ONKO 50 mg /150-600 Million Live Bcg Bacilli/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
   1. You should carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.
   2. Table of contents of the leaflet
5. What is Onko BCG 50, Onko BCG 100, and what is it used for
6. 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 operating machinery
7. How to use Onko BCG 50, Onko BCG 100
   1. The medicine is prepared for use and administered by qualified medical personnel in the following way:
   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. Omission of Onko BCG 50, Onko BCG 100 administration
8. 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 sensation of side effects, you should:
   5. Reporting side effects
9. How to store Onko BCG 50, Onko BCG 100
10. Contents of the packaging and other information
    1. What Onko BCG 50, Onko BCG 100 contain
    2. What Onko BCG 50, Onko BCG 100 look like and what the packaging contains
    3. Packaging
    4. Marketing authorization holder and manufacturer
    5. Date of last revision 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

BCG ad immunocurationem
BCG for immunotherapy

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 inform 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 vial or 1 ampoule of the medicine contains live, attenuated BCG bacteria -
(Bacillus Calmette-Guerin), Brazilian Moreau strain in a 5% sodium glutamate solution,
freeze-dried under high vacuum.
1 vial or 1 ampoule of Onko BCG 50 contains from 1.5 x 10 to 6.0 x 10 live BCG bacteria.
1 vial or 1 ampoule of Onko BCG 100 contains from 3.0 x 10 to 12.0 x 10 live BCG bacteria.
The medicine does not contain any preservatives.
Onko BCG 50 and Onko BCG 100 are used to treat superficial, non-invasive bladder cancer (urothelial carcinoma T, T, T).
Onko BCG 50 may be used despite the occurrence of side effects (dysuria, elevated body temperature).
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 immunosuppressants (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,
• before 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 is defined as latent BCG infection, which may exacerbate after many years from the initial infection, especially with granulomatous pneumonia, abscesses, infections in the aneurysm, implant, transplant, or surrounding tissue. The patient must be informed about the possibility of transitioning from latent to active disease caused by BCG bacteria 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 active 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. Topical steroids do not constitute a contraindication to therapy with the medicine.
During BCG treatment, 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 or breastfeeding women.

Driving and operating machinery

Some side effects may affect the ability to drive and operate machinery.

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 vial or 1 ampoule (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 vial or 1 ampoule (100 mg) reconstituted in 1 ml of isotonic sodium chloride solution.

The medicine is prepared for use and administered by qualified medical personnel in the following way:

Before opening, the neck of the vial with the powder and the vial with the solvent should be thoroughly disinfected with a swab moistened with 70% ethyl alcohol, before and after grinding, as well as the vial before and after removing the plastic cap, and wait for it to dry.
After opening the vial or after puncturing the rubber stopper of the vial with the powder, exactly 1 ml of isotonic sodium chloride solution should be introduced using a syringe.
The solvent should be introduced in a gentle stream along the wall of the vial. Then, the entire contents should be drawn into a syringe and gently reintroduced into the vial, avoiding foaming. This operation should be repeated until a uniform suspension is obtained.
Then, the suspension from the vial should be drawn into a sterile 50 ml syringe and added to a container with 49 ml of solvent (sterile isotonic sodium chloride solution). After reconstitution, a homogeneous, uniform suspension is obtained, without visible conglomerates.
The bladder should be emptied of urine using a catheter inserted through the urethra.
Then, the entire dose (50 ml) of the BCG suspension should be introduced through the catheter using a sterile 50 ml syringe, and this operation should be performed slowly.
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 should change their body position every 15 minutes (on their stomach, back, and sides), and after 2 hours, they should empty their bladder.
Intravesical administration should be performed no earlier than 14 days after tumor biopsy or bladder mucosa biopsy, or after electroresection of the tumor (TUR).
The procedure should be performed once a week, for six consecutive weeks. To achieve optimal efficacy, the BCG suspension should be administered in a maintenance scheme, and it is recommended to use maintenance treatment once a week for three consecutive weeks after 3, 6, 12, 18, 24, 30, and 36 months.
There are many different maintenance treatment schemes, starting from 10 instillations administered over 18-27 weeks for a period of 3 years. However, it cannot be definitively stated which scheme is the most effective.
In case of late recurrence of the tumor:

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

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 the retained urine.
The toilet after urination should be disinfected with typical disinfectant preparations.

Important information

If the doctor does not recommend otherwise after using the medicine, you should increase the amount of fluids you drink 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 inserting 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 granulomatous and allergic complications.

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

In case of administration of too large a dose or too long retention of the medicine in the bladder, the bladder should be rinsed several times with sterile, physiological sodium chloride solution. The catheter should be used to remove the 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.

Omission of Onko BCG 50, Onko BCG 100 administration

You should inform your doctor about omitting 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 unwanted symptoms may occur, both locally and generally.
Granulomatous changes have been observed in the lungs and liver.
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 unwanted consequences of therapy are also known, such as granulomatous inflammation of the deeper layers of the bladder wall, prostatitis and/or epididymitis with the formation of serous necrosis foci.
In people with granulomatous prostatitis or persistent subfebrile conditions, a 6-week treatment should be used, administering two drugs daily: 10 mg/kg body weight of rifampicin (600 mg) and 5 mg/kg body weight of isoniazid.
In people with severe septic symptoms and arthritis, a 4-month treatment scheme can be used, administering:

• daily for 2 months, three drugs: 10 mg/kg body weight of rifampicin, 5 mg/kg body weight of isoniazid, and 15 mg/kg body weight of ethambutol, and
• three times a week for the next 2 months, two drugs: 600 mg of rifampicin and 10 mg/kg body weight of isoniazid. In case of arthritis symptoms, it may be 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. Side effects related to possible BCG infection usually resolve after antitubercular treatment.

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

• allergic reaction:difficulty breathing, coughing, rash, facial swelling,
• BCG infection: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,
• eye inflammation,
• 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 reduced 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 sensation of side effects, you should:

• stop smoking (if you are a tobacco smoker),
• rest when you feel 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 - granulomatous inflammation of the deeper layers of the bladder wall, BCG 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 serous necrosis foci
Immune system disorders
frequency not known - allergic reaction (difficulty breathing, coughing, rash, facial swelling)
Eye disorders
frequency not known - eye inflammation, yellow eyes
Respiratory, thoracic, and mediastinal disorders
frequency not known - granulomatous changes in the lungs
Gastrointestinal disorders
frequency not known - diarrhea, nausea, gray or pale 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 - 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 this leaflet, you should inform 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 vials or ampoules should be stored in the outer packaging.
After reconstitution, use immediately.
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.
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 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 vial or ampoule with powder contains: BCG bacteria - 50 mg

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

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

White or light cream-colored powder.

Packaging

1 vial with powder 50 mg and 1 vial with solvent 1 ml
1 vial with powder 50 mg and 1 ampoule with solvent 1 ml
5 vials with powder 50 mg and 5 vials with solvent 1 ml
5 ampoules with powder 50 mg and 5 vials with solvent 1 ml
1 vial with powder 100 mg and 1 vial with solvent 1 ml
1 vial with powder 100 mg and 1 ampoule with solvent 1 ml
5 vials with powder 100 mg and 5 vials with solvent 1 ml
5 ampoules with powder 100 mg and 5 vials 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 revision of the leaflet: