TheraCys, BCG Live (Intravesical) is a freeze-dried preparation made from the Connaught strain of Bacillus Calmette and Guérin, which is an attenuated strain of Mycobacterium bovis.

The BCG organisms in the product are grown on media containing potatoes, glycerine, asparagine, citric acid, potassium phosphate, magnesium sulfate, ferric ammonium citrate, calcium chloride, copper sulfate and zinc sulfate. Monosodium glutamate is added to the BCG organisms prior to freeze-drying.

Each vial of TheraCys contains 81 mg of freeze-dried BCG. Prior to use, each vial is reconstituted with the accompanying diluent (3 mL), which contains 0.85% w/v sodium chloride, 0.025% w/v polysorbate 80, 0.06% w/v sodium dihydrogen phosphate and 0.25% w/v disodium hydrogen phosphate. Neither the freeze-dried BCG nor the diluent contain preservative.

One dose of TheraCys consists of one 81mg vial of reconstituted material further diluted in 50 mL sterile, preservative-free saline.

The BCG organisms are viable upon reconstitution. In vitro potency is determined by an assay of the number of colonies grown on solid medium. The reconstituted product contains 10.5 ± 8.7 x 10⁸ colony-forming units (CFU) per vial when resuspended in the diluent provided.

Last updated on RxList: 10/28/2008

TheraCys is indicated for intravesical use in the treatment and prophylaxis of carcinoma in situ (CIS) of the urinary bladder and for the prophylaxis of primary or recurrent stage Ta and/or T1 papillary tumors following transurethral resection (TUR). TheraCys is not recommended for stage TaG1 papillary tumors, unless they are judged to be at high risk oftumor recurrence.

TheraCys is not indicated as an immunizing agent for the prevention oftuberculosis.

One dose of TheraCys, BCG Live (Intravesical) consists of the intravesical instillation of 81 mg (dry weight) BCG. This dose is prepared by reconstituting 1 vial containing 81 mg freeze-dried BCG with the contents of 1 vial containing 3 mL diluent. The reconstituted BCG is further diluted in 50 mL of sterile, preservative-free saline, for a total of 53 mL instillation volume. (See Preparation ofAgent.)

For intravesical instillation only. Do not inject subcutaneously or intravenously.

A urethral catheter is inserted into the bladder under aseptic conditions, the bladder is drained and then 53 mL suspension of TheraCys is instilled slowly by gravity, following which the catheter is withdrawn.

The patient retains the suspension for as long as possible for a total of up to two hours. During the first 15 minutes following instillation, the patient should lie prone. Thereafter, the patient is allowed to be up. At the end of 2 hours, all patients should void in a seated position for safety reasons. Patients should be instructed to increase fluid intake in order to flush the bladder in the hours following BCG treatment.

Preparation ofAgent

The preparation of the TheraCys suspension should be done using aseptic technique. To avoid cross-contamination, parenteral drugs should not be prepared in areas where BCG has been prepared. A separate area for the preparation of the TheraCys suspension is strongly recommended. All equipment, supplies and receptacles in contact with TheraCys should be handled and disposed of as biohazardous. The pharmacist or individual responsible for mixing the agent should wear gloves and eye protection and take precautions to avoid contact of BCG with broken skin. If the preparation cannot be performed in a biocontainment hood, then a mask and gown may be worn to avoid inhalation of BCG organisms and inadvertent exposure to broken skin.

TheraCys should not be handled by persons with an immunologic deficiency.

Do not remove the rubber stopper from the vial.

Apply a sterile piece of cotton moistened with a suitable antiseptic to the surface of the rubber stoppers of the vial of diluent and vial of TheraCys. Reconstitute the freeze-dried material with the total 3 mL volume of diluent. Shake the vial gently until a fine, even suspension results. Avoid foaming since this will prevent withdrawal of the proper dose. Withdraw the entire contents (approximately 3 mL) of the reconstituted material into the syringe.

The reconstituted material from the vial (1 dose) is further diluted in an additional 50 mL of sterile, preservative-free saline to a final volume of 53 mL for intravesical instillation.

TheraCys should be used immediately after reconstitution. However, if there is an unavoidable delay between reconstitution and administration, this delay must not exceed 2 hours. Any reconstituted product which exhibits flocculation or clumping that cannot be dispersed with gentle shaking should not be used.

Reconstituted product should not be exposed to sunlight, direct or indirect. Exposure to artificial light should be kept to a minimum.

Instructions for Disposal

After use, unused product, packaging and all equipment and materials used for instillation of the product (eg, syringes, catheters) should be placed immediately in a container for biohazardous materials and disposed of according to local requirements applicable to biohazardous materials.

Urine voided during the 6 hour period following TheraCys instillation should be disinfected with an equal volume of 5% hypochlorite solution (undiluted household bleach) and allowed to stand for 15 minutes before flushing. (See PRECAUTIONS: PATIENT INFORMATION.)

Treatment Schedule

Intravesical treatment of the urinary bladder should begin 7 to 14 days after biopsy or transurethral resection and consists of induction and maintenance therapy. For the induction therapy, one dose of TheraCys is administered each week for 6 consecutive weeks. Induction therapy should be followed by maintenance therapy, consisting of one dose given 3, 6, 12, 18 and 24 months following the initial dose.

TheraCys is supplied in packages containing one vial of the freeze-dried product, containing 81 mg (dry weight) (10.5 ± 8.7 x 10⁸ CFU) and one vial containing 3 mL of diluent - Product No. 49281-880-01.

CPT Code: 90586

CPT is a registered trademark ofthe American Medical Association.

Storage

TheraCys, BCG Live (Intravesical) and the accompanying diluent should be refrigerated at 2°to 8°C (35°to 46°F). It should not be used after the expiration date marked on the vial, otherwise it may be inactive.

At no time should the freeze-dried TheraCys be exposed to sunlight, direct or indirect. Exposure to artificial light should be kept to a minimum.

Manufactured by: Sanofi Pasteur Limited, Toronto, Ontario, Canada. Distributed by: Sanofi Pasteur Inc. Swiftwater, PA 18370 USA. FDA Rev date: n/a

Last updated on RxList: 10/28/2008

Data from Clinical Studies

Administration of TheraCys causes an inflammatory response in the bladder and has been frequently associated with transient fever, hematuria, urinary frequency and dysuria; careful patient monitoring is required. Symptoms of bladder irritability are reported in approximately 50% of patients receiving TheraCys and typically begin 4-6 hours after instillation and last 24-72 hours. The irritative side effects are usually seen following the third instillation and tend to increase in severity after each administration. The mechanism of action of the irritative side effects has not been studied, but is most consistent with an immunological mechanism. There is no evidence that dose reduction or antituberculous drug therapy can prevent or lessen the irritative symptoms ofTheraCys.

The adverse reactions which occurred among 127 recipients of TheraCys during a US clinical trial are listed in Table 2. (4) The adverse reactions are combined totals caused by both the original bladder cancer and the TheraCys treatment.

Table 2: Adverse Reactions: Toxicity Data Derived From a US Clinical Trial (4)

The following adverse reactions were reported in < 5% of patients: coagulopathy, abdominal pain, liver involvement, systemic infection, pulmonary infection, cardiac (unclassified), headache, skin rash, tissue in urine, local infection, constipation, dizziness, fatigue, thrombocytopenia, ureteral obstruction and flank pain.

In a US Clinical Trial, 112 patients received TheraCys. The incidence of adverse reactions associated with intravesical TheraCys is given below.

The following adverse events were reported in =1% of patients: tissue in urine, local infection, constipation, dizziness, fatigue, thrombocytopenia and flank pain.

In this study, local irritative symptoms were more common with TheraCys than with doxorubicin; however, grade ≥ 3 irritative toxicity was similar, occurring in approximately 2-7% of patients. Systemic symptoms (fever, chills, malaise, etc.) were also more common with TheraCys. Overall, grade ≥ 3 toxicities were seen in 26 patients (23%) treated with TheraCys and 25 patients (21%) treated with doxorubicin. "Systemic infection" was reported to occur in three patients treated with TheraCys (one grade 2 and two grade 3) and one patient treated with doxorubicin (grade 2). In four patients, treatment was discontinued because of toxicity (two with irritative symptoms, one with severe hematuria and one with possible BCG infection). In addition, six patients refused further treatment because of severe local toxicity and/or chills. Six of these ten patients received TheraCys. Table 3 compares the common adverse events reported in this study.

Table 3: Comparative Toxicity from a US Clinical Trial (4)

Acute, localized irritative side effects of TheraCys may be accompanied by systemic manifestations consistent with a "flu-like" syndrome. Systemic adverse effects of 1-2 days' duration such as malaise, fever and chills often reflect hypersensitivity reactions.

However, symptoms such as fever of ≥ 38.5°C, or acute localized inflammation such as epididymitis, prostatitis, or orchitis, persisting longer than 48 hours suggest active infection and evaluation for serious infectious complication should be considered.

Data from Postmarketing Experience

These events were reported voluntarily from a population of uncertain size, it is not possible to reliably calculate their frequencies.

Symptomatic granulomatous prostatitis, epididymo-orchitis, and renal abscess associated with administration of intravesical BCG have been reported.

Ocular symptoms (including uveitis, conjunctivitis, iritis, keratitis, granulomatous choreoretinitis) alone, or in combination with joint symptoms (arthritis or arthralgia), urinary symptoms and/or skin rash, have been reported following administration of intravesical BCG. The risk appears to be elevated among patients who are positive for HLA-B27. (13)

Skin rash, arthralgia and migratory arthritis may be allergic reactions.

Serious infectious complications of intravesical BCG have been reported. The most serious infectious complication of BCG is disseminated sepsis associated with death. In addition, BCG infections have been reported in eye, lung, liver, bone, bone marrow, kidney, regional lymph nodes, peritoneum and prostate in patients who have received intravesical BCG. Some male genitourinary tract infections (orchitis/epididymitis) have been refractory to multiple drug antimycobacterial therapy and required orchiectomy.

Treatment ofAdverse Reactions

If a patient develops persistent fever or experiences an acute febrile illness consistent with BCG infection, BCG instillations should be permanently discontinued, the patient immediately evaluated and treated for BCG infection and an infectious disease consultation sought. (See WARNINGS and PRECAUTIONS.) Treatment with two or more antimycobacterial agents should be initiated promptly while diagnostic evaluation, including cultures, is conducted. Negative cultures do not necessarily rule out infection. TheraCys is sensitive to the most commonly used antimycobacterial agents (isoniazid, rifampin and ethambutol). TheraCys is not sensitive to pyrazinamide. (14)

Reporting ofAdverse Reactions

Patients should be encouraged to report all adverse events after treatment with TheraCys. Adverse events should be reported by health care providers to MEDWATCH (call 1-800-FDA-1088 or report on line to www.fda.gov/medwatch). Physicians, physician assistants, nurses and pharmacists should report adverse occurrences temporally related to the administration of the product to the Pharmacovigilance Department, Sanofi Pasteur Inc., Discovery Drive, Swiftwater PA 18370 or call 1-800-822-2463.

Treatment combinations using immunosuppressants and/myelosuppressants and/or radiation interfere with the development of the immune response to TheraCys and increase the risk of disseminated BCG infection. Antimicrobial therapy for other infections may interfere with the effectiveness ofTheraCys. (12)

As there are no data to suggest that the acute, local urinary tract symptoms common with intravesical BCG are due to mycobacterial infection, antimycobacterial drugs (eg, isoniazid) should not be used prophylactically to prevent the local, irritative side effects ofTheraCys.

For patients with a condition that may in the future require mandatory immunosuppression (eg, awaiting an organ transplant, myasthenia gravis) the decision to treat with TheraCys should be considered carefully.

REFERENCES

13. Wittes RC, et al. Characterization of BCG-associated sterile arthritis and Reiter's syndrome. New Delhi, India: 10th International Congress of Immunology. 1998:1245-9.

14. van der Meijden APM, et al. The possible influence of antibiotics on results of Bacillus Calmette-Guérin intravesical therapy for superficial bladder cancer. J Urol 1991;146:444-6. Product Information as ofJuly 2006.

Last updated on RxList: 10/28/2008

Systemic BCG Reaction

A systemic BCG reaction is a systemic granulomatous illness, which may occur subsequent to exposure to BCG. Because it is usually difficult to isolate BCG organisms from affected organs, it is often unclear to what extent such a reaction is caused by an infectious process versus an inflammatory hypersensitivity reaction, hence the term "systemic BCG reaction". Based on past clinical experience with intravesical BCG, "systemic BCG reaction" may be defined as the presence of any of the following signs, if no other etiologies for such signs are detectable: fever ≥ 39.5°C for ≥ 12 hours; fever ≥ 38.5°C for ≥ 48 hours; pneumonitis; hepatitis; other organ dysfunction outside of the genitourinary tract with granulomatous inflammation on biopsy; or the classical signs of sepsis, including circulatory collapse, acute respiratory distress and disseminated intravascular coagulation. (6) If TheraCys is administered within one week of either biopsy, TUR or traumatic bladder catheterization (associated with hematuria), a systemic BCG reaction is much more likely to occur. Death has been reported with the use of TheraCys in association with systemic BCG reaction in post-marketing experience.

Patients should be monitored for the presence of symptoms and signs of toxicity after each intravesical treatment. If a patient develops persistent fever or experiences an acute febrile illness consistent with BCG infection, BCG instillations should be permanently discontinued, the patient immediately evaluated and treated for BCG infection and an infectious diseases consultation sought. (See PRECAUTIONS.)

Additional Warnings

TheraCys is not a vaccine for the prevention ofcancer.

TheraCys 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 antimycobacterial therapy. Special culture media are required for mycobacteria and physicians administering intravesical BCG should have these media readily available.

The use of TheraCys may cause tuberculin sensitivity. Since this is a valuable aid in the diagnosis of tuberculosis, it may be advisable to determine the tuberculin reactivity by testing before treatment.

Intravesical instillations of BCG should be postponed during treatment with antibiotics, since antimicrobial therapy may interfere with the effectiveness of TheraCys. (See DRUG INTERACTIONS) TheraCys should not be used in individuals with concurrent infections.

In patients with small bladder capacity, increased risk of bladder contracture should be considered in decisions to treat with TheraCys.

BCG infection of aneurysms and prosthetic devices (including arterial grafts, cardiac devices and artificial joints) have been reported following intravesical administration of BCG. (7) (8) The risk of these ectopic BCG infections has not been determined. The benefits of BCG therapy must be carefully weighed against the possibility of an ectopic BCG infection in patients with pre-existing arterial aneurysms or prosthetic devices ofany kind.

If a bacterial urinary tract infection (UTI) occurs during the course of TheraCys treatment, TheraCys instillation should be withheld until complete resolution of the bacterial UTI for two reasons: • the combination of a UTI and BCG-induced cystitis may lead to more severe adverse effects on the genitourinary tract and • BCG bacilli are sensitive to a wide variety of antibiotics; (9) antimicrobial administration may therefore diminish the efficacy of TheraCys. Similarly, patients undergoing antimicrobial therapy for other infections should be evaluated to assess whether the therapy might diminish the efficacy of TheraCys .

Caution: the stopper ofthe vial for this product contains natural rubber latex which may cause allergic reactions.

Management of Serious BCG Complications

Acute, localized irritative toxicities of TheraCys may be accompanied by systemic manifestations, consistent with a "flu-like" syndrome. Systemic adverse effects of 1-2 days' duration such as malaise, fever and chills often reflect hypersensitivity reactions. However, symptoms such as fever of ≥ 101.3°F (38.5°C), or acute localized inflammation such as epididymitis, prostatitis, or orchitis persisting longer than 2-3 days suggest active infection and evaluation for serious infectious complications should be considered.

In patients who develop persistent fever or experience an acute febrile illness consistent with BCG infection, two 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.

TheraCys is sensitive to the most commonly used antimycobacterial agents (isoniazid, rifampin and ethambutol). TheraCys is not sensitive to pyrazinamide.

General

TheraCys contains live mycobacteria and should be prepared and handled using aseptic technique. (See DOSAGE AND ADMINISTRATION, Preparation of Agent.) BCG infections have been reported in health care workers preparing BCG for administration. Needle stick injuries should be avoided during the handling and mixing of TheraCys.

Nosocomial infections have been reported in immunosuppressed patients receiving parenteral drugs that were prepared in areas in which BCG was prepared. (10) (11)

BCG is capable of dissemination when administered by intravesical route and serious infections, including fatal infections, have been reported in patients receiving intravesical BCG. (6) Care should be taken not to traumatize the urinary tract or to introduce contaminants into the urinary system. Seven to 14 days should elapse before TheraCys is administered following TUR, biopsy, or traumatic catheterization.

TheraCys may be administered to persons in groups at high risk for HIV infection only after careful evaluation of risk/benefit and with extra caution.

The use of TheraCys may cause a falsely positive tuberculin reaction sensitivity. It may therefore be advisable to test to determine the true tuberculin reactivity before treatment. (5)

Pregnancy Category C

Animal reproduction studies have not been conducted with TheraCys. It is also not known whether TheraCys can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. TheraCys should not be given to a pregnant woman unless clearly needed. Women should be advised not to become pregnant while on therapy.

Nursing Mothers

It is not known whether TheraCys can be excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions from TheraCys in nursing infants, it is advisable to discontinue nursing or to discontinue the drug, taking into account the importance ofthe drug to the mother.

Pediatric Use

Safety and effectiveness of TheraCys for the treatment of superficial bladder cancer in pediatric patients have not been established. Therefore, TheraCys should not be used in pediatric patients.

REFERENCES

5. CDC. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings. MMWR 2005;54(RR-17):1-89.

6. Lamm DL, et al. Incidence and treatment of complications of Bacillus Calmette-Guérin intravesical therapy in superficial bladder cancer. J Urol 1992;147:596-600.

7. Stone D. Mycobacterium bovis infection of an implantable defibrillator following intravesical therapy with bacille Calmette-Guérin. Clin InfDis 1993;16:825-6.

8. Wolf YG, et al. Infection of a ruptured aortic aneurysm and an aortic graft with bacille Calmette-Guérin after intravesical administration for bladder cancer. J Vasc Surg 1995;22:80-4.

9. Durek C, et al. Interference of modern antibacterials with bacillus Calmette-Guérin viability. J Urol 1999;162:1959-62.

10. Stone MM, et al. Brief report: Meningitis due to iatrogenic BCG infection in two immunocompromised children. N Engl J Med 1995,333:561-3.

11. Waecker NJ, et al. Nosocomial transmission of Mycobacterium bovis bacille Calmette-Guérin to children receiving cancer therapy and to their health-care providers. Clin Infect Dis 2000;30:356-62.

12. Böhle A, Jocham D. Intravesical immunotherapy with Bacillus Calmette-Guérin, facts, figures and results. München, Germany: Urban & Fischer; 2000. p. 111-2.

Last updated on RxList: 10/28/2008

Overdosage occurs if more than one vial of TheraCys is administered per instillation. If overdosage occurs, the patient should be closely monitored for signs of active local or systemic infection. For acute local or systemic reactions suggesting active infection, an infectious disease specialist experienced in BCG complications should be consulted.

Because of the risk of disseminated BCG infection, TheraCys should not be used in immunosuppressed patients or persons with congenital or acquired immune deficiencies, whether due to concurrent disease (eg, AIDS, leukemia, lymphoma), cancer therapy (eg, cytotoxic drugs, radiation), or immunosuppressive therapy (eg, corticosteroids). (See PRECAUTIONS: DRUG INTERACTIONS.)

TheraCys is contraindicated for patients with current symptoms or a previous history of systemic BCG reaction. (See WARNINGS.) Treatment should be postponed until resolution ofa concurrent febrile illness, urinary tract infection, or gross hematuria. Seven to 14 days should elapse before TheraCys is administered following biopsy, TUR, or traumatic catheterization.

TheraCys should not be administered to persons with active tuberculosis. Active tuberculosis should be ruled out before starting treatment with TheraCys. A test for detecting Mycobacterium tuberculosis infection should be performed if PPD (purified protein derivative of tuberculin) status is unknown. A positive Mantoux test, by itself, is not a contraindication to using TheraCys but an assessment must be made regarding whether the patient has signs, symptoms and/or a chest x-ray consistent with active or latent tuberculosis that requires treatment with antimycobacterial drugs. (5)

REFERENCES

5. CDC. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings. MMWR 2005;54(RR-17):1-89.

Last updated on RxList: 10/28/2008

When administered intravesically as a cancer therapy, BCG promotes a local acute inflammatory and sub-acute granulomatous reaction with macrophage and lymphocyte infiltration in the urothelium and lamina propria of the urinary bladder. (1) (2) The exact mechanism of action is unknown, but the anti-tumor effect appears to be T-lymphocyte-dependent. (2) (3)

Clinical Studies

In a multicenter randomized clinical trial, TheraCys was compared to doxorubicin hydrochloride (Adriamycin®) in patients with carcinoma in situ (CIS) of the urinary bladder, recurrent Ta/T1 papillary tumors of the urinary bladder, or both. (4) Patients were stratified by the presence or absence of CIS and analyzed separately. All papillary tumors were completely resected prior to study entry. The study endpoints were disease-free survival and 2-year disease-free survival. TheraCys was administered intravesically weekly for 6 weeks, with an additional single instillation at 3, 6, 12, 18 and 24 months following the initiation of treatment (total of 11 instillations over 2 years). The initial treatment with doxorubicin was given within 3 days of TUR, followed by 4 weekly treatments and then by 11 monthly treatments (total of 16 instillations over 1 year). Cytology and cystoscopy were obtained every 3 months for 2 years. A total of 285 patients were randomized: 142 to treatment with doxorubicin (69 CIS and 73 non-CIS) and 143 to treatment with TheraCys (70 CIS and 73 non-CIS). An intent-to-treat analysis was performed.

For patients with CIS, the complete response rate (ie, negative biopsies and urine cytology) within 6 months of the initiation of treatment was 33% with doxorubicin and 71% with TheraCys (p < 0.001, Fisher's Exact Test). The probability of being disease-free at 2 years was 23% with doxorubicin and 51% with TheraCys (p < 0.001, Z Test). The median disease-free survival was 4.9 months for doxorubicin and 30 months for TheraCys (p < 0.001, Log Rank Test).

For patients with Ta/T1 papillary tumors only, the 2-year disease-free survival was 29% with doxorubicin and 50% with TheraCys (p=0.008, Z Test). The median disease-free survival was 10.5 months with doxorubicin and 22.5 months with TheraCys (p=0.001, Log Rank Test).

The results are summarized in Table 1.

Table 1: US Clinical Trial – Efficacy (4)

REFERENCES

1. Mikkelsen DJ, Ratliff TL. Mechanisms of action of intravesical Bacillus Calmette-Guérin for bladder cancer. In: Urologic Oncology. 1989:195-211.

2. O'Donnell MA, DeWolf WC. BCG immunotherapy for superficial bladder cancer. New prospects for an old warhorse. Surg Oncol Clin North Amer 1995;4:189-202.

3. Prescott S, et al. Intravesical Evans strain BCG therapy: quantitative immunohistochemical analysis of the immune response within the bladder wall. J Urol 1992:147:1636-42.

4. Lamm DL, et al. A randomized trial of intravesical doxorubicin and immunotherapy with Bacille Calmette-Guérin for transitional-cell carcinoma of the bladder. N Eng J Med 1991;325:1205-9.

Last updated on RxList: 10/28/2008

TheraCys is retained in the bladder for as long as possible up to 2 hours and then voided. To avoid transmission of BCG to others, for 6 hours after treatment, patients should void while seated in order to avoid splashing of urine. Urine voided during this time should be disinfected for 15 minutes with an equal volume of household bleach before flushing or disposal. Unless medically contraindicated, patients should be instructed to increase fluid intake in order to "flush" the bladder for several hours following treatment with TheraCys. Patients may experience burning with the first void after treatment.

Because TheraCys contains live mycobacteria, excreted urine may also contain live bacteria. Patients should be advised on appropriate infection control procedures to protect family and close contacts from infection.

Fever, chills, malaise, flu-like symptoms, increased fatigue or an increase in urinary symptoms, (such as burning or pain on urination) are not uncommon. However, patients should notify their physicians if any of these symptoms last more than 48 hours or increase in severity. Patients should also notify their physicians if they experience any of the following: an increase in urinary symptoms (such as urgency, frequency of urination, blood in urine), joint pain, eye complaints (such as pain, irritation or redness), cough, skin rash, jaundice or vomiting.

Last updated on RxList: 10/28/2008

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

BCG VACCINE - INTRAVESICAL

COMMON BRAND NAME(S): Theracys

WARNING: This medication contains live bacteria that have been weakened to decrease the chances of causing an illness. However, this medication has rarely caused very serious, possibly fatal infections. Tell your doctor immediately if you develop any signs of infection (e.g., high/persistent fever).

USES: This medication is used to treat a certain type of bladder cancer (carcinoma in situ-CIS) and prevent it from returning. It is also used to prevent another type of bladder cancer (papillary tumor) from returning after surgery to remove it. This medication works by causing the body's defense system (immune system) to become more active.

This form of the medication is not used to prevent tuberculosis.

HOW TO USE: This medication is given into the bladder through a tube (catheter) as directed by your doctor. Do not give this medication by injection. Read and learn all preparation and usage instructions supplied by the manufacturer. Follow all instructions for proper handling and mixing with the correct fluids. This medication is usually given weekly for the first 6 weeks and then less often thereafter as directed by your doctor.

Do not drink any fluids for 4 hours before treatment. The medication is left in the bladder for up to 2 hours and then released by urinating. Follow your doctor's instructions carefully. There may be some burning pain when you first urinate. Since the urine contains live bacteria that may infect you or others, you must sit down to urinate for 6 hours after treatment to avoid splashing of the urine. After each time you urinate during this 6-hour period, pour household bleach (about the same amount of bleach as the amount of urine) into the toilet, then wait 15 minutes before flushing. Always wash your hands afterward. Talk to your doctor about other important things you must do to prevent infection.

Drink plenty of fluids after your first urination unless otherwise directed by your doctor. Doing so helps clear the medication from your body.

SIDE EFFECTS: Bladder irritation (e.g., difficult/painful/frequent/bloody urination), fever, or chills may occur. High/persistent fever may be a sign of an infection. Tell your doctor or pharmacist promptly if any of these effects occur, persist, or worsen. Your doctor may prescribe additional medications to help control these symptoms. Nausea, vomiting, loss of appetite, or diarrhea may also occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: muscle/joint pain, pain/swelling of the testes, unusual tiredness, fast/pounding heartbeat, shortness of breath, cough, vision changes, redness/swelling/pain in the eye, eye sensitivity to light, severe stomach/abdominal pain, yellowing skin/eyes.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before receiving this medication, tell your doctor or pharmacist if you are allergic to it; or to latex; or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: immune system problems (e.g., HIV, certain cancers such as leukemia/lymphoma), radiation treatment, current infection/fever (e.g., bladder infection, active tuberculosis), injury/procedure in the bladder within the last 7 days (e.g., catheterization, biopsy, signs of bloody urine).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: certain blood vessel disease (aneurysm), man-made medical devices/parts in the body (e.g., pacemakers, artificial joints, arterial grafts).

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor. It is recommended that women receiving this medication avoid pregnancy. Consult your doctor for more details and to discuss using at least 2 reliable forms of birth control (e.g., condoms, birth control pills) while receiving this medication. If you become pregnant or think you may be pregnant, tell your doctor immediately.

It is not known whether this drug passes into breast milk. Because of the possible risk to the infant, breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

This drug should not be used with the following medications because very serious interactions may occur: antibiotics (e.g., isoniazid, rifampin, penicillins such as amoxicillin, macrolides such as erythromycin), drugs that weaken the immune system (e.g., abatacept, efalizumab, corticosteroids such as prednisone, cancer chemotherapy), mefloquine.

If you are currently using any of these medications listed above, tell your doctor or pharmacist before starting BCG vaccine.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use.

This medication may interfere with the tuberculosis (TB) skin test, possibly causing false test results. If a skin test is needed, it is recommended that patients finish it before treatment.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Keep all regular medical and laboratory appointments.

MISSED DOSE: For the best possible benefit, it is important to receive each scheduled dose of this medication as directed. If you miss a dose, contact your doctor to establish a new dosing schedule.

STORAGE: Refrigerate between 35-46 degrees F (2-8 degrees C) away from light. After mixing, the medication must be used or discarded within 2 hours. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.