BCG immunotherapy for bladder cancer (Vaccinum BCG for immunotherape cancer of vesica urinaria)
L03AX03 BCG vaccine
Immunomodulatory agents [Vaccines, serums, toxoids and phages]
The nosological classification (ICD-10)
C67 Malignant neoplasm of bladder
Lyophilisate for suspension for intravesical administration of 1 vial.
viable BCG cells (Mycobacterium bovis, RIVM strain) 2 × 108-8 × 108
Excipients: polygeline – 250 mg; anhydrous glucose – 1080 mg;
polysorbate-80 – 0.5 mg
solvent – Sodium chloride 0.9% solution
Mode of action – immunomodulatory.
Dosing and Administration
The drug is used in the form of instillation into the bladder.
For 3-11 days prior to immunotherapy, a patient put intradermal Mantoux test with 2 TU of tuberculin purified in the standard dilution.
Staging tests and taking into account the response is carried out in accordance with the instructions for use of tuberculin. Mantoux test is carried out in the TB dispensary, or a person who has a special certificate-tolerance. Use of the drug is allowed papules size less than 17 mm in diameter.
For a single intravesical instillation using the contents of 1 vial.
The drug should be used immediately after preparation of the suspension. Instructions for the preparation of the suspension are given in “Instructions for use” section.
Duration of treatment
Treatment of preinvasive bladder cancer. According to the standard scheme of therapy, administered BCG instillation Uro-Medak once a week for 6 consecutive weeks at induction. BCG instillation should not start earlier than 2-3 weeks after transurethral resection (TUR). Then spend not less than 1 year of maintenance therapy. Scheme maintenance therapy given below.
Prevention of recurrence of bladder cancer. An induction course of BCG therapy should be started 2-3 weeks after transurethral resection (TUR), or biopsy of the bladder, with no signs of traumatic catheterization, and continue once a week for 6 weeks. In the case of tumors of high and intermediate risk after the induction course necessary to carry out a course of maintenance therapy. Scheme maintenance therapy given below.
Maintenance therapy is carried out by one of the following standard patterns:
– The scheme №1: Uro-drug BCG Medak used 1 time per month for 12 months, the rate begin within 4 weeks after the last injection as part of an induction course;
– Circuit №2: drug use 1 instillation a week for 3 weeks with weekly intervals at the 3rd, 6th, 12th, 18th, 24th, 30th and 36th months of starting induction course of therapy. Under this scheme, taking into account the initial course of induction therapy is carried out for a total of 27 instillations drug within 3 years.
The above scheme of maintenance therapy have been studied in numerous clinical studies, including a large number of patients with the use of drugs of different BCG strains. There is currently no evidence to suggest that any of these circuits is superior to another.
The use of Uro-BCG Medak should be conducted under the same conditions provided for intravesical endoscopy. The patient should not drink for 4 hours before the test and 2 hours after instillation. Before instillation of BCG should empty the bladder.
Uro Medac BCG-injected into the bladder under low pressure by means of flexible urethral catheter. Uro-slurry introduced Medac BCG should remain in the bladder, if possible, during 2 hours. During this time it is necessary to provide sufficient contact with the slurry across the mucosa of the bladder formulation. To do this, the patient needs as much as possible to move. Bedridden patients must be turned from the back to the abdomen and vice versa every 15 minutes. After 2 hr after instillation of the patient should empty the bladder, preferably in a sitting position.
In the absence of contraindications the patient after each instillation for 48 hours conducting hydration is recommended.
For the treatment with BCG Uro-specific instructions Medak elderly patients are not provided.
Instructions for use
Before using the drug Uro-BCG Medak under aseptic conditions must be restored to a state of suspension.
1) Only in the case of vial with lyophilisate in a carton box (without a closed system) – with 50 mL of 0.9% sodium chloride solution for injection;
2) in the case of set – vial, a solvent, an adapter for a catheter and PE package – using the supplied set of solvent – 0.9% sodium chloride solution for injection in a polymeric container with a connecting flange and luerovskim adapter.
The procedure for preparation of the suspension and the preparation of a drug for instillation
It should be handled with gloves.
The re-suspension of the drug must be protected from the effects of daily sunlight and used immediately after preparation. After dissolving the freeze-dried preparation should be a coarse suspension in light gray (dissolution time – no more than 3 minutes). Visible particulate drug does not affect its efficacy and safety.
1. If you are using only a bottle with lyophilisate in a carton box (without a closed system), then for suspension for intravesical formulation as a solvent used any drug of 0.9% sodium chloride solution for injection. Preparation of the suspension and its introduction produced aseptically. With the vial with lyophilisate remove the protective plastic cover. From container used with a suitable solvent with a sterile syringe with a needle of 0.8 mm internal diameter were taken 20 ml of solvent, and then punctures the rubber stopper of the vial with the lyophilisate, a solution is slowly added from a syringe into the vial. Gently shake the vial until complete dissolution of the lyophilizate. Then, using a sterile syringe with a needle of 0.8 mm internal diameter of the vial contents was transferred into a sterile container, the volume is adjusted to 0.9% sodium chloride 50 ml solution for injection and mixed. The resulting drug suspension is introduced into the bladder via a urethral catheter elastic.
2. If you are using a kit containing a vial with lyophilisate, 50 ml of solvent (0.9% sodium chloride solution) in the polymer container with a connecting flange and luerovskim adapter adapter with luerovskim adapter for connection of the catheter and PE bag for recycling materials used, the order of actions should be as follows:
- – Open the protective bag in which the container is packed with the solvent, but not completely removing the container! Thus luerovsky adapter (connector) instillyatsionnoy system until the last moment will be protected from contamination by foreign matter and infectious agents;
- – Fracture mechanism protective tube connection flange adapter, applying a bending force alternately in opposite directions while manipulating the tube and not the vial. This will ensure that cross-connection is established;
- – Flip the system so that the vial is turned from below and, if necessary applying a compressive force to the small container with a solvent to ensure penetration of the solvent into the vial to fill about half its volume. It is necessary to avoid excessive squeezing force on the container so as to prevent depressurization of the system. Do not attempt to fill the entire volume of solvent bottle! Gently rocking the vial should be to achieve complete dissolution of the freeze-dried;
- – Turn combined system such that vial on top, and prepared to give suspensions of BCG to flow through the compound with the solvent container occasional gentle pressing on the container to help the air to fill the inner space of the vial. Make sure that the suspension is completely flowed into instillyatsionnuyu system. Bottle not delete. Keep instillyatsionnuyu system vertically;
- – Completely remove the protective bag. In the case of a urethral catheter connector to connect with luerovskim luerovsky adapter (connector) instillyatsionnoy system luerovskim catheter connector. Cracked closing mechanism in the tube (applying a bending force alternately in opposite directions), providing cross-established connection with a catheter, and a drug instilled into the bladder. In the case of a urethral catheter with a tapered connector to use a part of the adapter kit adapter to the catheter. Connect the connector luerovsky instillyatsionnoy system luerovskim plug adapter;
- – Connect the adapter to the catheter to the catheter. Cracked closing mechanism in the tube container terminal, providing cross-established connection with urethral catheter, and a drug instilled into the bladder. At the end of instillation free the catheter from drug residue by squeezing the container of solvent, and then remove the catheter from the bladder;
- – Then put instillyatsionnuyu system with a catheter in the waste bag. Disposal of waste and used materials is carried out in accordance with the rules on the handling and disposal of infectious material received in the hospital. Methods and waste treatment modes and materials shall comply with the requirements of the existing sanitary norms and rules of decontamination of mycobacteria.
1. The lyophilizate comprising from 2 × 108 to 8 × 108 viable BCG bacteria. In a glass vial, with a capacity of 25 ml (type 1 EF). One vial with lyophilisate in a carton box.
1. The lyophilizate containing 2 × 108 to 8 × 108 viable BCG bacteria. In a glass vial of 25 ml capacity (type 1 EF). 1 vial with lyophilisate in a carton box.
2. 50 ml of the solvent (sodium chloride 0.9%) in a polymeric container with a connecting flange and luerovskim adapter in a sealed blister pack made of PE.
3. luerovskim adapter with an adapter for connection of the catheter in a sealed PE / paper packaging.
4. PE bag for recycling used materials.
1 pack containing 1 vial, 1 Plastic container with solvent, 1 adapter and 1 PE bag in carton box.