Vaccine Information: BCG VACCINE (Page 2 of 3)

PRECAUTIONS

General

BCG VACCINE contains live bacteria and should be used with aseptic technique. To avoid cross-contamination, parenteral drugs should not be prepared in areas where BCG VACCINE has been in use.{19} A separate sterile multiple puncture device must be used for each patient and appropriately discarded after use. All equipment, supplies and receptacles in contact with BCG VACCINE should be handled and disposed of as biohazardous (see DOSAGE AND ADMINISTRATION).

BCG VACCINE administration should not be attempted in individuals with severe immune deficiency disease. BCG VACCINE should be administered with caution to persons in groups at high risk for HIV infection.

A review of each patient’s immunization records to include history on reactions to immunizations should be completed prior to vaccination. All precautions should be taken for the prevention of allergic or any other side reactions, including understanding the use of the biological and the nature of the adverse reactions that may follow its use. Epinephrine injection (1:1000) for the control of immediate allergic reactions must be available should an acute anaphylactic reaction occur.

Vaccination is recommended only for those who are tuberculin negative to a recent skin test with 5 TU.

After BCG vaccination, it is usually not possible to clearly distinguish between a tuberculin reaction caused by persistent post-vaccination sensitivity and one caused by a virulent suprainfection. Caution is advised in attributing a positive skin test to BCG vaccination. A sharp rise in the tuberculin reaction since the latest test should be further investigated (except in the immediate post-vaccination period).

Information for Patients

Before administration of BCG VACCINE, health care personnel should inform patients or guardians of the benefits and risks of immunization and inquire about the health status of the patient. Health care workers considering BCG vaccination should be counseled regarding the risks and benefits associated with both BCG vaccination and TB preventive therapy. They should be informed about (a) the variable data concerning the efficacy of BCG vaccination, (b) the interference with the diagnosis of newly acquired M. tuberculosis infections in BCG-vaccinated persons, and (c) the potential serious complications associated with BCG vaccination of immunocompromised individuals. Health care workers should be informed about (a) the lack of data regarding the efficacy of preventive therapy for MDR-TB infections and (b) the risks of drug toxicity associated with multi-drug preventive therapy regimens.

Following BCG vaccination, no dressing is required; however, it is recommended that the site be loosely covered and kept dry for 24 hours. The vaccination site should be kept clean until the local reaction has disappeared. The patient should be advised that the vaccine contains live organisms. Although the vaccine will not survive in a dry state for long, infection of others is possible. Following vaccination with BCG, initial skin lesions usually appear within 10–14 days and consist of small red papules at the vaccination site. The papules reach a maximum diameter (about 3 mm) after 4 to 6 weeks, after which they may scale and slowly subside. Six months afterwards there is usually no visible sign of the vaccination, though on occasion, a faintly discernible pattern of the points from the multiple puncture device may be visible. On individuals whose skin tends to form keloids, there may be slightly more visible evidence of the vaccination. Any unusual adverse reactions should be reported to the health care provider.

Patients may experience “flu-like” symptoms for 24–48 hours following BCG vaccination. However, the patient should consult with their physician immediately if they experience fever of 103°F or greater, or acute local reactions persisting longer than 2–3 days.

Laboratory Tests

BCG vaccination results in tuberculin skin test reactivity. Tuberculin skin test reactivity as a result of BCG vaccination cannot be readily differentiated from reactivity following exposure to tuberculosis. BCG vaccination should not be administered to individuals with a positive tuberculin skin test.

Prior administration of BCG vaccine has not been associated with a positive interferon gamma release assay (IGRA) test, which are indirect tests for M. tuberculosis infection (including disease) and are intended for use in conjunction with risk assessment, radiography and other medical and diagnostic evaluations.{20,21}

Drug Interactions

Antimicrobial or immunosuppressive agents may interfere with the development of the immune response and should be used only under medical supervision.

Since BCG is a live vaccine, the immune response to the vaccine might be impaired if administered within 30 days of another live vaccine. However, no evidence exists for currently available vaccines to support this concern. Whenever possible, live vaccines administered on different days should be administered at least 30 days apart.{22}

Carcinogenesis, Mutagenesis, Impairment of Fertility

BCG VACCINE has not been evaluated for carcinogenic, mutagenic potentials or impairment of fertility.

Pregnancy

Animal reproduction studies have not been conducted with BCG VACCINE. It is also not known whether BCG VACCINE can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Although no harmful effects to the fetus have been associated with BCG VACCINE, its use is not recommended during pregnancy.{3}

Nursing Mothers

It is not known whether BCG is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions from BCG in nursing infants, a decision should be made whether to discontinue nursing or not to vaccinate, taking into account the importance of tuberculosis vaccination to the mother.

Pediatric Use

See Treatment and Schedule under DOSAGE AND ADMINISTRATION section. Precautions should be taken with respect to infants vaccinated with BCG and exposed to persons with active tuberculosis.{23}

Geriatric Use

Clinical studies of BCG VACCINE 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 response between elderly and younger patients. An intact immune system is a prerequisite for BCG vaccination. If the immune status of an elderly patient, or any patient, is in question, the BCG vaccination should be held until the immune status of the patient has been evaluated.

ADVERSE REACTIONS

Although BCG vaccination often causes local reactions, serious or long-term complications are rare.{3} Reactions that can be expected after vaccination include moderate axillary or cervical lymphadenopathy and induration and subsequent pustule formation at the injection site; these reactions can persist for as long as 3 months after vaccination. More serious local reactions include ulceration at the vaccination site, regional suppurative lymphadenitis with draining sinuses, and caseous lesions or purulent draining at the puncture site. These manifestations might occur up to 5 months after vaccination and could persist for several weeks. The intensity and duration of the local reaction depends on the depth of penetration of the multiple puncture device and individual variations in patients’ tissue reactions. Slight tenderness at the puncture site may be encountered as well as some itching. The initial skin lesions usually appear within 10–14 days and consist of small red papules at the site. The papules reach maximum diameter (about 3 mm) after 4 to 6 weeks, after which they may scale and then slowly subside.

The most serious complication of BCG vaccination is disseminated BCG infection.{24,25} The most frequent disseminated infection is BCG osteomyelitis (0.01 to 43 cases per million doses of vaccine administered) which usually occurs 4 months to 2 years after vaccination. Fatal disseminated BCG infection has occurred at a rate of 0.06–1.56 cases per million doses; these deaths occurred primarily among immunocompromised persons.

BCG Vaccination of Individuals Infected with HIV

The safety of BCG vaccination in HIV-infected adults and children, including infants, has not been determined by controlled or large studies. This is a concern because of the association between disseminated BCG infection and underlying immunosuppression. Individuals with HIV infection should not receive the BCG VACCINE.{3}

Treatment of Adverse Reactions

If a systemic BCG infection occurs, an infectious disease expert should be consulted and anti-tuberculosis therapy should be initiated. Since BCG strains are resistant to pyrazinamide, this antibiotic should not be used.

Reporting of Adverse Reactions

All suspected adverse reactions to BCG vaccination should be reported to Merck Sharp & Dohme LLC, Rahway, NJ USA at 1-877-888-4231 and to the Vaccine Adverse Event Reporting System (VAERS); telephone 1-800-822-7967. These reactions occasionally could occur more than 1 year after vaccination.

OVERDOSAGE

Accidental overdosages if treated immediately with anti-tuberculous drugs have not led to complications.{26} If the vaccination response is allowed to progress it can still be treated successfully with anti-tuberculous drugs but complications can include regional adenitis, lupus vulgaris, subcutaneous cold abscesses, ocular lesions, and others.{27}

DOSAGE AND ADMINISTRATION

Preparation of Agent

The preparation of the BCG VACCINE suspension should be done using aseptic technique. To avoid cross-contamination, parenteral drugs should not be prepared in areas where BCG VACCINE has been prepared. A separate area for the preparation of the BCG VACCINE suspension is recommended. All equipment, supplies and receptacles in contact with BCG VACCINE should be handled and disposed of as biohazardous. The pharmacist or individual responsible for mixing the agent should wear gloves and take precautions to avoid contact of BCG with broken skin. If preparation cannot be performed in a biocontainment hood, then a mask and gown should be worn to avoid inhalation of BCG organisms and inadvertent exposure to broken skin.

Using aseptic methods, 1 mL of Sterile Water for Injection, USP at 4-25°C (39-77°F), is added to one vial of vaccine (see Pediatric Dose below for pediatric use). Gently swirl the vial until a homogenous suspension is obtained. Avoid forceful agitation which may cause clumping of the mycobacteria.

Persons administering vaccines should take necessary precautions to minimize risk for spreading disease. Hands should be washed before each new patient is seen. Syringes and needles used for applications must be sterile and preferably disposable to minimize the risk of contamination. A separate needle and syringe should be used for each application. Disposable needles and the multiple puncture device should be discarded as biohazardous waste in labeled, puncture-proof containers to prevent inadvertent needlestick injury or reuse.{22} After use, any unused vaccine and all materials exposed to the product should be immediately placed in a biohazard container and disposed of in an appropriate manner.

Reconstituted vaccine should be kept refrigerated, protected from exposure to direct sunlight, and used within 2 hours. Freezing of the reconstituted product is not recommended. Discard unused portion.

Note: DO NOT filter the contents of the BCG VACCINE vial. Precautions should be taken to avoid exposing the BCG VACCINE to direct sunlight. Bacteriostatic solutions must be avoided. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Reconstitution should result in a uniform suspension of the bacilli.

Treatment and Schedule

BCG vaccination is reserved for persons who have a reaction of less than 5mm induration after skin testing with 5 TU of PPD tuberculin. The preferred method of skin testing is the Mantoux tuberculin skin-test using 0.1 mL of 5 tuberculin units (TU) of PPD.{3} It is recommended that a Mantoux skin-test be performed prior to BCG vaccination to demonstrate the absence of tuberculous infection.

The vaccine is to be administered after fully explaining the risks and benefits to the vaccinee, parent, or guardian. BCG vaccination should not be given to individuals previously infected with M. tuberculosis. The vaccine is administered percutaneously utilizing a sterile, single-use multiple puncture device. The multiple puncture device consists of a plastic holder for a thin, wafer-like stainless steel plate from which 36 points protrude (Figure 1). After the vaccine is prepared, the skin site is cleansed with an alcohol or acetone sponge and allowed to dry thoroughly.

Figure 1

1.

Administer the vaccine in the deltoid region (Figure 2). Position the arm to maintain a horizontal surface where the vaccine is to be placed.

Figure 2

2.

Drop the immunizing dose of 0.2–0.3 mL of BCG VACCINE from the syringe and needle onto the cleansed surface of the skin (Figure 3) and spread over a 1″ by 2″ area using the smooth edge of the multiple puncture device (Figure 4).

Figure 3

Figure 4

3.

Grasp the arm firmly from underneath, tensing the skin. Center the multiple puncture device over the vaccine and apply firm downward pressure such that the device points are well buried in the skin (Figure 5).

Figure 5

4.

Maintain pressure for 5 seconds. Do not “rock” the device. Release the pressure underneath the arm and remove the device. In a successful procedure the points puncture the skin. If the points do not puncture the skin, the puncture procedure must be repeated.

5.

After successful puncture, spread vaccine as evenly as possible over the puncture area with the smooth edge of the device (Figure 4). An additional 1–2 drops of BCG VACCINE may be added to ensure a very wet vaccination site.

6.

Use the multiple puncture device once and discard in a standard biohazardous sharps container.

7.

Loosely cover the site and keep dry for 24 hours.

8.

Advise the patient that the vaccine contains live organisms. Although the vaccine will not survive in a dry state for long, infection of others is possible.

Tuberculin reactivity resulting from BCG vaccination should be documented. A vaccinated person should be tuberculin skin tested 2–3 months after BCG administration, and the test results, in millimeters of induration, should be recorded in the person’s medical record.{9} Vaccination should be repeated for those who remain tuberculin negative to 5 TU of tuberculin after 2–3 months.