BACILLUS CALMETTE-GUERIN

INDICATIONS AND USAGE TICE ® BCG is indicated for: the treatment and prophylaxis of carcinoma in situ (CIS) of the urinary bladder the prophylaxis of primary or recurrent stage Ta and/or T1 papillary tumors following transurethral resection (TUR) Limitations of Use: TICE BCG is not recommended for stage TaG1 papillary tumors, unless they are judged to be at high risk of tumor recurrence. TICE BCG is not indicated for papillary tumors of stages higher than T1.

WARNINGS BCG LIVE (TICE ® BCG) is not a vaccine for the prevention of cancer. BCG Vaccine, not BCG LIVE (TICE BCG), should be used for the prevention of tuberculosis. For vaccination use, refer to BCG Vaccine prescribing information. Handling Precautions TICE BCG is an infectious agent. Physicians using this product should be familiar with the literature on the prevention and treatment of BCG-related complications, and should be prepared in such emergencies to contact an infectious disease specialist with experience in treating the infectious complications of intravesical BCG. The treatment of the infectious complications of BCG requires long-term, multiple-drug antibiotic therapy. Special culture media are required for mycobacteria, and physicians administering intravesical BCG or those caring for these patients should have these media readily available. BCG Infection Instillation of TICE BCG with an actively bleeding mucosa may promote systemic BCG infection. Treatment should be postponed for at least 1 week following transurethral resection, biopsy, traumatic catheterization, or gross hematuria. Systemic BCG Reaction Deaths have been reported as a result of systemic BCG infection and sepsis. 2,3 Patients should be monitored for the presence of symptoms and signs of toxicity after each intravesical treatment. Febrile episodes with flu-like symptoms lasting more than 72 hours, fever ≥103°F, systemic manifestations increasing in intensity with repeated instillations, or persistent abnormalities of liver function tests suggest systemic BCG infection and may require antituberculous therapy. Local symptoms (prostatitis, epididymitis, orchitis) lasting more than 2 to 3 days may also suggest active infection (see WARNINGS, Management of Serious BCG Complications section). Laboratory Tests The use of TICE BCG may cause tuberculin sensitivity. Since this is a valuable aid in the diagnosis of tuberculosis, it is advisable to determine the tuberculin reactivity by PPD skin testing before treatment. Antimicrobial Therapy Intravesical instillations of BCG should be postponed during treatment with antibiotics, since antimicrobial therapy may interfere with the effectiveness of TICE BCG (see PRECAUTIONS ). TICE 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 in deciding to use TICE BCG therapy. Management of Serious BCG Complications. Acute, localized irritative toxicities of TICE BCG may be accompanied by systemic manifestations, consistent with a "flu-like" syndrome. Systemic adverse effects of 1 to 2 days' duration such as malaise, fever, and chills often reflect hypersensitivity reactions. However, symptoms such as fever of ≥ 38.5°C (101.3°F), or acute localized inflammation such as epididymitis, prostatitis, or orchitis persisting longer than 2 to 3 days suggest active infection, and evaluation for serious infectious complication should be considered. In patients who develop persistent fever or experience an acute febrile illness consistent with BCG infection, 2 or more antimycobacterial agents should be administered while diagnostic evaluation, including cultures, is conducted. BCG treatment should be discontinued. Negative cultures do not necessarily rule out infection. Physicians using 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. TICE BCG is sensitive to the most commonly used antituberculous agents (isoniazid, rifampin, and ethambutol). TICE BCG is not sensitive to pyrazinamide.