CALGEVAX
Calmette Guérin Vaccine
 
Description:
Calgevax – Calmette Guérin Vaccine – is a preparation specially designed for cancer immunotherapy.

Composition:

Calgevax 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


Form:
Powder for suspension.
The product is dry white mass; after resuspending in 1 ml sterile saline a homogeneous suspension is observed.


Indications:

In all kind of malignant tumors in which adjuvant immunotherapy is recommended, especially for bladder tumors, malignant melanoma etc.
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.

Calgevax administration is indicated for the treatment of malignant melanoma as well as for nonspecific adjuvant immunostimulating therapy of other malignant tumors.

Information before application:

Contraindications:
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:
*Symptoms 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 antituberculous therapy.
*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:
The 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.

Safety and effectiveness of the preparation for bladder tumors in children have not been established.


Pregnancy and lactation:
It 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:

Intravesical Use:
Fourteen 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.

Precautions should be taken to avoid exposing the Calgevax to light.

After 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).

The maintenance therapy is determined individually for every case.

The following 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 instillation).

Precutaneous Use:
The 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 scarification.
In the both cases a dose of 0.5 ml of the prepared vaccine is applied on the surface for scarification.

Using 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 reactions:
Local 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 pancytopenia, splenomegalia.

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.

Symptoms 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 more rarely. 

Storage:
Calgevax 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.

Expiry date:

Not 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:

BB- NCIPD Ltd. BULGARIA
1504 Sofia, 26 Yanko Sakazov Blvd.,
Tel.: **359 2 944 69 99 / 281
Fax: **359 2 943 30 75
E-mail: bulbio@bulbio.com

Last Revision: December 2001


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