BCG (Intravesical) (Monograph)

Brand name: TICE BCG
Drug class: Antineoplastic Agents

Warning

BCG contains live, attenuated mycobacteria. Because of the potential risk for transmission, prepare, handle, and dispose of TICE BCG as a biohazard material.
BCG infections have been reported in healthcare workers, primarily from exposures resulting from accidental needle sticks or skin lacerations during preparation of BCG.
Nosocomial infections have been reported in patients receiving parenteral drugs that were prepared in areas in which BCG was reconstituted.
BCG is capable of dissemination when administered by the intravesical route; serious infections, including fatal infections, have been reported.

Introduction

Lyophilized preparation of live, attenuated organisms of the Calmette-Guérin strain of Mycobacterium bovis.

Uses for BCG (Intravesical)

Bladder Cancer

Used intravesically for treatment and prophylaxis of carcinoma in situ (CIS) of the urinary bladder and for prophylaxis of primary or recurrent stage Ta and/or T1 papillary tumors following transurethral resection (TUR).

Do not use for stage TaG1 papillary tumors unless judged to be at high risk of tumor recurrence.

Not indicated for papillary tumors of stages higher than T1.

Non-muscle invasive bladder cancer (NMIBC; previously referred to as superficial bladder cancer) is usually treated initially with surgical resection and/or fulguration. NMIBC includes papillary tumors limited to the epithelial mucosa (stage Ta), tumors invading the subepithelial tissue but not extending beyond the lamina propria of the bladder (stage T1), and carcinoma in situ (stage Tis). Because of high rates of recurrence following surgery, adjuvant treatment with intravesical therapy (with immunotherapeutic or chemotherapeutic agents) is indicated in patients with intermediate to high risk of progression and/or recurrence of disease.

Intravesical instillation of BCG, an immunotherapeutic agent, is a preferred regimen for adjuvant therapy for NMIBC in patients at high risk of disease progression and/or recurrence and the treatment of choice for CIS.

BCG (Intravesical) Dosage and Administration

General

Pretreatment Screening

Intravesical BCG should be administered at least 7 to 14 days following transurethral resection (TUR), biopsy, or traumatic catheterization.
Rule out active tuberculosis in individuals who are PPD positive before starting treatment with intravesical BCG.
Patients should not drink fluids for 4 hours before treatment and should empty their bladder prior to BCG administration.

Patient Monitoring

Monitor patients for signs and symptoms of BCG infection after each intravesical treatment.

Dispensing and Administration Precautions

BCG contains live organisms and is an infectious agent. A separate area for preparation of the intravesical suspension is recommended. All equipment and supplies in contact with BCG should be handled and disposed of properly in biohazardous containers.
Individuals who prepare BCG should take necessary precautions to minimize the risk of spreading disease including wearing gloves and avoiding 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.

Administration

Administer by intravesical instillation after reconstitution. Do not inject sub-Q or IV.

Allow 7 to 14 days to elapse after bladder biopsy before BCG is administered. Patients should not drink fluids for 4 hours before treatment and should empty their bladder prior to BCG administration.

To prepare suspension, withdraw 1 mL of 0.9% sodium chloride injection at 4–25°C into a small syringe (e.g., 3 mL) and add to 1 vial of TICE BCG to resuspend; avoid bacteriostatic solutions. Gently swirl vial until a homogenous suspension is obtained. Avoid forceful agitation. Dilute the cloudy BCG suspension in sterile, preservative-free saline to final volume of 50 mL. Mix suspension gently prior to intravesical instillation. Do not filter contents of the BCG vial.

Instill reconstituted suspension into the bladder by gravity flow via catheter. After instillation is complete, remove the catheter. Retain BCG in the bladder for 2 hours and then void. Patients unable to retain the suspension for 2 hours should be allowed to void sooner, if necessary. While BCG is retained in bladder, reposition patients every 15 minutes.

Dosage

Adults

Bladder Cancer

Intravesical

Recommended dose is 1 vial containing 1–8 × 10⁸ colony-forming units (CFUs) suspended in 50 mL preservative-free saline for treatment of carcinoma in situ and for prophylaxis of recurrent papillary tumors.

Standard course of BCG therapy is once weekly instillation for 6 consecutive weeks. A second 6-week course of therapy may be required for optimal response. A rest interval between the 2 courses has been employed to avoid suppression of immune response and optimize tumor response. Thereafter, intravesical administration of BCG may be continued at approximately monthly intervals for at least 6 to 12 months.

Cautions for BCG (Intravesical)

Contraindications

Immunosuppressed patients with congenital or acquired immune deficiencies, whether due to concurrent disease (e.g., AIDS, leukemia, lymphoma), cancer therapy (e.g., cytotoxic drugs, radiation), or immunosuppressive therapy (e.g., corticosteroids).
Patients with increased risk of BCG infection.
Patients with active tuberculosis.

Warnings/Precautions

Warnings

Risk of BCG Infections

BCG is an infectious agent and can potentially cause serious (including fatal) infections. (See Boxed Warning.) Contraindicated in patients with increased risk of BCG infection.

Special handling precautions and procedures for proper disposal required.

Clinicians who administer BCG should be familiar with the prevention and treatment of BCG-related complications.

If BCG-related complications occur, consultation with an experienced infectious diseases specialist is recommended.

Long-term multiple-drug antibiotic therapy is required for treatment of BCG infection.

Special culture media required for mycobacteria should be readily available when administering intravesical BCG.

Other Warnings and Precautions

Confusion with BCG Vaccine

Intravesical BCG is not a vaccine for the prevention of cancer and should not be used for the prevention of tuberculosis. BCG vaccine (administered via percutaneous route) should be used for vaccination against tuberculosis.

Antimicrobial Therapy

Antimicrobial therapy may interfere with the effectiveness of BCG; therefore, intravesical instillations of BCG should be postponed during treatment with antibiotics and BCG should not be used in individuals with concurrent infections.

Bladder Capacity

Small bladder capacity has been associated with increased risk of severe local reactions and should be considered when deciding whether to use BCG therapy.

Laboratory Test Interferences

BCG may cause tuberculin sensitivity. Since this is a valuable aid in the diagnosis of tuberculosis, it is recommended to determine tuberculin reactivity by PPD skin testing before treatment.

Specific Populations

Pregnancy

Animal reproduction studies not conducted. It is not known whether BCG can cause fetal harm when administered to a pregnant woman or affect reproductive capacity.

Avoid use of intravesical BCG during pregnancy except when clearly needed.

Lactation

Not known whether intravesical BCG is excreted in human milk. Discontinue nursing or the drug.

Females and Males of Reproductive Potential

Advise females of reproductive potential to not become pregnant while on BCG therapy.

Pediatric Use

Safety and effectiveness for treatment of superficial bladder cancer in pediatric patients not established.

Geriatric Use

Average age of patients in studies with intravesical BCG was 66 years. No overall difference in safety or effectiveness observed between older and younger subjects. Other reported clinical experience has not identified differences in response between elderly and younger patients, but greater sensitivity of some older individuals to BCG cannot be ruled out.

Common Adverse Effects

Common adverse effects (≥5%): bladder irritation, dysuria, urinary frequency, flu-like syndrome, hematuria, fever, malaise/fatigue, cystitis, urgency, nocturia.

Drug Interactions

Antimicrobial Agents

Antimicrobial agents may interfere with the effectiveness of BCG.

Immunosuppressive Agents

Immunosuppressive agents and radiation therapy may interfere with the development of immune response to BCG and should not be used concomitantly with intravesical BCG.

Stability

Storage

Intravesical

Powder for suspension

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

Store reconstituted suspension refrigerated (2–8°C) and protect from exposure to direct sunlight; use within 2 hours and discard any unused portion.

Actions

BCG for intravesical instillation is a lyophilized preparation of live, attenuated organisms of the Calmette-Guérin strain of M. bovis; commercially available in the US as TICE BCG, which contains the TICE substrain.
Precise mechanism of action not determined; however, both inflammatory effects and immune response are believed to be involved. Administration of BCG intravesically with the adherence of live, attenuated BCG organisms to the bladder mucosa and tumor cells appears to be important for the development of an antitumor immune response, which includes T-lymphocyte activation and cytokine release.

Advice to Patients

Advise patients that intravesical BCG is retained in the bladder for 2 hours and then voided. Patients should void while seated in order to avoid splashing of urine. For the 6 hours after treatment, urine voided should be disinfected for 15 minutes with an equal volume of household bleach before flushing.
Instruct patients to increase fluid intake in order to "flush" the bladder in the hours following BCG treatment. Patients may experience burning with the first void after treatment.
Advise patients to monitor for adverse effects, such as fever, chills, malaise, flu-like symptoms, or increased fatigue.
If severe urinary adverse effects, such as burning or pain on urination, urgency, frequency of urination, blood in urine, or other symptoms such as joint pain, cough, or skin rash occur, advise patients to notify their clinician.
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.
Advise patients to inform their clinician if they are or plan to become pregnant or plan to breast-feed.
Inform patients of other important precautionary information.

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

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.