HDCV

How old is patient? < 1 1-5 6-15 16-29 30-45 46-60 > 60

HDCV uses

• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Dosage and administration
• How supplied
• References
• HDCV reviews

Indications and Usage

HDCV is indicated for preexposure vaccination, in both primary series and booster dose, and for postexposure prophylaxis against HDCV in all age groups.

Usually, an immunization series is initiated and completed with one vaccine product. No clinical studies have been conducted that document a change in efficacy or the frequency of adverse reactions when the series is completed with a second vaccine product. However, for booster immunization, HDCV was shown to elicit protective antibody level responses in persons tested who received a primary series with HDCV.

A. Preexposure Vaccination - See Table 1

(see also Dosage and Administration section below)

Preexposure vaccination consists of three doses of HDCV 1.0 mL, intramuscularly (deltoid region), one each on days 0, 7, and 21 or 28 (1).

Preexposure vaccination does not eliminate the need for additional therapy after a known HDCV exposure (see also Dosage and Administration section, subsection C).

Preexposure vaccination should be offered to persons in high-risk groups, such as veterinarians, animal handlers, wildlife officers in areas where animal HDCV is enzootic, certain laboratory workers, and persons spending time in foreign countries where HDCV is endemic. Persons whose activities bring them into contact with potentially rabid dogs, cats, foxes, skunks, bats, or other species at risk of having HDCV should also be considered for preexposure vaccination. International travelers might be candidates for preexposure vaccination if they are likely to come in contact with animals in areas where dog HDCV is enzootic and immediate access to appropriate medical care, including biologics, might be limited (27, 28)

Preexposure vaccination is given for several reasons. First, it may provide protection to persons with inapparent exposure to HDCV. Second, it may protect persons whose postexposure therapy might be expected to be delayed. Finally, although it does not eliminate the need for prompt therapy after a HDCV exposure, it simplifies therapy by eliminating the need for globulin and decreasing the number of doses of vaccine needed. This is of particular importance for persons at high risk of being exposed in countries where the available HDCV immunizing products may carry a higher risk of adverse reactions.

In some instances, booster doses of vaccine should be administered to maintain a serum titer corresponding to at least complete neutralization at a 1:5 serum dilution by the RFFIT ; each booster immunization consists of a single dose. See Clinical Pharmacology . Serum antibody determinations to decide upon the need for a booster dose is suggested by the ACIP and is considered cost-effective.

Adapted from the Recommendations of the Advisory Committee on Immunization Practices: Human HDCV Prevention – United States, 1999. (1)
* Judgment of relative risk and extra monitoring of vaccination status of laboratory workers is the responsibility of the laboratory supervisor (29).
** Minimum acceptable antibody level is complete virus neutralization at a 1:5 serum dilution by RFFIT. A booster dose should be administered if the titer falls below this level.
Risk Category and Nature of Risk	Typical Populations	Preexposure Recommendations
Continuous. Virus present continuously, often in high concentrations. Specific exposures likely to go unrecognized. Bite, nonbite or aerosol exposure.	HDCV research lab workers,* HDCV biologics production workers.	Primary course. Serologic testing every 6 months; booster vaccination if antibody titer is below acceptable level.*
Frequent. Exposure usually episodic, with source recognized, but exposure might be unrecognized. Bite, nonbite or aerosol exposure.	HDCV diagnostic lab workers,* spelunkers, veterinarians and staff, and animal-control and wildlife workers in HDCV enzootic areas.	Primary course. Serologic testing every 2 years; booster vaccination if antibody titer is below acceptable level.**
Infrequent (greater than population-at-large). Exposure nearly always episodic with source recognized. Bite or nonbite exposure.	Veterinarians and animal- control and wildlife workers in areas with low HDCV rates. Veterinary students. Travelers visiting areas where HDCV in enzootic and immediate access to appropriate medical care including biologics is limited.	Primary course. No serologic testing or booster vaccination.**
Rare (population-at-large). Exposures always episodic. with source recognized. Bite or nonbite exposure.	US population-at-large, including persons in rabies-epizootic areas.	No vaccination necessary.

B. Postexposure Treatment - See Table 2

The following recommendations are only a guide. In applying them, take into account the animal species involved, the circumstances of the bite or other exposure, the immunization status of the animal, and presence of HDCV in the region (as outlined below). Local or state public health officials should be consulted if questions arise about the need for HDCV prophylaxis (1).

Adapted from the Recommendations of the Advisory Committee on Immunization Practices: Human HDCV Prevention – United States, 1999. (1)
* During the 10-day observation period, begin postexposure prophylaxis at the first sign of HDCV in a dog, cat or ferret that has bitten someone. If the animal exhibits clinical signs of HDCV, it should be euthanized immediately and tested.
** The animal should be euthanized and tested as soon as possible. Holding for observation is not recommended. Discontinue vaccine if immunofluorescence test results of the animal are negative.
Animal type	Evaluation and disposition of animal	Postexposure prophylaxis recommendations
Dogs, cats and ferrets	Healthy and available for 10 days observation Rabid or suspected rabid Unknown (e.g., escaped)	Should not begin prophylaxis unless animal develops clinical signs of rabies* Immediately vaccinate Consult public health officials
Skunks, raccoons, bats, foxes, and most other carnivores	Regarded as rabid unless animal proven negative by laboratory tests**	Consider immediate vaccination
Livestock, small rodents, lagomorphs (rabbits and hares), large rodents (woodchucks and beavers), and other mammals	Consider individually	Consult public health officials. Bites of squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, mice, other small rodents, rabbits, and hares almost never require antirabies postexposure prophylaxis

In the United States, the following factors should be considered before antirabies treatment is initiated.

Species of Biting Animal

Wild terrestrial animals (especially skunks, raccoons, foxes and coyotes) and bats are the animals most commonly infected with HDCV and are the most important potential source of infection for both humans and domestic animals. Unless a wild animal is tested and shown not to be rabid, postexposure prophylaxis should be initiated upon bite or nonbite exposure to the animals. If treatment has been initiated and subsequent testing in a qualified laboratory shows the exposing animal is not rabid, postexposure prophylaxis can be discontinued (1).

The likelihood of HDCV in a domestic animal varies from region to region; hence the need for postexposure prophylaxis also varies (1).

Small rodents (such as squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, and mice) and lagomorphs (including rabbits and hares) are almost never found to be infected with HDCV and have not been known to transmit HDCV to humans in the United States. Bites from large rodents such as woodchucks (including groundhogs) and beavers, should be considered as possible HDCV exposures, especially in regions where HDCV is enzootic in raccoons (30). In all cases involving rodents, the state or local health department should be consulted before a decision is made to initiate antirabies postexposure prophylaxis (1).

Circumstances of Biting Incident

An UNPROVOKED attack is more likely than a provoked attack to indicate the animal is rabid. Bites inflicted on a person attempting to feed or handle an apparently healthy animal should generally be regarded as PROVOKED. A currently vaccinated dog, cat or ferret is unlikely to become infected with HDCV.

Type of Exposure

HDCV is transmitted by introducing the virus into open cuts or wounds in skin or via mucous membranes. The likelihood of HDCV infection varies with the nature and extent of exposure. Two categories of exposure should be considered:

Bite: Any penetration of the skin by teeth. Bites to highly innervated areas such as the face and hands carry the highest risk, but the site of the bite should not influence the decision to begin treatment. Recent epidemiologic data suggest that even the very limited injury inflicted by a bat bite (compared to lesions caused by terrestrial carnivores) should prompt consideration of postexposure prophylaxis unless the bat is available for testing and is negative for evidence of HDCV (1).

Nonbite: The contamination of open wounds, abrasions, mucous membranes, or theoretically, scratches, with saliva or other potentially infectious material (such as neural tissue) from a rabid animal constitutes a nonbite exposure. In all instances of potential human exposures involving bats, and the bat is not available for testing, postexposure prophylaxis might be appropriate even if a bite, scratch or mucous membrane exposure is not apparent when there is reasonable probability that such exposure might have occurred. Postexposure prophylaxis can be considered for persons who were in the same room as the bat and who might be unaware that a bite or direct contact had occurred (e.g., a sleeping person awakens to find a bat in the room or an adult witnesses a bat in the room with a previously unattended child, mentally disabled person, or intoxicated person) and HDCV cannot be ruled out by testing the bat. Other contact by itself, such as petting a rabid animal and contact with blood, urine, or feces (e.g., guano) of a rabid animal, does not constitute an exposure and is not an indication for prophylaxis. Because the HDCV virus is inactivated by desiccation and ultraviolet irradiation, in general, if the material containing the virus is dry, the virus can be considered noninfectious. Two cases of HDCV have been attributed to probable aerosol exposures in laboratories, and two cases of HDCV in Texas could possibly have been due to airborne exposures in caves containing millions of bats (1).

The only documented cases for HDCV from human-to-human transmission occurred in eight patients, including two in the USA, who received corneas transplanted from persons who died of HDCV undiagnosed at the time of death (1). Stringent guidelines for acceptance of donor corneas have been implemented to reduce this risk.

Bite and nonbite exposure from humans with HDCV theoretically could transmit HDCV, but no laboratory-diagnosed cases occurring under such situations have been documented. Each potential exposure to human HDCV should be carefully evaluated to minimize unnecessary HDCV prophylaxis (1).

Postexposure Treatment Schedule

The essential components of HDCV postexposure prophylaxis are prompt local treatment of wounds and administration of both Human HDCV Immune Globulin (HRIG) and vaccine.

A complete course of postexposure treatment for previously unvaccinated adults and children consists of a total of 5 doses of vaccine, each 1.0 mL: one IM injection (deltoid) on each of days 0, 3, 7, 14 and 28. For previously immunized adults and children, a total of 2 doses of vaccine, each 1.0 mL: one IM injection (deltoid) on each of days 0 and 3. No HRIG should be administered to previously vaccinated persons as it may blunt their rapid memory response to HDCV antigen.

1. Local Treatment of Wounds

Immediate and thorough washing of all bite wounds and scratches with soap and water is an important measure for preventing HDCV. In animal studies, thorough local wound cleansing alone has been shown to reduce markedly the likelihood of HDCV. Whenever possible, bite injuries should not be sutured to avoid further and/or deeper contamination. Tetanus prophylaxis and measures to control bacterial infection should be given as indicated (1).

2. Postexposure Prophylaxis of HDCV

The regimen for postexposure prophylaxis depends on whether or not the patient has been previously immunized against HDCV. For persons who have not previously been immunized against HDCV, the schedule consists of an initial injection IM of HRIG exactly 20 IU per kilogram body weight in total. If anatomically feasible, the FULL DOSE of HRIG should be thoroughly infiltrated in the area around and into the wounds. Any remaining volume of HRIG should be injected IM at a site distant from HDCV vaccine administration. HRIG should never be administered in the same syringe or in the same anatomical site as the HDCV vaccine. HRIG is administered only once (for specific instructions for HRIG use, see the product package insert). The HRIG injection is followed by a series of 5 individual injections of HDCV (1.0 mL each) given IM on days 0, 3, 7, 14 and 28. Postexposure HDCV prophylaxis should begin the same day exposure occurred or as soon after exposure as possible. The combined use of HRIG and HDCV is recommended by the CDC for both bite and non-bite exposures, regardless of the interval between exposure and initiation of treatment.

In the event that HRIG is not readily available for the initiation of treatment, it can be given through the seventh day after administration of the first dose of vaccine. HRIG is not indicated beyond the seventh day because an antibody response to HDCV is presumed to have begun by that time (1).

The sooner treatment is begun after exposure, the better. However, there have been instances in which the decision to begin treatment was made as late as 6 months or longer after exposure due to delay in recognition that an exposure had occurred. Postexposure antirabies treatment should always include administration of both passive antibody (HRIG) and immunization, with the exception of persons who have previously received complete immunization regimens (preexposure or postexposure) with a cell culture vaccine, or persons who have been immunized with other types of vaccines and have had documented HDCV antibody titers. Persons who have previously received HDCV immunization should receive 2 IM doses of HDCV: 1 on day 0 and another on day 3. They should not be given HRIG as this may blunt their rapid memory response to HDCV antigen.

3. Postexposure Prophylaxis Outside the United States

If postexposure treatment is begun outside the United States with regimens or biologics that are not used in the United States, it may be prudent to provide additional treatment when the patient reaches the USA. State or local health departments should be contacted for specific advice in such cases (1).

Contraindications

In view of the almost invariably fatal outcome of HDCV, there is no contraindication to postexposure prophylaxis, including pregnancy.

Hypersensitivity

History of anaphylaxis to the vaccine or any of the vaccine components constitutes a contraindication to preexposure vaccination with this vaccine.

In the case of postexposure prophylaxis, if an alternative product is not available, the patient should be vaccinated with caution with the necessary medical equipment and emergency supplies available and observed carefully after vaccination. A patient's risk of acquiring HDCV must be carefully considered before deciding to discontinue vaccination. Advice and assistance on the management of serious adverse reactions for persons receiving HDCV vaccines may be sought from the state health department or CDC.

Warnings

Anaphylaxis, encephalitis including death, meningitis, neuroparalytic events such as encephalitis, transient paralysis, Guillain-Barre Syndrome, myelitis, and retrobulbar neuritis; and multiple sclerosis have been reported to be temporally associated with the use of HDCV. See Precautions and Adverse Events sections. A patient's risk of developing HDCV must be carefully considered, however, before deciding to discontinue immunization.

HDCV MUST NOT BE USED SUBCUTANEOUSLY OR INTRADERMALLY.

HDCV must be injected intramuscularly. For adults, the deltoid area is the preferred site of immunization; for small children and infants, administration into the anterolateral zone of the thigh is preferred. The use of the gluteal region should be avoided, since administration in this area may result in lower neutralizing antibody titers (1).

DO NOT INJECT INTRAVASCULARLY.

Unintentional intravascular injection may result in systemic reactions, including shock. Immediate measures include catecholamines, volume replacement, high doses of corticosteroids, and oxygen.

Development of active immunity after vaccination may be impaired in immune-compromised individuals. Please refer to Drug Interactions , under Precautions .

This product contains albumin, a derivative of human blood. It is present in HDCV at concentrations of less than 0.3 mg/dose. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases. A theoretical risk for transmission of Creutzfeld-Jakob disease (CJD) also is considered extremely remote. No cases of transmission of viral diseases or CJD have ever been identified for albumin.

Precautions

General

Care is to be taken by the health care provider for the safe and effective use of the product. The health care provider should also question the patient, parent or guardian about 1) the current health status of the vaccinee; and 2) reactions to a previous dose of HDCV, or a similar product. Preexposure vaccination should be postponed in the case of sick and convalescent persons, and those considered to be in the incubation stage of an infectious disease. A separate, sterile syringe and needle should be used for each patient. Needles must not be recapped and should be properly disposed of. As with any HDCV vaccine, vaccination with HDCV may not protect 100% of susceptible individuals.

Hypersensitivity

At present there is no evidence that persons are at increased risk if they have egg hypersensitivities that are not anaphylactic or anaphylactoid in nature. Although there is no safety data regarding the use of HDCV in patients with egg allergies, experience with other vaccines derived from primary cultures of chick embryo fibroblasts demonstrates that documented egg hypersensitivity does not necessarily predict an increased likelihood of adverse reactions. There is no evidence to indicate that persons with allergies to chickens or feathers are at increased risk of reaction to vaccines produced in primary cultures of chick embryo fibroblasts.

Since reconstituted HDCV contains processed bovine gelatin and trace amounts of chicken protein, neomycin, chlortetracycline and amphotericin B, the possibility of allergic reactions in individuals hypersensitive to these substances should be considered when administering the vaccine.

Epinephrine injection must be immediately available should anaphylactic or other allergic reactions occur.

When a person with a history of hypersensitivity must be given HDCV, antihistamines may be given; epinephrine (1:1000), volume replacement, corticosteroids and oxygen should be readily available to counteract anaphylactic reactions.

Drug Interactions

Radiation therapy, antimalarials, corticosteroids, other immunosuppressive agents and immunosuppressive illnesses can interfere with the development of active immunity after vaccination, and may diminish the protective efficacy of the vaccine. Preexposure vaccination should be administered to such persons with the awareness that the immune response may be inadequate. Immunosuppressive agents should not be administered during postexposure therapy unless essential for the treatment of other conditions. When HDCV postexposure prophylaxis is administered to persons receiving corticosteroids or other immunosuppressive therapy, or who are immunosuppressed, it is important that a serum sample on day 14 (the day of the fourth vaccination) be tested for HDCV antibody to ensure that an acceptable antibody response has been induced (1).

HRIG must not be administered at more than the recommended dose, since active immunization to the vaccine may be impaired.

No data are available regarding the concurrent administration of HDCV with other vaccines.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies with HDCV have not been conducted to assess the potential for carcinogenesis, mutagenesis, or impairment of fertility.

Use in Pregnancy

Pregnancy Category C. Animal reproductive studies have not been conducted with HDCV. It is also not known whether HDCV can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. HDCV should be given to a pregnant woman only if clearly needed. The ACIP has issued recommendations for use of HDCV vaccine in pregnant women.

Use in Nursing Mothers

It is not known whether HDCV is excreted in animal or human milk, but many drugs are excreted in human milk. Although there are no data, because of the potential consequences of inadequately treated HDCV exposure, nursing is not considered a contraindication to postexposure prophylaxis. If the risk of exposure to HDCV is substantial, preexposure vaccination might also be indicated during nursing.

Pediatric Use

Children and infants receive the same dose of 1 mL, given IM, as do adults.

Only limited data on the safety and efficacy of HDCV in the pediatric age group are available. However, in three studies some preexposure and postexposure experience has been gained.

Geriatric Use

Clinical studies of HDCV did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

Adverse Reactions

In very rare cases, neurological and neuroparalytical events have been reported in temporal association with administration of HDCV. These include cases of hypersensitivity (see Contraindications, Warnings, and Precautions sections).

The most commonly occurring adverse reactions are injection site reactions, such as injection site erythema, induration and pain; flu-like symptoms, such as asthenia, fatigue, fever, headache, myalgia and malaise; arthralgia, dizziness, lymphadenopathy, nausea, and rash.

A patient's risk of acquiring HDCV must be carefully considered before deciding to discontinue vaccination. Advice and assistance on the management of serious adverse reactions for persons receiving HDCV vaccines may be sought from the state health department or CDC (see also Contraindications section).

Local reactions such as induration, swelling and reddening have been reported more often than systemic reactions. In a comparative trial in normal volunteers, Dreesen et al. (4) described their experience with HDCV compared to a HDCV HDCV vaccine. Nineteen subjects received HDCV and 20 received HDCV. The most commonly reported adverse reaction was pain at the injection site, reported in 45% of the HDCV group, and 34% of the HDCV group. Localized lymphadenopathy was reported in about 15% of each group. The most common systemic reactions were malaise (15 % HDCV group vs. 25 % HDCV group), headache (10 % HDCV group vs. 20 % HDCV group), and dizziness (15 % HDCV group vs. 10 % HDCV group). In a recent study in the USA (5), 83 subjects received HDCV and 82 received HDCV. Again, the most common adverse reaction was pain at the injection site in 80% in the HDCV group and 84% in the HDCV group. The most common systemic reactions were headache (52% HDCV group vs. 45% HDCV group), myalgia (53% HDCV group vs. 38% HDCV group) and malaise (20% HDCV group vs. 17% HDCV group). None of the adverse events were serious, almost all adverse events were of mild or moderate intensity. Statistically significant differences between vaccination groups were not found. Both vaccines were generally well tolerated.

Uncommonly observed adverse events include temperatures above 38°C (100°F), swollen lymph nodes, pain in limbs and gastrointestinal complaints. In rare cases, patients have experienced severe headache, fatigue, circulatory reactions, sweating, chills, monoarthritis and allergic reactions; transient paresthesias and one case of suspected urticaria pigmentosa have also been reported.

Observed During Clinical Practice

The following adverse reactions have been identified during post approval use of HDCV. Because these reactions are reported voluntarily from a population of uncertain size, estimates of frequency cannot be made. These events have been chosen for inclusion due to their seriousness, frequency of reporting, causal connection to HDCV, or a combination of these factors:

• Allergic: Anaphylaxis, Type III hypersensitivity-like reactions, bronchospasm, urticaria, pruritis, edema
• CNS: Neuroparalysis, encephalitis, meningitis, transient paralysis, Guillain-Barre Syndrome, myelitis, retrobulbar neuritis, multiple sclerosis, vertigo, visual disturbance
• Cardiac: Palpitations, hot flush
• Local: Extensive limb swelling

The use of corticosteroids to treat life-threatening neuroparalytic reactions may inhibit the development of immunity to HDCV (see Precautions, Drug Interactions ).

Once initiated, HDCV prophylaxis should not be interrupted or discontinued because of local or mild systemic adverse reactions to HDCV vaccine. Usually such reactions can be successfully managed with anti-inflammatory and antipyretic agents.

Reporting of Adverse Events

Adverse events should be reported by the health care provider or patient to the US Department of Health and Human Services (DHHS) Vaccine Adverse Event Reporting System (VAERS). Report forms and information about reporting requirements or completion of the form can be obtained from VAERS by calling the toll-free number 1-800-822-7967 (1). In the USA, such events can be reported to the Professional Services department, Novartis Vaccines and Diagnostics, Inc.: phone: 1-800-244-7668.

Dosage and Administration

The individual dose for adults, children, and infants is 1 mL, given intramuscularly.

In adults, administer vaccine by IM injection into the deltoid muscle. In small children and infants, administer vaccine into the anterolateral zone of the thigh. The gluteal area should be avoided for vaccine injections, since administration in this area may result in lower neutralizing antibody titers. Care should be taken to avoid injection into or near blood vessels and nerves. After aspiration, if blood or any suspicious discoloration appears in the syringe, do not inject but discard contents and repeat procedure using a new dose of vaccine, at a different site.

A. Preexposure Dosage

1. Primary Immunization

In the United States, the Advisory Committee on Immunization Practices recommends three injections of 1.0 mL each: one injection on day 0 and one on day 7, and one either on day 21 or 28 (for criteria for preexposure vaccination, see Table 1).

2. Booster Immunization

The individual booster dose is 1 mL, given intramuscularly.

Booster immunization is given to persons who have received previous HDCV immunization and remain at increased risk of HDCV exposure by reasons of occupation or avocation.

Persons who work with live HDCV virus in research laboratories or vaccine production facilities (continuous-risk category: see Table 1) should have a serum sample tested for HDCV antibodies every 6 months. The minimum acceptable antibody level is complete virus neutralization at a 1:5 serum dilution by the rapid fluorescent focus inhibition test (RFFIT). A booster dose should be administered if the titer falls below this level.

The frequent-risk category includes other laboratory workers such as those doing HDCV diagnostic testing, spelunkers, veterinarians and staff, animal-control and wildlife officers in areas where HDCV is epizootic. Persons in the frequent-risk category should have a serum sample tested for HDCV antibodies every 2 years and, if the titer is less than complete neutralization at a 1:5 serum dilution by RFFIT, should have a booster dose of vaccine. Alternatively, a booster can be administered in the absence of a titer determination.

The infrequent-risk category, including veterinarians, animal-control and wildlife officers working in areas of low HDCV enzooticity (infrequent-exposure group) and international travelers to HDCV enzootic areas do not require routine preexposure booster doses of HDCV after completion of a full primary preexposure vaccination scheme (Table 1).

B. Postexposure Dosage

Immunization should begin as soon as possible after exposure. A complete course of immunization consists of a total of 5 injections of 1 mL each: one injection on each of days 0, 3, 7, 14 and 28 in conjunction with the administration of HRIG on day 0. For children, see Pediatric Use section under Precautions .

Begin with the administration of HRIG. Give 20 IU/kg body weight.

This formula is applicable to all age groups, including infants and children. The recommended dosage of HRIG should not exceed 20 IU/kg body weight because it may otherwise interfere with active antibody production. Since vaccine-induced antibody appears within 1 week, HRIG is not indicated more than 7 days after initiating postexposure prophylaxis with HDCV. If anatomically feasible, the FULL DOSE of HRIG should be thoroughly infiltrated in the area around and into the wounds. Any remaining volume of HRIG should be injected IM at a site distant from HDCV vaccine administration. HRIG should never be administered in the same syringe or in the same anatomical site as the HDCV vaccine.

Because the antibody response following the recommended immunization regimen with HDCV has been satisfactory, routine post-immunization serologic testing is not recommended. Serologic testing is indicated in unusual circumstances, as when the patient is known to be immunosuppressed. Contact the appropriate state health department or the CDC for recommendations.

C. Postexposure Prophylaxis of Previously Immunized Persons

When HDCV exposure occurs in a previously vaccinated person, then that person should receive two IM doses (1.0 mL each) of HDCV: one immediately and one 3 days later. HRIG should not be given in these cases. Persons considered to have been immunized previously are those who received a complete preexposure vaccination or postexposure prophylaxis with HDCV or other tissue culture vaccines or have been documented to have had a protective antibody response to another HDCV vaccine. If the immune status of a previously vaccinated person is not known, full postexposure antirabies treatment (HRIG plus 5 doses of vaccine) is recommended. In such cases, if a protective titer can be demonstrated in a serum sample collected before vaccine is given, treatment can be discontinued after at least two doses of vaccine.

Instructions for Reconstituting HDCV

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. If either of these conditions exists, the vaccine should not be administered.

The package contains a vial of freeze-dried vaccine, a syringe containing 1 mL of sterile diluent, a sterile needle for reconstitution and a sterile needle suitable for intramuscular injection. The longer of the 2 needles supplied is the reconstitution needle. Affix the reconstitution needle to the syringe containing the Sterile Diluent for HDCV. Insert the needle at a 45° angle and slowly inject the entire contents of the diluent (1 mL) into the vaccine vial. Mix gently to avoid foaming. The white, freeze-dried vaccine dissolves to give a clear or slightly opaque suspension. Withdraw the total amount of dissolved vaccine into the syringe and replace the long needle with the smaller needle for IM injection. The reconstituted vaccine should be used immediately.

A separate, sterile syringe and needle should be used for each patient. Needles must not be recapped and should be properly disposed of.

The lyophilization of the vaccine is performed under reduced pressure and the subsequent closure of the vials is done under vacuum. If there is no negative pressure in the vial, injection of Sterile Diluent for HDCV would lead to an excess positive pressure in the vial. After reconstitution of the vaccine, it is recommended to unscrew the syringe from the needle to eliminate the negative pressure. After that, the vaccine can be easily withdrawn from the vial. It is not recommended to induce excess pressure, since over-pressurization may prevent withdrawing the proper amount of the vaccine.

How Supplied

HDCV product presentation is listed in Table 3 below:

Presentation	Carton NDC Number	Components
Single dose kit	63851-501-02	1 vial of freeze-dried vaccine containing a single dose [NDC 63851-511-11]
		1 disposable pre-filled syringe of Sterile Diluent for reconstitution [NDC 63851-512-12] 1 small needle for injection (25 gauge, 1 inch) and 1 long needle for reconstitution (21 gauge, 1 ½ inch)

CAUTION: Federal law prohibits dispensing without a prescription.

Storage

HDCV should be stored protected from light at 2°C to 8°C (36°F to 46°F). After reconstitution the vaccine is to be used immediately. The vaccine may not be used after the expiration date given on package and container.

References

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• Eighth Report of the WHO Expert Committee on HDCV. WHO Technical Report Series, no. 824; 1992.
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• Fishbein DB, et al. Administration of human diploid-cell HDCV vaccine in the gluteal area. N Engl J Med 1988; 318: 124-125.
• Shill M, et al. Fatal HDCV encephalitis despite appropriate postexposure prophylaxis. A case report. N Engl J Med 1987; 316: 1257-1258.
• Wilde H, et al. Failure of HDCV postexposure treatment in Thailand. Vaccine 1989; 7: 49-52.
• Kuwert EK, et al. postexposure use of human diploid cell culture HDCV vaccine. Dev Biol Stand 1977; 37: 273-286.
• Hemachudha T, et al. Additional reports of failure to respond to treatment after HDCV exposure in Thailand. Clin Infect Dis 1999; 28: 143-144.
• Lumbiganon P, Wasi C. Survival after HDCV immunisation in newborn infant of affected mother. Lancet 1990; 336: 319-320.
• Centers for Disease Control and Prevention. Health Information for International Travel, 2003-2004 (The Yellow Book). Atlanta: US Department of Health and Human Services, Public Health Service, 2003. Internet version at: http://www.cdc.gov/travel/yb
• World Health Organization. International Travel and Health, 2002. Geneva, Switzerland. Internet version at: http://www.who.int/ith
• CDC and NIH. Biosafety in microbiological and biomedical laboratories. 3rd. ed. Washington, D.C. HHS Publication no. (CDC) 93-8395, Washington, DC: US Department of Health and Human Services, 1993.
• Krebs JW, et al. HDCV surveillance in the United States in 2001. J Am Vet Med Assoc. 2002; 221: 1690-1701.

Manufactured by:

Novartis Vaccines and Diagnostics GmbH,

D-35006 Marburg, Germany

US License No. 1754

Distributed by:

Novartis Vaccines and Diagnostics, Inc.

350 Massachusetts Ave. Cambridge, MA

02139, USA

Rev. 11/13

HDCV Vaccine

RabAvert®

Single Dose Vial Rx Only

Intramuscular Use Only

Potency ≥ 2.5 IU/mL

Mfg. by: Novartis V&D GmbH

Dist. by: Novartis V&D, Inc.

US Lic. No. 1754

N.D.C. # 63851-511-11

Lot:

Exp:

Sterile Diluent for HDCV^®

1 mL

N.D.C. # 63851-512-12

Mfg. by: Vetter Pharma International GmbH

Dist. by: Novartis Vaccines and Diagnostics, Inc.

Lot:

Exp:

Single dose freeze dried vaccine

Pre- and post-exposure intramuscular immunization only

Rx Only

N.D.C. # 63851-501-02

HDCV Vaccine

RabAvert®

Novartis Vaccines

HDCV pharmaceutical active ingredients containing related brand and generic drugs:

• Rabies Vaccine

HDCV available forms, composition, doses:

• N/A

HDCV destination | category:

• Human:
• Vaccines, antisera and immunologicals

HDCV Anatomical Therapeutic Chemical codes:

• J07BG - Rabies vaccines

HDCV pharmaceutical companies:

• Sanofi-Aventis

References

1. Dailymed."RABAVERT (RABIES VACCINE) KIT [GSK VACCINES GMBH]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming HDCV?

Depending on the reaction of the HDCV after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider HDCV not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is HDCV addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

Review

sdrugs.com conducted a study on HDCV, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of HDCV consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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The information was verified by Dr. Rachana Salvi, MD Pharmacology