Administration should be by the percutaneous route with the multiple puncture device as described below. DO NOT INJECT INTRAVENOUSLY, SUBCUTANEOUSLY, OR INTRADERMALLY.
Although BCG vaccination often results in local adverse effects, serious or long-term complications are rare. 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 severe local reactions include ulceration at the vaccination site, regional suppurative lymphadenitis with draining sinuses, and caseous lesions or purulent drainage at the puncture site; these manifestations might occur within the 5 months after vaccination and could persist for several weeks.
Acute, localized irritative toxicities of BCG may be accompanied by systemic manifestations, consistent with a "flu-like" syndrome. Systemic adverse effects of 12 days' duration such as fever, anorexia, myalgia, and neuralgia, often reflect hypersensitivity reactions. However, symptoms such as fever of 103°F or greater, or acute localized inflammation persisting longer than 23 days suggest active infections, and evaluation for serious infectious complication should be considered. If a BCG infection is suspected, the physician should consult with an infectious disease expert before therapy is initiated. Treatment should be started without delay. In patients who develop persistent fever or experience an acute febrile illness consistent with BCG infection, two or more antimycobacterial agents should be administered while diagnostic evaluation, including cultures, is conducted. Negative cultures do not necessarily rule out infection. Physicians or persons caring for patients that use this product should be familiar with the literature on prevention, diagnosis, and treatment of BCG-related complications and, when appropriate, should consult an infectious disease specialist or other physician with experience in the diagnosis and treatment of mycobacterial infections.
The most serious complication of BCG vaccination is disseminated BCG infection. BCG osteitis affecting the epiphyses of the long bones, particularly the epiphyses of the leg, can occur from 4 months to 2 years after vaccination. Fatal disseminated BCG disease has occurred at a rate of 0.061.56 cases per million doses of vaccine administered; these deaths occurred primarily among immunocompromised persons.3 The appropriate therapy for systemic BCG infections is discussed in the ADVERSE REACTIONS section.
BCG VACCINE contains live bacteria and should be used with aseptic technique. To avoid crosscontamination, 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 to the Patient
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 1014 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 discernable 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 2448 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 23 days.
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.
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.20
Carcinogenesis, Mutagenesis, Impairment of Fertility
BCG VACCINE has not been evaluated for carcinogenic, mutagenic potentials or impairment of fertility.
Pregnancy Category C
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
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.
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.21
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.