BCG Live

Trade Names:Tice BCG- Powder for suspension, lyophilized 1 to 8 × 10 ⁸ colony-forming units

Trade Names:TheraCys- Powder for suspension, lyophilized 10.5 ± 8.7 × 10 ⁸ colony-forming units

Pharmacology

Bacille Calmette-Guérin (BCG) is a lyophilized preparation of an attenuated, live culture preparation of the BCG strain of Mycobacterium bovis used in carcinoma in situ of the urinary bladder and as prophylaxis of primary or recurrent stage Ta or T1 papillary tumors following TUR. Precise mechanism of action is unknown.

Indications and Usage

Treatment and prophylaxis of carcinoma in situ of the urinary bladder; prophylaxis of primary or recurrent stage Ta and/or T1 papillary tumors following transurethral resection TUR.

Unlabeled Uses

Local control of accessible tumor.

Contraindications

Immunosuppressed patients or persons with congenital or acquired immune deficiencies; patients with current symptoms or a previous history of systemic BCG reaction; persons with active tuberculosis; postpone treatment until resolution of a concurrent febrile illness, UTI, or gross hematuria; allow 14 days to elapse following biopsy, TUR, or traumatic catheterization.

Dosage and Administration

Intravesical Each dose is administered intravesically via catheter once a wk for 6 wk followed by maintenance therapy consisting of 1 dose given at 3, 6, 12, 18, and 24 mo after initial treatment.

Intravesical Each dose is administered intravesically via catheter once a wk for 6 wk. This schedule may be repeated once if tumor remission is not achieved and if deemed clinically necessary; thereafter, administer 1 dose at approximately monthly intervals for at least 6 to 12 mo.

General Advice

• The suspension is instilled into the bladder slowly by gravity flow, via the catheter. Do not force the flow.
• Reconstitute and dilute immediately prior to use. If there is a delay between reconstitution and administration, it must not exceed 2 h.
• Do not inject subcutaneously or IV.
• Patients should be instructed to increase fluid intake in order to flush the bladder following BCG treatment.
• Individuals mixing the agent should wear gloves and eye protection and avoid contact of BCG with broken skin.
• BCG should not be handled by persons with an immunological deficiency.
• After use of the product, place packaging and all equipment and materials used for installation in a container for biohazardous materials and disposed of according to local requirements.
• BCG should be retained in the bladder for 2 h before voiding.
• Disinfect urine voided during the 6 h period following installation with an equal volume of 5% hypochlorite solution (undiluted household bleach) and allow to stand for 15 min before flushing.
• Tice : Patients should not drink fluids for 4 h before treatment and should empty the bladder prior to BCG administration.

Storage/Stability

Keep BCG and any accompanying diluent refrigerated between 35° and 46°F. Use immediately after reconstitution and discard after 2 h. Do not expose the freeze-dried or reconstituted BCG to sunlight, direct or indirect. Keep exposure to artificial light to a minimum. Do not use any reconstituted product that exhibits flocculation or clumping that cannot be dispersed with gentle shaking. Do not use after expiration date printed on label.

Drug Interactions

Antimicrobial therapy for other infections may interfere with the effectiveness of BCG therapy.

May impair immune response to BCG.

Laboratory Test Interactions

May result in tuberculin skin reactivity.

Adverse Reactions

Cardiovascular

Cardiac (unclassified), coagulopathy (less than 5%).

CNS

Malaise (40%); fatigue (7%); neurologic unclassified, pyuria (1%); dizziness, headache (less than 5%).

Dermatologic

Skin rash (less than 5%).

EENT

Conjunctivitis, BCG eye infection, granulomatous chorioretinitis, iritis, keratitis, uveitis (postmarketing).

GI

Nausea/vomiting (16%); anorexia (11%); diarrhea (6%); abdominal pain, constipation (less than 5%).

Genitourinary

Dysuria (60%); urinary frequency (50%); hematuria (39%); cystitis (29%); urgency, UTI (18%); genital pain, renal toxicity (10%); hemorrhagic cystitis (9%); bladder cramps (8%); urinary incontinence (6%); contracted bladder (5%); urinary debris (2%); epididymitis/prostatitis, orchitis, urethritis, urinary obstruction (1%); tissue in urine, urethral obstruction (less than 5%); BCG kidney infection, epididymo-orchitis, genitourinary tract infections, granulomatous prostatitis, peritoneum and prostate infections, renal abscess, urinary symptoms (postmarketing).

Hematologic-Lymphatic

Anemia (21%); leukopenia (5%); thrombocytopenia (less than 5%); BCG bone, bone marrow, and regional lymph node infections (postmarketing).

Hepatic

Liver involvement (less than 5%); hepatic granuloma, hepatitis (1%); BCG liver infection (postmarketing).

Metabolic-Nutritional

Anorexia (11%); weight loss (2%).

Musculoskeletal

Arthralgia, myalgia (7%); rigors (3%); arthritis, migratory arthritis (postmarketing).

Respiratory

Pulmonary infection (less than 5%); respiratory unclassified (2%); pneumonitis (1%); BCG lung infection (postmarketing).

Miscellaneous

Fever (38%); chills (34%); flu-like syndrome (33%); pain (17%); flank pain, local infection, systemic infection (less than 5%); diaphoresis (3%); allergy (2%); BCG sepsis (1%); serious infections including disseminated sepsis and death (postmarketing).

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

No overall difference in safety or efficacy was observed between older and younger patients.

Hypersensitivity

Systemic adverse reactions (eg, malaise, fever, chills) of 1 to 2 days' duration may represent hypersensitivity reactions and can be treated with antihistamines.

BCG infection

Fever of 103°F or more, or acute localized inflammation persisting longer than 2 or 3 days suggest active infections and evaluation for serious infectious complications should be considered.

The acute, localized irritative toxicities of BCG may be accompanied by systemic manifestations consistent with flu-like syndrome.

Bladder contracture

Risk of occurrence may be increased in patients with small bladder capacity.

Immune deficiency syndromes

Administer with caution to persons at high risk for HIV infection. Do not vaccinate children with a family history of immune deficiency disease.

Infection of aneurysms and prosthetic devices

BCG infection of aneurysms and prosthetic devices (eg, arterial grafts, artificial joints, cardiac devices) have been reported following intravesical administration of BCG.

Rubber latex

The vial stopper for TheraCys contains natural rubber latex that may cause allergic reactions.

TUR

Do not give intravesical BCG any sooner than 1 to 2 wk following TUR, biopsy, traumatic catheterization, or gross hematuria.

UTI

Do not use in the presence of a UTI because administration may increase the risk of disseminated BCG infection or increase the severity of bladder irritation.

Overdosage

Symptoms

Overdosage (eg, active local or systemic BCG infection) occurs if more than 1 amp/vial is given per instillation.

Patient Information

• Check with health care provider as soon as possible if there is an increase in existing symptoms, if symptoms persist even after receiving a number of treatments, or if any of the following symptoms develop: blood in urine, chills, cough, fever, flu-like symptoms, frequent urge to urinate, increased frequency of urination, increased tiredness/fatigue, joint pain, painful urination, skin rash.
• Notify health care provider immediately if a cough develops.
• Void in a seated position to avoid splashing of urine.
• Disinfect urine voided for 6 h after instillation with an equal volume of 5% sodium hypochlorite solution (undiluted household bleach); allow to disinfect for 15 min before flushing.
• Increase fluid intake to flush the bladder in the hours following BCG treatment. Patients may experience burning with the first void after treatment.

Copyright © 2009 Wolters Kluwer Health.