Bacillus Calmette-Guérin (BCG Live Mucosal-Local )


VA CLASSIFICATION
Primary: AN900

Commonly used brand name(s): ImmuCyst; PACIS; TICE BCG; TheraCys.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antineoplastic. —

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Carcinoma, bladder (prophylaxis and treatment)— BCG is used intravesically for prophylaxis and treatment of primary (multifocal, high grade {76}) and relapsed superficial transitional cell bladder carcinoma {01} {02} {05} {06} {07} {08} {11} {13} {20} {21} {22} {23} {24} {25} {28} {79} {84}. It is used to reduce frequency of tumor recurrence {01} {05} {06} {07} {08} {10} {11} {21} {22} {79} after transurethral resection {05} {06} {10} {11} {13} {15} {20} {23} {24} {25} {28} {80}{84} and to eliminate existing tumors {01} {13} {20} {21} {22} {79}{84}, including [Ta {13} {20} {21} {22} {24} {25} {28} and T1 {05} {07} {13} {15} {20} {21} {22} {23} {24} {25} {28} tumors] and carcinoma in situ (CIS tumors) with or without associated papillary tumors {01} {05} {07} {08} {10} {11} {12} {13} {20} {21} {22} {23} {24} {25} {28} {79}. It is not indicated for treatment of papillary tumors occurring alone {01} {80}{84} or for prevention of papillary tumors after transurethral resection {84}.

Unaccepted
The product labeled for use only in treatment of bladder carcinoma is not intended to be used as an immunizing agent for the prevention of tuberculosis{01} {79}{84}; the product labeled for both uses can be used for both. BCG is not a vaccine for the prevention of cancer {01} {79}{84}.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Source—
    It is a live culture of the attenuated bacillus Calmette-Guérin strain of Mycobacterium bovis {01} {02} {03} {05}. Commercially available strains (which are substrains of the Pasteur Institute strain) include the Armand-Frappier, Connaught, Glaxo/Evans, and Tice substrains; of these, only the Connaught and Tice strains are approved for bladder carcinoma.

Mechanism of action/Effect:

The effect of BCG against carcinoma is not completely understood. It may be related to an inflammatory response {01} {04} {08} {17} {29} {30} {79} and possibly also to an immune response {04} {07} {08} {30}.

Intravesical BCG suspension produces a granulomatous response locally and in regional lymph nodes {05}; the inflammatory response stimulates production of macrophages that have tumoricidal effects {03} {05} {08}. The presence of interleukin-2, which is a substance produced by activated helper T lymphocytes and which activates natural killer cells, has also been noted in the urine of patients who responded to BCG treatment {05}. However, the relationship of these effects to the antineoplastic effect of BCG is unknown {01} {79}.


Other actions/effects:

Induces active immunity against tuberculosis by unknown mechanism; may involve stimulating the reticuloendothelial system (RES) to produce macrophages and other activated cells that prevent multiplication of virulent Mycobacterium tuberculosis {02} {03} {49}.

Viability and immunogenicity may vary between strains {03} {04} {05} {07} {13} and viability varies between lots of any one strain {02} {05} {07} {13}. With intracavitary BCG, positive conversion of tuberculin (purified protein derivative [PPD]) skin test occurs in a majority of patients, usually after 3 to 12 weeks {03} {06} {10} {13} {22} {50} {62}. Positive conversion of PPD skin test, when it occurs, is usually not permanent {02} {03} {31}, although duration is variable and sometimes long {32}.


Precautions to Consider

Tumorigenicity

Two cases of nephrogenic adenoma (adenomatous metaplasia of the bladder), which is usually benign and believed to result from chronic irritation or trauma, have been reported {19}.

Pregnancy/Reproduction

Pregnancy—
Studies have not been done in humans {01}.

Studies have not been done in animals.

FDA Pregnancy Category C.

Breast-feeding

It is not known whether intravesical BCG is distributed into breast milk. However, problems in humans have not been documented.

Pediatrics

No information is available on the relationship of age to the effects of BCG in pediatric patients. Safety and efficacy have not been established {01} {79}.


Geriatrics


Studies performed to date have not demonstrated geriatrics-specific problems that would limit the usefulness of BCG as an antineoplastic in the elderly {33}.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Antimicrobial therapy    (potential negative effect on actions of BCG {01} {79})


» Bone marrow depressants{01}{79} (see Appendix II ) or
» Immunosuppressants{01}{79} or
» Radiation{01}{79}    (may impair immune response to BCG {01} {03} {79}. The interval between discontinuation of medications that cause immunosuppression and restoration of the patient's ability to respond to BCG depends on the intensity and type of immunosuppression-causing therapy used, the underlying disease, and other factors; estimates vary from 3 months to 1 year {03}. Also, may increase the risk of osteomyelitis {01} {02} {03} {04} {05} {19} {79} or disseminated BCG infection {01} {03} {19} {79})


» Vaccines, killed or live virus    (concurrent administration with BCG is not recommended; it is recommended that live virus vaccines be given 6 to 8 weeks after BCG {56} {61}; it is recommended that killed virus vaccines be given 7 days before or 10 days after BCG {55} {61})



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Hepatic function tests    (abnormalities have been reported rarely {04} {06} {07} {25})


Tuberculin (purified protein derivative [PPD]) skin test    (positive conversion is produced in a majority of patients, usually after 3 to 12 weeks of intravesical BCG therapy {03} {06} {10} {13} {22} {50} {57} {62}; may complicate future interpretations of tuberculin skin test reactions in the diagnosis of suspected mycobacterial infections {01} {79})


Microscopic examination of urine    (microscopic pyuria commonly seen; however, bacterial growth in urine is uncommon; returns to normal after completion of a course of BCG therapy {08})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problems exist:
» Fever{01}{79}    (BCG should not be administered until the cause has been determined; if fever is caused by infection, BCG should be withheld until the patient is afebrile and off all therapy {01} {79})


» Urinary tract infection{01}{06}{35}{79}    (risk of disseminated BCG infection; increased severity of bladder irritation {36})


Risk-benefit should be considered when the following medical problems exist
» Hematuria, gross, existing{51}    (risk of disseminated BCG infection {51}; caution is necessary especially if the hematuria is induced by recent biopsy or resection, and it is recommended that intravesical BCG not be given until gross hematuria has cleared {63}; if hematuria is from the tumor itself, BCG can still be given, but with caution because irritable bladder symptoms may be increased {63})


» Impaired immune response{34}    (decreased response to treatment {07}; risk of osteomyelitis {02} {03} {04} {05} {19} or disseminated BCG infection {01} {02} {03} {04} {05} {19} {34} {79})


» Sensitivity to BCG live{01}{79}
Small bladder capacity    (increased incidence and severity of local irritation {19}; in addition, therapy with BCG may rarely cause bladder contracture, which further decreases capacity {58})



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

» Bladder biopsy, cold cup    (recommended at regular intervals to assess response {11} {12} {15} {20} {22} {24} {25} {37}; also recommended for any suspicious area found by cystoscopy or cytology studies {06} {07} {08} {21} {23} {28} {37} {53})


» Cystoscopy{05}{06}{07}{08}{10}{11}{13}{15}{19}{20}{21}{22}{23}{24}{25}{28}{38} and
» Urine cytology studies{07}{08}{10}{11}{12}{13}{14}{15}{20}{21}{22}{23}{24}{25}{28}{38}    (recommended at regular intervals during and after treatment to assess response and confirm that the tumor is not progressing)


Hepatic function determinations    (recommended if persistent [e.g., 101 °F for longer than 2 days] or severe [e.g., greater than 103 °F] fever or continuing malaise occurs {01} {64} {79})


Needle biopsy of prostate{77} in males    (recommended as indicated by presence of clinical signs of granulomatous prostatitis {16} {21} {27} {52})


Tuberculin (PPD) skin test    (recommended before treatment {01} {20} {21} {22} {79} and at periodic intervals during treatment {39}. However, although it may predict responsiveness to BCG treatment in general, this is controversial and it is unlikely to provide a prognosis for a specific individual patient {13} {15} {16} {17} {19} {20} {26} {39}, especially since positive conversion does not occur in all patients who respond to BCG therapy)


Urine cultures    (recommended before and at periodic intervals during treatment {07} {08}; recommended if urinalysis or clinical symptoms suggest presence of urinary tract infection {40})




Side/Adverse Effects

Note: Side/adverse effects are usually mild to moderate and transient {05} {15} {19}, but may be cumulative {19} {25} {41}.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
    
Bladder infection{07}{08}{11}{13} , secondary to bladder irritation{11} —usually asymptomatic
    
bladder irritation{01}{05}{06}{07}{08}{19}{79} (blood in urine{01}{05}{07}{10}{11}{19}{20}{23}{25}{79}; frequent urge to urinate{01}{11}{19}{20}{79}; increased frequency of urination{01}{05}{10}{11}{19}{20}{22}{23}{25}{79}; painful urination, severe or continuing{01}{05}{10}{11}{19}{22}{23}{25}{79})
    
flu-like syndrome{05}{06}{07}{08}{10}{11}{12}{19}{20}{22}{23}{25} (fever and chills{04}{05}{06}{07}{10}{11}{12}{19}{20}{22}{23}{25}; joint pain{04}{05}{11}{19}; nausea and vomiting{04}{05}{06}{19}; in a few patients, has progressed to a severe systemic reaction with high fever, malaise, and anorexia{08}{19})
    
granulomatous prostatitis{05}{09}{10}{17}{19}{27} (appears as nodularity, enlargement, induration, and distortion of the prostate{09}{27} , which is clinically indistinguishable from prostatic carcinoma{09})—usually asymptomatic

Note: Bladder infection responds rapidly to antibiotic treatment {07} {13}.
Bladder irritation occurs in most patients, but is usually transient {05} {07} {11}; may be severe in some patients {11}. May predict antitumor response {19}. Symptoms usually begin within 2 to 4 hours after a dose {01} {06} {08} {79} and last 24 to 72 hours {01} {06} {07} {08} {11} {19} {23} {79}. Granulomatous inflammation is seen on the histological examination {07} {13} {19}; lesions that may be confused with tumors appear commonly within 4 weeks after BCG treatment {07} {08} {19}; inflammation usually disappears within about 4 to 6 months after treatment {07} {19}.
Symptoms of the flu-like syndrome usually begin within 4 hours after a dose {04} {06} {07} {08} {11} {19} {23} and last 24 to 72 hours {01} {04} {06} {07} {08} {11} {19} {23} {79}.


Incidence rare
    
Allergic reaction or erythema nodosum {05}{11}{19}(skin rash)
    
BCG infection, disseminated, with lung or liver involvement{04}{05}{07}{19} (fever{04}{19}; cough{19})
    
bladder contracture{05}{11}{12}
    
hepatic function impairment{06}{07}{25} —asymptomatic
    
hypotension{05}{19}
    
leukopenia —asymptomatic

Note: Symptoms of disseminated BCG infection may be difficult to distinguish from those of gram-negative sepsis or severe hypersensitivity reactions {65}, or of progressing malignancy {04} {65}. Disseminated infection, with associated fever, may occur as late as 6 months or more after BCG therapy {43} and may persist for 1 to 3 weeks after antituberculosis therapy is begun {04} {19}. It is usually diagnosed clinically based on the presence of fever (over 39 °C [103 °F] or persistently over 38 °C [101 °F] over 2 days) {01} {72} {79} and chills, especially when associated with malaise {01} {72} {79} and other systemic symptoms, negative blood and urine cultures, chest x-ray or computed tomography (CT) to exclude other pulmonary diseases, and hepatic function tests {72}. Deaths have been reported {01} {79}.
Hepatic function impairment is usually mild and transient {07}; abnormalities peak by 20 days and may persist months after BCG administration {04}.




Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Burning, slight, during first void after treatment{80}



Those indicating the need for medical attention if they occur after medication is discontinued
    
BCG infection, disseminated, with lung or liver involvement{04}{05}{07}{19} (fever{04}{19}; cough{19})




Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Bacillus Calmette-Guérin (BCG) Live (Mucosal-Local).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to BCG
Other medications, especially bone marrow depressants or immunosuppressants or radiation therapy
Other medical problems, especially fever, gross hematuria, impaired immune response, or urinary tract infection

Proper use of this medication
Emptying bladder before instillation of each dose

» Following physician's instructions for holding solution in bladder; holding in bladder for 2 hours; telling physician if unable to retain solution for prescribed time; physician may recommend lying down for 15 minutes each in prone and supine positions, and on each side, during first hour {78}; sitting down while voiding {59}

» Importance of ample fluid intake for several hours after instillation {80}

Bacteria will be present in urine; treating all urine voided within 6 hours after each instillation with an equal volume of 5% hypochlorite solution (undiluted household bleach; usually 6 to 8 ounces {67}) and allowing to stand for 15 minutes before flushing {59} {66}

» Proper dosing

Precautions while using this medication
Avoiding persons with active tuberculosis for 6 to 12 weeks after treatment {02}; telling physician about any exposure to active tuberculosis

Avoiding immunizations unless approved by physician


Side/adverse effects
Signs of potential side effects, especially bladder infection, bladder irritation, flu-like syndrome, allergic reaction, erythema nodosum, disseminated BCG infection, bladder contracture, and hypotension


General Dosing Information
Patients receiving intravesical BCG should be under the supervision of a physician experienced in immunotherapy.

Prior to BCG administration, the bladder is emptied either by voiding or drainage through a urethral catheter inserted into the bladder under aseptic conditions {01} {79} {80}. BCG is then instilled into the bladder by gravity flow via the catheter {01} {79} {80}; the plunger should not be depressed to force the flow {80}.

It is recommended that BCG instillation and equipment and materials used in preparation of the instillation be treated as biohazardous waste {01} {59} {69} {79}.

BCG should not be injected intravenously, subcutaneously, or intramuscularly {03} {74}.

Care and aseptic technique are necessary during administration of intravesical BCG therapy so as not to introduce contaminants into the urinary tract or to unduly traumatize the urinary mucosa {01} {59} {79}.

If the physician believes that the bladder catheterization has been traumatic (e.g., associated with bleeding or possible false passage), instillation of BCG should be delayed by at least 1 week {01} {59} {70} {79}. However, beginning with the delayed dose, subsequent doses should be administered according to the original schedule (i.e., no doses should be omitted) {01} {59} {70} {79}.

It is recommended that BCG therapy not be started until 7 to 14 days after bladder tumor resection or biopsy because fatalities from disseminated BCG infection have been reported with use of BCG after traumatic catheterization {01} {45} {79} {80}.

If development of systemic BCG infection is suspected, it is recommended that BCG be withheld and fast-acting antituberculosis therapy initiated {01} {79}.

Patients who do not respond after two 6-week courses of BCG therapy are not likely to respond, and consideration of alternative therapy is recommended {05} {21}.

Most severe adverse effects can be prevented or reduced in severity with prophylactic isoniazid treatment given for 3 days beginning the morning of BCG treatment {05} {08} {12}. Some clinicians also recommend use of antihistamines {08} {12} {19} and nonsteroidal anti-inflammatory agents {08} {12} {19}.

Safety considerations for handling this medication
There is concern that personnel involved in preparation and administration of intravesical BCG may be at some risk because of the infectious potential of this agent {01} {79}, although the actual risk is unknown. USP advisory panels recommend cautious handling both in preparation and disposal of BCG for intravesical use. Precautions that have been suggested include {68}:    • Use of a biological containment cabinet during reconstitution and dilution of parenteral medications and wearing of disposable surgical gloves and masks {01} {79} {80}.
   • Use of proper technique to prevent contamination of the medication, work area, and operator during transfer between containers (including proper training of personnel in this technique).
   • Cautious and proper disposal of needles, syringes, vials, ampuls, and unused medication.
A number of medical centers have developed detailed guidelines for handling of antineoplastic and similar agents.

For treatment of adverse effects
Most adverse effects respond to a reduction in BCG dose {19} {20} {24} or temporary interruption of therapy {19}; however, in some patients withdrawal of BCG therapy may be necessary {19}.

Mild bladder irritation can usually be treated symptomatically with phenazopyridine hydrochloride {01} {79} and antispasmodics such as propantheline bromide {01} {06} {12} {19} {79} or oxybutynin {75}.

Recommended treatment of moderate to severe bladder irritation and flu-like syndrome may consist of the following:    • Isoniazid {06} {08} {12}.
   • Antihistamines {06} {08} {19}, such as diphenhydramine hydrochloride {01} {79}.
   • Nonsteroidal anti-inflammatory agents {01} {04} {08} {12} {19} {79}; parenteral narcotic analgesics may be necessary for severe bladder irritation {13}.


Recommended treatment of disseminated BCG infection with liver and lung involvement consists of the following:    • Triple-drug antituberculosis therapy {04} {05} {06} {46} or
   • A fast-acting antituberculosis medication such as cycloserine {71}.


No specific treatment of granulomatous prostatitis secondary to BCG therapy is required {27}.


Topical Dosage Forms

BCG LIVE (CONNAUGHT STRAIN)

Usual adult dose
Bladder carcinoma
Intracavitary, 1 vial (81 mg), reconstituted and then diluted with 50 mL of sterile, preservative-free 0.9% sodium chloride injection, to a final volume of 53 mL {01} {05} {06} {08} {11} {24} {25} {79} (less in patients with reduced bladder capacity {19}), instilled into the empty bladder and retained for one to two hours (depending on irritative symptoms and the patient's ability to retain the solution) {01} {05} {06} {08} {11} {22} {24} {25} {27} {79}. The procedure is repeated once a week for six weeks {01} {05} {10} {11} {12} {13} {15} {20} {22} {23} {24} {27} {79}, followed by one treatment given at three, six, twelve, eighteen, and twenty-four months following the initial treatment {01} {79} or according to response {05} {08} {10} {11} {12} {24} {27}.


Note: During the first hour after instillation, the patient may lie down for 15 minutes in the prone position, followed by the supine position, and on each side, then may be up for the second hour while the suspension is retained {01} {78} {79}.
The patient voids in a seated position {01} {79}.


Usual pediatric dose
Safety and efficacy have not been established {01} {79}.

Size(s) usually available:
U.S.—


81 mg (dry weight) or 10.5 ± 8.7 × 10 8 colony-forming units (CFU) per vial (1 vial per package) (Rx) [TheraCys (monosodium glutamate 5% w/v plus diluent)]

Canada—


Approximately 3 × 10 8 colony-forming units (CFU) per vial (3 vials per package) (Rx) [ImmuCyst ( monosodium glutamate 5% w/v plus diluent)]

Packaging and storage:
Store between 2 and 8 °C (36 and 46 °F). Protect from light.

Preparation of dosage form:
BCG live (Connaught strain) is reconstituted by adding to the vial 1 mL of diluent provided by manufacturer . The vial is then shaken gently until a fine, even suspension results. {01} {59} The suspension is then diluted in a suitable quantity of sterile, preservative-free 0.9% sodium chloride injection for administration.

Note: Aseptic technique must be used for reconstitution and dilution {01} {79}.
The product should not be handled by persons with a known immunologic deficiency {01} {79}.


Stability:
Reconstituted suspension should be used immediately {01} {59} {79}; otherwise, it should be refrigerated until use and should be discarded after 2 hours {01} {79}.

Note: Commercially available BCG strains are not interchangeable. One product should not be substituted for another. If patients are to be transferred from one to another, appropriate changes in dosage may be necessary.


Additional information:
After usage, all equipment and materials used for instillation of BCG into the bladder should be placed immediately into plastic bags labeled as infectious waste and disposed of properly as biohazardous waste {01} {59} {73} {79}.

Any unused portion of reconstituted BCG, and urine voided for 6 hours after instillation, should be disinfected with an equal volume of 5% hypochlorite solution (undiluted household bleach) and allowed to stand for 15 minutes before being flushed {01} {59} {73} {79}.


BCG LIVE (MONTREAL STRAIN)

Usual adult dose
Bladder carcinoma
Intracavitary, a single dose of 120 mg, reconstituted and then diluted with 50 mL of sterile, preservative-free 0.9% sodium chloride injection instilled into the bladder once a week for six weeks {83}{84}. The bladder should be drained via a urethral catheter under aseptic conditions prior to administration of the recommended dose {83}. The induction therapy may be followed by a single instillation given at three, six, twelve, and twenty-four months following the initial treatment {83}.


Note: During the first hour following instillation, the patient should lie down for 15 minutes in the prone position, supine position, and on each side {83}{84}. After this procedure, the patient should be allowed to be up; however, the suspension should be retained for another 60 minutes for a total of 2 hours {83}{84}. Some patients may not be able to retain the suspension for 2 hours and should be instructed to void in less time if necessary {83}{84}. At the end of treatment all patients should void in a seated position for safety reasons {83}. Patients should be instructed to drink enough liquid after treatment to maintain adequate hydration {83}{84}.


Usual pediatric dose
Safety and efficacy have not been established {83}{84}.

Size(s) usually available:
U.S.—


2.4 to 12 x 10 8 colony-forming units (CFU) per vial (Rx) [PACIS (lactose 15% w/v){84}]

Canada—


2 to 10 × 10 6 colony-forming units (CFU) per vial (Rx) [PACIS (lactose 15% w/v plus diluent){83}]

Packaging and storage:
Store between 2 and 8 °C (35 and 46 °F) {83}{84}.

Protect from light {83}{84}.

Note: Freezing will not harm the BCG; however, the sterile diluent should not be used if it has been frozen {83}. At no time should the lyophilized preparation be exposed to sunlight, direct or indirect {83}.


Preparation of dosage form:
BCG live (Montreal strain) is reconstituted by adding to the vial 1 mL of diluent provided by manufacturer {83}. The diluent should be left in contact with BCG live for about 1 minute {83}. Then the suspension should be mixed by withdrawing it into the syringe and expelling it gently back to into the vial two or three times {83}. To prevent the formation of foam, the suspension should not be shaken {83}. The suspension is then diluted in a suitable quantity of sterile, preservative-free 0.9% sodium chloride injection for administration {83}.

BCG live (Montreal strain) is reconstituted by adding 1 mL of preservative-free 0.9% Sodium Chloride Injection to the ampule{84}. The diluent should be left in contact with BCG live for about 1 minute{83}. Then the suspension should be mixed by withdrawing it into the syringe and expelling it gently back to into the ampule two or three times{84}. To prevent the formation of foam, the suspension should not be shaken{84}. The suspension is then diluted in a suitable quantity of sterile, preservative-free 0.9% sodium chloride injection for administration{84}

Note: BCG live (Montreal strain) should be handled as infectious material {84}. Persons handling this product should wear masks and gloves {84}. The product should not be handled by persons with a known immunologic deficiency{84}.


Stability:
BCG live (Montreal strain) should be used immediately after preparation {84}.

Additional information:
After usage, all equipment and materials used for instillation of BCG into the bladder should be placed immediately into plastic bags labeled as infectious waste and disposed of properly as biohazardous waste{84}.


BCG VACCINE (TICE STRAIN) USP

Usual adult dose
Bladder carcinoma
Intracavitary, 1 vial ( 1 to 8 × 10 8 colony-forming units [CFU]), reconstituted and then diluted to a total volume of 50 mL with sterile, preservative-free 0.9% sodium chloride injection {05} {06} {08} {11} {24} {25} {80} (less in patients with reduced bladder capacity {19}), instilled into the empty bladder and retained for one to two hours (depending on irritative symptoms and the patient's ability to retain the solution) {05} {06} {08} {11} {22} {24} {25} {27} {80}. The procedure is repeated once a week for six weeks {05} {10} {11} {12} {13} {15} {20} {22} {23} {24} {27} {80}; the schedule may be repeated once if circumstances warrant {80}. This is followed by treatment at approximately monthly intervals for at least six to twelve months {80} or according to response {05} {08} {10} {11} {12} {24} {27}.


Note: During the first hour after instillation, the patient may lie for 15 minutes in the prone position, followed by the supine position, and on each side {78} {80}, then may be up for the second hour while the suspension is retained.
The patient voids in a seated position {80}.


Usual pediatric dose
Safety and efficacy have not been established {80}.

Size(s) usually available:
U.S.—


1 to 8 × 10 8 CFU or approximately 50 mg (wet weight) per vial, (Rx) [TICE BCG (lactose)]

Canada—
Not commercially available.

Packaging and storage:
Store between 2 and 8 °C (36 and 46 °F). Protect from light.

Preparation of dosage form:
BCG Vaccine USP (Tice Strain) is reconstituted by adding 1 mL of sterile, preservative-free 0.9% sodium chloride injection to ampul, drawing the mixture back into the syringe and expelling it into the ampul three times to mix it thoroughly (minimizes clumping of mycobacteria) {80}. The suspension is then diluted in a suitable quantity of sterile, preservative-free 0.9% sodium chloride injection for administration.

Note: Aseptic technique must be used for reconstitution and dilution {80}.
The product should not be handled by persons with a known immunologic deficiency {80}.


Stability:
Reconstituted suspension should be used immediately and any unused portion discarded after 2 hours {80}.

Additional information:
After usage, all equipment and materials used for instillation of BCG into the bladder should be placed immediately into plastic bags labeled as infectious waste and disposed of properly as biohazardous waste {59} {73}.

Any unused portion of reconstituted BCG, and urine voided for 6 hours after instillation, should be disinfected with an equal volume of 5% hypochlorite solution (undiluted household bleach) and allowed to stand for 15 minutes before being flushed {59} {73}.



Revised: 08/17/2000



References

Note: References used in the development and subsequent revisions of this monograph have not been incorporated into the database and therefore are not listed below.

  1. TheraCys package insert (Connaught—US), Rec 8/1/90; Rec 7/10/93.
  1. Facts and Comparisons, October 1987, p. 457-457b.
  1. AHFS 1987. p. 1800-3.
  1. Dorr RT, Fritz WL. Cancer chemotherapy handbook. New York: Elsevier; 1981. p. 251-65.
  1. JAMA 1988 Apr 8; 259: 2153-5.
  1. J Urol 1982 Jul; 128: 27-30.
  1. J Urol 1984 Sep; 132: 457-9.
  1. Urology 1984 Apr; 23(4 Suppl): 82-7.
  1. Acta Cytol 1985 Nov-Dec; 29: 961-6.
  1. Cancer Treat Rep 1985 Jan; 69: 47-53.
  1. J Urol 1985 Apr; 133: 598-601.
  1. J Urol 1985 Jul; 134: 36-9.
  1. J Urol 1985 Jul; 134: 48-53.
  1. Cancer 1986 Dec 15: 58(12): 2751-7 [abstract].
  1. J Urol 1986 Feb; 135: 265-7.
  1. J Urol 1986 Feb; 135: 268-71.
  1. J Urol 1986 Feb; 135: 331-3.
  1. J Urol 1986 Feb; 135: 359-61.
  1. Cancer 1987 Aug 1; 60: 326-33.
  1. J Clin Oncol 1987 Mar; 5: 441-9.
  1. J Urol 1987 Feb; 137: 220-4.
  1. J Urol 1987 Aug; 138: 295-8.
  1. J Urol 1987 Aug; 138: 299-301.
  1. J Clin Oncol 1988 Sep; 6: 1450-5.
  1. J Urol 1988 May; 139: 935-40.
  1. J Urol 1988 May; 139: 941-4.
  1. J Urol 1988 Oct; 140: 751-4.
  1. J Urol 1989 Jan; 141: 22-9.
  1. Panel comment, 1990 revision, 1st round.
  1. Panel comment, 1990 revision, 1st round, question #3.
  1. Responses to panel question #4, 1990 revision, 1st round.
  1. Panel comment, panel question #4, 1990 revision, 1st round.
  1. Panel comments, 1990 revision, 1st round.
  1. Reviewers" responses to panel question #8, 1990 revision, 1st round.
  1. Reviewers" responses to panel question #9a, 1990 revision, 1st round.
  1. Reviewers" responses to panel question #9b, 1990 revision, 1st round.
  1. Reviewers" responses to panel question # 11a & b, 1990 revision, 1st round.
  1. Reviewers" responses to panel question #12, 1990 revision, 1st round.
  1. Reviewers" responses to panel question #13, 1990 revision, 1st round.
  1. Reviewers" responses to panel question #14, 1990 revision, 1st round.
  1. Reviewers" responses to panel question #15, 1990 revision, 1st round.
  1. Reviewers" responses to panel question #16, 1990 revision, 1st round.
  1. Panel comment, 1990 revision, 1st round.
  1. Panel comment, 1990 revision, 1st round.
  1. Panel comments, 1990 revision, 1st round.
  1. Reviewers" responses to panel question #21, 1990 revision, 1st round.
  1. Panel comments, 1990 revision, 1st round.
  1. Reviewers" responses to panel question #22, 1990 revision, 1st round.
  1. Reviewers" responses to panel question #1, 1990 revision, 2nd round.
  1. Reviewers" responses to panel question #2, 1990 revision, 2nd round.
  1. Reviewers" responses to panel question #3, 1990 revision, 2nd round.
  1. Reviewers" responses to panel question #5, 1990 revision, 2nd round.
  1. Reviewers" responses to panel question #6, 1990 revision, 2nd round.
  1. Reviewers" responses to panel question #8, 1990 revision, 2nd round.
  1. Panel comments, 1990 revision, 2nd round.
  1. Panel comments, 1990 revision, 1st round.
  1. Panel comments, 1990 revision, 2nd round.
  1. Reviewers" responses to panel question #4, 1990 revision, 2nd round.
  1. Reviewer comments, 1990 revision, 2nd round of panel review.
  1. Panel comments, 1990 revision, 2nd round.
  1. Reviewers" responses to panel question #1, 1991 revision.
  1. Panel comment, 1991 revision.
  1. Reviewers" responses to panel question #2, 1991 revision.
  1. Panel comments, 1991 revision.
  1. Reviewers" responses to panel question #3, 1991 revision.
  1. Reviewers" responses to panel question #4a, 1991 revision.
  1. Reviewers" responses to panel question #4b, 1991 revision.
  1. Reviewers" responses to panel question #5a, 1991 revision.
  1. Panel comments, 1991 revision.
  1. Reviewers" responses to panel question #6a & b, 1991 revision.
  1. Reviewers" responses to panel question #7a, 1991 revision.
  1. Reviewers" response to panel question #7b, 1991 revision.
  1. Reviewers" responses to panel question #8, 1991 revision.
  1. Reviewer comment, 2/91.
  1. Panelist comment, 2/91.
  1. Panelist comments, 2/91.
  1. Panel comment, 2/91.
  1. Panel comments, 2/91.
  1. ImmuCyst package insert (Connaught—Canada), Rec 8/14/90.
  1. TICE BCG package insert (Organon—US), Rev 8/90.
  1. Diagnostic and Therapeutic Technology Assessment (DATTA). BCG immunotherapy in bladder cancer: a reassessment. JAMA 1988 Apr 8; 259: 2153-5.
  1. Debruyne FMJ, Denis L, van der Meijden APM, editors. EORTC Genitourinary Group Monograph 6. BCG in superficial bladder cancer. Proceedings of an EORTC Genitourinary Group sponsored meeting held at Erenstein Castle, Kerkrade, The Netherlands, September 7-8, 1988. New York: Alan R. Liss, Inc; 1989.
  1. Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 32nd ed. Ottawa: Canadian Pharmaceutical Association; 1997. p. 1179-80.
  1. Product Information: Pacis®, BCG, live. UroCor, Inc., Oklahoma City, OK (received 2/2000) reviewed 8/2000.
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