunch or shoulder). AIg injection location must be differ from that one for the vaccine.

Check individual susceptibility for equine protein before heterologous AIg injection.

Prophylactic immunization

Indications: Prophylactic immunization is indicated for persons dealing with stray animals, for hunters, veterinaries, foresters, slaughterhouse workers, taxidermists, for those who deal with “street” rabies virus.

Prophylactic immunization scheme

Primary immunization	Three injections at 0^th, 7^th and 30^th day, 1.0 ml each
Revaccination after 1 year	Single injection, 1.0 ml
Further revaccinations each 3 years	Single injection, 1.0 ml

Contra-indications for prophylactic immunization

Acute infectious and non-infectious deseases, acute phase or decompensation of chronical desease. Vaccination is not possible untill one month after convalescence or remission.
System allergic reactions on previous administration of the preparetions (generalized rash, Quincke’s edema etc.).
Allergic reaction on antibiotics.
Pregnancy

Reactions on antirabies preparations administration

Vaccine injection may cause local or generalized reaction. Local reaction is declared itself as a slight cutaneous swelling, redness, itch, and as a regional lymph nodes enlargement. Generalized reaction is declared itself as indisposition, headache, weakness, and as a body temperature increasing. In these cases symptomatic therapia and hyposensibilic and antihistamine preparations administration are recommended.

Neurologic symptoms are rarely registered. In this case the patient must be hospitalized immediately.

The following complications may accure from equine antirabies immunoglobulin injection: anaphylactic shock, local allergic reaction at 1^st-2^nd day after the injection, serum sickness at 6^th-8^th day after the injection. In case of anaphylactoid reaction it is recommended intracutaneous injection of 0,3-1,0 ml adrenaline (1:1000) or 0,2-1,0 ml ephedrine (5%), depending on patient’s age. In case of serum sickness symptoms it is recommended parenteral injection of antihistamine preparations, corticosteroids, and Ca-containing drugs.

Dosage form

Vaccine is produced in set: one ampoules containing 1.0 ml (single dose) of the vaccine and one ampoule containing 1.0 ml of diluent (distilled water for injection). Each box includes 5 sets: 5 ampoules containing the vaccine and 5 ones — with the diluent.

Equine antirabies immunoglobulin is produced in set: one ampoules containing 5.0 ml or 10.0 ml of the preparation and one ampoule containing 1.0 ml of diluted (1:100) immunoglobulin. Each box includes 5 sets.

Shelf life, storage and transportation conditions

Shelf life for the vaccine is 1.5 years. Shelf life for immunoglobulin is 2 years. The vaccine should be stored and transported at temperature from +2 to +8 Celsium. It is possible to transport the vaccine at temperature +25 Celsium during no more than 2 days.

In case of complications or falling sick after or during the complete course of vaccination it is needed notify immediately local Healthcare Administration, Ministry of Health L.A.Tarasevich State Research Institute for Standartisation and Control of Medical and Biological Preparations (GISK), (Sivtsev Vrazhek 41, Moscow 119002 Russia, Tel. +7 495 241 3922), and manufacturer of the vaccine or immunoglobulin. Administration of the particular vaccine series must be rejected. Samples of the vaccine or inmmunoglobulin should be sent to GISK.

In case of vaccinee death it is needed to conduct autopsy and diagnostical study of brain tissues. For this purpose the samples of corps brain tissue (ammon horn, brainstem, cerebellum, cortex) extracted aseptically should be placed in hermetically closed vial with 50% water-glycerin solution, cooled below -20 Celsium and immediately sent to diagnostical laboratory.

Immunization scheme

Injury category	Contact characteristics*	Animal details	Treatment
1	No injury or salivation of skin. No direct contact	Rabid animal	Not administered
2	Salivation of uninjured skin; solitary superficial bites or scratches and abrasions on body and extremities (excluding head, face, neck, hands, fingers and genitals) caused by pests and farming animals	If the animal is still healthy after 10 days of investigation, the treatment can be stoped after 3^rd injection of the vaccine. In any other cases and in that case when investigation is impossible (the animal desapeared, escaped or was shooted), the treatment must be continued in accordance with the present scheme	Start treatment immediately: vaccine injections 1.0 ml each at 0^th , 3^rd , 7^th , 14^th , 30^th and 90^th day
3	Any salivation of mucous, any beats of head, face, neck, hands, fingers and genitals; multiple beats and deep solitary beats of any localisation caused by pests, farming animals. Any salivation and injury caused by wild predators, bats or rodents	If the animal is still healthy after 10 days of investigation, the treatment can be stoped after 3^rd injection of the vaccine. In any other cases and in that case when investigation is impossible, the treatment must be continued in accordance with the present scheme	Start combined treatment immediately and simultaneously: AIg (see Antirabies immunoglobulin (AIg) dosage) at 0^th day; antirabies vaccine injections 1.0 ml each at 0^th , 3^rd , 7^th , 14^th , 30^th and 90^th day

*Contact means any beats, scratches, abrasions and salivation.

Comments

Dosage and scheme of immunization are the same for kids as for adults. Vaccination is indicated independently on term of contact with rabid, suspected for rabies or unknown animals, even several month after the contact (excluding AIg treatment).
It is indicated just three injections of the vaccine 1.0 ml each at 0^th, 3^rd and 7^th day for that persons who have already got complete course of vaccination during no more than one year before a new occurrence. In case of more than one year after previous vaccination or incomplete previous vaccination a comlete course of vaccination is indicated in accordance with the above scheme.
Corticosteroid and immunodepressant therapy may lead to unsuccessful vaccination. In case of simultaneous administration of corticosteroids or immunodepressants and the vaccine laboratory control of antiviral antibodies level in patient’s blood is obligatory. An additional course of vaccination is indicated in case of low level or absence of the antibodies.
It is prohibited to take alcoholic drinks druring vaccination period and 6 month after. Vaccinee should avoid overfatigue, supercooling, and overheating.