Imuron-vac, lyophilizate 8-15 ml/mg 50 mg 2 pcs

Immuron-vac represents a culture of microbial cells of BCG-1 vaccine strain (M.bovis BCG-1, Russia) lyophilized in 1.5% sodium glutamate monohydrate solution.

Immuron-vac stimulates the immune system and has antitumor activity. During intravesical instillation BCG acts as a nonspecific immunomodulator, causing: a whole complex of immune reactions, which involves a number of immune system cells, including T and B lymphocytes, macrophages, a number of cytokines.

Indications

Treatment of non-invasive urothelial bladder cancer:

Treatment of preinvasive Tis-stage (carcinoma in situ) cancer.

The prevention of bladder cancer recurrence after radical treatment:

Stage T_a (carcinoma infiltrating only the bladder mucosa): T_a G1-G2 for multifocal and/or recurrent tumor; T_a G3;

Stage T₁ (tumor infiltrating subepithelial connective tissue and not affecting the muscularis bladder);

– stage Tis (preinvasive carcinoma, carcinoma in situ).

Active ingredient

BCG bladder cancer vaccine

Interaction

During a course of intravesical instillations of Imuron-vac, concomitant administration of agents to which Mycobacterium BCG is sensitive should be avoided: anti-tuberculosis drugs, fluoroquinolones, doxycycline or gentamicin.

Special Instructions

The BCG vaccine should not be used for p/u, i.v., i.m. or i.v. administration or for the purpose of vaccination.

The patient should be warned about the possibility of complications from BCG therapy. If systemic reactions to BCG vaccine occur, a consultation with a phthisiatrician is necessary.

In therapy with BCG vaccine for immunotherapy of bladder cancer, adverse reactions are common, but these reactions are usually not severe and are usually transient. As the number of instillations increases, the risk of adverse events increases.

When prescribing BCG therapy, the risk of severe systemic BCG reactions/infections, which include: fever >39.5 °C for at least 12 h; fever >38.5 °C for at least 48 h; BCG-induced miliary pneumonia; granulomatous hepatitis; abnormal liver function parameters; organ dysfunction (not related to the urogenital system) with granulomatous inflammation confirmed by biopsy; Reiter syndrome.

Traumatic instillation may lead to BCG-associated sepsis with possible septic shock and risk of death.

Before each intravesical instillation of BCG vaccine, a urinary tract infection should be ruled out (inflammation of the bladder mucosa may increase the risk of hematogenous BCG infections). If a urinary tract infection is detected during BCG vaccine therapy, treatment should be interrupted until antibiotic therapy is completed and urinalysis is normalized.

Infections of implants and grafts have been reported in patients with, for example, an aneurysm.

A single case of BCG bacteria persisting in the urinary tract for more than 16 months has been reported.

In cases of fever or macrohematuria, administration of the vaccine should be delayed until these symptoms have resolved.

Patients with decreased bladder capacity have an increased risk of bladder shrinkage.

HLA-B27 (human leukocyte antigen B27) positive patients have an increased risk of developing reactive arthritis or Reiter’s syndrome.

The drug should not be used in the same setting or by those employees associated with the preparation of cytotoxic drugs for parenteral administration. Persons with established immunodeficiency should not work with the drug. Contact of the drug with skin and mucous membranes should be avoided.

Intravesical therapy with the drug may cause the development of sensitivity to tuberculin and subsequently complicate the interpretation of tuberculin skin tests in the diagnosis of mycobacterial infection. Therefore, a tuberculin test should be performed before administration of the vaccine.

Sexual transmission. Sexual transmission of BCG has not yet been reported, but a condom should be used during sexual intercourse for one week after administration.

Treated patients are advised to wash their hands and genitals thoroughly after urinating.

Spilled solution of the drug should be decontaminated using the methods and regimens specified in the current sanitary standards and regulations for mycobacterial decontamination.

If skin contact occurs, the contaminated area should be treated with a suitable disinfectant.

Contraindications

Hypersensitivity; active tuberculosis; previous history of tuberculosis; local reaction size to a 2-dose (Mantoux) injection of tuberculin 17 mm or more; Congenital or acquired immunodeficiency due to comorbidities (e.g., HIV, leukemia, lymphoma), treatment for malignancies (e.g., cytostatics, radiation) or immunosuppressive therapy (e.g., GCS); acute cystitis or macrohematuria (until clinical signs disappear); bladder perforation; severe comorbidities in decompensation stage.

Traumatic catheterization or bleeding after bladder catheterization are contraindications to BCG instillation on that day.

BCG therapy may not be started until 2-3 weeks after transurethral bladder resection (TUR), bladder biopsy, or traumatic catheterization (depending on the rate of wound healing).

It is not recommended for use in children due to lack of efficacy and safety data.

Side effects

The side effects are grouped according to frequency of occurrence, and within each group the effects are arranged in decreasing order of severity.

Very common (>1/10)

General complications: discomfort, nausea, malaise, chills, fever.

Main urinary tract disorders: cystitis and inflammatory (granulomatous) reactions from the bladder, rapid urination accompanied by discomfort and pain.

Reproductive system disorders: asymptomatic granulomatous prostatitis.

Immune system disorders: transient systemic reaction to BCG (fever up to 38.5 °C, flu-like symptoms).

Often (>1/100, <1/10)

General disorders: fever over 38.5 °C.

Infrequent (>1/1000, < 1/100)

Infections: development of severe systemic BCG reactions/infections.

Hematopoietic system: cytopenia, most often erythropenia, manifested as anemia.

Immune system disorders: Reiter’s syndrome (conjunctivitis, asymmetric oligoarthritis, urethritis).

Respiratory system disorders: miliary pneumonia, pulmonary granuloma.

Hepatobiliary system disorders: hepatitis.

Skin changes: skin rash, skin abscess.

Skeletal and muscular system disorders: arthritis, arthralgia, in most cases a manifestation of hypersensitivity to BCG.

More urinary system disorders: development of urinary tract infections, macrohematuria, bladder retraction, urinary tract obstruction, bladder contracture.

Anxiety of the genitourinary system: orchitis, epididymitis, granulomatous prostatitis with pronounced symptoms.

General disorders: decreased BP.

Rarely (>1/10000, <1/1000)

Vascular disorders: development of infectious vascular lesions (e.g., infected aneurysm).

Kidney diseases: renal abscess.

Infections: BCG-related sepsis.

Very rare (< 1/10000), including isolated reports

Infections: BCG infection of implants and adjacent tissues (e.g., infection of aortic graft, cardiac defibrillator, hip or knee arthroplasty).

Lymphatic system disorders: cervical lymphadenitis, pelvic lymph node infection.

Immune system disorders: allergic reactions (manifested by symptoms such as eyelid swelling).

An organ of vision: chorioretinitis, conjunctivitis, uveitis.

vascular disorders: vascular fistula.

Gastrointestinal disorders: vomiting, intestinal fistula, peritonitis.

Musculoskeletal and connective tissue lesions: bone marrow infection, osteomyelitis, lumbar muscle abscess.

Urogenital system disorders: orchitis, epididymitis, resistant to anti-tuberculosis therapy, development of infection of the penis head.

The frequency is unknown (cannot be estimated on the basis of available data)

Reproductive system disorders: possible development of symptoms such as vaginal pain, dyspareunia (pain during intercourse).

Some side effects of BCG vaccine therapy are common, but usually mild and transient. As the number of instillations increases, the risk of adverse events increases.

Sometimes arthritis/arthralgia and skin rashes can be manifestations of hypersensitivity reactions to BCG. In these cases, withdrawal of therapy with the drug may be necessary.

Local adverse reactions

Uncomfortable sensations and pain when urinating, as well as frequent urination are observed in 90% of patients. Cystitis and an inflammatory (granulomatous) reaction may be integral to the antitumor activity of the drug.

Transient systemic BCG reactions

A body temperature of up to 38.5 °C, flu-like symptoms and general malaise may occur after BCG vaccine instillations – these symptoms usually subside after 24-48 h; if they develop, standard symptomatic treatment should be given. These symptoms are signs of an incipient immune reaction. All patients who are prescribed instillations should be closely monitored and be instructed to report all episodes of fever and other non-urethral reactions.

Severe systemic adverse reactions/infections

Systemic reactions/infections include fever over 39.5 °C for at least 12 h; fever over 38.5 °C for at least 48 h; BCG-induced miliary pneumonia Granulomatous hepatitis; abnormal liver function indicators; dysfunction of internal organs other than the genitourinary system caused by granulomatous inflammation confirmed by biopsy; Reiter’s syndrome. Severe infections caused by BCG vaccine can lead to sepsis.

Therapeutic recommendations for the treatment of symptoms and syndromes arising from BCG vaccine therapy

1) Symptoms of bladder irritation lasting no more than 48 hours. Symptomatic treatment is administered.

2) Symptoms of bladder irritation lasting ≥48 h. Vaccine therapy should be interrupted and treatment with quinolones should be started. If there is no complete resolution of symptoms after 10 days, treatment with isoniazid* of 3 months should be prescribed.

If anti-tuberculosis therapy is given, the vaccine treatment should be stopped.

3) Concomitant bacterial infection of the urinary tract. Vaccine treatment should be postponed until completion of antibiotic therapy and normalization of urinalysis.

4) Other adverse effects in the urinary tract: granulomatous prostatitis, epididymitis and orchitis, urinary tract obstruction, renal abscess. Cancel vaccine treatment.

Prescribe treatment with isoniazid* and rifampicin* for 3-6 months, depending on the severity of the case.

If anti-tuberculosis therapy is given, the vaccine treatment should be withdrawn.

5) Fever with fever < 38.5 °C for less than 48 hours. Symptomatic treatment with paracetamol.

6) Skin rash, arthralgia or arthritis, Reiter’s syndrome. Interrupt therapy with the vaccine.

Prescribe antihistamines or NSAIDs.

If there is no response to ongoing therapy, start treatment with isoniazid* for 3 months.

If anti-tuberculosis therapy is given, the vaccine treatment should be permanently withdrawn.

7) Systemic BCG reaction/infection without signs of septic shock. Cancel vaccine therapy.

Consider the need for consultation with an infectious disease physician. Prescribe a 6-month course of three-drug antituberculosis therapy*.

8) Systemic BCG reaction/infection with signs of septic shock. Cancel vaccine treatment.

Immediately administer three-drug antituberculosis therapy* in combination with high-dose, rapid-acting GCS therapy.

Consult with an infectious disease physician.

* Caution: BCG bacteria are sensitive to all modern TB drugs except pyrazinamide. A combination of isoniazid, rifampicin, and ethambutol is usually recommended if triple-drug antituberculosis therapy is necessary.

Overdose

There is no evidence that overdose can cause other symptoms than the described adverse reactions.