Onko bcg 50

Package leaflet: Information for the user

Onko BCG 50
Onko BCG 100
Powder and solvent for solution for bladder instillation
BCG ad immunocurationem
BCG for immunotherapy
Please read all of this leaflet carefully before using this medicine, because it contains
important information for the patient.

• Keep this leaflet for future reference.
• If you have any questions, please consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet

1. What Onko BCG 50 and Onko BCG 100 are and what they are used for
2. Important information before using Onko BCG 50 and Onko BCG 100
3. How to use Onko BCG 50 and Onko BCG 100
4. Possible side effects
5. How to store Onko BCG 50 and Onko BCG 100
6. Contents of the pack and other information

1. What Onko BCG 50 and Onko BCG 100 are and what they are used for

One ampoule or one vial of the medicine contains live, attenuated (i.e. rendered non-virulent) BCG bacilli –
(Bacillus Calmette-Guérin), Moreau strain (Brazilian substrain), in 5% sodium glutamate solution,
lyophilized under high vacuum from the frozen state.
One ampoule or one vial of Onko BCG 50 contains 1.5 x 10 to 6.0 x 10 live BCG bacilli.
One ampoule or one vial of Onko BCG 100 contains 3.0 x 10 to 12.0 x 10 live BCG bacilli.
The medicine does not contain any preservatives.
Onko BCG 50 and Onko BCG 100 are used in the treatment of superficial, non-invasive urothelial
tumours of the urinary bladder (carcinoma urotheliale T, T, T).
Onko BCG 50 may be used despite the occurrence of adverse reactions (dysuria, elevated body temperature).
BCG bacilli have been used as a non-specific immunostimulatory agent in the treatment of certain types of cancer.
Intravesical administration of BCG aims to destroy the primary tumour or delay or prevent its recurrence.
The exact mechanism of action of BCG is not fully understood. It is believed that the drug acts by stimulating
an inflammatory process within the bladder wall, which protects the body against disease progression,
and by activating the patient's immune system.

2. Important information before using Onko BCG 50, Onko BCG 100

When not to use Onko BCG 50, Onko BCG 100:

• if the patient is allergic to the active substance or to any of the other components of this medicinal product (listed in section 6), and in individuals:
• with congenital or acquired immunodeficiency,
• receiving immunosuppressive treatment (e.g. corticosteroids, cytostatic agents, or radiotherapy),
• with urinary tract infection, until sterile urine culture is obtained,
• with significant bleeding from the urinary bladder,
• with active tuberculosis or other disease treated with antituberculosis drugs,
• within 2–3 weeks after transurethral resection (TUR),
• with bladder perforation.

Warnings and precautions
Before starting treatment with Onko BCG 50, Onko BCG 100, discuss this with your doctor.
Exacerbation of latent BCG infection (including delayed diagnosis)
There is a possibility that after administration of the medicinal product, BCG bacilli may persist in the patient's body for several years. This is defined as latent BCG infection, which may reactivate many years after the initial infection, particularly manifesting as granulomatous pneumonia, abscesses, or infection within an aneurysm, implant, transplant, or surrounding tissue. The patient must be informed about the possibility of latent infection progressing to active disease caused by BCG bacilli and must be advised on the actions to take if symptoms such as fever and unexplained weight loss occur. In case of suspected active BCG infection, consultation with a physician specialized in infectious diseases is required.

Onko BCG 50, Onko BCG 100 and other medicines
Inform your doctor about all medicines currently or recently taken, as well as any medicines planned for future use.
Onko BCG 50, Onko BCG 100 should not be used in patients concurrently treated with cytostatic agents and systemic steroids. Topically administered steroids do not constitute a contraindication to therapy.
During BCG treatment, administration of antibiotics with bactericidal activity against mycobacteria should be avoided, as well as use of acetylsalicylic acid derivatives (e.g. Aspirin) and certain anticoagulant drugs.

Pregnancy and breastfeeding
Onko BCG 50, Onko BCG 100 should not be used during pregnancy and breastfeeding.

Driving and operating machinery
Some adverse effects may affect the ability to drive or operate machinery.

3. How to use Onko BCG 50, Onko BCG 100

This medicine must always be used as directed by the physician. If in doubt, consult your doctor or pharmacist.

One dose of Onko BCG 50, corresponding to one dose used for one intravesical instillation, consists of the contents of one ampoule or vial (50 mg) reconstituted in 1 ml of isotonic sodium chloride solution.

One dose of Onko BCG 100, corresponding to one dose used for one intravesical instillation, consists of the contents of one ampoule or vial (100 mg) reconstituted in 1 ml of isotonic sodium chloride solution.

The medicine is prepared and administered by qualified medical personnel as follows:

Before opening, disinfect the necks of the ampoule containing the powder and the ampoule containing the solvent, both before and after scoring, as well as the vial before and after removing the plastic cap, using a swab moistened with 70% ethyl alcohol, and allow to dry completely.

After opening the ampoule or piercing the rubber stopper of the vial containing the powder, introduce exactly 1 ml of isotonic sodium chloride solution using a syringe.

The solvent should be added gently along the wall of the ampoule or vial. Then withdraw the entire contents into a syringe and gently reintroduce it back into the ampoule or vial, avoiding foaming. Repeat this step until a uniform suspension is obtained.

Next, transfer the suspension from the ampoule or vial into a sterile 50 ml syringe and add it to a container containing 49 ml of solvent (sterile isotonic sodium chloride solution). After reconstitution, a homogeneous, uniform suspension without visible aggregates is obtained.

Empty the urinary bladder via a catheter inserted through the urethra. Then slowly instill the entire dose (50 ml) of BCG suspension through the catheter using a sterile 50 ml syringe.

The patient should refrain from drinking fluids for 3–4 hours before and 2 hours after administration of the product.

After instillation through the catheter, remove the catheter.

The instilled BCG suspension must remain in the urinary bladder for 2 hours. During this time, the patient should change body position every 15 minutes (lying on the abdomen, on the back, and on each side). After 2 hours, the bladder should be emptied.

Intravesical instillation should not be performed earlier than 14 days after biopsy of the tumor or bladder mucosa, or after transurethral resection of the tumor (TUR).

The procedure should be performed once a week for six consecutive weeks. To achieve optimal efficacy, BCG suspension should be administered according to a maintenance regimen. Therefore, maintenance therapy is recommended once a week for three consecutive weeks at 3, 6, 12, 18, 24, 30, and 36 months.

There are many different maintenance treatment schedules, ranging from 10 instillations administered over 18–27 weeks during a 3-year period. However, it is not possible to definitively determine which of these schedules is the most effective.

In case of late tumor recurrence:

• in situ (T ) 12 months after the last exposure to BCG,
• T and T HG (high risk) 6 months after the last exposure to BCG, a full course of treatment should be repeated.

Urination procedure
Two hours after drug administration, the patient should be instructed to urinate. If difficulties occur in completely emptying the bladder (urinary retention after urination), medical personnel should insert a catheter to drain residual urine from the bladder.
The toilet should be disinfected with standard disinfectants after urination.

Important information
Unless otherwise advised by the physician, fluid intake should be increased for 24 hours after the first urination. During this time, at least 12 glasses of fluids should be consumed. Urinate regularly.

Sexual abstinence is recommended for 48 hours after the instillation. Condoms should be used for at least 1 week following the instillation.

This medicine must not be administered intravenously, subcutaneously, or intramuscularly.

Lubricants used during catheter insertion must not contain tuberculostatic substances.

The BCG bacillus suspension for intravesical administration should be prepared immediately before the procedure.

Precautions should be taken when managing granulomatous and allergic complications.

Overdose of Onko BCG 50, Onko BCG 100
In case of administration of an excessive dose or prolonged retention of the drug in the bladder, the urinary bladder should be repeatedly irrigated with sterile physiological saline solution. Residual urine in the bladder (in patients with urinary retention) should be removed using a catheter. In case of septic symptoms, antituberculosis therapy should be initiated.

These procedures must be performed by qualified medical personnel.

Missed dose of Onko BCG 50, Onko BCG 100
If a recommended dose is missed, inform the physician immediately.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Intravesical administration of Onko BCG 50 or Onko BCG 100 for the treatment of non-invasive bladder cancer is well tolerated by most patients, but both local and systemic adverse effects may occur.
Granulomatous changes in the lungs and liver have been observed.
The most common complication is symptoms of cystitis (cistitis acuta), usually occurring after the second or third instillation. Frequency of urination, haematuria, and dysuria occurring on the day of administration typically resolve within a few hours.
More serious adverse effects of therapy are also known, such as granulomatous inflammation of the deeper layers of the bladder wall, prostatitis and/or epididymitis with caseous necrosis foci formation.
In patients with granulomatous prostatitis or persistent low-grade fever, a six-week treatment regimen should be applied using daily administration of two drugs: 10 mg/kg b.w. rifampicin (600 mg) and 5 mg/kg b.w. isoniazid.
In patients with severe septic symptoms and/or arthritis, a 4-month treatment regimen may be applied:

• daily for the first 2 months: three drugs – 10 mg/kg b.w. rifampicin, 5 mg/kg b.w. isoniazid, and 15 mg/kg b.w. ethambutol; followed by
• three times weekly for the next 2 months: two drugs – 600 mg rifampicin and 10 mg/kg b.w. isoniazid.
  In cases of arthritis, corticosteroids may sometimes be necessary.
  In patients presenting with the above-mentioned symptoms of systemic infection, treatment with the product must be discontinued immediately.

In addition to local reactions, general reactions may occur, such as malaise, transient increase in body temperature (38°C–39°C), chills, nausea, muscle and joint pain, diarrhoea, and pain in the genital area. General symptoms usually last 1–3 days. Very rarely, the above-mentioned symptoms necessitate discontinuation of therapy and initiation of anti-tuberculosis treatment. Adverse effects related to possible BCG infection usually resolve with anti-tuberculosis therapy.

Immediately inform a doctor or go to the nearest hospital if any of the following symptoms occur:

• Allergic reaction: difficulty breathing, cough, rash, facial swelling may occur.
• BCG infection: cough, high fever lasting longer than 12 hours (temperature above 39.5°C), or fever lasting longer than 2 days (temperature above 38.5°C).

Inform your doctor as soon as possible if any of the following symptoms are noticed:

• yellowing of the eyes or skin,
• pale or clay-coloured stools,
• fever (temperature below 38.5°C) with chills, headache, muscle or joint pain lasting more than 2 days,
• severe pain during urination or excessive urination,
• inflammation of the eyeball,
• blood in the urine (haematuria).

BCG infection after completion of immunotherapy
In isolated cases, BCG infection may manifest after completion of therapy (see section 2). Diagnosis may be difficult because physicians usually do not suspect a causal relationship between symptoms and prior BCG therapy. Early diagnosis and appropriate treatment are crucial for treatment outcome, especially in elderly patients or those with compromised immunity, to prevent severe complications. A patient warning card focusing on this issue has been developed, which the patient should receive after administration of the medicine.

To help alleviate adverse effects:

• stop smoking (if the patient is a smoker),
• rest when feeling tired,
• avoid alcohol consumption,
• follow all medical advice and take prescribed medications as directed.

The frequency of adverse reactions has been classified as follows: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000), single cases, frequency not known.

Infections and parasitic infections
Frequency not known – granulomatous inflammation of deeper layers of the bladder wall, BCG infection (cough, high fever lasting longer than 12 hours (above 39.5°C) or fever lasting longer than 2 days (temperature above 38.5°C), prostatitis and/or epididymitis with caseous necrosis foci formation

Immune system disorders
Frequency not known – allergic reaction (difficulty breathing, cough, rash, facial swelling)

Eye disorders
Frequency not known – inflammation of the eyeball, yellow eyes

Respiratory, thoracic and mediastinal disorders
Frequency not known – granulomatous changes in the lungs

Gastrointestinal disorders
Frequency not known – diarrhoea, nausea, pale or clay-coloured stools

Hepatobiliary disorders
Frequency not known – granulomatous changes in the liver

Skin and subcutaneous tissue disorders
Frequency not known – yellow skin

Musculoskeletal and connective tissue disorders
Frequency not known – muscle pain, joint pain, arthritis

Renal and urinary disorders
Frequency not known – dysuria occurring on the day of administration, frequency of urination, haematuria, excessive urination, severe pain during urination, cystitis

Reproductive system and breast disorders
Frequency not known – pain in the genital area

General disorders and administration site conditions
Frequency not known – chills, fever (below 38.5°C) with chills, headache, muscle or joint pain lasting longer than 2 days, transient increase in body temperature (38°C–39°C), malaise

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49-21-301, fax: +48 22 49-21-309, website: https://smz.ezdrowie.gov.pl.
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Onko BCG 50, Onko BCG 100

Store in a refrigerator (2°C - 8°C).
To protect from light, keep the ampoules or vials in the outer packaging.
After reconstitution, use immediately.
Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging.
The expiry date refers to the last day of the stated month.
After completion of the procedure, equipment and materials should be disposed of according to regulations for hazardous waste.
Batch number (Lot)
Expiry date (EXP)

6. Contents of the pack and other information

What Onko BCG 50, Onko BCG 100 contains

• The active substance is BCG bacilli (Bacillus Calmette-Guérin), Brazilian strain Moreau.
• The excipient is: sodium glutamate.

Onko BCG 50
One vial or ampoule with powder contains:
BCG bacilli – 50 mg

Onko BCG 100
One vial or ampoule with powder contains:
BCG bacilli – 100 mg
One ampoule with solvent contains: isotonic sodium chloride solution – 1 ml

What Onko BCG 50, Onko BCG 100 looks like and contents of the pack
A dry, amorphous powder, white or light cream in colour.

Packaging

• 1 ampoule with 50 mg of powder and 1 ampoule with 1 ml of solvent
• 1 vial with 50 mg of powder and 1 ampoule with 1 ml of solvent
• 5 ampoules with 50 mg of powder and 5 ampoules with 1 ml of solvent
• 5 vials with 50 mg of powder and 5 ampoules with 1 ml of solvent
• 1 ampoule with 100 mg of powder and 1 ampoule with 1 ml of solvent
• 1 vial with 100 mg of powder and 1 ampoule with 1 ml of solvent
• 5 ampoules with 100 mg of powder and 5 ampoules with 1 ml of solvent
• 5 vials with 100 mg of powder and 5 ampoules with 1 ml of solvent

Marketing Authorisation Holder and Manufacturer
Synthaverse S.A.
ul. Uniwersytecka 10, 20-029 Lublin
tel 81 533 82 21
fax 81 533 80 60
e-mail [email protected]