RABIVAX-S: A Reliable and Effective Rabies Vaccine for Pre- and Post-Exposure Protection.. pharmacyteach.com

 

RABIES VACCINE INACTIVATED

 

RABIVAX-S

RABIVAX-S (Rabies Vaccine Inactivated (Freeze-dried)] is a sterile, purified inactivated rabies vaccine prepared on Vero cells. RABIVAX-S is freeze dried and is provided with diluent (1 dose of powder in vial and 1 ml of diluent in ampoule). The vaccine has the appearance of a white dry cake. The vaccine conforms to the World Health Organization (W.H.O.) requirements.

COMPOSITION

Each dose of 1 mi contains:

Purified Rabies Antigen (Rabies virus Pitman-Moore Strain 3218 VERO adapted and grown on Vero cells, inactivated by using propiolactone) not less than 2.5 IU reconstitute with 1 ml of Sterile Water for Injections.

Dose: 1 ml by intramuscular injection.

Diluent: Sterile Water for Injections.

Excipients: Sucrose, glycine, human serum albumin (HSA).

Introduction of RABIES Vaccine

Rabies is a viral disease that can be transmitted from animals to humans, classified as a zoonotic infection. It affects both domestic and wild animals and is spread through direct contact with the saliva of infected creatures, such as through bites, scratches, or licks on open wounds and mucous membranes. Once clinical symptoms manifest, rabies is invariably fatal classified as a zoonotic infection that can be transmitted from animals to humans for both animals and humans. Unlike many other infectious diseases, rabies can be prevented through prompt vaccination, even after potential exposure to the virus.

Two primary types of vaccines are available for human rabies prevention: nerve tissue and cell culture vaccines. The World Health Organization (WHO) advocates for the transition from nerve tissue vaccines to the more effective and safer cell culture vaccines at the earliest opportunity. Recent advancements have led to the development of cell culture vaccines that are not only more effective but also more cost-efficient and require smaller doses.

The use of intradermal immunization with cell-culture-based rabies vaccines is a valid alternative to the traditional intramuscular administration method. Studies have demonstrated that intradermal vaccination is equally safe and immunogenic as intramuscular vaccination, while utilizing a smaller quantity of vaccine for both pre- and post-exposure prophylaxis. This method can lead to reduced direct costs and should be considered in situations where financial or supply limitations exist.

Individuals at continual, frequent, or elevated risk of rabies virus exposure, whether due to their living conditions or job responsibilities, are advised to receive pre-exposure prophylaxis.

For those in occupations with ongoing or frequent exposure risks, periodic booster shots are recommended as an additional precaution. If possible, it is preferable to monitor antibody levels in at-risk individuals rather than routinely administering boosters.

INDICATIONS

RABIVAX-5 is indicated for the prevention of rabies in children and adults. It can be used before or after exposure, as a primary immunization or as a booster dose.

 

a) Pre-Exposure prophylaxis

 

Pre-exposure vaccination should be offered to subjects at high risk of contamination by the rabies virus. This vaccination is particularly recommended for veterinarians, veterinary medicine students, animal keepers, hunters, forestry workers, animal handlers, butchers, personnel in rables research laboratories etc., children at high risk of exposure or prior to visits to areas in which rabies is endemic.

 

b) Post-Exposure prophylaxis

`RABIVAX-S is indicated in post-exposure prophylaxis of rabies infection, when given to individuals with suspected rabies exposure. RABIVAX-S must always be used as per recommendations of the World Health Organization (WHO), depending on the type of Contact with a suspected rabid animal.

Category	Type of contact	Recommended treatment
I	Touching or feeding animals, licks on the intact skin.	No treatment is required.
II	Nibbling of uncovered skin, minor scratches or abrasions without bleeding.	Immediate vaccination.
III	Single or multiple transdermal bites or scratches, contamination of mucous membrane with saliva from licks, licks on broken skin, exposure to bats.	Immediate vaccination and administration of immunoglobulin.

 

For all categories, immediate washing and flushing of all wounds and scratches is recommended. If indicated tetanus prophylaxis should also be given with tetanus toxoid.

Treatment should be started as early as possible after exposure, but in no case should it be denied to exposed persons whatever time interval has elapsed.

CONTRAINDICATIONS

a) Pre-exposure prophylaxis

 

In case of fever or an acute illness, vaccination should be postponed, in case of previous severe reaction to any components of the vaccine, RABIVAX-5 is contraindicated.

 Read About: Meningococcal Vaccine (Menactra): Effectiveness, Safety & Who Needs It?

b) Post-exposure prophylaxis 

Because of the life-threatening risk of rabies, there are no contraindications to the administration of post-exposure prophylaxis using RABIVAX-S. The Intradermal route must not be used in individuals receiving long-term corticosteroid or other Immunosuppressive therapy or chloroquine for malaria treatment or prophylaxis and in immunocompromised individuals. Such individuals may have a reduced response to intradermal rabies vaccination and should instead receive the vaccine intramuscularly

The vaccine may contain traces of neomycin. Anaphylactic or anaphylactoid reactions to neomycin, history of anaphylactic or anaphylactoid reactions are absolute contraindications.

 

WARNINGS

Do not administer the vaccine by intravascular route. Immunoglobulins and rabies vaccines should not be combined in the same syringe or injected at the same site. If anaphylaxis or severe allergic reactions occur, administer appropriate medications (e.g., adrenaline) and provide supportive care as required.

 

PRECAUTIONS

The possibility of allergic reactions in individuals sensitive to components of the product should be evaluated, Adrenaline hydrochloride Solution (1:1000) and other appropriate agents should be readily available for immediate use in case an anaphylactic or acute hypersensitivity reaction occurs as per the current recommendations.

Special care should be taken to ensure that the product is not injected into a blood vessel. Under no circumstances should RABIVAX-She administered to the same syringe or at the same site as rabies immunoglobulin.

A separate sterile needle and syringe must be used for each individual patient to prevent the transmission of infectious agents. RABIVAX-S must not be administered intravenously. As with all preparations given intramuscularly, bleeding complications may be encountered in patients with bleeding disorders.

 

 

SPECIAL PRECAUTIONS FOR THE INTRADERMAL ROUTE

It is essential that intradermal administration of RABIVAX-5 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, a sterile syringe with fixed needle insulin type) is preferred. Correct intradermal injection should result in a raised papule with an orange peel (peau d'orange) 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. If papule is not seen after 2 successive attempts, the patient should be given the dose intramuscularly RABIVAX-5 does not contain preservative, therefore great care must be taken to avoid contamination of reconstituted vaccine.

Vaccine may be used up to 6 hours after reconstitution provided it is maintained at 2°C to 8 ^oC. Unused vaccine must be discarded after 6 hours. A new sterile needle and syringe must be used to withdraw and administer each dose of vaccine for each patient to avoid cross infection.

DRUG INTERACTIONS

Corticosteroids, chloroquine and other immunosuppressive treatments can interfere with the immune response of the vaccine and lead to the failure of the vaccination.

Immunoglobulins must be administered at a different site from that of the vaccine (the contralateral side). The recommended dose of rabies immunoglobulin should not exceed nor should repeated doses of the same be administered once the vaccination course has been started since a higher dose could interfere with the immune response to rabies vaccine.

 

PREGNANCY AND LACTATION 

RABIVAX S is safe, non-teratogenicity and did not cause developmental toxicity in a prenatal developmental toxicity study in pregnant rats.

It is not known whether RABIVAX-S can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. It is also not known whether RABIVAX-S is secreted in breast milk. It is advisable to carefully weigh expected benefits against potential risks prior to pre-exposure prophylaxis with RABIVAX-5 during pregnancy and breastfeeding. Because of the life-threatening risk due to rabies, pregnancy and lactation are not contraindications for post-exposure prophylaxis with RABIVAX-S.

 

ADVERSE REACTIONS

RABIVAX-S may cause injection site reactions such as pain, erythema, edema, pruritus and induration and systemic reactions such as fever, shivering, faintness, asthenia, headache, dizziness, myalgia, nausea, abdominal pain and arthralgia. Usually these reactions are mild in severity, transient and resolve uneventfully. Rarely erythema multiforme has been reported with other tissue culture rabies vaccines.

 

DOSAGE AND ADMINISTRATION

RABIVAX-S should be reconstituted only with the entire contents of the diluent supplied (Sterile Water for Injections) using a sterile syringe and needle, with gentle shaking until the dried cake is easily dissolved. After reconstitution the vaccine should be used immediately.

The vaccine vial monitor (see figure), for this type of vaccine is attached to the vial cap and should be discarded when the vaccine is being reconstituted.

The diluent and reconstituted vaccine should be inspected visually for any foreign particulate matter and / or variation of Physical aspects prior to administration. In the event of either being observed, discard the diluent or reconstituted vaccine. For adults and children aged 2 years, the vaccine should always be administered in the deltoid area of the arm; for children aged < 2 years, the anterolateral area of the thigh is recommended. Rabies vaccine should not be administered in the gluteal area, as the induction of an adequate immune response may be less reliable.

Intradermal regimen may be used for people with category II and III exposures in countries where the intradermal route has been endorsed by national health authorities.

Pre- Exposure prophylaxis

The following schedule should be followed for pre-exposure prophylaxis in high risk population:

Route	Dose	Number of Doses	Schedule
Intramuscular	1ml	3	Day:  0, 3, 7 , 14, or 28
Intradermal	0.1ml	3	Day:  0, 3 , 7, and 28

 

Periodic booster injections are recommended as an extra precaution only for people whose occupation puts them at continual or frequent risk of exposure. For people who are potentially at risk of laboratory exposure to high concentrations of live rabies virus, antibody testing should be done every 6 months. Those professionals, who are not at continual risk of exposure through their activities, should have serological monitoring every 2 years. Because vaccine-induced immunity persists in most cases for years, a booster should be administered if rabies virus neutralizing antibody titers fall to < 0.5 IU/ml.

 

b) Post-Exposure prophylaxis

In order to remove as much of the rabies virus as possible, immediately cleanse the wound with soap and wash thoroughly with water. Then treat with alcohol (70%) or an iodine tincture.

The following schedule should be followed for post-exposure prophylaxis in previously unimmunized individuals.

Route	Dose	Number of Doses	Schedule
Intramuscular	1ml	5	Day:  0, 3, 7 , 14, or 28
Intradermal	0.1ml + 0.1ml	4	Day:  0, 3 , 7, and 28

 

For intradermal route, four doses should be administered (2 injections of 0.1 ml at 2 different sites) as per the Updated Thai Red Cross regimen (2-2-2-0-2) as given above.

In those previously immunized by complete vaccination schedule (pre-exposure or post-exposure prophylaxis), 2 doses of 1 ml given by intramuscular route or 2 doses of 0.1 ml by intradermal route on Day 0 and Day 3 are recommended.

In cases of Category III exposures and of category II exposures in immune deficient patients, human rabies immunoglobulin (20 IU/kg) or equine rabies immunoglobulin (40 IU per kg) should be given in conjunction with RABIVAX-S on Day 0. If anatomically feasible, the full dose of rabies immunoglobulin should be thoroughly infiltrated in the area around and into the wounds. Any remaining volume should be injected intramuscularly at a site distant from vaccine administration. Rabies immunoglobulin may be diluted to a volume sufficient for all wounds to be effectively and safely infiltrated.

If rabies immunoglobulin is not available at the time of the first vaccination, it must be administered no later than 7 days after the first vaccination since later administration would result in interference with immune response of the vaccine.

STORAGE

The vaccine should be stored between 2°C and 8°C. The diluent should not be frozen, but should be kept cool.

Presentation

RABIVAX-S is supplied as:

1 dose- 1ml vial plus diluent (1ml)

1 dose- 1ml vial, diluent (1ml) syringe and needle

5*1 dose – 1 ml vials and 5 diluent (1ml), ampoules

The vaccine Vial monitor (VVM)