Usage
Bacillus Calmette-Guérin (BCG) is primarily prescribed for:
- Bladder cancer: BCG is used for the treatment and prophylaxis of carcinoma in situ (CIS) of the bladder and to prevent recurrence of non-muscle invasive bladder cancer after transurethral resection (TUR).
- Tuberculosis: BCG is used as a vaccine for the prevention of tuberculosis, particularly in high-risk individuals.
Pharmacological Classification: BCG is classified as an immunotherapeutic agent (for bladder cancer) and a vaccine (for tuberculosis).
Mechanism of Action: BCG works by stimulating a local immune response in the bladder wall. The exact mechanism is not fully understood, but it is believed to involve activation of the immune system, leading to a granulomatous reaction and destruction of tumor cells. For tuberculosis, BCG instills immunity by prompting a cell-mediated immune response.
Alternate Names
BCG has several strain designations and brand names including:
- TICE BCG
- Connaught BCG
- Tokyo 172
- BCG-Medac
- RIVM BCG
- Danish 1331
- Russian BCG-I
- OncoTICE®
- TheraCys®
- VERITY-BCG®
- TUBERVAC
How It Works
Pharmacodynamics: BCG administered intravesically for bladder cancer triggers a complex immune response involving the recruitment and activation of macrophages, T cells, and other immune cells to the bladder wall. This results in inflammation and destruction of tumor cells. For tuberculosis prevention, BCG induces cell-mediated immunity.
Pharmacokinetics: When administered intravesically, BCG remains localized in the bladder with minimal systemic absorption. The pharmacokinetics after intradermal administration (for tuberculosis prevention) are less well defined.
Mode of Action: BCG interacts with fibronectin receptors (α5β1 integrins), potentially contributing to antitumor effects. BCG binds to urothelial cells and is internalized.
Elimination pathways: The elimination of BCG after intravesical administration is primarily via excretion in the urine.
Dosage
Standard Dosage
Adults:
- Bladder Cancer: One vial (containing a specific amount of colony-forming units or CFU depending on the strain— commonly ranging from 1-8 x 10^8 CFU) is reconstituted and diluted in 50 mL of preservative-free saline and instilled into the bladder via a catheter weekly for 6 weeks (induction). Maintenance therapy schedules vary but may involve instillations at 3, 6, and 12 months, sometimes extending for up to 3 years.
- Tuberculosis: 0.1 mL intradermally.
Children:
- Tuberculosis: 0.05 mL (under 1 month) to 0.1 mL (1 month to 1 year) intradermally.
Special Cases:
- Elderly Patients: No specific dose adjustment is routinely recommended, but caution is advised in patients with compromised immune function.
- Patients with Renal/Hepatic Impairment: No specific dose adjustment is required for intravesical administration as systemic absorption is minimal.
- Patients with Comorbid Conditions: Caution should be used in immunocompromised individuals.
Clinical Use Cases BCG is not typically used in the clinical settings you mentioned (intubation, surgical procedures, mechanical ventilation, ICU use, emergency situations). Its use is confined to the treatment/prophylaxis of bladder cancer and vaccination against tuberculosis.
Dosage Adjustments
Dose reduction may be considered in patients experiencing significant local adverse effects from intravesical BCG. Some strains, such as Tokyo 172, are more potent and might justify lower dose administration (e.g., 25% of the standard dose).
Side Effects
Common Side Effects:
Bladder irritability (dysuria, frequency, urgency), hematuria, flu-like symptoms (fever, chills, malaise).
Rare but Serious Side Effects:
BCG sepsis (disseminated infection), hepatitis, pneumonitis, rash, arthritis.
Long-Term Effects:
Chronic cystitis is a possible long-term complication of intravesical BCG.
Adverse Drug Reactions (ADR):
Severe bladder inflammation, systemic BCG infection, and other serious manifestations of BCG infection.
Contraindications
- Hypersensitivity to BCG or any component of the formulation.
- Concurrent use of anti-tuberculosis medications.
- Immunocompromised patients (including HIV-positive individuals).
- Active tuberculosis.
- Pregnancy.
- Febrile illness.
- Urinary tract infection.
- Recent bladder surgery or trauma.
Drug Interactions
- Immunosuppressants can increase the risk of BCG infection.
- Anti-tuberculosis medications should not be used concurrently with intravesical BCG.
Pregnancy and Breastfeeding
BCG is contraindicated during pregnancy. It is not known whether BCG is excreted in breast milk.
Drug Profile Summary
- Mechanism of Action: Stimulates immune response in bladder wall/ induces cell-mediated immunity.
- Side Effects: Bladder irritability, flu-like symptoms, rarely BCG sepsis.
- Contraindications: Immunocompromise, active tuberculosis, pregnancy.
- Drug Interactions: Immunosuppressants.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy.
- Dosage: Varies by indication and BCG strain; see dosage section.
- Monitoring Parameters: Urinalysis, monitoring for signs of BCG infection.
Popular Combinations
BCG is not typically used in combination with other drugs for intravesical therapy of bladder cancer.
Precautions
- Ensure the integrity of the bladder wall before instillation.
- Administer using strict aseptic technique.
- Educate patients about proper disposal of urine after BCG instillation.
- Monitor for signs of local or systemic BCG infection.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Bacillus Calmette-Guerin strain?
A: The dosage varies depending on the indication (bladder cancer vs. tuberculosis), the specific BCG strain being used, and the individual patient. Refer to the detailed dosage guidelines above.
Q2: What are the common side effects of BCG?
A: Common side effects include bladder irritation (dysuria, frequency, urgency), hematuria, and flu-like symptoms (fever, chills, malaise).
Q3: What are the serious side effects of BCG?
A: Serious side effects, while rare, include BCG sepsis (disseminated infection), which can be life-threatening.
Q4: Who should not receive BCG?
A: BCG is contraindicated in immunocompromised individuals, pregnant women, patients with active tuberculosis, and those with hypersensitivity to BCG.
Q5: How is BCG administered for bladder cancer?
A: BCG is instilled directly into the bladder via a catheter.
Q6: How is BCG administered for tuberculosis prevention?
A: BCG is administered intradermally.
Q7: How should urine be handled after BCG instillation for bladder cancer?
A: Patients should be instructed on proper hygiene practices, which may include adding bleach to the toilet after voiding for a specified period and allowing it to stand before flushing.
Q8: What is the duration of BCG treatment for bladder cancer?
A: Treatment typically involves an induction phase of 6 weekly instillations followed by a maintenance phase, which can vary but may last up to 3 years.
Q9: What should be done if a patient experiences a fever after BCG instillation?
A: Patients with high-grade fever after BCG should be evaluated for BCG sepsis and may require hospitalization and treatment with anti-tuberculosis medications.
Q10: Can BCG be used in patients with impaired renal or hepatic function?
A: Yes, for intravesical BCG, no dose adjustment is needed for renal or hepatic impairment as systemic absorption is minimal. Caution should be used in severe cases.
