Vaccine types Four formulations of three inactivated rabies virus vaccines are licensed for use by the U.S.

Food and Drug Administration (FDA). Two RIG formulations are also FDA-licensed. HUMAN DIPLOID CELL VACCINE (HDCV) Human diploid cell vaccines (HDCVs) use inactivated rabies viruses. HDCV comes in two formulations: one for intramuscular (IM) injection and one for intradermal (ID) injection into a deep layer of skin. PURIFIED CHICK EMBRYO CELL VACCINE (PCEC) Purified chick embryo cell (PCEC) vaccine became available in the United States in 1997. PCEC is made from rabies virus grown in cultures of chicken embryos and then inactivated. The drug is formulated for IM administration only. RABIES VACCINE ADSORBED (RVA) Rabies vaccine adsorbed (RVA) is manufactured from virus grown in cell cultures of fetal rhesus monkey lung cells and then inactivated. RABIES IMMUNE GLOBULIN (RIG) Human rabies immune globulin (RIG, HRIG) is a vaccine made from human serum that contains high levels of antibodies against rabies. It is used in conjunction with an inactivated-rabies vaccine for post-exposure prophylaxis. RIG provides immediate but short-lived protection against rabies. Approximately one-half of the antibodies are lost within 21 days after administration. RIG is separated from the blood plasma of hyperimmunized human donors. Numerous procedures are used to clear the serum of rabies virus. OTHER VACCINES Although the four types of inactivated-rabies vaccines and the two RIGs are the only rabies vaccines available in the United States, various other rabies vaccines are produced throughout the world. Although inactivated-rabies vaccines from diploid cell cultures are safe and effective, they are expensive. In developing countries, rabies vaccines often contain nerve tissue which can cause adverse effects. Various less expensive but safe and effective vaccines are under development.

General use Inactivated-rabies vaccines are injected, either before or after exposure to the virus, in 1.0-ml. doses containing at least 2.5 IU/ml. of rabies virus antigen. This is the recommended standard of the World Health Organization (WHO). The size and number of vaccine doses are the same for children and adults. Although the same rabies vaccine usually is used throughout an immunization series, there is no evidence of adverse reactions or loss of effectiveness when two different vaccines are used in the same series. Modern rabies vaccines are relatively painless.

Pre-exposure prophylaxis For preventative rabies immunization in an unexposed child, an inactivated-rabies vaccine is administered in three 1.0-ml. doses, with the second dose seven days after the first, and the third dose 21 or 28 days after the first. The vaccine is injected into the upper arm. Studies have found that this regimen produces adequate antibodies against rabies in the blood serum of all subjects. Post-exposure prophylaxis Following an animal bite or contact between a child's mucous membranes and an animal's saliva, an attempt is usually made to determine whether the animal has rabies. If there is a threat of rabies, an unvaccinated child receives RIG and a series of five rabies vaccinations over a 28-day period. Ideally, treatment should begin within two days of exposure, however it may be started at any time thereafter. The wound is cleaned thoroughly and, if possible, RIG is injected into the wound and the surrounding tissues to block the virus's entry into the central nervous system. The recommended dose is 20 IU/kg (1 kg = 2.2 lb) of body weight. This is equivalent to 22 mg of the antibody immunoglobulin G (IgG) per kilogram of body weight. Any remaining RIG is injected intramuscularly at a site removed from the vaccination site. RIG also may be injected into the buttocks. RIG is never injected with the same syringe or at the same site as the vaccine. RIG is used only once to provide antibodies until the child's immune system begins producing its own antibodies in response to the vaccine. RIG is administered concurrently with the first dose of inactivated-rabies vaccine or up to seven days thereafter. Additional treatment with RIG may interfere with antibody production in response to the inactivated-rabies vaccine. Inactivated-rabies vaccine is administered in 1.0-ml. doses, at three, seven, 14, and 28 days after the first vaccination. It is injected intramuscularly in the upper arm or the upper thigh. If an animal is found to be rabies-free after the vaccination series has been initiated, the series can be discontinued. Exposure following vaccination Children exposed to rabies following vaccination receive a 1.0-ml. dose of vaccine immediately and a second dose three days later. These children do not receive RIG because it will diminish the rapid antibody response resulting from the previous vaccination. Precautions Precautions should be taken before vaccinating a child who has:
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a weakened immune system due to HIV/AIDS or other disease or condition cancer

had a life-threatening reaction to a previous rabies vaccine or to any component of the vaccine

Children with suppressed immune systems should not receive pre-exposure prophylaxis against rabies. Medical conditions and medications that suppress the immune system can interfere with antibody production in response to a rabies vaccine. If a child has exhibited a serious hypersensitivity to a previous rabies vaccine, antihistamines may be used concurrently. Children who are allergic to eggs should not be give vaccines cultured in chicken embryos. A minor illness, such as a cold, does not preclude rabies vaccination. However pre-exposure vaccination should be postponed if the child has a moderate or severe illness. Post-exposure prophylaxis should be administered regardless of any other illness or condition. Children should not be vaccinated against measles or chickenpox (varicella) for four months after being treated with RIG. Children receiving post-exposure prophylaxis outside of the United States should have their antibody levels against rabies measured after their return. Side effects Side effects from the rabies vaccines currently used in the United States are much less common and less severe than the side effects of earlier rabies vaccines. However side effects may vary with the brand of vaccine and adverse reactions to rabies vaccines used in some other countries are quite common. The risk of side effects also increases with the number of vaccine doses. However a vaccination series should not be interrupted because of localized or mild side effects. Mild side effects from rabies vaccines include:
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soreness, redness, swelling, itching , or pain at the site of the injection in 30 74 percent of recipients headache, nausea , abdominal pain, muscle aches, or dizziness in 5 40 percent of recipients

More serious side effects of rabies vaccines include:

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hives, joint pain, or fever in about 6 percent of those receiving a booster vaccination very rarely, an illness resembling Guillain-Barr syndrome, a disorder of the motor nerves that can result in temporary paralysis, lasting no longer than 12 weeks and resulting in complete recovery Other nervous system disorders occur so rarely following rabies vaccination that they may not be related to the vaccine. However, a physician should be consulted if a high fever or behavioral changes occur following rabies vaccination.

Reported side effects of RIG include:

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local pain

low-grade fever

Although any vaccine is capable of inducing an allergic reaction, serious reactions to rabies vaccine are very rare. Signs of an allergic reaction include:
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paleness weakness dizziness hoarseness or wheezing difficulty breathing a fast heartbeat

In case of a serious reaction to a rabies vaccine:

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A doctor should be consulted immediately. The date, time, and type of reaction should be recorded. Medical personnel or the local health department should file a Vaccine Adverse Event Report.

Preparing a child for an injection Most children are afraid of injections; however there are simple methods for easing a child's fear . Prior to the vaccination parents should:
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Tell children that they will be getting a shot. Explain to children that the shot will prevent them from becoming sick. Have older siblings comfort and reassure a younger child. Bring along the child's favorite toy or blanket. Never threaten children by telling them they will get a shot. Read the vaccination information statement (VIS) and ask questions of the medical practitioner.

During the vaccination parents should:

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Hold the child.

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Make eye contact with the child and smile. Talk softly and comfort the child. Distract the child by using a hand puppet or pointing out pictures or objects. Sing or tell the child a story. Have the child tell a story. Teach the child to focus on something other than the shot. Help the child take deep breaths. Allow the child to cry. Stay calm.

After the injection Following an injection parents should:

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Hold and caress a child or breastfeed an infant. Talk soothingly and reassuringly. Hug and praise the child for doing well. Use a cool, wet cloth to reduce soreness or swelling at the injection site.

Parents should also be aware that: KEY TERMS Antibody A special protein made by the body's immune system as a defense against foreign material (bacteria, viruses, etc.) that enters the body. It is uniquely designed to attack and neutralize the specific antigen that triggered the immune response. Antigen A substance (usually a protein) identified as foreign by the body's immune system, triggering the release of antibodies as part of the body's immune response. Booster immunization An additional dose of a vaccine to maintain immunity to the disease.

------------------------------------------------------------------------------------------------------------------COMPOSITION: Each 5 ml vial contains: Equine anti rabies immunoglobulin fragments .. Not less than 1500 IU. Chloro-m-Cresol I.P........................................... Not more than 0.25%v/v. -------------------------------------------------------------------------------------------------------------------

PHARMACEUTICAL FORM Solution for injection by intramuscular or subcutaneous route 5ml vial, 1500IU ------------------------------------------------------------------------------------------------------------------THERAPEUTIC INDICATIONS: AbhayRIG provides passive immunization against rabies. AbhayRIG is for prevention of rabies in patients at risk of being exposed to rabies after contact with a rabid animal or an animal presumed to be rabid. AbhayRIG itself does not constitute an anti rabies treatment and should always be used in conjunction with rabies vaccine. CONTRA-INDICATIONS: Should be used with extreme caution in subject with a history of allergic symptoms or hypersensitivity to horse serum. In case of doubt, it is essential to ask your doctor or pharmacist

for advice. ------------------------------------------------------------------------------------------------------------------SPECIAL WARNINGS AND PRECAUTIONS FOR USE: Despite the high degree of purification of the serum, it is recommended to perform a skin test before administering heterologus serum. The skin test consists of a intradermal injection of 0.1ml of 1:10 dilution of AbhayRIG on the outside of the forearm so as to obtain an orange ring type appearance (3 mm diameter induration). An equivalent intradermal injection of physiological saline solution is used as control. The observations made 15 minutes after intradermal injection is considered to be positive if erythrema (>6mm), local oedema or a systemic reaction is observed and the control is negative. A positve test result is not a formal contra-indication for the use of serotherapy, but it should be considered as a warning. A negative test is not an absolute guarantee for the absence of an immediate allergic type reaction. ------------------------------------------------------------------------------------------------------------------DRUG INTERACTIONS: Rabies prevention requires simultaneous administration of antirabies immunoglobulin and vaccine. Anti rabies vaccine should be inoculated in different parts of the body contra-laterally if possible. In this case interference is minimized. AbhayRIG should not be administered in the same syringe as the vaccine.

FIRST-AID TREATMENT: All the areas of the body and the bite or scratch site which may be infected with rabies virus should be immediately and thoroughly washed with soap or detergent with running water and 70% alcohol or an iodine preparation is applied. AbhayRIG should be injected as soon as possible in case of suspected exposure. ------------------------------------------------------------------------------------------------------------------DOSAGE AND ADMINISTRATION OF ABHAYRIG:

For Prevention of rabies, combined immunoglobulin and rabies vaccine treatment is recommended for all Category III exposure as per WHO classification of Exposure. The recommended dose of AbhayRIG is 40 IU/Kg. of body weight infiltrated in and around the wound as much as anatomically feasible. Administer the remainder of the dose, if any by deep intramuscular injection at a site separate from that used for the vaccine. Ensure that the wound has been adequately infiltrated with immunoglobulin locally before suturing, if suturing is necessary. The first dose of the vaccine should be inoculated at the same time as that of AbhayRIG, but at a different site on the body. In no cases should the dosage of AbhayRIG be exceeded because immunoglobulin may partially suppress active production of antibodies. Children and adults receive the same dose of 40 IU/Kg of body weight. Incase the volume of AbhayRIG is low or insufficient for infiltration in case of a child or in case of large bite site then it can be diluted in normal saline.When indicated, begin anti-tetanus treatment and administer antimicrobial drugs to control infections other than rabies. Discard any unused portion. ------------------------------------------------------------------------------------------------------------------UNDESIRABLE EFFECTS: Immediate or delayed hypersensitive type reactions may be developed on administration of AbhayRIG. The observed immediate reactions are anaphylactoid reactions with hypotension, dyspnea, urticaria. Delayed reactions consist of inflammatory reaction, fever, pruritis, rash or urticaria, adenopathy and arthralagia. Inform your doctor or pharmacist if you experience any undesirable effect. ------------------------------------------------------------------------------------------------------------------STORAGE CONDITIONS : Store at a temperature between 2*C and 8*C in a refrigerator. DO NOT FREEZE. ------------------------------------------------------------------------------------------------------------------PRESENTATION : Vials of 5 ml, Each vial contains 300IU/ml of equine anti-rabies immunoglobulin.