BCG intravesical live

Action and Spectrum

Actions and spectrum: 

BCG intravesical live is a form of immunotherapy used in the treatment of bladder cancer. BCG stands for Bacillus Calmette-Guérin, which is a weakened strain of Mycobacterium bovis, a bacterium closely related to the bacteria that cause tuberculosis.

When administered directly into the bladder, BCG stimulates the immune system to fight against bladder cancer cells. The exact mechanisms of action are not known, but BCG is believed to induce an inflammatory response and activate immune cells to recognize and destroy cancer cells. BCG intravesical live is specifically indicated for non-muscle invasive bladder cancer. 

Drug Interaction

Adverse Reaction

Frequency defined 

1-10% 

Renal toxicity (10%) 

Myalgia (7%) 

Urinary retention (6%) 

Coagulopathy (<5%) 

Contracted bladder (5%) 

Skin rash (<5%) 

Diarrhea (3%) 

Respiratory unclassified (2%) 

Hepatic granuloma (1%) 

Pneumonitis (1%) 

Urinary obstruction (1%) 

Genital pain (10%) 

Arthralgia (7%) 

Urinary incontinence (7%) 

Abdominal pain (5%) 

Constipation (<5%) 

Pulmonary infection (<5%) 

Thrombocytopenia (<5%) 

Rigors (3%) 

Weight loss (2%) 

Hepatitis (1%) 

Urethritis (1%) 

>10% 

Urinary frequency (50%) 

Fever (38%) 

Flu like syndrome (33%) 

Anemia (21%) 

UTI (18%) 

Nausea (16%) 

Anorexia (11%) 

Leukopenia (5%) 

Dysuria (60%)
Hematuria (39%) 

Chills (34%) 

Cystitis (29%) 

Urinary urgency (18%) 

Pain (17%) 

Vomiting (16%) 

Nocturia (11%) 

Black Box Warning

Black Box Warning: 

BCG intravesical live carries a black box warning due to the potential risk of disseminated BCG infection. Disseminated BCG infection can occur in individuals with weakened immune systems or those who have had recent bladder surgery or trauma. It is important to note that BCG is a live bacterial vaccine, and there is a risk of systemic infection if it enters the bloodstream. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Known hypersensitivity or allergy to BCG vaccine or any of its components. 
• Active urinary tract infection or active tuberculosis infection. 
• Immunocompromised individuals, such as those with HIV/AIDS, organ transplant recipients, or individuals undergoing immunosuppressive therapy. 
• Pregnancy, as the safety of BCG intravesical live during pregnancy has not been established. 
• Severe bladder inflammation or ulceration.

Caution: 

• Immunocompromised patients: BCG intravesical live should be used with caution in individuals with compromised immune systems, such as those with HIV/AIDS or receiving immunosuppressive therapy. Close monitoring is necessary to ensure that the benefits outweigh the risks. 
• Previous adverse reactions: Individuals who have previously experienced severe adverse reactions to BCG intravesical live should be closely monitored and the potential risks and benefits of further treatment should be carefully assessed. 
• Active infections: BCG intravesical live should not be administered in the presence of an active urinary tract infection or active tuberculosis infection. Treating the infection prior to initiating BCG therapy is important. 
• Bladder inflammation or ulceration: Individuals with severe bladder inflammation or ulceration should be closely monitored during BCG intravesical live treatment due to the potential risk of exacerbating these conditions. 
• Pregnancy and lactation: The use of BCG intravesical live during pregnancy and lactation should be approached with caution due to limited safety data. 

Comorbidities: 

• Immunodeficiency: Patients with immunodeficiency disorders, such as HIV/AIDS or those receiving immunosuppressive therapy, may have a higher risk of complications or reduced response to BCG therapy. 
• Active infections: Individuals with active urinary tract infections or active tuberculosis infections should not receive BCG intravesical live until the infection is adequately treated. 
• Bladder dysfunction: Patients with underlying bladder dysfunction, such as bladder outlet obstruction or neurogenic bladder, may require careful monitoring and management during BCG therapy. 
• Allergies or hypersensitivity: Patients with known allergies or hypersensitivity reactions to BCG or any of its components should avoid BCG intravesical live therapy. 
• Other malignancies: Individuals with a history of other malignancies or concurrent malignancies may require careful evaluation and monitoring during BCG therapy. 

Pregnancy / Lactation

Pregnancy consideration: US FDA pregnancy category: C 

Lactation: Excreted into human milk: Unknown  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.   
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

BCG intravesical live is a vaccine that contains live attenuated Bacillus Calmette-Guérin (BCG) bacteria. When administered intravesically, it stimulates an immune response in the bladder, leading to the activation of various immune cells and the release of cytokines. This immune response helps in the treatment of bladder cancer by targeting and destroying cancer cells. 

BCG intravesical live activates innate immune cells like macrophages, dendritic cells, and natural killer cells. These cells release cytokines, including interferons and interleukins, which promote an inflammatory response and enhance the antitumor immune response. BCG also stimulates the production of T-lymphocytes, which further contribute to the immune-mediated destruction of cancer cells. 

The precise mechanisms of action of BCG intravesical live in bladder cancer treatment are not fully understood. However, it is believed to involve a combination of direct cytotoxic effects on cancer cells, stimulation of immune responses, and induction of immunological memory.  

Pharmacodynamics: 

• Immune activation: BCG intravesical live stimulates the immune system, particularly the innate immune response. It activates macrophages and natural killer cells, which are important in recognizing and eliminating cancer cells in the bladder. 
• Cytokine release: BCG induces the release of various cytokines, including interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). These cytokines help to enhance the immune response against bladder cancer cells. 
• Induction of local inflammation: BCG intravesical live causes an inflammatory response in the bladder, leading to the recruitment of immune cells and activation of the immune system within the tumor microenvironment. 
• Formation of granulomas: BCG can induce the formation of granulomas, which are aggregates of immune cells. Granulomas play a role in containing the infection and promoting an immune response against bladder cancer cells. 
• Direct cytotoxicity: BCG intravesical live has direct cytotoxic effects on bladder cancer cells. It can invade cancer cells and induce their destruction.

Pharmacokinetics: 

Absorption 

BCG is administered directly into the bladder through intravesical instillation. It primarily remains localized within the bladder and does not undergo significant systemic absorption. 

Distribution 

BCG remains within the bladder and does not distribute extensively to other tissues or organs in the body. 

Metabolism 

BCG is a live attenuated vaccine consisting of live Mycobacterium bovis strain. Within the bladder, BCG is phagocytosed by immune cells, leading to the activation of an immune response against bladder cancer cells. 

Elimination and excretion 

BCG is excreted primarily through urine. After administration, BCG is flushed out of the bladder during urination. 

Adminstartion

Administration: 

• Preparation: The BCG vaccine is supplied in a lyophilized form and needs to be reconstituted with a diluent provided by the manufacturer. The reconstitution process should be done according to the instructions provided. 
• Catheterization: The patient will undergo catheterization to empty the bladder and ensure it is empty before the BCG instillation. A sterile catheter is used for this purpose. 
• Instillation: After catheterization, the BCG suspension is instilled into the bladder through the catheter. The volume and duration of instillation may vary depending on the specific treatment protocol and the patient’s condition. 
• Retention: Once the BCG is instilled, the patient is instructed to hold the medication in the bladder for a specific period of time. This allows the BCG to come into contact with the bladder walls and exert its therapeutic effects. 
• Emptying the bladder: After the recommended retention time, the patient is allowed to empty the bladder and flush out the BCG solution. Proper disposal measures should be followed to minimize exposure to others. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: BCG intravesical live 

Pronounced: (B-C-G in-tra-VES-i-kal) 

Why do we use BCG intravesical live? 

• Adjuvant Therapy: BCG is used as adjuvant therapy after transurethral resection of bladder tumor (TURBT) to prevent tumor recurrence. It is commonly used in high-grade Ta/T1 bladder tumors or carcinoma in situ (CIS). 
• Treatment of CIS: BCG is also effective in treating CIS, which is a high-grade, flat lesion confined to the urothelium. It can be used as a primary treatment or after TURBT. 
• Prophylaxis: BCG is used as prophylactic therapy in patients at high risk of tumor recurrence, such as those with multiple or recurrent low-grade tumors.