Uro-BCG

Specific immunomodulating medication Uro-BCG has the immunological and biological properties inherent in BCG vaccines.

Indications of the uro-BCG

The appointment of Uro-BCG for the following purposes is allowed:

• for the therapy of the preinvasive cancer process;
• as a prophylaxis of the repeated development of cancer in the bladder after radical therapy;
• for the treatment of bladder cancer in stage T _a;
• for the treatment of bladder cancer in stage T ₁;
• for the prevention of urothelial preinvasive carcinoma.

[1], [2], [3],

Release form

The drug Uro-BCG is produced in the form of a powder mass for the manufacture of a suspension, which is subsequently used for infusion into the bladder cavity. Powder is packaged in 25 ml vials packed in cardboard boxes.

The composition of Uro-BCG is represented by living cells of BCG bacteria (strain RIVM, 2 * 108-8 * 108).

In the packaging, in addition to the Uro-BCG medication, 50 ml of the solvent in the form of saline solution, transient devices with a syringe adapter for connection to the catheter, and a collection bag for the used material are placed.

[4], [5]

Pharmacodynamics

The powdered mass of Uro-BCG contains viable BCG bacteria, which when injected into the bladder cavity lead to a nonspecific local immune response, which becomes the main provoker of the antitumor effect of Uro-BCG.

Intrapubraznoe infusion of the drug leads to an increased number of granulocytes, monocytes and t-lymphocytes, as well as to increased production of cytokines and TNF-α (tumor necrosis factor).

[6], [7], [8]

Pharmacokinetics

The main amount of mycobacteria is excreted from the body together with the urinary fluid during the first few hours after the intra-tubular infusion.

It is not known whether bacteria penetrate the mucous tissues of the bladder - at the moment the possibility of penetration of bacilli is not proven.

[9], [10],

Dosing and administration

The volume of one bottle of Uro-BCG is sufficient for a single infusion into the bladder cavity.

• For the treatment of the preinvasive cancer process in the bladder, one administration of Uro-BCG is performed per week, for one and a half months. If the development of the tumor has not been stopped during the proposed time, then the therapy regimen can be repeated. After a 1-month time interval, the administration of Uro-BCG can be resumed in the form of maintenance treatment.
• Prophylactic immunotherapy is started 2-3 weeks after surgery for transurethral resection or after tissue biopsy, if the urinary tract has not been traumatized after catheterization. Usually the treatment regimen includes one administration of Uro-BCG to the bladder once a week for one and a half months. If there are tumor processes with increased risk of recurrence, then the introduction of Uro-BCG is continued in the form of maintenance therapy.
• Supportive therapy consists of three weekly injections in the third, sixth, twelfth, eighteenth, twenty fourth, thirtieth and thirty-sixth months after transurethral resection. In total, over the course of 3 years, 27 injections of Uro-BCG into the bladder are carried out.

Powdered mass of Uro-BCG from the vial should be diluted in the attached solvent - saline solution. The resulting suspension should be gently but thoroughly mixed.

Work with the drug should be carried out in aseptic conditions, using rubber gloves.

How to use the drug Uro-BCG:

1. Tear the protective film on the container with saline solution without removing it completely.
2. Remove protective caps from the bottle and adapter, send them to a special disposal package.
3. Press the flask to the adapter.
4. Damage the biasing mechanism to establish the connection.
5. Pump saline into the bottle.
6. Wrap the container in such a way that the vial with the suspension is at the top, and the suspension flows freely into the container.
7. Hold the container with the suspension vertically, remove the remnants of the protective film, connect the adapter to the catheter. Damage the biasing mechanism inside the tube and introduce a suspension of Uro-BCG into the bladder.
8. Leave the container in a compressed state and throw it and the catheter into the disposal bag.

Patients are not recommended to drink fluid four hours before and two hours after the administration of Uro-BCG into the bladder. Immediately before the introduction, you must visit the toilet for urination.

It is desirable that the injected substance is in the bladder for two hours. To better distribute the drug Uro-BCG, the patient should often change the position of the trunk - for example, turn on the stomach and back every 15 minutes. Two hours after the introduction, the urea can be emptied while sitting.

Within two days after the procedure, it is recommended to use more liquid (if there are no contraindications).

[14],

Use of the uro-BCG during pregnancy

The drug Uro-BCG is not used to treat pregnant and lactating women.

Contraindications

Uro-BCG can not be used:

• with a tendency to an allergic response of the body to the administration of the drug;
• if the patient previously had tuberculosis;
• if the Mantoux test resulted in the development of a local reaction with a diameter of 17 mm or more;
• if previously the patient was given radiation therapy on the bladder;
• with congenital or acquired immunodeficiency associated with leukemia, HIV, lymphoma;
• in the treatment of cytostatics, or the use of radiation or immunosuppressive therapy;
• at various decompensated states;
• in childhood.

A relative contraindication is the appearance of bloody discharge during bladder catheterization.

[11], [12],

Side effects of the uro-BCG

The infusion of Uro-BCG is almost always accompanied by the appearance of side effects of varying severity. The most common are such negative symptoms:

• inflammatory process in the bladder, increased frequency of urination, soreness during urination, obstruction of the urinary tract;
• granulomatous prostatitis, inflammation of the testicles;
• febrile state with a rise in temperature to 38.5 ° C, influenza state, weakness, septic state, infection of implants (arthroplasty, vascular implants);
• nausea, hepatitis;
• anemia, cytopenia;
• miliary pneumonia, lung granuloma;
• skin rashes, abscesses;
• pain in the joints, bone marrow damage, osteomyelitis;
• lowering of blood pressure, infectious vascular complications;
• puffiness of the eyelids, coughing;
• Reiter's syndrome, characterized by inflammation of the conjunctiva of the eye, asymmetric oligoarthritis and inflammation of the bladder.

[13]

Overdose

In case of an overdose of Uro-BCG, there may be an increase in adverse events.

Symptomatic drugs and antibiotics are used for treatment.

[15], [16], [17],

Interactions with other drugs

During the treatment of Uro-BCG, anti-TB medications such as Etambutol, Streptomycin, PASC, Rifampicin, Isoniazid should not be taken. Also, do not take fluoroquinolone antibiotics, gentamicin, doxycycline, since mycobacteria can be sensitive to these drugs.

Uro-BCG is not combined with a hypotonic and hypertonic solution.

[18], [19], [20],

Storage conditions

Packages with Uro-BCG are stored in a special room in a locked refrigerator, outside the children's access area and unauthorized persons who are not related to the medical staff. The temperature regime for storage of the drug is from +2 to + 8 ° C. Do not expose the product to frost.

The diluted Uro-BCG suspension should be used immediately.

If the suspension enters the skin, it is necessary to treat them with 0.5% chloramine and warm running water with detergent.

If the suspension is accidentally spilled onto the floor, it should be rendered harmless with 5% chloramine.

[21], [22], [23],

Shelf life

Vials with Uro-BCG can be stored for up to 2 years if the number of viable bacteria in the preparation is less than 5 * 10 ⁸ KUE in the vial.

Vials with Uro-BCG retain up to 3 years if the number of viable bacteria in the preparation exceeds 5 * 10 ⁸ KUE in the vial.

[24], [25], [26]