BCG Vaccine (Immunization)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injectable, Injection:

Generic: 50 mg (1 ea)

Pharmacology

Mechanism of Action

BCG vaccine is an attenuated, live bacterial culture of the Bacillus of Calmette and Guérin (BCG) strain of Mycobacterium bovis and induces active immunity against Mycobacterium tuberculosis.

Use: Labeled Indications

Mycobacterium tuberculosis disease prevention: Active immunization against Mycobacterium tuberculosis in persons not previously infected and who are at high risk for exposure

BCG vaccine is not routinely administered for the prevention of M. tuberculosis in the United States. The Advisory Committee on Immunization Practices (ACIP) recommends vaccination be considered for the following (CDC/ACIP [Villarino 1996]):

- Infants and children with a negative tuberculin skin test who are continually exposed to (and cannot be separated from) patients who are untreated or ineffectively treated for infectious pulmonary TB disease when the child cannot be given long-term treatment for infection or if the patient has infectious pulmonary TB caused by strains resistant to isoniazid and rifampin.

- Health care workers with a high percentage of patients with M. tuberculosis strains resistant to both isoniazid and rifampin, if there is ongoing transmission of the resistant strains and subsequent infection is likely, or if comprehensive infection-control precautions have not been successful. In addition, health care workers should be counseled on the risks and benefits of vaccination and treatment of latent TB infection

The Advisory Council for the Elimination of Tuberculosis (ACET) recommends BCG vaccination for health care and humanitarian workers who travel to work where the incidence of multidrug-resistant tuberculosis is high and potential transmission may occur. The ACET recommends a set of risk-reduction measures for such workers, noting that interferon-gamma release assays can differentiate tuberculosis infection from BCG vaccination effect (Seaworth 2014).

Use: Off Label

Prevention of leprosyb

Evidence from meta-analyses of controlled trials, cohort studies, and case-control studies indicate that the use of BCG vaccine is partially protective in the prevention of leprosy. Data are limited by high levels of heterogeneity for experimental trials and case-control studies.

Contraindications

Prior hypersensitivity to the vaccine or any component of the formulation; immunosuppressed patients or persons with congenital or acquired immune deficiencies (eg, HIV infection, leukemia, lymphoma, cancer therapy, immunosuppressive therapy such as corticosteroids); active tuberculosis

Dosage and Administration

Dosing: Adult

Note: Dosing and administration based on US percutaneous product (TICE strain); formulation/dosing/route may vary in other regions (consult local product labeling).

Immunization against tuberculosis: Percutaneous: 0.2 to 0.3 mL (full-strength dilution); conduct postvaccinal tuberculin test in 2 to 3 months; if test is negative, repeat vaccination. Note: Initial lesions usually appear after 10 to 14 days and consist of small, red papules at injection site, which reach maximum diameter of 3 mm in 4 to 6 weeks.

Prevention of leprosy (off-label use): Percutaneous: 0.2 to 0.3 mL (full-strength dilution); a single dose offers partial protection against leprosy; an additional dose may confer greater protection, however, studies do not specify appropriate interval (Bertolli 1997; Karonga Prevention Trial Group 1996; Setia 2006; Zodpey 2007). Note: Timing of vaccination and chemoprophylaxis should be taken into consideration since chemoprophylaxis may kill BCG (Rodrigues 2011).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Dosing and administration based on US percutaneous product (TICE strain); formulation/dosing/route may vary in other regions (consult local product labeling). According to ACIP, doses administered ≤4 days before minimum interval or age are considered valid; however, local or state mandates may supersede this timeframe (ACIP [Kroger 2017]).

Immunization against tuberculosis: Infants, Children, and Adolescents: Percutaneous: Full-strength: 0.2 to 0.3 mL as a single dose; conduct postvaccinal tuberculin test in 2 to 3 months; if test is negative, repeat vaccination (at age ≥1 year). Note: Initial lesion usually appears after 10 to 14 days consisting of small, red papule at injection site and reaches maximum diameter of 3 mm in 4 to 6 weeks.

Leprosy, prophylaxis in areas with high incidence: Limited data available (Setia 2006; Zodbey 2007): Infants, Children, and Adolescents with no evidence of immunity: Percutaneous: Full-strength: 0.2 to 0.3 mL as a single dose (WHO 2017)

Reconstitution

Prepare using aseptic technique. Do not prepare parenteral medications in an area where BCG has been prepared. Do not filter. Reconstitute with 1 mL of SWFI; swirl gently, do not vigorously shake.

Administration

Note: Administration based on US percutaneous product (TICE strain); formulation/dosing/route may vary in other regions around the globe (consult local product labeling).

Should only be given percutaneously; do not administer IV, SubQ, IM, or intradermally. Do not mix with other vaccines or injections; separate needles and syringes should be used for each injection (ACIP [Kroger 2017]).

Apply vaccine with syringe and needle by dropping onto 1 to 2 inch area of horizontally positioned surface of cleansed, dry site (deltoid region of arm preferred); pulling skin tight, puncture skin with multiple puncture device centered over the vaccine; apply pressure for 5 seconds (do not "rock" device). After successful puncture, spread vaccine evenly using the edge of the device over puncture area; an additional 1 to 2 drops of vaccine may be added to ensure a very wet vaccination site. Apply loose covering and keep dry for 24 hours.

When used for immunization against tuberculosis, US federal law requires that the name of medication, date of administration, the vaccine manufacturer, lot number of vaccine, and the administering person's name, title, and address be entered into the patient's permanent medical record.

Storage

Store intact vials at 2°C to 8°C (36°F to 46°F). Protect from sunlight. Store reconstituted vaccine in refrigerator; use within 2 hours of mixing. Do not freeze vaccine after reconstitution.

Drug Interactions

Antibiotics: May diminish the therapeutic effect of BCG Vaccine (Immunization). Exceptions: Acetic Acid (Otic); Acetic Acid (Topical); Aluminum Acetate; Azithromycin (Ophthalmic); Aztreonam (Oral Inhalation); Bacitracin (Ophthalmic); Bacitracin (Topical); Chlortetracycline; Ciprofloxacin (Ophthalmic); Clindamycin (Topical); Dapsone (Topical); Dibrompropamidine (Ophthalmic); Dibrompropamidine (Topical); Erythromycin (Ophthalmic); Erythromycin (Topical); Fidaxomicin; Framycetin; Fusidic Acid (Ophthalmic); Fusidic Acid (Topical); Gatifloxacin; Gentamicin (Ophthalmic); Gentamicin (Topical); MetroNIDAZOLE (Topical); Mupirocin; Nitrofurazone; Ozenoxacin; Sulfacetamide (Ophthalmic); Tobramycin (Ophthalmic). Monitor therapy

Axicabtagene Ciloleucel: May enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of infection may be increased. Axicabtagene Ciloleucel may diminish the therapeutic effect of Vaccines (Live). Management: Avoid live virus vaccines for at least 6 weeks prior to initiation of lymphodepleting therapy, during axicabtagene ciloleucel infusion, and after treatment until full immune recovery is achieved. Consider therapy modification

AzaTHIOprine: May enhance the adverse/toxic effect of Vaccines (Live). AzaTHIOprine may diminish the therapeutic effect of Vaccines (Live). Management: Low-dose azathioprine (3 mg/kg/day or less) is not considered sufficiently immunosuppressive to create vaccine safety concerns and is not a contraindication for administration of zoster vaccine. Higher doses of azathioprine should be avoided. Consider therapy modification

Belimumab: May enhance the adverse/toxic effect of Vaccines (Live). Avoid combination

Corticosteroids (Systemic): May enhance the adverse/toxic effect of Vaccines (Live). Corticosteroids (Systemic) may diminish the therapeutic effect of Vaccines (Live). Management: Doses equivalent to less than 2 mg/kg or 20 mg per day of prednisone administered for less than 2 weeks are not considered sufficiently immunosuppressive to create vaccine safety concerns. Higher doses and longer durations should be avoided. Consider therapy modification

Daclizumab: May enhance the adverse/toxic effect of Vaccines (Live). Daclizumab may diminish the therapeutic effect of Vaccines (Live). Avoid combination

Dimethyl Fumarate: May enhance the adverse/toxic effect of Vaccines (Live). Specifically, Dimethyl Fumarate may increase the risk of vaccinal infection. Dimethyl Fumarate may diminish the therapeutic effect of Vaccines (Live). Management: Canadian labeling for dimethyl fumarate states that live attenuated vaccine administration is not recommended during treatment. U.S. labeling does not mention this. Consider therapy modification

Dupilumab: May enhance the adverse/toxic effect of Vaccines (Live). Avoid combination

Fingolimod: May enhance the adverse/toxic effect of Vaccines (Live). Vaccinal infections may develop. Fingolimod may diminish the therapeutic effect of Vaccines (Live). Avoid combination

Guselkumab: May enhance the adverse/toxic effect of Vaccines (Live). Avoid combination

Immune Globulins: May diminish the therapeutic effect of Vaccines (Live). Management: Consult full interaction monograph for dose interval recommendations. This interaction does not apply to oral Ty21a typhoid vaccine or others listed as exceptions. Consider therapy modification

Immunosuppressants: May enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Exceptions: AzaTHIOprine; Beclomethasone (Oral Inhalation); Betamethasone (Systemic); Budesonide (Systemic); Corticotropin; Cortisone; Cytarabine (Liposomal); Deflazacort; DexAMETHasone (Systemic); Fludrocortisone; Fluticasone (Oral Inhalation); Hydrocortisone (Systemic); Leflunomide; Mercaptopurine; Methotrexate; MethylPREDNISolone; PrednisoLONE (Systemic); PredniSONE; Triamcinolone (Systemic). Avoid combination

Leflunomide: May enhance the adverse/toxic effect of Vaccines (Live). Leflunomide may diminish the therapeutic effect of Vaccines (Live). Management: The ACIP guidelines state that live-attenuated vaccines should generally be avoided for at least 3 months after cessation of immunosuppressant therapy. However, the ACR does not recommend avoiding live vaccines in patients being treated with leflunomide. Consider therapy modification

Mercaptopurine: May enhance the adverse/toxic effect of Vaccines (Live). Mercaptopurine may diminish the therapeutic effect of Vaccines (Live). Management: Low-dose 6-mercaptopurine (1.5 mg/kg/day or less) is not considered sufficiently immunosuppressive to create vaccine safety concerns and is not a contraindication for administration of zoster vaccine. Higher doses of mercaptopurine should be avoided. Consider therapy modification

Methotrexate: May enhance the adverse/toxic effect of Vaccines (Live). Methotrexate may diminish the therapeutic effect of Vaccines (Live). Management: Low-dose methotrexate (0.4 mg/kg/week or less) is not considered sufficiently immunosuppressive to create vaccine safety concerns. Higher doses of methotrexate should be avoided. Consider therapy modification

Ocrelizumab: May enhance the adverse/toxic effect of Vaccines (Live). Ocrelizumab may diminish the therapeutic effect of Vaccines (Live). Avoid combination

Rabies Immune Globulin (Human): May diminish the therapeutic effect of Vaccines (Live). Management: Avoid administering the measles vaccine within 4 months after administration of rabies immune globulin. Avoid administering other live vaccines within 3 months after administration of rabies immune globulin. Consider therapy modification

Risankizumab: May enhance the adverse/toxic effect of Vaccines (Live). Avoid combination

Tildrakizumab: May enhance the adverse/toxic effect of Vaccines (Live). The risk for contracting an infection from the vaccine may be increased. Tildrakizumab may diminish the therapeutic effect of Vaccines (Live). Avoid combination

Tisagenlecleucel: May enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of infection may be increased. Tisagenlecleucel may diminish the therapeutic effect of Vaccines (Live). Management: Avoid live virus vaccines for two weeks prior to initiation of lymphodepleting therapy, during tisagenlecleucel infusion, and after treatment until full immune recovery is achieved. Consider therapy modification

Tuberculin Tests: Vaccines (Live) may diminish the diagnostic effect of Tuberculin Tests. Management: If a parenteral live vaccine has been recently administered, a scheduled PPD skin test should not be administered for at least 4-6 weeks following the administration of the vaccine. Consider therapy modification

Vaccines (Live): May diminish the therapeutic effect of other Vaccines (Live). Management: Two or more injectable or nasally administered live vaccines not administered on the same day should be separated by at least 28 days (ie, 4 weeks). If not, the vaccine administered second should be repeated at least 4 week later. Exceptions: Adenovirus (Types 4, 7) Vaccine; Cholera Vaccine; Rotavirus Vaccine. Monitor therapy

Venetoclax: May enhance the adverse/toxic effect of Vaccines (Live). Venetoclax may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live, attenuated vaccines before, during, or after (prior to B-cell recovery) venetoclax treatment. Avoid combination

Test Interactions

PPD intradermal test: BCG results in reactive tuberculin skin test; rule out active tuberculosis prior to initiating intravesicular BCG treatment. BCG vaccine may be administered to persons with a PPD reaction of <5 mm induration; PPD should be used again 2 to 3 months after vaccination to ensure reactivity to vaccine (document in mm of induration). Vaccinees with a positive PPD test (>5 mm) should not be tested again unless exposed to tuberculosis. In this situation, an increase of induration may indicate a newly acquired TB infection. Vaccinees with a negative PPD test (<5 mm induration) may continue periodic skin testing as long as the results remain <5 mm (CDC/ACIP, [Villarino 1996]).

Interferon-gamma release assay (IGRA) tests for latent TB infection (LTBI) are not affected by BCG vaccination history and are considered acceptable for monitoring occupational exposures in healthcare workers (Mazurek 2010).

Adverse Reactions

Local reactions may persist for up to 3 months; more severe manifestations may occur up to 5 months after vaccination and persist for several weeks.

Frequency not defined:

Dermatologic: Pustules (at injection site), skin ulceration at injection site

Hematologic & oncologic: Cervical lymphadenopathy, lymphadenitis (includes local and suppurative), lymphadenopathy (axillary)

Infection: BCG infection (BCG osteomyelitis; may occur from 4 months to 2 years after vaccination)

Local: Induration at injection site, injection site lesion, itching at injection site, tenderness at injection site

Respiratory: Flu-like symptoms

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactoid/hypersensitivity reactions: Immediate treatment (including epinephrine 1 mg/mL) for anaphylactoid and/or hypersensitivity reactions should be available during vaccine use (ACIP [Kroger 2017]).
• BCG reaction: Local adverse effects may include moderate axillary or cervical lymphadenopathy and induration/pustule formation at the injection site; lasting as long as 3 months or more. Severe ulceration, regional suppurative lymphadenitis with draining sinuses, and caseous lesions or purulent drainage may occur within 5 months and persist for several weeks. Systemic adverse effects lasting 1 to 2 days and similar to a flu-like syndrome (fever, anorexia, myalgia, and neuralgia) are generally caused by hypersensitivity to the vaccine.
• Disseminated infections: May cause BCG infection, particularly in immunocompromised patients. If signs and symptoms of a systemic BCG infection occur (eg, fever of ≥103°F or acute local reactions lasting longer than 2 to 3 days), permanently discontinue BCG vaccination and begin therapy with ≥2 antimycobacterial agents while conducting a diagnostic evaluation. Infection from vaccine is not sensitive to pyrazinamide. BCG osteomyelitis affecting the epiphyses of the long bones is the most common disseminated infection and may occur 4 months to 2 years after vaccination.
• Syncope: Syncope has been reported with use of injectable vaccines and may result in serious secondary injury (eg, skull fracture, cerebral hemorrhage); typically reported in adolescents and young adults and within 15 minutes after vaccination. Procedures should be in place to avoid injuries from falling and to restore cerebral perfusion if syncope occurs (ACIP [Kroger 2017]).

Disease-related concerns:

• Acute illness: The decision to administer or delay vaccination because of current or recent febrile illness depends on the severity of symptoms and the etiology of the disease. Defer administration in patients with moderate or severe acute illness (with or without fever); vaccination should not be delayed for patients with mild acute illness (with or without fever) (ACIP [Kroger 2017]).
• HIV: Use is contraindicated in HIV-infected persons (ACIP [Kroger 2017]). Should be administered with caution to persons in groups at high risk for HIV. HIV-infected persons thought to be infected with Mycobacterium tuberculosis should be strongly recommended for tuberculosis preventive therapy.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
• Vaccines: In order to maximize vaccination rates, the ACIP recommends simultaneous administration (ie, >1 vaccine on the same day at different anatomic sites) of all age-appropriate vaccines (live or inactivated) for which a person is eligible at a single clinic visit, unless contraindications exist (ACIP [Kroger 2017]).

Special populations:

• Altered immunocompetence: Use is contraindicated in immunocompromised patients (eg, patients receiving chemo/radiation therapy or other immunosuppressive therapy [including high-dose corticosteroids]). Household and close contacts of persons with altered immunocompetence may receive most age appropriate vaccines (ACIP [Kroger 2017]). Live vaccines should be administered ≥4 weeks prior to planned immunosuppression and avoided within 2 weeks of immunosuppression when feasible; live vaccines should not be administered for at least 3 months after immunosuppressive therapy (ACIP [Kroger 2017]; (IDSA [Rubin 2014]).
• Positive PPD reaction: Determine PPD status prior to use. BCG vaccination is not recommended for persons with a positive PPD reaction.

Special handling:

• Biohazard agent: Contains live, attenuated mycobacteria. Use appropriate precautions for handling and disposal. BCG is a biohazard; proper preparation technique, handling, and disposal of all equipment in contact with BCG as a biohazard material is recommended. BCG infections have been reported in healthcare workers due to accidental exposure (needlestick, skin laceration); nosocomial infections have been reported in patients receiving parenteral medications prepared in areas where BCG was prepared. To avoid cross contamination, do not prepare parenteral medications in an area where BCG has been prepared.

Other warnings/precautions:

• Antipyretics: Antipyretics have not been shown to prevent febrile seizures; antipyretics may be used to treat fever or discomfort following vaccination (ACIP [Kroger 2017]). One study reported that routine prophylactic administration of acetaminophen prior to vaccination to prevent fever decreased the immune response of some vaccines; the clinical significance of this reduction in immune response has not been established (Prymula 2009).
• Appropriate use: BCG vaccine should not be used for the active treatment of tuberculosis.
• Effective immunity: Vaccination may not result in effective immunity in all patients. Response depends upon multiple factors (eg, type of vaccine, age of patient) and may be improved by administering the vaccine at the recommended dose, route, and interval. Vaccines may not be effective if administered during periods of altered immune competence (ACIP [Kroger 2017]).

Monitoring Parameters

PPD test prior to vaccination. Flu-like symptoms ≥72 hours, fever ≥103°F, acute local reactions lasting >2 to 3 days. Monitor for anaphylaxis and syncope for 15 minutes following administration (ACIP [Kroger 2017]). If seizure-like activity associated with syncope occurs, maintain patient in supine or Trendelenburg position to reestablish adequate cerebral perfusion.

Pregnancy

Pregnancy Considerations

Animal reproduction studies have not been conducted. BCG vaccine is not recommended for use in pregnant women. Because of the theoretical risk to the fetus, women known to be pregnant generally should not receive live, attenuated virus vaccines; avoid conception for 4 weeks after vaccination with live vaccines (ACIP [Kroger 2017]).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience loss of strength and energy or swollen glands. Have patient report immediately to prescriber flu-like symptoms longer than 2 days, bone pain, severe fever, skin ulcers, or severe injection site irritation, redness, pain, or edema (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.