BCG vaccine is a lyophilized preparation of live, attenuated organisms of the Calmette-Guérin strain of Mycobacterium bovis .1
BCG is used intravesically for the treatment and prophylaxis of carcinoma in situ (CIS) of the urinary bladder.1 Intravesical BCG is also used for prophylaxis of primary or recurrent stage Ta and/or T1 papillary tumors following transurethral resection (TUR).1 BCG should not be used for stage TaG1 papillary tumors unless they are judged to be at high risk of tumor recurrence.1 BCG is not indicated for papillary tumors of stages higher than T1.1
Non-muscle invasive bladder cancer (NMIBC; previously referred to as superficial bladder cancer) represents approximately 75% of newly diagnosed bladder tumors and is usually treated initially with surgical resection and/or fulguration.4 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).4 Risk stratification is recommended in patients with NMIBC to guide treatment decisions.4 At the time of each occurrence or recurrence, patients should be assigned a clinical stage and classified as "low-", "intermediate-", or "high-risk".4 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.4, 137, 151, 173
Intravesical instillation of BCG, an immunotherapeutic agent, is a preferred regimen for adjuvant therapy for NMIBC in patients who are at high risk of disease progression and/or recurrence and the treatment of choice for CIS;4, 126, 131, 132, 151, 152, 153, 154, 175, 181 prognostic factors indicating high risk of disease progression and/or recurrence have included multiple lesions, frequent recurrence of lesions (more than 3 times in a year), involvement of a large portion of bladder wall, high-grade lesions (i.e., poorly differentiated tumors), carcinoma in situ or papillary tumors associated with carcinoma in situ, T1 lesions, and tumors with overexpression of nuclear p53 protein.132, 133, 136, 151, 156 Compared with surgery alone, treatment with surgery plus adjuvant therapy with intravesical BCG has been shown to cause regression of existing tumor, particularly in patients with residual carcinoma in situ; delay progression to muscle-invasive and/or metastatic disease; reduce the risk of tumor recurrence; increase the likelihood of bladder preservation; and decrease the risk of death from bladder cancer.129, 131, 137, 141, 143, 152, 154, 155, 156
In a randomized study comparing administration of both intravesical and subcutaneous BCG with intravesical doxorubicin, the BCG regimen was associated with higher response rates and decreased recurrence rates in patients with recurrent papillary tumors and/or carcinoma in situ.144 In patients with carcinoma in situ, intravesical BCG therapy produces complete response rates of approximately 70% and reduces or delays the need for salvage cystectomy; however, no effect on overall survival has been observed.129, 143, 144 Intravesical BCG also has been shown to be superior to intravesical mitomycin in preventing tumor recurrence in patients with high risk of recurrence and/or progression of NMIBC;132, 152, 157, 182 although improvement in disease-free survival was noted with use of intravesical BCG versus intravesical mitomycin at 5 years of follow-up, no difference in disease progression or overall survival has been observed.182
Intravesical regimens of alternating or sequential mitomycin and BCG appear to have similar efficacy and toxicity as mitomycin alone in patients with NMIBC at intermediate to high risk of recurrence.183, 184 In patients with NMIBC who have low to intermediate risk of recurrence, intravesical mitomycin has been shown to be equally effective in preventing tumor recurrence and is less toxic compared with intravesical BCG.4, 132, 158, 159, 185 Because of the greater frequency of adverse effects, including cystitis, as well as the rare but sometimes fatal occurrence of BCG sepsis, use of intravesical BCG generally is reserved for adjuvant therapy in patients with NMIBC who have high risk of recurrence and/or progression of disease.4, 147, 175 BCG also has been used as second-line therapy in patients with disease that is refractory to intravesical treatment with chemotherapeutic agents.132, 143, 147
Dispensing and Administration Precautions
BCG is administered by intravesical instillation after reconstitution.1 Do not inject subcutaneously or IV.1
Intact vials of BCG lyophilized powder for intravesical instillation should be refrigerated at 2-8°C.1 The powder should be protected from direct sunlight.1
To prepare the 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 the use of bacteriostatic solutions.1 Ensure that the needle is inserted through the center of the rubber stopper of the vial.1 Gently swirl vial until a homogenous suspension is obtained.1 Avoid forceful agitation, which may cause clumping of the mycobacteria.1 Dilute the cloudy BCG suspension in sterile, preservative-free saline to a final volume of 50 mL.1 Mix the suspension gently prior to intravesical instillation.1 Do not filter contents of the BCG vial.1 Store the reconstituted suspension refrigerated (2-8°C) and protect from exposure to direct sunlight; use within 2 hours and discard any unused portion.1
After reconstitution, instill the BCG suspension into the bladder by gravity flow via a catheter.1 After instillation is complete, remove the catheter; BCG should be retained in the patient's bladder for 2 hours and then voided.1 Patients unable to retain the suspension for 2 hours should be allowed to void sooner, if necessary.1 While BCG is retained in the bladder, patients should be repositioned every 15 minutes to maximize bladder surface exposure to the drug.1
The recommended adult dose of BCG (TICE strain) administered by intravesical instillation for the treatment of carcinoma in situ and for prophylaxis of recurrent papillary tumors is 1 vial containing 1-8 × 108 colony-forming units (CFUs) suspended in 50 mL of preservative-free saline.1
The standard course of BCG therapy is once weekly instillation of BCG for 6 consecutive weeks.1, 145 A second 6-week course of therapy with intravesical BCG may be required for optimal response.1, 130, 138, 145 An interval of rest between the 2 courses of therapy has been employed to avoid suppression of immune response and to optimize tumor response to intravesical BCG.131 Thereafter, intravesical administration of BCG may be continued at approximately monthly intervals for at least 6 to 12 months.1
BCG used for intravesical therapy is a living organism and infection may occur as a complication of therapy; a boxed warning has been included in the prescribing information for intravesical BCG regarding this risk.1, 134, 152 Systemic infection, including pneumonitis, hepatitis, and sepsis, has been reported in up to 1% of patients.134 Miliary tuberculosis has been reported in at least 2 patients receiving intravesical BCG.140 The most serious complication is disseminated BCG sepsis, diagnosed clinically in patients with high fever and shaking chills followed by hypotension.1, 130, 134, 152 At least 10 deaths related to BCG toxicity have been reported,134, 152 and intravascular absorption of BCG (e.g., secondary to intravasation from traumatic catheterization and bleeding) appears to be an important contributing factor in most cases.130, 134, 147, 152 BCG infections have been reported in healthcare workers, primarily from exposures resulting from accidental needle sticks or skin lacerations during preparation of BCG, and nosocomial infections have been reported in patients receiving parenteral drugs that were prepared in areas in which BCG was reconstituted.1
Special handling precautions and procedures for proper disposal are required to prevent transmission of BCG infection.1 Care should be taken not to traumatize the urinary tract or to introduce contaminants into the urinary system.1 Clinicians administering the drug should be familiar with the prevention and treatment of BCG-related complications; if such complications occur, consultation with an experienced infectious diseases specialist is recommended.1 Treatment of infectious complications of BCG requires long-term, multiple-drug antibiotic therapy.1 Special culture media required for mycobacteria should be readily available when administering intravesical BCG.1 Intravesical BCG therapy should be initiated no sooner than 1 week following transurethral resection, bladder biopsy, or traumatic catheterization to allow time for healing and to reduce the risk of systemic toxicity.1, 130, 134, 143, 147 Because of the risk of developing systemic BCG infection, the use of intravesical BCG is contraindicated in patients who are immunocompromised.1
Monitor patients for signs and symptoms of BCG infection and sepsis after each intravesical treatment.1 Signs and symptoms suggestive of systemic BCG infection include flu-like symptoms lasting more than 72 hours, fever ≥103°F, acute localized inflammation, systemic manifestations increasing in intensity with repeated instillations, or persistent liver function abnormalities.1 Local symptoms (prostatitis, epididymitis, orchitis) lasting more than 2 to 3 days may also suggest active infection.1 If patients develop a persistent fever or acute febrile illness consistent with BCG infection, discontinue BCG; immediately evaluate the patient and administer appropriate treatment.1 Treatment with antimycobacterial agents should not be delayed while the diagnostic evaluation, including cultures, is being conducted.1 Negative cultures do not necessarily rule out infection.1 When appropriate, consult with an infectious diseases specialist or other clinician experienced in the diagnosis and treatment of mycobacterial infections.1
Other Warnings and Precautions
Intravesical BCG is not a vaccine for the prevention of cancer and should not be used for the prevention of tuberculosis.1 BCG vaccine (administered via percutaneous route) should be used for vaccination against tuberculosis.1
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.1
Small bladder capacity has been associated with increased risk of severe local reactions and should be considered when deciding whether to use BCG therapy.1
BCG may cause tuberculin sensitivity.1 Since this is a valuable aid in the diagnosis of tuberculosis, it is recommended to determine tuberculin reactivity by PPD skin testing before treatment.1
Animal reproduction studies have not been conducted with intravesical BCG.1 It is also not known whether BCG can cause fetal harm when administered to a pregnant woman or affect reproductive capacity.1 Intravesical BCG should not be given to a pregnant woman except when clearly needed.1
It is not known whether intravesical BCG is excreted into human milk.1 Because many drugs are excreted in human milk and because of the potential for serious adverse reactions from BCG in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the mother.1
Females and Males of Reproductive Potential
Females of reproductive potential should be advised not to become pregnant while on BCG therapy.1
Safety and effectiveness of intravesical BCG for the treatment of superficial bladder cancer in pediatric patients have not been established.1
Of the total number of patients in clinical studies of intravesical BCG, the average age was 66 years.1 No overall difference in safety or effectiveness was observed between older and younger subjects.1 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.1
Bladder irritability is a common adverse effect of intravesical BCG, reported in approximately 60% of patients.1 Other common adverse effects occurring at a frequency of ≥5% include dysuria, urinary frequency, flu-like syndrome, hematuria, fever, malaise/fatigue, cystitis, urgency, and nocturia.1
Antimicrobial agents may interfere with the effectiveness of BCG.1
Immunosuppressive agents and radiation therapy may interfere with the development of immune response to BCG and should not be used concomitantly with intravesical BCG.1
BCG for intravesical instillation is a lyophilized preparation of live, attenuated organisms of the Calmette-Guérin strain of M. bovis and is commercially available in the US as TICE® BCG, which contains the TICE substrain.1 Following reconstitution as directed, each vial of TICE® BCG contains 1-8 × 108 CFU of BCG.1
The precise mechanism of action of intravesical BCG has not been determined;1, 130, 135 however, both inflammatory effects and immune response are believed to be involved.130 A BCG-induced granulomatous reaction within the bladder wall leads to sloughing of the epithelium and destruction of cancer cells in superficial bladder cancer.143 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.130, 135, 149
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.
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.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | For injection, for intravesical instillation | 1-8 × 108 CFU of BCG bacillus | TICE® BCG | Merck Sharp and Dohme |
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions August 10, 2025. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
1. Merck Sharp and Dohme. TICE BCG (BCG Live) for intravesical use prescribing information. Durham, NC; 2022 Aug.
4. Holzbeierlein JM, Bixler BR, Buckley DI, et al. Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer: AUA/SUO Guideline: 2024 Amendment [published correction appears in J Urol. 2024 Dec;212(6):936. doi: 10.1097/JU.0000000000004251.]. J Urol. 2024;211(4):533-538. doi:10.1097/JU.0000000000003846
126. Hall RR. Application of clinical trials to the care of patients with bladder cancer. Eur Urol . 1997; 31(Suppl 1):42-6. [PubMed 9076485]
129. Hudson MA, Herr HW. Carcinoma in situ of the bladder. J Urol . 1995; 153:564-72. [PubMed 7861485]
130. Hrouda D, Muir GH, Dalgleish AG. The role of immunotherapy for urological tumours. Br J Urol . 1997; 79:307-16. [PubMed 9117,206]
131. Lamm DL. Optimal BCG treatment of superficial bladder cancer as defined by American trials. Eur Urol . 1992; 21(Suppl 2):12-6. [PubMed 1396941]
132. Kurth KH. Diagnosis and treatment of superficial transitional cell carcinoma of the bladder: facts and perspectives. Eur Urol . 1997; 31(Suppl 1):10-9. [PubMed 9076481]
133. Reading J, Hall RR, Parmar MKB. The application of prognostic factor analysis for Ta.T1 bladder cancer in routine urological practice. Br J Urol . 1995; 75:604-7. [PubMed 7613798]
134. Lamm DL. Complications of bacillus Calmette-Guérin immunotherapy. Urol Clin North Am . 1992; 19:565-72. [PubMed 1636240]
135. Sargent ER, Williams RD. Immunotherapeutic alternatives in superficial bladder cancer: interferon, interleukin-2, and keyhole-limpet hemocyanin. Urol Clin North Am . 1992; 19:581-9. [PubMed 1378983]
136. Caliskan M, Türkeri LN, Mansuroglu B et al. Nuclear accumulation of mutant p53 protein: a possible predictor of failure of intravesical therapy in bladder cancer. Br J Urol . 1997; 79:373-7. [PubMed 9117216]
137. Lamm DL, Griffith JG. Intravesical therapy: does it affect the natural history of superficial bladder cancer? Semin Urol . 1992; 10:39-44.
138. Bui TT, Schellhammer PF. Additional bacillus Calmette-Guérin therapy for recurrent transitional cell carcinoma after an initial complete response. Urology . 1997; 49:687-91. [PubMed 9145971]
140. Foster DR. Miliary tuberculosis following intravesical BCG treatment. Br J Radiol . 1997; 70:429. [PubMed 9166085]
141. Herr HW, Schwalb DM, Zhang ZF et al. Intravesical bacillus Calmette-Guérin therapy prevents tumor progression and death from superficial bladder cancer: ten-year follow-up of a prospective randomized trial. J Clin Oncol .
143. De Jager R, Guinan P, Lamm D et al. Long-term complete remission in bladder carcinoma in situ with intravesical TICE bacillus Calmette-Guerin: overview analysis of six phase II clinical trials. Urology . 1991; 38:507-13. [PubMed 1836081]
144. Lamm DL, Blumenstein BA, Crawford ED et al. A randomized trial of intravesical doxorubicin and immunotherapy with bacillus Calmette-Guérin for transitional-cell carcinoma of the bladder. N Engl J Med . 1991; 325:1205-9. [PubMed 1922207]
145. Coplen DE, Marcus MD, Myers JA et al. Long-term followup of patients treated with 1 or 2, 6-week courses of intravesical bacillus Calmette-Guerin: analysis of possible predictors of response free of tumor. J Urol . 1990; 144:652-7. [PubMed 2388321]
147. Lamm DL, van der Meijden APM, Morales A et al. Incidence and treatment of complications of bacillus Calmette-Guerin intravesical therapy in superficial bladder cancer. J Urol . 1992; 147:596-600. [PubMed 1538436]
149. Zhang Y, Khoo HE, Esuvaranathan K. Effects of bacillus Calmette-Guérin and interferon-α-2b on human bladder cancer in vitro . Int J Cancer . 1997; 71:851-7. [PubMed 9180156]
151. Bouffioux C. Intravesical adjuvant treatment in superficial bladder cancer: a review of the question after 15 years of experience with the EORTC GU group. Scand J Urol Nephrol Suppl . 1991; 138:167-77. [PubMed 1838428]
152. Nseyo UO, Lamm DL. Therapy of superficial bladder cancer. Semin Oncol . 1996; 23:598-604. [PubMed 8893870]
153. Badalament RA, Schervish EW. Bladder cancer: current diagnostic methods and treatment options. Postgrad Med . 1996; 100:217-9. [PubMed 8700819]
154. Lamm DL. Long-term results of intravesical therapy for superficial bladder cancer. Urol Clin North Am . 1992; 19:573-80. [PubMed 1636241]
155. Sarosdy MF, Lamm DL. Long-term results of intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer. J Urol . 1989; 142:719-22. [PubMed 2769847]
156. Herr HW. Progression of stage T1 bladder tumors after intravesical bacillus Calmette-Guerin. J Urol . 1991; 145:40-4. [PubMed 1984096]
157. Lundholm C, Norlén BJ, Ekman P et al. A randomized prospective study comparing long-term intravesical instillations of mitomycin C and bacillus Calmette-Guerin in patients with superficical bladder carcinoma. J Urol . 1996; 156:372-6. [PubMed 8683682]
158. Witjes JA, Meijden APM, Witjes WPJ et al. A randomised prospective study comparing intravesical instillations of mitomycin-C, BCG-Tice, and BCG-RIVM in pTa-pT1 tumours and primary carcinoma in situ of the urinary bladder. Eur J Cancer . 1993; 29A:1672-6. [PubMed 8398292]
159. Krege S, Giani G, Meyer R et al. A randomized multicenter trial of adjuvant therapy in superficial bladder cancer: transurethral resection only versus transurethral resection plus mitomycin C versus transurethral resection plus bacillus Calmette-Guerin. J Urol . 1996; 156:962-6. [PubMed 8709374]
173. Smith JA Jr, Labasky RF, Cockett ATK et al. Bladder cancer clinical guidelines panel summary report on the management of nonmuscle invasive bladder cancer (stages Ta, T1 and TIS). The American Urological Association. J Urol . 1999; 162:1697-701. [PubMed 10524909]
175. Reviewers' comments (personal observations) on bladder cancer.
181. Martinez-Pineiro JA, Jimenez Leon J, Martinez-Pineiro L Jr et al. Bacillus Calmette-Guerin versus doxorubicin versus thiotepa: a randomized prospective study in 202 patients with superficial bladder cancer. J Urol . 1990; 143:502-6. [PubMed 2106041]
182. Malmstrom PU, Wijkstrom H, Lundholm C et al. 5-year followup of a randomized prospective study comparing mitomycin C and bacillus Calmette-Guerin in patients with superficial bladder carcinoma. Swedish-Norwegian Bladder Cancer Study Group. J Urol . 1999; 161:1124-7. [PubMed 10081852]
183. Rintala E, Jauhiainen K, Kaasinen E et al. Alternating mitomycin C and bacillus Calmette-Guerin instillation prophylaxis for recurrent papillary (stages Ta to T1) superficial bladder cancer. Finnbladder Group. J Urol . 1996; 156:56-60. [PubMed 8648837]
184. Witjes JA, Caris CTM, Mungan NA et al. Results of a randomized phase III trial of sequential intravesical therapy with mitomycin C and bacillus Calmette-Guerin versus mitomycin C alone in patients with superficial bladder cancer. J Urol . 1998; 160:1668-72. [PubMed 9783928]
185. Witjes JA, v d Meijden APM, Collette L et al. Long-term follow-up of an EORTC randomized prospective trial comparing intravesical bacille Calmette-Guerin-RIVM and mitomycin C in superficial bladder cancer. EORTC GU Group and the Dutch South East Cooperative Urological Group. European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Collaborative Group. Urology . 1998; 52:403-10. [PubMed 9730451]