Composition, form of production and packaging
Lyophilizate for the preparation of a suspension for intravesical administration in the form of a powder or a porous mass of white or almost white with a grayish or yellowish hue.
1 f. (1 dose)
live mycobacteria BCG (Mycobacterium bovis, strain RIVM) 2-8 Г— 10 8 cells
Excipients: polygelin, dextrose anhydrous, polysorbate 80.
Vials with a capacity of 25 ml (1) - packs of cardboard.
Set: bottles of 25 ml capacity (1) + solvent - 0.9% sodium chloride solution (polymer containers with connecting flange and Luer adapter) 50 ml (1) + adapters with Luer adapter for catheter (1) + polyethylene bags (1) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2012.
Antitumor drug of bacterial origin. Uro-BCG medak is a lyophilized suspension of live mycobacteria BCG.
Live mycobacteria cause nonspecific local immune process, which determines the antitumor activity of the drug.
The instillation of BCG leads to an increase in the level of granulocytes, monocytes / macrophages and T-lymphocytes, and an increase in the production of IL-1, IL-2 and IL-6 cytokines, tumor necrosis factor (TNF-alpha).
Most of the bacilli is excreted together with the urine in the first hours after instillation. The fact of penetration of mycobacteria through the mucous membrane of the bladder has not been proven.
Treatment of preinvasive carcinoma (Tis, carcinoma in situ).
Prevention of recurrence of bladder cancer after radical treatment:
- stage Ta (carcinoma, infiltrating only the mucosa of the bladder): Ta G1-G2 with multifocal and / or recurrent tumors; Ta G3;
- stage T1 (a tumor infiltrating the subepithelial connective tissue and not affecting the muscular layer of the bladder);
- preinvasive carcinoma (Tis, carcinoma in situ).
The drug is used in the form of instillations in the bladder.
For 3-11 days before the immunotherapy, the patient is given an intradermal Mantoux test with 2 TE purified tuberculin in standard dilution. The sample is taken and the response is taken into account in accordance with the instructions for use of tuberculin. Mantoux test is performed in a TB dispensary or a person who has a special certificate-admission. The use of the drug is allowed at a papule size of less than 17 mm in diameter.
For one intravesical installation use the contents of one vial.
In the treatment of pre-invasive Tis carcinoma (carcinoma in situ) , according to the standard induction therapy schedule, 1 intravesical instillation of Uro-BCG medak is prescribed 1 time per week for 6 weeks. If tumor remission is not achieved, then a 6-week course of therapy can be repeated, but only if it is clinically justified. After a 4-week break, the intravesical treatment should be continued using one of the maintenance therapies described below.
To prevent the recurrence of bladder cancer, BCG installations should be started 2-3 weeks after transurethral resection (TUR) or bladder biopsy, with no signs of traumatic catheterization. According to the standard therapy scheme, 1 intravesical instillation of Uro-BCG medak is prescribed 1 time per week for 6 weeks. After that, supportive therapy is prescribed using one of the schemes described below. Supportive therapy is certainly justified in tumors with a high risk of recurrence.
According to one of the two standard maintenance regimens, 1 intravesical instillation of Uro-BCG medak is given at intervals of 1 month for 12 months. In another scheme of maintenance therapy, 3 weekly instillations of Uro-BCG medak are prescribed at the 3rd, 6th, 12th, 18th, 24th, 30th and 36th months from the onset of the induction course of therapy. Under this scheme, a total of 27 Uro-BCG instalations are conducted for 3 years.
The above treatment regimens were used in a large number of patients with the use of preparations of various strains of BCG. At the present time, it can not be asserted that any of these schemes exceeds the other.
Rules of drug administration
Uro-BCG medak should be administered under the same conditions as those prescribed for intravesical endoscopy. The patient should not drink for 4 hours before the procedure and 2 hours after instillation. Before instillation should empty the bladder. Uro-BCG medak is injected into the bladder by means of an elastic catheter. The introduced suspension of Uro-BCG medak should remain in the bladder, if possible, within 2 hours. In order to achieve an even contact of the suspension with the entire surface of the bladder mucosa, it is desirable that the patient change the position of the body and move as much as possible. Lezhachih patients must be turned from the back to the abdomen and vice versa every 15 minutes. 2 hours after instillation, the patient should empty the bladder in a container containing 500 ml of disinfectant solution (5% chloramine solution), exposure time 6 hours.
If the patient has no contraindications, after each instillation within 48 hours it is recommended to perform hyperhydration.
For the treatment of the drug Uro-BCG medaka elderly patients special instructions are not provided.
Instructions for use
Before use, the Uro-BCG medication in aseptic conditions should be reconstituted to a suspension:
I) in the case of a package containing only a vial of lyophilizate in a cardboard bundle - using 50 ml of a commercially available sodium chloride solution of 0.9% for injection.
II) in the case of a package containing the kit - the vial with the preparation, the solvent, the catheter adapter and the polyethylene bag - using the supplied 50 ml solvent-sodium chloride solution of 0.9% in a polymer container with a connecting flange and Luer adapter.
The procedure for preparing the suspension and preparing the preparation for instillation .
It is necessary to work in gloves.
The reconstituted suspension of the drug should be protected from the effects of daylight and used immediately after preparation. The vaccine vial and the infusion system with the catheter are placed in a disinfectant solution (5% chloramine solution) for 6 hours after use. The instrument can be disinfected by boiling for 40 minutes.
Visible particulate matter of the drug does not affect its effectiveness and safety.
I) If a package containing only a vial of lyophilizate is used in the carton, then any commercial preparation - sodium chloride solution 0.9% for injections - is used to prepare the suspension of the drug for intravesical administration as a solvent. The preparation of the suspension and its administration are carried out in accordance with the rules of antiseptics.
Remove the protective plastic cover from the vial with lyophilizate.
From the solvent container used, 20 ml of solvent are taken from a suitable sterile syringe with a 0.8 mm internal diameter needle, after which, puncture the rubber stopper of the vial with lyophilizate, slowly inject the solution from the syringe into the vial. Carefully shake the vial until the lyophilizate is completely dissolved.
Then, using a sterile syringe with a 0.8 mm internal diameter needle, transfer the contents of the vial into a sterile container, adjust the volume of sodium chloride with 0.9% solution for injections to 50 ml and mix.
The resulting suspension of the drug is injected into the bladder with a suitable catheter.
II) If a kit containing a lyophilisate vial is used, 50 ml of solvent (0.9% sodium chloride solution) in a polymeric container with a connecting flange and Luer adapter, an adapter with a Luer adapter for catheter connection, and a plastic bag for disposal of used materials, be as follows:
1. Open the protective package in which the solvent container is packed, but do not remove the container completely. Thus, the Luerov adapter of the installation system until the last moment will be protected from contamination by foreign particles and infectious agents.
2. Remove the caps from the vial and from the connecting flange of the container with the solvent. Prepare a package for waste disposal.
3. Tightly press the vial with lyophilizate to the flange of the container with the solvent.
4. Break the protective mechanism in the adapter flange of the connecting flange, ensuring the patency of the installed connection.
5. Turn the system over so that the bottle is on the bottom, and allow the solvent to penetrate into the bottle. In this case, it is necessary to avoid excessive pressure on the container in order to avoid depressurization of the system. Gently shaking the bottle, to achieve complete dissolution of the lyophilizate.
6. Turn the combined system over so that the bottle is on top, and allow the prepared suspension to flow through the joint into a container with a solvent. Make sure that the suspension has completely flowed into the instillation system. The bottle can not be removed.
7. Keep the instillation system upright. Now completely remove the protective package.
In the case of using the urethral catheter with the Luerov tip, connect the Luerov tip of the installation system with the Luerov tip of the catheter. Break the closing mechanism in the tube, ensuring the patency of the established connection with the catheter, and to instill the drug into the bladder.
If a urethral catheter with a conical tip is used, the adapter adapter for the catheter should be used. Connect the Lueur tip of the installation system with the Luer tip of the adapter. Connect the catheter adapter to the catheter. Break the closing mechanism in the tube of the Luer adapter, ensuring the patency of the established connection with the catheter, to instill the drug into the bladder.
8. After the end of the injection, remove the catheter from the bladder and release the catheter from the remnants of the drug, letting in through it a small amount of air into the instillation system from the surrounding atmosphere. After this, place the instillation system with the catheter in the waste package.
Disposal of waste and used materials is carried out in accordance with the rules adopted in the medical institution for the handling and disposal of infectious materials (live BCG vaccine). In the conditions of a medical institution, decontamination of waste and used materials can be carried out by steam sterilization at a pressure of 0.15 MPa at a temperature of 126 В± 2 В° C for 90 minutes (SP 1.3.2322-08) or by keeping them in a disinfectant solution (5% chloramine solution ) for 6 hours (in accordance with SP 18.104.22.1680-02).
Adverse reactions during therapy with the drug Uro-BCG medak are observed quite often, but usually are not of a serious nature and, as a rule, are transient. Adverse reactions usually increase with an increase in the number of BCG installations.
Frequency Adverse reactions and complications
Very often (> 1/10)
From the digestive system: nausea
On the part of the urinary system: cystitis and inflammatory (granulomatous) reactions from the bladder, frequent urination, discomfort and pain when urinating
On the part of the reproductive system: asymptomatic granulomatous prostatitis
Common disorders: fever <38.5 В° C, flu-like symptoms (malaise, fever, chills), general malaise
Often (> 1/100 <1/10)
Common disorders: fever> 38.5 В° РЎ
Infrequently (> 1/1000 <1/100)
On the part of the hematopoiesis system: cytopenia, anemia
On the part of the immune system: Reiter's syndrome (conjunctivitis, asymmetric oligoarthritis, urethritis, cystitis)
On the part of the respiratory system: miliary pneumonia, pulmonary granuloma
From the liver and gallbladder: hepatitis
Dermatological reactions: skin rash, cutaneous abscess
From the musculoskeletal system: arthritis, arthralgia
From the urinary system: urinary tract infections, macrogematuria, bladder retraction, obstruction of the urinary tract
On the part of the reproductive system: orchitis, epididymitis
Common disorders: arterial hypotension
Rarely (> 1/10 000 <1/1000)
Infections: sepsis due to BCG
Vascular disorders: infection with vascular lesions (eg, an infected aneurysm)
From the urinary system: renal abscess
From the genital system: granulomatous prostatitis with clinical symptoms
Very rarely (<1/10 000), including individual messages
Infections: BCG infection of implants and adjacent tissues (eg, infection of aortic graft, cardiac defibrillator, hip or knee arthroplasty)
From the side of the lymphatic system: regional lymphadenitis, infection of the regional lymph node
On the part of the immune system: allergic reactions (manifested in the form of such symptoms as, for example, edema of the eyelids, cough)
From the musculoskeletal system: BCG-infection of the bone marrow, osteomyelitis, abscess of lumbar muscles
From the side of the organ of vision: chorioretinitis, conjunctivitis, uveitis
Vascular disorders: vascular fistula
On the part of the digestive system: vomiting, intestinal fistula, peritonitis
On the part of the reproductive system: BCG infection of the penis head, orchitis, epididymitis, resistant to antituberculous therapy
Local reactions: unpleasant sensations and pain with urination, as well as frequent urination are observed in 90% of patients. Cystitis and inflammatory (granulomatous) reaction of the mucosa of the bladder are considered an integral part of the antitumor activity of the drug. Infrequent - macrohematuria, acute cystitis, not passing by the time of the next instillation, violation of the passage of urine, orchitis, epididymitis. Acute cystitis, which does not pass by the time of the next injection, requires additional examination of the patient in order to determine the pathogen.
Rarely abscess of the kidney.
Systemic reactions: fever> 39.5 В° C for at least 12 hours, fever> 38.5 В° C for at least 48 hours; miliary pneumonia caused by BCG; granulomatous hepatitis; deviation of indicators characterizing liver function; organ dysfunction (not related to the genitourinary system); granulomatous inflammation, confirmed by biopsy; Reiter's syndrome.
After instillation of Uro-BCG medak often subfebrile temperature, flu-like symptoms and general malaise are often noted. These symptoms usually weaken after 24-48 hours, and standard symptomatic treatment should be applied to them. These symptoms are signs of a beginning immune reaction. All patients assigned to Uro-BCG instillations should be closely monitored and instructed to report all episodes of fever and other reactions, including. not related to the urinary tract. It is rare to have sepsis caused by BCG, which is a threat to life. In rare cases, arthritis / arthralgia, skin rash may develop. Most of the cases of arthritis, arthralgia and skin rash can be explained by the patient's allergic reactions to BCG. In some cases, it may be necessary to cancel the treatment of Uro-BCG medak.
Treatment of symptoms and syndromes
Symptoms, signs and syndrome Treatment
1) Symptoms of irritation of the bladder for a period not exceeding 48 h Symptomatic treatment
2) Symptoms of irritation of the bladder for> 48 hours Suspend Uro-BCG medak therapy and begin treatment with quinolones. If after 10 days of complete disappearance of symptoms is not observed, it is necessary to appoint a course of treatment with isoniazid * lasting 3 months. In the case of anti-tuberculosis therapy, the treatment of Uro-BCG medak should be finally abolished.
3) Concomitant bacterial infection of the urinary tract Treatment of Uro-BCG medak should be postponed until the completion of the course of antibiotic therapy and the normalization of urinalysis.
4) Other undesirable effects from the urogenital tract: granulomatous prostatitis, epididymitis and orchitis, urinary tract obstruction and kidney abscess Suspend the treatment of Uro-BCG medak. Prescribe a course of treatment with isoniazid * and rifampicin * for a duration of 3-6 months, depending on the severity of the case. In the case of anti-tuberculosis therapy, the treatment of Uro-BCG medak should be finally abolished.
5) Fever <38.5 В° C for less than 48 h Symptomatic treatment with paracetamol before relieving symptoms. If the fever persists for more than 48 hours, a phthisiatric consultation is needed.
6) Skin rash, arthralgia or arthritis, Reiter's syndrome Suspend the therapy of Uro-BCG medak. Assign antihistamines or non-steroidal anti-inflammatory drugs. If there is no response to ongoing therapy, prescribe a course of treatment with isoniazid * lasting 3 months. In the case of anti-tuberculosis therapy, the treatment of Uro-BCG medak should be finally abolished.
7) Systemic reaction ** to BCG without signs of septic shock. Finally, cancel the therapy of Uro-BCG medak. Assign 6-month course of TB treatment * with three drugs. Consult with a TB specialist.
8) System reaction ** BCG with signs of septic shock, Definitively cancel treatment Uro-BCG Medak. Immediately appoint a course of anti-tuberculosis therapy * three drugs in combination therapy with high doses of corticosteroids. Consult with a TB specialist.
* Caution: BCG bacteria are sensitive to all modern anti-TB drugs except pyrazinamide. If there is a need in TB therapy with three drugs it is generally recommended a combination of isoniazid, rifampicin and ethambutol.
**cm. determination of systemic response to BCG.
- previous myocardial tuberculosis;
- the size of a local reaction to intradermal injection of tuberculin in a dose of 2 TE (Mantoux test) 17 mm or more;
- exposure of the bladder in history;
- congenital immunodeficiency or acquired as a result of concomitant diseases (e.g., AIDS, leukemia, lymphoma);
- the treatment of malignant tumors (e.g. cytostatics, irradiation) or immunosuppressive therapy (e.g., corticosteroid);
- severe concomitant disease decompensated;
- the appearance of blood after catheterization is a temporary contraindication for instillation;
- Use in children (efficacy and safety have not been proven for this group of patients);
- lactation period;
- Hypersensitivity to the components of the drug.
PREGNANCY AND LACTATION
Contraindicated in pregnancy and lactation.
Before the start of treatment should stop breastfeeding.
APPLICATION FOR CHILDREN
Contraindicated in childhood.
APPLICATION IN ELDERLY PATIENTS
For treatment with Uro-BCG Medak elderly patients specific instructions is not provided.
Uro-BCG Medac not intended to n / k, intradermal, w / o or w / w of administration, as well as for vaccination.
Should not be made installation of BCG-Medak earlier than 15-21 days after transurethral resection of bladder biopsy or a traumatic catheterisation (depending on the rate of wound healing).
Traumatic installation can lead to BCG sepsis conditionality with the possible development of septic shock and likely fatal.
Before each installation intravesical BCG should be deleted urinary tract infection (inflammation of the bladder mucosa may increase the risk of disseminated BCG infection by hematogenous). If urinary tract infection is detected on the background of BCG therapy, treatment should not continue for as long as is not completed a course of antibiotic therapy and is not normalized urine.
Patients should be warned about the possible complications of BCG therapy.
In the event of systemic reactions to the BCG TB specialist consultation is necessary.
Reported cases of human infection of implants and grafts in patients, such as an aneurysm.
In the case of fever or macrohematuria preceding treatment, administration Uro-Medac BCG should be postponed until relief of these symptoms.
In the group of HLA-B27 (human leukocyte antigen B27) positive patients may increase the incidence of reactive arthritis or Reiter's syndrome.
Patients undergoing treatment with BCG Uro-Medak, should avoid contact with persons with established immunodeficiency.
Intravesical therapy with BCG Medak Uro-can cause the development of sensitivity to tuberculin and subsequently complicate the interpretation of tuberculin skin testing in the diagnosis of mycobacterial infection. Therefore, before using the Uro-BCG Medak need to spend an intradermal Mantoux test and record the result in a map of the patient.
Cases of transmission of sexually BCG has not yet been recorded, however, within a week after completion of BCG therapy during intercourse, use a condom.
Uro-BCG Medak stored in a dedicated room in the refrigerator under lock and key. Utensils and tools used for preparation of a suspension of the drug and conduct-immunotherapy with BCG can not be used for other purposes. They are stored in a separate cabinet under lock and key.
The drug should not be used in those areas as well as by the same personnel that are associated with the preparation of cytotoxic drugs for parenteral administration. Individuals with established immunodeficiency should not work with Uro-BCG Medak. Uro-prolyl solution Medac BCG should neutralize using a disinfectant, e.g., 5% chlorine bleach solution.
If the product is rubbed on the skin it swab moistened with 0.5% chloramine solution, then washed with warm water and soap.
Disposal of waste and used materials is carried out in accordance with the rules adopted at the hospital for the treatment of infectious materials.
The deactivation conditions hospital waste and used materials can be carried out by steam sterilization at a pressure of 0.15 MPa at a temperature of 126 В± 2 В° C for 90 min (JV 1.3.2322-08) or by keeping them in a disinfecting solution (5% solution of chloramine ) for 6 hours (according to SP 22.214.171.1240-02).
Impact on the ability to drive vehicles and manage mechanisms
Local or systemic toxicity arising on a background therapy with Uro-BCG Medak, may affect the ability to drive or operate machinery.
Overdosing is unlikely, since the bottle 1 Uro-BCG Medac corresponds to 1 dose.
There are no data indicating that an overdose can cause symptoms that differ from those described adverse reactions.
BCG bacteria are sensitive to antituberculosis drugs (e.g., ethambutol, streptomycin, PASK, isoniazid and rifampicin), antibiotics, antiseptics and lubricants. BCG observed resistance to pyrazinamide and cycloserine.
During the course of intravesical BCG installations avoid simultaneous administration of anti-tuberculosis drugs and antibacterial drugs such as quinolones, doxycycline or gentamicin, since BCG sensitivity to these drugs.
Uro-BCG Medac pharmaceutically incompatible with hypotonic and hypertonic solutions.
To prepare the suspension formulation should be used only sodium chloride 0.9% solution included in the kit formulation, or available commercial preparation of sodium chloride 0.9% for injection.
TERMS OF RELEASE FROM PHARMACY
The drug is intended for use in health care facilities.
TERMS AND CONDITIONS OF STORAGE
The drug is stored protected from light in the reach of children at a temperature of from 2 В° to 8 В° C; Do not freeze. Shelf life - 2 years.
Transporting the drug - at a temperature of from 2 В° to 8 В° C under conditions excluding freezing.