RAVAC 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 rabies research laboratories etc., children at high risk of exposure or prior to visits to areas in which rabies is endemic.

b)  Post-Exposure prophylaxis

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

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

a)       Pre-Exposure prophylaxis

The  following  schedule  should  be  followed  for  pre-exposure  prophylaxis  in  high  risk populations.

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 titres 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.

For Intradermal route, four doses should be administered (2 injections of 0.1 ml at 2 different sites).

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 immunodeficient patients,

human rabies immunoglobulin (20 IU/kg) or equine rabies immunoglobulin (40 IU per kg) should be given in conjunction with Rabies Vaccine 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.

Do not administer vaccine by intravascular route. Immunoglobulins and rabies vaccine 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.

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 RAVAC be administered in 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. RAVAC 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 RAVAC 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.

RAVAC does not contain a 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°C. 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.

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 be exceeded 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.

Rabies Vaccine Inactivated (Freeze-Dried) RAVAC was safe, non-teratogenic and did not cause developmental toxicity in a prenatal developmental toxicity study in pregnant rats.

It is not known whether Rabies Vaccine Inactivated (Freeze-Dried) RAVAC can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. It is also not known whether Rabies Vaccine Inactivated (Freeze-Dried) RAVAC is secreted in breast milk.

It is advisable to carefully weigh expected benefits against potential risks prior to pre- exposure prophylaxis with Rabies Vaccine Inactivated (Freeze-Dried) RAVAC during pregnancy and breastfeeding. Because of the life-threatening risk due to rabies, pregnancy and lactation are not contraindications for post-exposure prophylaxis with Rabies Vaccine Inactivated (Freeze-Dried) RAVAC.

Effect of Rabies Vaccine Inactivated (Freeze-Dried) RAVAC on ability to drive and use machines is not known.

Following adverse reactions have been reported during the phase II/III clinical trial of Rabies Vaccine Inactivated (Freeze-Dried) RAVAC administered with or without HRIG as per WHO recommended post-exposure prophylaxis regimen. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness:

Most of the events were of mild severity and resolved within 3 days without any sequelae. Incidence was comparable with the comparator licensed rabies vaccine.

To reports any side effect(s):

Saudi Arabia:

·       The National Pharmacovigilance Centre (NPC):

-       SFDA Call Center: 19999

-       E-mail: npc.drug@sfda.gov.sa

-       Website: https://ade.sfda.gov.sa/

Other GCC States:

-       Please contact the relevant competent authority.

No case of overdose has been reported.

    ATC Code: J07BG01

1.1.  Pharmacodynamic properties

RAVAC is a lyophilized, stabilized suspension of inactivated Pitman-Moore rabies virus strain (PM-Vero), adapted and grown on vero cells and inactivated by beta-propiolactone.

a)  Pre-exposure Prophylaxis:

In a phase I clinical trial in previously unimmunized healthy adults, all subjects achieved a protective antibody titre (≥ 0.5 IU/ml) by day 21 of a primary series of three injections of RAVAC when given according to the recommended schedule of Day 0, 7 and 21 by the  intramuscular and intradermal route.

b)  Post-exposure Prophylaxis:

In a phase II/III clinical trial of RAVAC in patients with potential rabies exposure of category II and III, all subjects achieved a protective antibody titre (≥ 0.5 IU/ml) by day 7 (with only 2 doses) of a primary series of five injections of RAVAC when given according to the WHO recommended schedule of Day 0, 3, 7, 14 and 28 by the intramuscular injection of 1 ml each OR a primary series of four injections of RAVAC when given on Day 0, 3, 7, and 28 by the intradermal injection of 0.1 ml on each deltoid. Patients with category II exposure received only vaccine and patients with category III exposure received human rabies immunoglobulin and Day 0 along with vaccine.

Not applicable.

Rabies Vaccine Inactivated (Freeze-Dried) RAVAC had undergone single dose and repeated-dose toxicity studies in rats and mice by intramuscular route and local tolerance by intradermal route in rats. Results of single dose toxicity studies concluded that Rabies Vaccine Inactivated (Freeze-Dried) RAVAC did not cause any observable toxicity in mice at a dose equal to one human dose in absolute terms and in rats at a dose equal to 2 times the human dose in absolute term. Rabies Vaccine Inactivated (Freeze-Dried) RAVAC also was found safe in repeated dose toxicity and local tolerance study by intradermal route.

Rabies Vaccine Inactivated (Freeze-Dried) RAVAC was safe, non-teratogenic and did not cause developmental toxicity in a prenatal developmental toxicity study in pregnant rats. Non-clinical data revealed no special hazard for humans.

Rabies Vaccine Inactivated (Freeze-Dried) RAVAC contains the following Excipients;

Under no circumstances should Rabies Vaccine Inactivated (Freeze-Dried) RAVAC be administered in the same syringe or at the same site as rabies immunoglobulin or any other medicinal products.

Store the vaccine in a refrigerator (2°C- 8°C).

The diluent should not be frozen but should be kept cool.

Rabies Vaccine Inactivated (Freeze Dried) is filled in 13 mm USP Type 1 clear tubular glass vials of 16.5 mm diameter and 40 mm height and 5.0 mL overflow volume. Vials are stoppered with a 13 mm Bromobutyl Rubber ‘Lyo’ stopper and sealed with 13 mm red coloured plastic Flip top aluminum seal.

No special requirements for disposal are required.  Any unused product or waste material should be disposed of in accordance with local requirements.