SII-ONCO-BCG (BCG for Immunotherapy B.P.) for intravesical
instillation is a live freeze-dried preparation derived
from attenuated strain of Mycobacterium bovis (Bacillus Calmette
Each vial contains :
Bacillus Calmette-Guerin strain
(between 1-19.2 x 108 CFU)
Sodium Glutamate 5%
Reconstitute each vial with 50 ml of sodium
Carcinoma in situ of Urinary bladder (CIS):
The treatment schedule includes weekly repeated instillation with
SII-ONCO-BCG during the first 6 weeks.
Followed by induction treatment, periodic repeated instillations
for a period of at least 12 months.
Adjunctive therapy after TUR (Trans-urethral resection) of
superficial carcinoma of Urinary bladder:
Treatment should be started 10-15 days after performing TUR. The
treatment schedule is- a weekly repeated instillation with the
drug during first 6 weeks, followed by an instillation in the 8th
week and 12th week and then monthly instillations for 4 months.
The duration of maintenance treatment should be evaluated on the
basis of tumour classification and clinical diagnosis.
For the treatment of flat
urothelial cell carcinoma in situ of urinary bladder and as
adjunctive therapy following transurethral resection of primary or
relapsing superficial noninvasive papillary tumors that are
limited to the bladder mucosa (stage Ta/T1- Grade 1,2 or3).
METHOD OF ADMINISTRATION
FOR INTRAVESICAL INSTILLATION.
The following procedures are recommended under aseptic precautions
prior to use:
Add 1 ml of a sterile isotonic preservative free saline (0.9 % NaCl)
by means of a sterile syringe to the contents of 1 vial of
SII-ONCO-BCG and allow stand for a few minutes. Then gently swirl
the vial until a homogenous suspension is obtained (caution: avoid
forceful agitation). The above procedure may be repeated to
reconstitute each subsequent vial/s used.
PREPARATION OF SOLUTION FOR INSTILLATION
Transfer the reconstituted suspension from the vial/s into a 50 ml
syringe. Rinse the empty vial/s with 1 ml each of sterile isotonic
saline. Add the rinse fluid to the reconstituted suspension in the
50 ml syringe. Finally dilute the contents of the 50 ml syringe (by
adding sterile physiological saline solution) up to a total volume
of 50 ml. Mix the suspension carefully. The suspension is now ready
Insert a catheter by aseptic technique through urethra into
bladder and drain completely. Attach the syringe containing the
prepared solution to the catheter and instill in to the bladder. On
completion of instillation, remove the catheter. The prepared
SII-ONCO-BCG suspension should be retained in the bladder for 2
hours. Care should be taken that instilled suspension is in contact
with the whole mucosal surface of the bladder. Once retained in the
bladder for 2 hours, the patient should be made to void the
instilled contents in a sitting position. The patient should not
ingest any fluid 4 hours before and 2 hours after instillation.
Ensure proper cleansing of genital area and hands.
Per instillation, the content of SII-ONCO-BCG (80-120 mg) i.e.
2-3 vials reconstituted and diluted as indicated above for
instillation into the urinary bladder.
Adverse effects are generally mild and transient. They appear to
be directly related to cumulated CFU count of BCG administered in
various instillations. Common side effects are:
Frequency, urgency of micturition
and dysuria- these symptoms usually occur from 2nd or 3rd
Cystitis and typical granulomatous
inflammatory reactions which occur in the mucosa of Urinary
bladder may be an essential component of anti-tumour activity
of the drug. The symptoms usually disappear within 2 days and
do not require treatment. Cystitis may be more prolonged
during maintenance treatment and if severe, Isoniazid 300 mg
daily can be given with analgesics until symptoms disappear.
Malaise and low-medium grade fever
and/ or a flu like syndrome. These symptoms usually occur
after 4 hours of instillation and disappear within 24-48
Fever more than 39°C. The fever
resolves within 24-48 hours with antipyretics and fluids.
Systemic BCG infections due to
traumatic catheterization, perforation of bladder or early BCG
instillation after extensive TUR which may be manifested by
pneumonitis, hepatitis or cytopenia. Patients with such
symptoms should be treated with tuberculostatic drugs as per
treatment schedules used. Triple drug therapy with or without
Cycloserine for some weeks should be used.
Arthritis, Arthralgia, Haematuria,
Orchitis, Transient urethral obstruction, Epididymitis or
bladder contraction may occur.
BCG for Immunotherapy B.P. for intravesical
instillation carcinoma in situ of bladder should not be used in:
Impaired immune response irrespective of whether this impairment is
congenital or caused by disease, drugs or other therapy.
Positive HIV serology.
Pregnancy and lactation.
Positive tuberculin reaction in conjunction with clinical evidence
of existing active tuberculosis.
Urinary tract infections: treatment should be withheld till urine
culture is negative and antibiotic therapy is stopped.
Trauma to urinary bladder.
A patient with fever needs careful evaluation before therapy is
Safety of the mode of therapy in pregnant women, nursing mothers and
children has not been evaluated.
On going treatment with antitubercular treatment.
BCG for Immunotherapy B.P. should not be administered
intravenously, subcutaneously or intramuscularly.
The product is not intended for immunisation.
The preparation contains live attenuated mycobacterium (BCG) and
should be used with aseptic technique. All equipment, supplies and
receptacles in contact with BCG should be handled and disposed off
as biohazardous. Urine voided for 6 hours after instillation also
needs to be properly disinfected.
PRECAUTIONS FOR USE
Do not expose the contents to light
before and after reconstitution.
Use immediately after
reconstitution and discard unused portion.
SII-ONCO-BCG should not be
administered I.V., S.C., I.M.
Reconstitution, preparation and
administration should be performed under aseptic conditions.
Before the first instillation
Tuberculin test should be performed, in case positive, the
drug is contraindicated only if there is an evidence of active
Delay treatment in-patients who
experience traumatic catheterization till mucosal damage has
Adequate HIV assays are recommended
in-patients who are at risk of HIV infection.
It is recommended to refrain from
intercourse for one week after instillation or use a condom.
SII-ONCO-BCG is sensitive to most antibiotics specially
to anti-tubercular drugs like Streptomycin, Isoniazid, Ethambutol,
Rifampicin and PAS (Para-amino Salicylic Acid). It is not known
whether interactions occur during intra-vesical instillation of
SII-ONCO-BCG or whether the interactions result in clinically
relevant reduction of multiplication activity of SII-ONCO-BCG.
Hence, it is not clear whether activity of SII-ONCO-BCG is
influenced by concomitant therapy with antibiotics. If a patient is
receiving antibiotics treatment then intra-vesical instillation
should be postponed till completion of antibiotics treatment (Also
see the "Contraindications"). Studies on interaction with other
drugs are not performed.
SII-ONCO-BCG should be stored in dark at 2° to 8°C. Do not expose
the contents to light before and after reconstitution. Use
immediately after reconstitution. Discard unused portion.
SII-ONCO-BCG has a shelf life of 24 months provided it is stored in
dark at 2° to 8°C and protected from light.
One carton containing 1 vial of SII-ONCO-BCG.