|Calmette Guérin Vaccine
| Calgevax – Calmette Guérin Vaccine – is a preparation specially
designed for cancer immunotherapy.
consists of live bacteria derived from a culture of the
Bacillus of Calmette and Guérin (BCG).
Each ampoule contains:
* active substance: Mycobacterium bovis BCG 11.25 mg (
37.5 mg semi-dry bacterial mass)
* 1.0-3.0 x 108viable units
* stabilizer: Sodium glutamate 40 mg
The product is dry white mass; after resuspending in 1 ml
sterile saline a homogeneous suspension is observed.
In all kind of malignant tumors in which adjuvant immunotherapy
is recommended, especially for bladder tumors, malignant
administration is indicated for the treatment of malignant
melanoma as well as for nonspecific adjuvant immunostimulating
therapy of other malignant tumors.
Calgevax has demonstrated strong effect in the treatment
of superficial bladder tumors.
The intravesical administration is used as:
*prophylaxis against the recurrences of the superficial
tumors after transurethral resection;
* treatment of Carcinoma in situ of the bladder.
Information before application:
Calgevax should not be used in immunosuppressed
patients or persons with congenital or acquired immune deficiencies,
whether due to concurrent disease or cancer therapy.
The preparation should be avoided in asymptomatic carriers
with a positive HIV serology and in patients receiving steroids
at immunosuppresive doses or other immunosuppressive therapies.
Treatment with Calgevax should be postponed in the presence
of febrile illness, urinary tract infection, or gross hematuria,
or during treatment with antibiotics.
A positive Mantoux test is a contraindication only if there
is evidence of an tuberculosis infection.
Warnings and precautions:
of bladder irritability, related to the inflammatory response,
are associated with BCG administration: dysuria, hematuria,
urinary frequency, “flu-like” syndrome of 1-2 days duration.
*Small bladder capacity has been associated with increased
risk of severe local reactions and should be considered
in deciding to use Calgevax therapy.
*For systemic BCG infection suggested by febrile episodes
with “flu-like” symptoms lasting more than 48 hours, fever
above 390 C, systemic manifestations increasing in intensity
with repeated instillations, or persistent abnormalities
of liver function tests, an infectious diseases specialist
should be consulted and the patient promptly treated with
*Calgevax contains live attenuated microorganisms and
should be treated as infectious material. Persons with
immunosupression are not allowed to work with Calgevax.
*The catheterization of the bladder has to be performed
carefully in order that the traumatization be avoided.
Drug and other interactions:
application of Calgevax could result in increased sensitivity
to tuberculin. As the interpretation of the skin reactions
to tuberculin at future tuberculin testing would become
complicated, it is advisable to test the patient’s reactivity
to tuberculin before starting of the immunotherapy.
and effectiveness of the preparation for bladder tumors
in children have not been established.
Pregnancy and lactation:
is not know whether Calgevax can cause fetal harm when administered
to a pregnant woman. It is also not know whether is excreted
in human milk.
Application and Dosage:
days minimum should elapse before BCG is administered following
biopsy, TUR or traumatic catheterization.
The application of Calgevax should be done using sterile
technique and under medical control.
The intravesical dose consists of four ampoules of Calgevax.
Draw 1 ml of sterile saline (0,9 Sodium Chloride) into a
syringe and add to one ampoule of Calgevax to resuspend.
Shake the ampoule gently. Draw the mixture into the syringe
and gently expel back into the ampoule three times to ensure
through mixing. This mixing minimizes the clumping of the
mycobacteria. Dispense the suspension into the top end of
a catheter tip syringe which contains 49 ml saline diluent
bringing the total volume to 50 ml. Gently rotate the syringe.
The suspended Calgevax should be used immediately after
preparation. Unused suspension should be destroyed according
to the rules of destroying of infectious material.
should be taken to avoid exposing the Calgevax to light.
emptying the bladder, the reconstituted Calgevax is instilled
into the bladder through an urethral catheter. The vaccine
is retained in the bladder 2 hours and then voided. While
the Calgevax is retained in the bladder, the patient may
be repositioned form left side to right side and also
may alternately lie upon the back and abdomen, changing
these positions every 15 minutes to maximize bladder surface
exposure to the agent.
A standard treatment schedule consists of one intravesical
instillation per week for 6 weeks (Induction therapy).
maintenance therapy is determined individually for every
schemes could be used: monthly instillations during 6-12
months minimum or three weekly instillations at month 3,
6, 12, 18, 24, 30 and 36 (measured from the date of first
zone for scarification is cleaned with acetone (not alcohol).
10 horizontal and 10 vertical striae are done on a surface
of the skin (5 cm x 5 cm). Attention should be taken in order
to lacerate the epidermis only, without an abundant bleeding.
Galgevax can be administered percutaneously
utilizing a Heaf apparatus for multiple puncture. The multiple-punkture
disk with the points allows to regulate the depth of the
In the both cases a dose of 0.5 ml of the prepared vaccine
is applied on the surface for scarification.
sterile methods, 0.5 ml of sterile saline is added to one
ampoule of vaccine. The concentration of the suspension
is 75 mg/ml. One ampoule is used for one scarification.
The zone of the skin for the next scarification should be
different from the zone of the former application.
adverse effects: local pruritus or skin rash, painful ulcer,
lymphadenopathy of the regional lymph nodes.
Systemic adverse effects: general malaise,
fever, nausea, vomiting, headache, cramps/pain, abdominal
pain, diffused rash, liver function disturbances, disseminated
BCG infection, generalized hypersensitivity, erytema nodosum,
conjunctivitis, uveitis, vitiligo, arthritis, leucopenia or
When severe systemic adverse reactions
appear (which are considered to be very rare), the interval
between the instillations must be delayed. It is recommended
in such cases to contact the specialist who may decide to
stop the administration of Calgevax. The patient should be
monitored for signs of systemic BCG infection and treated
with antituberculous medication.
of bladder irritability, related to the inflammatory response
induced by intravesical Calgevax, begin 3-4 hours after instillation
and last 24-72 hours. Local or systemic BCG infection appears
should be stored in a dry, dark place at a temperature between
+2°C and +8°C. The vaccine should be protected from
the day light.
more than 24 months from the date of the issue and not more
than 36 monhs from the last satisfactory viability test.
Name and address of manufacturer:
NCIPD Ltd. BULGARIA
1504 Sofia, 26 Yanko Sakazov Blvd.,
Tel.: **359 2 944 69 99 / 281
Fax: **359 2 943 30 75
Last Revision: December 2001