ONKO 100 mg /Ml Powder

Contents of the leaflet

1. Leaflet attached to the packaging: information for the user
2. Onko BCG 50
3. Onko BCG 100
4. Powder and solvent for preparation of suspension for intravesical administration
5. You should carefully read the contents of the leaflet before using the medicine, as it contains
   1. Table of contents of the leaflet
6. What is Onko BCG 50, Onko BCG 100, and what is it used for
7. Important information before using Onko BCG 50, Onko BCG 100
   1. When not to use Onko BCG 50, Onko BCG 100:
   2. Warnings and precautions
   3. Onko BCG 50, Onko BCG 100 and other medicines
   4. Pregnancy and breastfeeding
   5. Driving and using machines
8. How to use Onko BCG 50, Onko BCG 100
   1. The medicine is prepared for use and administered by qualified medical personnel as follows:
   2. Urination method
   3. Important information
   4. Use of a higher than recommended dose of Onko BCG 50, Onko BCG 100
   5. These actions are performed by qualified medical personnel.
   6. Missed administration of Onko BCG 50, Onko BCG 100
9. Possible side effects
   1. You should inform your doctor immediately or go to the nearest hospital if you experience the following symptoms:
   2. You should inform your doctor as soon as possible if you notice the following symptoms:
   3. BCG infection after completion of immunotherapy
   4. To alleviate the symptoms of side effects, you should:
   5. Reporting side effects
10. How to store Onko BCG 50, Onko BCG 100
11. Contents of the packaging and other information
    1. What does Onko BCG 50, Onko BCG 100 contain
    2. What does Onko BCG 50, Onko BCG 100 look like and what does the packaging contain
    3. Packaging
    4. Marketing authorization holder and manufacturer
    5. Date of last update of the leaflet:

Leaflet attached to the packaging: information for the user

Onko BCG 50

Onko BCG 100

Powder and solvent for preparation of suspension for intravesical administration

You should carefully read the contents of the leaflet before using the medicine, as it contains

important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any doubts, you should consult a doctor, pharmacist, or nurse.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same as yours.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

• 1. What is Onko BCG 50, Onko BCG 100, and what is it used for
• 2. Important information before using Onko BCG 50, Onko BCG 100
• 3. How to use Onko BCG 50, Onko BCG 100
• 4. Possible side effects
• 5. How to store Onko BCG 50, Onko BCG 100
• 6. Contents of the packaging and other information

1. What is Onko BCG 50, Onko BCG 100, and what is it used for

1 ampoule or 1 vial of the medicine contains live, attenuated (i.e., non-pathogenic) BCG bacteria - (Bacillus Calmette-Guerin), Brazilian Moreau strain in a 5% sodium glutamate solution, freeze-dried under high vacuum.
1 ampoule or 1 vial of Onko BCG 50 contains at least 150 million live BCG bacteria.
1 ampoule or 1 vial of Onko BCG 100 contains at least 300 million live BCG bacteria.
The medicine does not contain any preservatives.
The medicine is used to treat superficial, non-invasive bladder cancer (carcinoma urotheliale T, T, T).
The medicine should not be used in invasive bladder cancer, as the chances of cure are minimal.
The medicine at a dose of 50 mg may be used in case of recurring side effects (dysuria, elevated body temperature) or an enhanced tuberculin reaction.
BCG bacteria have been used as a non-specific immunostimulating agent in the treatment of certain types of cancer.
Intravesical administration of BCG aims to destroy the primary tumor or delay or prevent its recurrence. The specific mechanism of action of BCG is not fully understood. It is believed that the action of the medicine involves stimulating the development of an inflammatory process in the bladder wall, which protects the body against the development of the disease and stimulates 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 any of the other ingredients of this medicine (listed in section 6) and in people:
• with congenital or acquired immune system defects,
• being treated with immunosuppressive agents (e.g., corticosteroids, cytostatics, or radiation therapy),
• with urinary tract infections, until a sterile urine culture is obtained,
• with significant bleeding from the bladder,
• with active tuberculosis or other diseases treated with antitubercular agents,
• within 2-3 weeks after TUR,
• with bladder perforation.

Warnings and precautions

Before starting treatment with Onko BCG 50, Onko BCG 100, you should discuss it with your doctor.
Exacerbation of latent BCG infection (including delayed diagnosis)
There is a possibility that after administration of the medicinal product, BCG bacteria may survive in the patient's body for several years. This latent BCG infection may worsen after many years from the initial infection, especially in the case of granulomatous pneumonia, abscesses, infection of an aneurysm, implant, transplant, or surrounding tissue. The patient must be informed about the possibility of later exacerbation of latent BCG infections and informed about the actions to be taken in case of symptoms such as fever and weight loss of unknown origin. In case of suspected exacerbation of latent BCG infection, you should consult a doctor specializing in infectious diseases.

Onko BCG 50, Onko BCG 100 and other medicines

You should tell your doctor about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.
The medicine should not be used in people being treated simultaneously with cytostatics and systemic steroids. Topically used steroids do not constitute a contraindication to therapy with the medicine.
During BCG therapy, the administration of antibiotics that may have a bactericidal effect on BCG bacteria, as well as the administration of acetylsalicylic acid derivatives (Aspirin) and some anticoagulant drugs, should be limited.

Pregnancy and breastfeeding

The medicine should not be used in pregnant women and during breastfeeding.

Driving and using machines

The effect of Onko BCG 50 and Onko BCG 100 on the ability to drive and use machines has not been studied.

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

This medicine should always be used according to the doctor's recommendations. In case of doubts, you should consult a doctor or pharmacist.
One dose of Onko BCG 50 corresponding to 1 dose used for 1 intravesical instillation, is the contents of 1 ampoule or 1 vial (50 mg) reconstituted in 1 ml of isotonic sodium chloride solution.
One dose of Onko BCG 100 corresponding to 1 dose used for 1 intravesical instillation, is the contents of 1 ampoule or 1 vial (100 mg) reconstituted in 1 ml of isotonic sodium chloride solution.

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

To the ampoule or vial containing the powder, add 1 ml of solvent (sterile isotonic sodium chloride solution) using a 2 ml or 5 ml sterile syringe. Gently aspirate and re-inject the contents of the ampoule or vial three times to obtain a uniform suspension (avoid shaking and foaming the suspension). Then, draw the suspension from the ampoule or vial into a sterile 50 ml syringe and add it to a container with 49 ml of solvent (sterile isotonic sodium chloride solution). Empty the bladder of urine using a catheter inserted through the urethra. Then, introduce the entire dose (50 ml) of BCG suspension through the catheter using a sterile 50 ml syringe, performing this action slowly. To completely empty the catheter of the BCG suspension, administer 5 ml of sterile isotonic sodium chloride solution after introducing the suspension.
The patient should not drink fluids for 3-4 hours before and 2 hours after administration of the product.
After administration through the catheter, the catheter should be removed.
The administered BCG suspension must remain in the bladder for 2 hours, during which time the patient changes their body position every 15 minutes (on their stomach, back, and sides), and after 2 hours, they empty their bladder.
Intravesical administration should be performed no earlier than 14 days after tumor or bladder mucosa biopsy or transurethral resection of the tumor (TUR).
The procedure should be performed once a week for six consecutive weeks, and then maintenance therapy is prescribed every 3 months, once a week for three consecutive weeks.
In case of tumor recurrence, the 6-week course should be repeated.
Before starting treatment, the patient should undergo a tuberculin skin test (Mantoux test) to assess the degree of immunological reactivity. If the skin reaction is very strong or exceeds 1 cm in diameter (a reaction with a diameter of more than 6 mm is considered positive), immunotherapy with the medicine should be abandoned. After completing the 6-week course, the tuberculin skin test should be repeated to assess the effect of treatment on the patient's overall immunological reactivity. In some patients, this reactivity increases significantly.

Urination method

After 2 hours of administration of the medicine, the patient should be advised to urinate. If there are difficulties in completely emptying the bladder (urine retention after urination), medical personnel should introduce a catheter into the patient's bladder to empty it of retained urine.
The toilet after urination is disinfected with typical disinfectants.

Important information

If the doctor does not recommend otherwise after using the medicine, you should increase the amount of fluids consumed for 24 hours after the first urination. During this time, you should drink at least 12 glasses of fluids. Urinate regularly.
Abstinence is recommended for 48 hours after instillation. For at least 1 week after instillation, use condoms.
The medicine should not be administered intravenously, subcutaneously, or intramuscularly.
Lubricants used when introducing the catheter should not contain antitubercular agents.
The BCG bacterial suspension for intravesical administration should be prepared immediately before the procedure.
Precautions should be taken in case of treatment of p-antitubercular and p-allergic complications.

Use of a higher than recommended dose of Onko BCG 50, Onko BCG 100

In case of administration of too high a dose or too long retention of the medicine in the bladder, the bladder should be flushed several times with sterile physiological sodium chloride solution. The catheter should be used to remove retained urine from the bladder (in people with urine retention), and in case of septic symptoms, antitubercular agents should be used.

These actions are performed by qualified medical personnel.

Missed administration of Onko BCG 50, Onko BCG 100

You should inform your doctor about missing the recommended dose.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Treatment of non-invasive bladder cancer with Onko BCG 50 or Onko BCG 100 in intravesical instillations is well-tolerated by most patients, but undesirable symptoms may occur, both locally and generally.
Tuberculosis-like granulomatous foci have been observed in the lungs.
The most common complication is symptoms of acute cystitis, usually occurring after the second or third administration. Frequent urination, hematuria, painful urination occurring on the day of administration, usually resolve after a few hours.
More serious undesirable consequences of intravesical administration of the product are also known, such as tuberculosis-like inflammation of the deeper layers of the bladder wall, prostatitis and/or epididymitis with the formation of caseous necrosis foci.
In people with tuberculous prostate or persistent subfebrile conditions, a 6-week treatment should be used, administering two drugs daily: 600 mg of rifampicin and 5 mg/kg of isoniazid.
In people with severe septic symptoms and arthritis, a 4-month treatment scheme can be used, as adopted in the treatment of urinary tuberculosis:
administering

• daily for 2 months three drugs: 600 mg of rifampicin, 5 mg/kg of isoniazid, and 25 mg/kg of ethambutol (or 1500 mg of pyrazinamide), and
• three times a week for the next 2 months two drugs: 600 mg of rifampicin and 10 mg/kg of isoniazid. In case of arthritis symptoms, it is sometimes necessary to include corticosteroids. In patients with the above-mentioned symptoms of generalized infection, treatment with the product should be discontinued without exception. Apart from local reactions, general reactions may occur, such as: malaise, short-term elevated body temperature (38°C - 39°C), chills, nausea, muscle and joint pain, diarrhea, pain in the genital area. General symptoms usually last for 1-3 days. Very rarely, the above symptoms force the discontinuation of therapy and the administration of antitubercular drugs. Tuberculosis-like granulomatous foci in the liver have also been observed. All more serious undesirable consequences of intravesical administration of the product usually resolve after 4-month antitubercular chemotherapy.

You should inform your doctor immediately or go to the nearest hospital if you experience the following symptoms:

• allergic reaction, which may manifest as difficulty breathing, coughing, rash, facial swelling,
• tuberculous infection, which may manifest as coughing, high fever lasting longer than 12 hours (above 39.5°C) or fever lasting longer than 2 days (above 38.5°C).

You should inform your doctor as soon as possible if you notice the following symptoms:

• yellow eyes or skin,
• gray or pale stools,
• fever (below 38.5°C) with chills, headache, muscle or joint pain lasting longer than 2 days,
• severe pain when urinating or excessive urination,
• inflammation of the eye,
• blood in the urine (hematuria).

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 doctors usually do not suspect a causal relationship between symptoms and previous BCG therapy. Early diagnosis and properly selected therapy are essential for the treatment outcome, especially in elderly patients or those with impaired immunity, to avoid severe complications. A warning card for the patient focusing on this topic has been developed, which the patient should receive after administration of the medicine.

To alleviate the symptoms of side effects, you should:

• stop smoking (if you are a smoker),
• rest when feeling tired,
• avoid drinking alcohol,
• follow all medical recommendations and take the medicines prescribed by your doctor.

The frequency of side effects has been classified as: very common (≥1/10), common (≥1/100 to <1>Infections and infestations
frequency not known – tuberculosis-like inflammation of the deeper layers of the bladder wall, tuberculous infection (coughing, high fever lasting longer than 12 hours (above 39.5°C) or fever lasting longer than 2 days (above 38.5°C), prostatitis and/or epididymitis with the formation of caseous necrosis foci
Immune system disorders
frequency not known – allergic reaction (difficulty breathing, coughing, rash, facial swelling)
Eye disorders
frequency not known – inflammation of the eye, yellow eyes
Respiratory, thoracic, and mediastinal disorders
frequency not known – tuberculosis-like granulomatous foci in the lungs
Gastrointestinal disorders
frequency not known – diarrhea, nausea, gray or pale stools
Hepatobiliary disorders
frequency not known – tuberculosis-like granulomatous foci 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 – painful urination occurring on the day of administration, frequent urination, hematuria, excessive urination, severe pain when urinating, 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, short-term elevated body temperature (38°C - 39°C), malaise

Reporting side effects

If you experience any side effects, including any side effects not listed in the leaflet, you should tell your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products:
Jerozolimskie Avenue 181C, 02-222 Warsaw, phone: +48 22 49-21-301, fax: +48 22 49-21-309, website: https://smz.ezdrowie.gov.pl.
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, you can help 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, the ampoules or vials should be stored in the outer packaging.
Use immediately after reconstitution.
The medicine should be stored 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 month stated.
After completion of the procedure, equipment and materials should be disposed of in accordance with the regulations on hazardous waste.
Batch number (Lot)
Expiry date (EXP)

6. Contents of the packaging and other information

What does Onko BCG 50, Onko BCG 100 contain

• The active substance of the medicine is BCG bacteria (Bacillus Calmette-Guerin), Brazilian Moreau strain
• The excipient is: sodium glutamate Onko BCG 50 One ampoule or vial with powder contains: BCG bacteria - 50 mg

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

What does Onko BCG 50, Onko BCG 100 look like and what does the packaging contain

White or light-cream-colored powder.

Packaging

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

Marketing authorization holder and manufacturer

Synthaverse S.A.
Uniwersytecka Street 10, 20-029 Lublin
phone 81 533 82 21
fax 81 533 80 60
e-mail [email protected]

Date of last update of the leaflet: