BCG Vaccine (Monograph)

Drug class: Vaccines

Introduction

Lyophilized preparation of live, attenuated organisms of the Calmette-Guérin strain of Mycobacterium bovis; stimulates active immunity to tuberculosis infection.¹

Uses for BCG Vaccine

Tuberculosis Prevention

Used for prevention of tuberculosis (TB) in individuals not previously infected with M. tuberculosis who are at high risk for exposure.^{1 110}

BCG vaccine is not routinely used in the US because of low risk of M. tuberculosis infection in the overall US population, variable effectiveness against pulmonary TB in adults, and potential for causing false-positive TB skin test reactions, which can complicate management of M. tuberculosis infection.^{1 110 111}

Widespread implementation of TB infection control measures in the US has successfully decreased outbreaks in the healthcare setting and decreased healthcare-associated transmission of M. tuberculosis.¹¹¹

The US Centers for Disease Control and Prevention (CDC) provides recommendations for the use of BCG vaccination in the US.¹¹⁰ The most current CDC guidelines recommend the use of BCG vaccine only in selected individuals who meet specific criteria and in consultation with a TB expert.¹¹⁰

CDC states that BCG vaccination should only be considered for children who have a negative TB test who are continuously exposed and cannot be separated from adults who are untreated or ineffectively treated for TB disease and who cannot be given long-term primary preventive treatment for TB infection; or have isoniazid- and rifampin-resistant strains of TB.¹¹⁰ BCG vaccination also should be considered in certain healthcare personnel on an individual basis in settings where the likelihood of transmission and subsequent infection with drug-resistant strains of M. tuberculosis is high and comprehensive TB infection control precautions in the workplace have been unsuccessful.¹¹⁰

Healthcare providers can consult their state or local TB control program for additional information regarding BCG vaccination for patients.¹¹⁰

BCG Vaccine Dosage and Administration

General

Pretreatment Screening

• Prior to administration, review a patient's immunization records for a history of vaccine hypersensitivity and assess the possibility of experiencing an allergic reaction to BCG vaccine.¹

• A Mantoux skin test is recommended prior to BCG vaccination to demonstrate the absence of tuberculous infection.¹

Dispensing and Administration Precautions

Handling and Disposal

• BCG vaccine contains live organisms.¹ All equipment and supplies in contact with the vaccine should be handled and disposed of properly in biohazardous containers.¹

• Individuals who prepare the vaccine should take necessary precautions to minimize the risk of spreading disease including wearing gloves and avoiding contact of BCG with broken skin.¹ If vaccine 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.¹

• Ensure that epinephrine injection (1:1000) is readily available in the event of an acute anaphylactic reaction.¹

Administration

Administer percutaneously in the deltoid region using a sterile, single-use, multiple-puncture device; do not administer IM, IV, sub-Q, or intradermally.¹

Commercially available as a lyophilized powder; reconstitute powder prior to administration.¹ To prepare an adult dose, reconstitute vaccine by adding 1 mL of sterile water for injection to one single-dose vial of the vaccine.¹ To prepare a pediatric dose, reconstitute vaccine by adding 2 mL of sterile water for injection to one single-dose vial of the vaccine.¹ Gently swirl vial until a homogenous suspension is obtained; avoid forceful agitation.¹

Do not filter contents of the vial.¹

To administer, prepare and clean skin; drop the immunizing dose (0.2–0.3 mL) of BCG onto surface of the skin and spread over a 1 by 2 inch area using the multiple-puncture device.¹ An additional 1–2 drops of the vaccine may be added to ensure a very wet vaccination site.¹ Loosely cover site and keep dry for 24 hours after administration.¹

Dosage

Pediatric Patients

Prevention of Tuberculosis

Percutaneous

Children ≥1 month of age: usual dose is 0.2–0.3 mL.¹

Neonates <1 month of age: decrease usual dose by 50% by reconstituting the vaccine with 2 mL instead of 1 mL of sterile water for injection without preservatives.¹ If indications for BCG vaccine persist and the neonate has an insignificant reaction to the tuberculin skin test, administer a full dose of the vaccine after 1 year of age.¹

Administer tuberculin skin test 2–3 months after BCG administration, and record test results (in mm of induration) in the medical record.¹ Repeat vaccination for those who remain tuberculin negative to 5 TU of tuberculin after 2–3 months.¹

Adults

Prevention of Tuberculosis

Percutaneous

Usual dose is 0.2–0.3 mL.¹

Administer tuberculin skin test 2–3 months after BCG administration, and record test results (in mm of induration) in the medical record.¹ Repeat vaccination for those who remain tuberculin negative to 5 TU of tuberculin after 2–3 months.¹

Cautions for BCG Vaccine

Contraindications

• Individuals with impaired immunologic responses because of HIV infection, congenital immunodeficiency (e.g., chronic granulomatous disease or interferon gamma receptor deficiency), leukemia, lymphoma, or generalized malignancy.¹

• Individuals who are immunosuppressed as a result of steroid use or treatment with alkylating agents, antimetabolites, or radiation.¹

• HIV-infected or immunocompromised infants, children, or adults.¹

• Individuals with allergies to any component of the vaccine or an anaphylactic or allergic reaction to a previous dose.¹

• Individuals with active tuberculosis (TB).¹

• Infants, children, or adults with severe immune deficiency syndromes, and children with a family history of immune deficiency disease.¹

Warnings/Precautions

Administration Precautions

Administer BCG vaccine by the percutaneous route with multiple-puncture device as described in the manufacturer's prescribing information.¹ Do not inject IV, IM, sub-Q, or intradermally.¹

The vaccine preparation contains live bacteria; use special precautions including aseptic technique when preparing vaccine.¹

All equipment and supplies used in vaccine preparation should be disposed of properly in biohazardous containers.¹

Parenteral drugs should not be prepared in areas where BCG has been handled to avoid cross-contamination.¹

Local Effects

Local effects may occur after vaccination and can persist for as long as 3 months; such reactions have included moderate axillary or cervical lymphadenopathy and induration and subsequent pustule formation at the injection site.¹

More severe local reactions may occur up to 5 months after vaccination and persist for several weeks including ulceration at the vaccination site, regional suppurative lymphadenitis with draining sinuses, and caseous lesions or purulent drainage at the puncture site.¹

The intensity and duration of local reactions depend on depth of penetration of the multiple-puncture device and individual patient response.¹

Systemic Effects

Systemic signs and symptoms consistent with a "flu-like" syndrome have occurred.¹ Manifestations including fever, anorexia, myalgia, and neuralgia usually lasting 24–48 hours are typically a result of hypersensitivity reactions.¹ However, a fever (≥103°F) or acute localized inflammation persisting longer than 2–3 days may be suggestive of active infections.¹

If active infection suspected, further evaluate patient and consult with infectious disease specialist.¹ Administer prompt treatment while diagnostic evaluation, including cultures, is being conducted.¹ Negative cultures do not necessarily rule out infection.¹

Disseminated BCG Infection

Disseminated BCG infection, which can be fatal, has occurred; most cases reported in immunocompromised individuals (e.g., those with HIV infection).^{1 100 105 120}

If systemic BCG infection occurs, consult an infectious disease expert and initiate appropriate anti-tuberculosis therapy.¹

Individuals with Altered Immunocompetence

BCG vaccine is contraindicated in individuals who are immunosuppressed (e.g., those with HIV infection, congenital immunodeficiency, leukemia, lymphomas, generalized malignancy, or receiving immunosuppressant agents or radiation therapy).¹

Administer the vaccine with caution to individuals at high risk for HIV infection.¹

Laboratory Test Interferences

Following administration of BCG vaccine, it is usually impossible to distinguish between tuberculin sensitivity caused by M. tuberculosis infection and tuberculin sensitivity resulting from the vaccine; use caution when interpreting tuberculin skin test reactions in patients who have received BCG vaccine.¹

CDC states that TB blood tests (interferon-gamma release assay [IGRA]) are preferred for individuals who have received the BCG vaccine, including children, since the BCG vaccine does not induce positive results when these tests are used.¹

Specific Populations

Pregnancy

Not known whether BCG vaccine can cause fetal harm if administered during pregnancy.¹ Animal reproduction studies not conducted.¹

CDC recommends that pregnant women not receive BCG vaccination pending further studies to support safety in this population.¹¹⁰

Lactation

Not known whether BCG vaccine is excreted in human milk.¹ A decision should be made to either not vaccinate or discontinue nursing; take into account the importance of TB vaccination to the mother.¹

Females and Males of Reproductive Potential

Not known whether BCG vaccine can affect reproductive capacity.¹

Pediatric Use

BCG vaccine is used in pediatric patients.¹ Infants <1 month of age should receive 1/2 of the usual dose.¹

Geriatric Use

Clinical studies did not include sufficient numbers of patients ≥65 years of age to determine whether they respond differently from younger patients.¹ Other reported clinical experience has not identified differences in response between elderly and younger patients.¹

An intact immune system is a prerequisite for BCG vaccination.¹ If the immune status of an elderly patient, or any patient, is in question, withhold BCG vaccination until immune status has been evaluated.¹

Common Adverse Effects

Local reactions are common after BCG vaccination.¹

Drug Interactions

Antimicrobial Agents

Antimicrobial agents may interfere with development of immune response to BCG vaccine; use only under medical supervision.¹

Immunosuppressive Agents

Immunosuppressive agents may interfere with development of immune response to BCG vaccine; use only under medical supervision.¹

Live Vaccines

Since BCG is a live vaccine, immune response to the vaccine may be impaired if administered within 30 days of another live vaccine.¹ Whenever possible, administer live vaccines at least 30 days apart.¹

Stability

Storage

Percutaneous

Lyophilized Powder

Store intact vials refrigerated at 2–8°C; protect from direct sunlight.¹

Store reconstituted vaccine refrigerated, protected from direct sunlight; use within 2 hours of reconstitution.¹ Do not freeze.¹

Actions

• Preparation of live, attenuated organisms of the Calmette-Guérin strain of Mycobacterium bovis.¹

• BCG vaccine commercially available in the US contains the TICE substrain of BCG and is administered by percutaneous administration via a multiple-puncture device.¹

• Vaccination with BCG promotes trained immunity mediated by innate immune cells such as monocytes, macrophages, and natural killer cells.¹²⁵

Advice to Patients

• Before administering BCG vaccine, inform patients and/or caregivers of the benefits and risks of immunization and inquire about the health status of the patient.¹ Inform patients that the efficacy of BCG vaccination has been variable and that BCG vaccination may interfere with the diagnosis of newly acquired M. tuberculosis infections; also inform patients about potential serious complications associated with BCG vaccination in immunocompromised individuals.¹

• Advise patients that following BCG vaccination, no dressing is required; however, it is recommended that the site be loosely covered and kept dry for 24 hours.¹ The vaccination site should be kept clean until the local reaction has disappeared.¹

• Advise patients that BCG vaccine contains live organisms.¹ Although the vaccine will not survive in a dry state for long, infection of others is possible.¹

• Advise patients that following BCG vaccination, initial skin lesions usually appear within 10–14 days and consist of small red papules at the vaccination site.¹ The papules reach a maximum diameter (about 3 mm) after 4 to 6 weeks, after which they may scale and slowly subside.¹ There is usually no visible sign of the vaccination at 6 months, although on occasion, a faintly discernible pattern of the points from the multiple puncture device may be visible.¹ Individuals with a predisposition to keloid formation may have more visible evidence of the vaccination.¹ Advise patients to report any unusual adverse reactions to their clinician.¹

• Advise patients that they may experience "flu-like" symptoms for 24–48 hours following BCG vaccination.¹ Patients should consult their physician immediately if they experience a fever of 103°F or greater, or acute local reactions persisting longer than 2–3 days.¹

• Advise patients to inform their clinician if they are or plan to become pregnant or plan to breast-feed.¹

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.¹

• Inform patients of other important precautionary information.¹

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

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