Instruction for use: Imuron-vac

Dosage form: Lyophilizate for suspension preparation for intravesical administration

Active substance: Vaccinum BCG for immunotherape cancer of vesica urinaria

ATX

L01XX Antineoplastic agents other

Pharmacological group:

Vaccines, serums, phages and toxoids

The nosological classification (ICD-10)

C67 Malignant neoplasm of bladder: Metastatic bladder cancer; Tumor of the bladder; Bladder cancer; Bladder cancer superficial; Malignant tumor of the bladder; Malignant neoplasms of the bladder; Bladder carcinoma; Transitional cell carcinoma of the bladder; Tumors of the bladder

Composition and release form

Lyophilizate for suspension preparation for intravesical injection 1 amp.

Live mycobacteria vaccine strain BCG-1, lyophilized in a 1.5% solution of sodium glutamate 25 mg

Auxiliary substances: stabilizer (sodium glutamate) - (14.3 ± 0.20) mg

Does not contain preservatives and antibiotics

In ampoules (complete with a knife ampoule); In a pack of cardboard 10 ampoules of 25 mg.

Description of dosage form

Powdery or in the form of a tablet porous mass of light yellow color, hygroscopic.

Characteristic

Imuron-vacc - BCG vaccine for immunotherapy of bladder cancer.

Pharmachologic effect

Mode action - immunomodulating, antitumor.

Pharmacodynamics

Live mycobacteria strain BCG-1, multiplying intracellularly, lead to nonspecific stimulation of the cellular immune response.

Indication of the drug Imurīn-vac

Adjuvant therapy of superficial (Ta, T1, Tis) bladder cancer;

Immunotherapy of non-invasive tumors of the bladder, whose surgical treatment is impossible.

Contraindications

Previously suffered from tuberculosis;

The size of local reaction to intradermal injection of tuberculin in a dose of 2 TE (Mantoux test) 17 mm or more;

Immunodeficiency states;

Acute cystitis or macrohematuria (before the disappearance of clinical manifestations);

Severe concomitant diseases in the stage of decompensation.

Traumatic catheterization or the appearance of blood after a catheterization of the bladder are contraindications for instilling BCG on a given day.

Side effects

Adverse reactions and complications are more common in patients with a small capacity of the bladder (less than 150 ml).

Adverse Reactions

1. Local. Dysuria is noted in 80%, macrohematuria - in 40% of patients. Appear after 2-3 BCG injections, begin 2-3 hours after instillation and last for 1-2 days. Pass, as a rule, independently and are a sign of a natural response to immunotherapy.

2. System. The increase in body temperature, not exceeding 38.5 ° C, is observed in 40% of patients on the instillation day. Usually, the duration of fever is not more than 48 hours. Special treatment is not required, it is possible to use antipyretic drugs.

Complications

1. Local. Acute cystitis, not passing by the time of the next instillation, is observed in 20% of patients. In such cases, treatment with Imuron-vacc should be interrupted. After the exclusion of bacterial cystitis of non-mycobacterial etiology, antituberculous drugs are prescribed prior to the disappearance of symptoms and within 2 weeks after the normalization of the condition. BCG therapy can be continued at a dose ranging from 10 to 30% of the original.

Symptomatic granulomatous cystitis, prostatitis, epididymitis in 3-5% of patients. With the development of such complications, BCG therapy is interrupted. Isoniazid therapy (300 mg / day) and rifampicin (600 mg / day) for 3 months are performed. In a number of patients, the development of granulomatous infiltrates in the ureteral region may lead to a violation of the passage of urine from the upper urinary tract and require temporary drainage.

Granulomatous lesions of the kidney parenchyma are rare. Further BCG therapy for these patients is contraindicated. Isoniazid is administered (300 mg / ut), rifampicin (600 mg / day) and ethambutol (1200 mg / day) up to 6 months.

2. System. In the development of systemic complications, the hematogenic spread of BCG is of paramount importance. As a rule, they develop with the introduction of BCG after gross traumatic catheterization of the bladder. The infection is facilitated by the weakening of immunity, caused by HIV infection, the use of immunosuppressants and other causes.

Allergic reactions. They are noted in the form of skin rash, arthritis, arthralgia in less than 1% of patients. Immunotherapy with a vaccine for these patients should be discontinued. Prescribe NSAIDs, antihistamines.

BCG-sepsis is extremely rare (isolated cases). It is characterized by a sharp onset: an increase in body temperature above 38.5 ° C, a chill, a sharp deterioration in the general condition. Sometimes there is a drop in blood pressure. Hepatic and renal failure rapidly develops. At a roentgenography of a thorax the focal changes and infiltrates in lungs can be revealed. After taking samples for bacteriological studies for the presence of an agent, treatment is started. Immunotherapy with a vaccine should be discontinued.

Prescribe therapy with three anti-tuberculosis drugs: isoniazid (300 mg / day), rifampicin (600 mg / day) and ethambutol (1200 mg / day). A broad-spectrum antibiotic for the treatment of possible urosepsis of non-tuberculous etiology is necessarily added. Antibiotic therapy is combined with the use of corticosteroids: hormonal therapy prevents a life-threatening hyperergic reaction.

The patient should be warned about possible complications.

Interaction

During the course of intravesical instillations of Imuron-vacc, simultaneous administration of funds to which BCG is susceptible should be avoided: antituberculosis drugs, fluoroquinolones, doxycycline or gentamicin.

Dosing and Administration

Intravesical.

For 3-11 days before the immunotherapy, the patient is given an intradermal Mantoux test with 2 TE purified tuberculin in standard dilution.

The setting of the Mantoux test and the recording of the response are carried out in accordance with the instruction on the use of tuberculin in the tuberculosis dispensary or an employee who has a special certificate-admission for tuberculin samples. The use of Imuron-vacc is allowed with a papule size of less than 17 mm in diameter.

It is recommended to begin intravesical instillation not earlier than 3 weeks after the biopsy in the treatment of superficial bladder cancer or after transurethral removal of the tumor.

In the presence of pyuria, bacteriuria, dysuria before the start of treatment, it is necessary to conduct antibacterial therapy before the complete elimination of clinical symptoms of cystitis.

Catheterization of the bladder is made by an elastic catheter, without traumatizing the urethral mucosa and bladder. After emptying the bladder, it should be washed with a sterile sodium chloride solution 0.9% for injection and make sure that there is no blood in the wash fluid. After that, the dose of the vaccine is diluted in 50 ml of 0.9% sodium chloride solution for injection and injected through the catheter into the bladder. The patient is recommended during this time to lie on the side where the TUR or tumor biopsy was performed, ensuring maximum contact of the Imuron-vacc suspension with a postoperative wound. After 2 hours, the bladder is emptied into a container with disinfectant solution and disinfection of the discharge before draining into the sewerage network.

Method 1. The induction course of immunotherapy consists of 6 weekly instillations of the drug. The recommended single dose of Imuron-vacc is 100 mg once a week for 6 weeks. The total exchange dose is 600 mg.

When complete tumor regression is achieved, it is advisable to carry out maintenance immunotherapy in the same or reduced dose at intervals of 3-6 months for 1-3 years.

Method 2. Two identical courses of immunotherapy with an interval of 4 weeks. The duration of each course is 11 days, a single dose of Imuron-vacc - 50 mg once a day every other day, the course dose of the vaccine is 300 mg, the total cumulative dose is 600 mg.

Breeding vaccine.

Ampoules with the vaccine are carefully examined before opening.

The drug is not applicable for:

- the absence of marking on the ampoule or its incorrect filling;

- Expired expiration date;

- the presence of cracks and incisions on the ampoule;

- changes in the physical properties of the drug (wrinkled tablet, discoloration, etc.).

Dry vaccine is diluted immediately before use. In aseptic conditions, the contents of 2-4 ampoules are dissolved in 50 ml of a 0.9% solution of sodium chloride for injection, thoroughly mixing with a syringe until a turbid coarse dispersed suspension of light yellow color is formed. The diluted vaccine must be protected from the effects of daylight and used immediately after breeding.

Ampoules from the vaccine, vial and catheter after the procedure are immersed in a disinfectant solution. To disinfect all materials used for vaccine and instillation, disinfectants are used, registered and approved for use in the Russian Federation for anti-tuberculosis regimens. The right to choose a disinfectant remains with the medical and preventive institution, the main criterion is disinfection of mycobacteria.

Disinfection of the instrument can be carried out by boiling for 40 minutes.

Special instructions

In the room intended for carrying out the procedures, it is necessary to irradiate the DB-30 (arc bactericidal) lamp for 30 minutes before and after the end of the operation.

During the procedure for instillation of the BCG vaccine, no other manipulation is carried out in this room.

Imuron-vacc is stored in a dedicated room in the refrigerator under lock and key. In the same room, catheters are treated and the vaccine is diluted. Utensils and instruments used for BCG immunotherapy are categorically forbidden to use for other purposes. They are stored in a separate closet under lock and key.

Storage conditions of the drug Imurīn-vac

At a temperature of 0-8 ° C.

Keep out of the reach of children.

Shelf life of the drug Imurīn-vac

2 years.

Do not use after the expiry date printed on the package.