TICE BCG

Other Irrigating Solutions

CAUTION: Bacillus Calmette-Guerin (BCG) Live, USP contains live bacteria and should be prepared in a biological safety cabinet and handled using aseptic technique. All equipment, supplies, and receptacles in contact with these products should be disposed of as biohazards. Do not prepare parenteral drugs in areas where BCG has been prepared. Nosocomial infections have been reported in patients receiving parenteral drugs prepared in areas in which BCG was reconstituted.
Hazardous Drugs Classification
NIOSH 2016 List: Group 1
NIOSH (Draft) 2020 List: Removed from the NIOSH list because it is an infectious agent and not classified as a drug by the FDA. For handling recommendations, see the drug package insert.
Health care professionals should wear gloves, gown, and mask to avoid inadvertent exposure to BCG organisms while preparing and administering the solution. Handling of the product by persons with an immunologic deficiency is not recommended.
 

Intravesical Administration
People with latex hypersensitivity may not be appropriate candidates for TheraCys drug preparation, as the vial stopper contains latex.
Patients should not drink liquids for 4 hours prior to treatment and empty their bladder prior to BCG administration.
 
Reconstitution (BCG Live, TICE BCG):
Add 1 mL of sterile, preservative-free NS to one vial of TICE BCG. Do not use bacteriostatic solutions.
Gently swirl until a homogenous, cloudy suspension is attained; avoid foaming or forceful agitation. NOTE: This solution contains live bacteria.
Withdraw suspension from the vial and dispense into a catheter-tip syringe containing 49 mL of preservative-free 0.9% Sodium Chloride injection. The final volume should be 50 mL.
Gently rotate the syringe to mix the suspension. Do not filter. Avoid exposure to direct sunlight.
Use immediately after preparation. May be refrigerated at 2-8 degrees C (36-46 degrees F) and protected from direct sunlight until use, but discard unused solution after 2 hours.
 
Reconstitution (TheraCys):
Do not remove the rubber stopper from the freeze-dried product. Apply a sterile piece of cotton moistened with a suitable antiseptic to the surface of both rubber stoppers (product and diluent). Add 3 mL of the preservative-free 0.9% Sodium Chloride diluent that is provided with the product to the BCG vial. Do not use any other diluent.
Gently swirl until suspension is attained; avoid foaming. NOTE: This solution contains live bacteria.
Withdraw suspension from the vial (3 mL) and dispense into a catheter-tip syringe containing 50 mL preservative-free saline. The final volume should be 53 mL.
Use immediately after preparation. The reconstituted product may be refrigerated until use, but discard solution after 2 hours if not used or if flocculation or clumping that cannot easily be dispersed occurs.
Avoid exposure to direct or indirect sunlight. Exposure to artificial light should be kept to a minimum.
 
Bladder instillation (BCG Live, TICE BCG or TheraCys):
Insert a urethral catheter into the bladder under aseptic conditions. Drain the bladder.
Instill BCG into the bladder by gravity flow via the catheter. Do NOT depress the plunger and force the solution flow. Try to avoid urinary tract trauma and contaminant introduction. Remove the catheter.
While BCG is retained in the bladder, patients should repositioned from the left side to right side and may lie upon the back and the abdomen, changing positions every 15 minutes to maximize bladder surface exposure to the agent.
The BCG solution should be retained in the bladder for 2 hours, if possible, then voided. During the first 24 hours after BCG instillation, the patient should sit down while urinating.

dysuria / Early / 4.0-11.0
hemorrhagic cystitis / Delayed / 9.0-9.0
fever / Early / 3.0-8.0
hematuria / Delayed / 7.0-7.0
increased urinary frequency / Early / 2.0-7.0
coagulopathy / Delayed / 0-5.0
chills / Rapid / 3.0-3.0
cystitis / Delayed / 0-2.0
malaise / Early / 0-2.0
urinary urgency / Early / 0-1.0
nocturia / Early / 1.0-1.0
bladder discomfort / Early / 0-1.0
nausea / Early / 0-1.0
abdominal pain / Early / 1.0-1.0
vomiting / Early / 0-1.0
anorexia / Delayed / 0-1.0
weight loss / Delayed / 0-1.0
arthralgia / Delayed / 1.0-1.0
myalgia / Early / 0-1.0
epididymitis / Delayed / 0-1.0
uveitis / Delayed / Incidence not known
keratitis / Delayed / Incidence not known

anemia / Delayed / 21.0-21.0
urinary incontinence / Early / 2.0-6.0
constipation / Delayed / 0-5.0
thrombocytopenia / Delayed / 0-5.0
leukopenia / Delayed / 5.0-5.0
flank pain / Delayed / 0-5.0
hepatitis / Delayed / 0-1.0
pyuria / Delayed / 0-1.0
prostatitis / Delayed / 0-1.0
pneumonitis / Delayed / 0-1.0
iritis / Delayed / Incidence not known
conjunctivitis / Delayed / Incidence not known

fatigue / Early / 0-7.0
diarrhea / Early / 0-6.0
dizziness / Early / 0-5.0
headache / Early / 0-5.0
rash / Early / 0-5.0
diaphoresis / Early / 3.0-3.0
infection / Delayed / Incidence not known

BCG is capable of dissemination when administered by the intravesical route and serious infection, including fatal infection, has been reported in patients receiving intravesical BCG. Clinicians should exercise caution to not cause trauma to the urinary tract or introduce contaminants into the urinary system. Seven to 14 days should elapse before BCG is administered following TUR, biopsy, or traumatic catheterization.

Precautions should be taken to avoid accidental exposure to BCG solutions during preparation and administration, as these solutions contain live, attenuated mycobacterium. After usage, all equipment and materials used for preparation and instillation of the BCG solution should be placed into plastic bags labeled 'Infectious Waste' and disposed of accordingly as biohazardous waste. Patients should be informed that any urine voided within 6 hours of instillation of BCG should be disinfected with an equal volume of 5% hypochlorite solution (undiluted household bleach) and allow to stand for 15 minutes before flushing. Patients should be advised to sit while urinating during the 24 hours following BCG instillation.

TICE BCG

Rx

Live, attenuated strain of M. bovis used in the treatment of bladder cancer; strains currently available for use in the U.S. include the Connaught and Tice strains; not a vaccine against cancer and should not be used as an immunizing agent for tuberculosis prevention.

The contents of 1 vial, appropriately prepared, instilled in the bladder for 2 hours, then voided. Instillation is repeated once weekly for 6 weeks. If tumor remission is not achieved, the schedule may be repeated. Thereafter, BCG instillation should be administered at monthly intervals for 6 to 12 months as maintenance therapy.

The contents of 1 vial, appropriately prepared, instilled in the bladder for 2 hours, then voided. Instillation is repeated once weekly for 6 weeks. BCG instillation is then given at 3, 6, 12, 18, and 24 months following the initial dose.

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

There are no drug interactions associated with Bacillus Calmette-Guerin Live, BCG products.

Theracys/TICE BCG Intravesical Inj Pwd: 50mg, 81mg

One vial/dose intravesically.

One vial/dose intravesically.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Bacillus Calmette-Guerin (BCG) is an immunostimulant. BCG treatment is used to mount a local inflammation and immune reaction against superficial cancers, but the exact mechanism of action is unknown. The Calmette-Guerin strain of Mycobacterium bovis present in BCG Live is immunologically similar to M. tuberculosis. Intravesical BCG produces a non-specific, localized immune reaction consisting of granulomatous and inflammation reactions with histocyte and leukocyte infiltration. Following intravesical administration, the live BCG mycobacteria attach to the urothelial lining. The bacterial cell surface glycoproteins act as antigens that stimulate the immune response including macrophages, T-lymphocytes, B-lymphocytes, natural killer cells, and killer cells. This leads the production of interleukin (IL)-1, IL-2, IL-6, interferon gamma, and tumor necrosis factor-alpha (TNF-alpha). The immunotherapeutic effects of BCG in bladder cancer are due to cytokines, which cause cytotoxic effects. Tumor cell motility is also thought to be inhibited. Biopsies following BCG administration show increased expression of human leukocyte antigen (HLA)-Dr on tumor cells and infiltration of tumor and stroma with lymphocytes, mostly T-helper cells, and macrophages. Systemically, an increased immune response to the BCG antigen and production of BCG antibody may be seen.

Bacillus Calmette-Guerin is administered as an intravesical solution (BCG Live, intravesical). Specific pharmacokinetic data are not available and may be strain specific.

Bacillus Calmette-Guerin (BCG) products are considered FDA pregnancy risk category C agents. It is not known whether BCG Live intravesical causes fetal harm if given to a pregnant woman. Therapy with BCG Live should be given to a pregnant woman only if clearly needed. Females of reproductive age should take precautions against becoming pregnant while on BCG Live therapy. 

It is not known whether BCG is excreted in breast milk. Because many drugs are excreted in breast milk and because of the potential for harm in nursing infants, a decision should be made whether to discontinue breast-feeding or to discontinue BCG therapy taking into account the importance of therapy to the mother. Consider the benefits of breast-feeding, the risk of infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.