BCG Medac

Package leaflet: Information for the user

BCG-medac, powder and solvent for endovesical suspension
Bacillus Calmette-Guérin
Please read this leaflet carefully before using this medicine because it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What BCG-medac is and what it is used for
2. What you need to know before using BCG-medac
3. How to use BCG-medac
4. Possible side effects
5. How to store BCG-medac
6. Contents of the pack and other information

1. What BCG-medac is and what it is used for

The full name of this medicine is BCG-medac, powder and solvent for suspension for endovesical use. It will be referred to as BCG-medac throughout the remainder of this package leaflet.
BCG-medac contains weakened (attenuated) Mycobacterium bovis bacteria with low infectious potential.
BCG-medac stimulates the immune system and is used in the treatment of several types of bladder cancer. It is effective when the cancer is confined to the cells lining the inside of the bladder (urothelium) and has not invaded the deeper layers of the bladder wall.
BCG-medac is administered directly into the bladder by instillation.
In flat lesion bladder cancer (carcinoma in situ), BCG-medac is used to treat disease confined to the bladder lining. There are different grades of cancer that may affect the bladder lining and the adjacent layer of cells (lamina propria).
BCG-medac is also used to prevent cancer recurrence (prophylactic treatment).

2. What you should know before using BCG-medac

Do not use BCG-medac,

• if you are allergic to live BCG (Bacillus Calmette-Guérin) bacteria or to any of the other ingredients of this medicine (listed in section 6).
• if your immune system activity is reduced or if you have immunodeficiency due to concomitant diseases (e.g. HIV positivity, leukemia, lymphoma), oncological therapy (e.g. cytostatic drugs, radiation) or immunosuppressive therapy (e.g. corticosteroids).
• if you have active tuberculosis.
• if you have previously undergone radiotherapy of the bladder or adjacent areas.
• if you are breastfeeding.
• if you have had transurethral surgery (transurethral resection, TUR), a bladder tissue sample taken (bladder biopsy), or suffered trauma from catheterization (traumatic catheterization) within the previous 2–3 weeks.
• if you have bladder perforation.
• if you notice blood in your urine (macrohematuria).
• if you have an acute urinary tract infection.

BCG-medac must not be used for subcutaneous, intradermal, intramuscular or intravenous administration, nor for vaccination. It must be administered directly into the bladder by instillation.
Warnings and precautions
Your doctor has given you a patient alert card, which you must always carry with you
(see also section 4).
Talk to your doctor or pharmacist before using BCG-medac

• if you have a fever or notice blood in your urine. In such cases, treatment with BCG-medac should be postponed.
• if you have reduced bladder capacity, as this may decrease further after treatment.
• if you are HLA-B27 positive (human leukocyte antigen B27), as this may increase the risk of developing joint inflammation (reactive arthritis).
• if you have arthritis with inflammation of the skin, eyes, and urinary tract (Reiter's syndrome).
• if you have a localized dilation of a blood vessel (aneurysm) or a prosthesis. Infection of implants or grafts may occur.
• if you have liver problems or are taking medications that may affect the liver. This is particularly important if triple antibiotic therapy with so-called anti-tuberculosis drugs is being considered.

General hygiene
After instillation, sit down before urinating to avoid splashing of urine that could contaminate the surrounding area with BCG bacteria.
It is recommended to wash your hands and genital area after urination. This is especially important during the first urinations after BCG treatment. In case of contamination of skin lesions, use an appropriate disinfectant (consult your doctor or pharmacist).
Detection of Calmette-Guérin bacilli
Detection of BCG bacilli is generally difficult. A negative test result does not exclude the presence of BCG infection outside the bladder.
Urinary tract infection
Your doctor must ensure that you do not have an acute urinary tract infection before each bladder treatment with BCG. If an acute urinary tract infection is diagnosed during BCG therapy, treatment must be suspended until urine test results return to normal and antibiotic therapy is completed.
Patients in contact with immunocompromised individuals
If you are being treated with BCG-medac, you must follow the general hygiene measures indicated above. This is particularly important if you come into contact with immunocompromised individuals, as BCG bacteria may be harmful to patients with a weakened immune system. However, no cases of human-to-human transmission of the bacterium have been reported to date.
Sexual transmission
For one week after BCG therapy, the use of a condom during sexual intercourse is recommended to ensure that the bacterium is not transmitted sexually.
Other medicines and BCG-medac
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
This is particularly important with the following medicines, as BCG bacteria are sensitive to:

• antituberculosis agents (e.g. ethambutol, streptomycin, p-aminosalicylic acid (PAS), isoniazid (INH), and rifampicin);
• antibiotics (fluoroquinolones, doxycycline, or gentamicin);
• antiseptics;
• lubricants.

BCG bacteria are resistant to pyrazinamide and cycloserine.
Pregnancy, breastfeeding and fertility
Pregnancy
You must not use BCG-medac if you are pregnant or think you might be pregnant.
Breastfeeding
Do not use BCG-medac if you are breastfeeding.
Fertility
It has been observed that BCG negatively affects sperm production and may cause reduced sperm concentration or absence of sperm in seminal fluid. This effect was reversible in animals. However, men should enquire about the possibility of sperm preservation before starting therapy.
Driving and using machines
This medicine may affect your ability to drive or operate machinery. Do not drive or operate machinery until you know how BCG-medac affects you.
If you have any doubts, consult your doctor, nurse, or pharmacist.

3. How to use BCG-medac

Dosage
BCG-medac is prepared and administered exclusively by experienced healthcare professionals. For a
bladder treatment, the contents of one vial are required.
Administration
BCG-medac is introduced into the bladder under low pressure using a catheter.
The medicine must remain in the bladder for a period of 2 hours. To ensure this, you must not drink
anything for 4 hours before treatment and for 2 hours after treatment.
While the suspension remains in the bladder, it must come into sufficient contact with the entire
mucosal surface; movement helps promote treatment. After 2 hours, you must empty your bladder while
sitting down to avoid leakage.
Unless you are on a fluid-restricted regimen, you are advised to drink plenty of fluids for 48 hours after
each treatment.
Use in children
The safety and efficacy of BCG-medac in children have not been established.
Use in the elderly
No specific dosage instructions are required for use in the elderly. However, liver function should be
considered before administering BCG.
Duration of treatment
As a standard treatment schedule (induction therapy), you will receive weekly intravesical treatments
with BCG-medac for 6 consecutive weeks. After a 4-week treatment-free period, you may receive an
additional intravesical administration, known as maintenance therapy, for at least one year, as described
below. Your doctor will discuss this with you.
Induction therapy

• BCG therapy should begin approximately 2–3 weeks after surgery via the urethra (transurethral resection, TUR) or tissue sample removal from the bladder (bladder biopsy), and in the absence of catheter-related injuries (traumatic catheterization). It will be repeated at weekly intervals for 6 weeks.
• After this, many patients receive maintenance therapy, which may involve further administrations.

Maintenance therapy

• Maintenance therapy consists of 3 treatments at weekly intervals, administered monthly at months 3, 6, 12, 18, 24, 30, and 36, for a minimum of 1 year and up to 3 years. With this regimen, you will receive a total of 15 to 27 treatments over 1–3 years. Your doctor will discuss with you the need for maintenance therapy every 6 months after the first year of treatment, if applicable.

Although maintenance therapy reduces the likelihood of cancer recurrence and may reduce its
progression, in some patients the adverse effects and discomfort associated with treatment may
outweigh the benefits. Therefore, it is important that your doctor discusses with you the potential
disadvantages of treatment and your personal preferences before starting or continuing maintenance
therapy.
If you use more BCG-medac than you should
Overdose is unlikely, as one vial of BCG-medac corresponds to a single intravesical instillation dose.
There are no data indicating that overdose would cause symptoms different from the adverse effects
described (see section 4).

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them. Side effects associated with BCG treatment are common, but usually mild and temporary. Adverse reactions typically increase with the number of BCG treatments administered.

However, the most serious side effect is a severe systemic infection. Inform your doctor immediately if you notice any of the following symptoms, which may occur at any time and sometimes appear late—weeks, months, or even years after your last dose.
Show your patient alert card to all your treating physicians.

• Fever above 39.5°C lasting for at least 12 hours, or fever above 38°C persisting for weeks; night sweats
• Unexplained weight loss
• Increasing feeling of malaise
• Various signs of inflammation presenting as: breathing difficulties or cough different from that of a common cold (miliary pneumonia), or liver problems: sensation of pressure in the upper abdomen or abnormal liver function tests (particularly of an enzyme known as alkaline phosphatase), or eye pain and redness, vision problems or blurred vision; "pink eye" (conjunctivitis)
• Documented granulomatous inflammation confirmed by biopsy

BCG systemic infection/reaction
If the bladder is accidentally injured during BCG treatment, or if BCG is inadvertently administered intramuscularly or intravenously, a severe generalized BCG infection may occur. A serious systemic BCG infection can lead to BCG sepsis, a potentially life-threatening condition. Inform your doctor immediately if you notice any sign or symptom that concerns you, or contact an infectious disease specialist! However, this infection is not contagious. Your doctor will prescribe medications to manage side effects, and BCG treatment may be discontinued.

In contrast to a BCG infection, a BCG reaction often presents with low-grade fever, flu-like symptoms, and general malaise lasting 24–48 hours as an initial immune response. Your doctor may prescribe medications to treat these symptoms. Speak with your doctor if symptoms worsen.

Late-onset BCG infection
In rare cases, BCG bacteria may remain in the body for years. This infection can manifest at any time, and signs and symptoms may appear late—sometimes even years after the last BCG dose. Signs of inflammation may resemble those of a severe BCG infection/reaction as described above. Problems related to implants or grafts may also be adverse effects of BCG treatment and may require urgent treatment.

Therefore, it is extremely important that you carry your patient alert card with you and show it to all physicians providing medical care, to ensure appropriate treatment should a late-onset BCG infection occur. The doctor will also be able to assess whether your symptoms are or are not an adverse effect of BCG therapy.

Listed below is a complete list of possible side effects:

Very common: may affect more than 1 in 10 people

• Nausea
• Bladder inflammation (cystitis), inflammatory reactions (granulomas) of the bladder. These side effects may be an essential part of the antitumor activity.
• Frequent urination, with discomfort and pain. This may affect up to 90% of patients.
• Inflammatory reactions of the prostate (asymptomatic granulomatous prostatitis)
• Temporary systemic reactions to BCG, such as fever below 38.5°C, flu-like symptoms (malaise, fever, chills), and general discomfort
• Fatigue

Common: may affect up to 1 in 10 people

• Fever above 38.5°C
• Muscle pain (myalgia)
• Diarrhea
• Abdominal pain
• Involuntary loss of urine (urinary incontinence)

Uncommon: may affect up to 1 in 100 people

• Severe systemic reaction/infection due to BCG, BCG sepsis (see below for more detailed information)
• Low blood cell counts (cytopenia)
• Anaemia (reduced haemoglobin in the blood)
• Reiter’s syndrome (arthritis with inflammation of the skin, eyes, and urinary tract)
• Lung inflammation (miliary pneumonia)
• Inflammatory reactions in the lungs (pulmonary granuloma)
• Liver inflammation (hepatitis)
• Skin abscess
• Skin rash, joint inflammation (arthritis), joint pain (arthralgia). In most cases, these side effects are signs of an allergic reaction (hypersensitivity) to BCG. In some cases, treatment may need to be discontinued.
• Urinary tract infection, presence of blood in the urine (macroscopic haematuria)
• Smaller-than-normal bladder (bladder retraction), reduced urinary flow (urinary obstruction), bladder contracture
• Inflammation of the testicles (orchitis)
• Inflammation of the epididymis (epididymitis)
• Inflammatory reaction of the prostate (symptomatic granulomatous prostatitis)
• Low blood pressure (hypotension)
• Abnormal liver function tests

Rare: may affect up to 1 in 1,000 people

• Vascular infection (e.g., infected localized blood vessel dilation)
• Renal abscess

Very rare: may affect up to 1 in 10,000 people

• BCG infection of implants and surrounding tissue (e.g., infection of aortic graft, cardiac defibrillator, hip or knee prosthesis)
• Inflammation of neck lymph nodes (cervical lymphadenitis), regional lymph node infection
• Allergic reaction (hypersensitivity) (e.g., eyelid oedema, cough)
• Inflammation of the inner eye (chorioretinitis)
• Conjunctivitis, uveitis (inflammation of the uvea of the eye)
• Vascular fistula
• Vomiting, intestinal fistula, inflammation of the peritoneum (peritonitis)
• Bone and bone marrow infection caused by bacteria (osteomyelitis)
• Bone marrow infection
• Psoas abscess (abscess of the side muscle)
• Inflammation of the testicles (orchitis) or epididymis (epididymitis) resistant to antitubercular therapy
• Infection of the glans penis
• Swelling of arms or legs

Not known: frequency cannot be estimated from the available data

• Inflammation of blood vessels (likely in the brain)
• Genital disorders (e.g., vaginal pain)
• Painful sexual intercourse (dyspareunia)
• Severe immunological reaction with fever, liver, spleen and lymph node enlargement, jaundice, and skin rash (haemophagocytic syndrome)
• Renal failure, inflammation of kidney tissue, renal cavities or pelvis (pyelonephritis, nephritis [including tubulo-interstitial nephritis, interstitial nephritis and glomerulonephritis])
• Absence or reduced level of sperm in semen (azoospermia, oligospermia)
• Increase in prostate-specific antigen (PSA, a laboratory test for the prostate)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store BCG-medac

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and carton after Exp.
Store in a refrigerator (2°C–8°C).
Do not freeze.
Store in the original packaging to protect the medicine from light.
Physical and chemical stability during use has been demonstrated for 24 hours when stored protected from light at room temperature (20°C–25°C) or in a refrigerator (2°C–8°C).
From a microbiological standpoint, the medicine should be used immediately.
If not used immediately, the storage times and conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at 2°C–8°C, unless reconstitution has been carried out under controlled and validated aseptic conditions.

6. Package contents and other information

What BCG-medac contains
The active substance is live BCG (Bacillus Calmette-Guérin) bacteria (RIVM strain derived from strain 1173-P2).
After reconstitution, one vial contains:
BCG strain RIVM derived from strain 1173-P2
from 2 x 10 to 3 x 10 live units
The other components of the powder are: polygeline, anhydrous glucose and polysorbate 80.
The other components of the solvent are: sodium chloride and water for injections.

Description of the appearance of BCG-medac and package contents
BCG-medac consists of a white or almost white powder or a porous mass with yellowish and greyish hues, and a clear, colourless solution used as solvent. Packs containing 1, 3, 5 or 6 vials are available, with or without catheter(s) and conical Luer-Lock connector(s). Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
medac
Gesellschaft für
klinische Spezialpräparate mbH
Theaterstr. 6
22880 Wedel
Germany

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• • The following information is intended exclusively for physicians or healthcare professionals:

Treatment of symptoms, signs, syndrome

Symptoms, signs or syndrome	Treatment
1) Bladder irritation symptoms lasting less than 48 hours	Symptomatic treatment.
Symptoms, signs or syndrome	Treatment
2) Bladder irritation symptoms lasting 48 hours or longer	Discontinue BCG-medac therapy and start treatment with quinolones. If complete resolution has not been observed after 10 days, administer isoniazide (INH)* for 3 months. In case of antitubercular treatment, BCG-medac therapy must be absolutely discontinued.
3) Concomitant bacterial urinary tract infection	Postpone BCG-medac therapy until urinary test results have normalized and antibiotic treatment has been completed.
4) Other genitourinary adverse effects: symptomatic prostatic granulomatosis, epididymitis and orchitis, urethral obstruction and renal abscess	Discontinue BCG-medac therapy. Consider consulting an infectious disease specialist. Administer isoniazide* and rifampicin* for 3 to 6 months depending on severity. In case of antitubercular treatment, BCG-medac therapy must be absolutely discontinued.
5) Fever below 38.5 °C lasting less than 48 hours	Symptomatic treatment with paracetamol.
6) Skin rash, arthralgia or arthritis or Reiter's syndrome	Discontinue BCG-medac therapy. Consider consulting an infectious disease specialist. Administer antihistamines or non-steroidal anti-inflammatory drugs. In case of an immune-mediated reaction, consider cortisone-based therapy. If no improvement is observed, administer isoniazide* for 3 months. In case of antitubercular treatment, BCG-medac therapy must be absolutely discontinued.
7) Systemic reaction/infection** to BCG without signs of septic shock	Immediately discontinue BCG-medac therapy. Consider consulting an infectious disease specialist. Administer a triple-drug combination anti-tuberculosis therapy* for 6 months and low-dose corticosteroid therapy.
8) Systemic reaction/infection to BCG with signs of septic shock	Immediately discontinue BCG-medac therapy. Promptly administer a triple-drug combination anti-tuberculosis therapy*, together with high-dose, rapid-acting corticosteroid therapy. Consult an infectious disease specialist.

* Warning: BCG bacteria are sensitive to all commonly used anti-tuberculosis drugs,
except pyrazinamide. If a three-drug combined anti-tuberculosis therapy is required,
the combination normally recommended includes: isoniazid (INH), rifampicin, and
ethambutol.
** see definition above
Important information on the use of BCG-medac
BCG-medac must be used exclusively by experienced healthcare professionals.
Check that storage conditions (see section 5) have been correctly maintained and that the packaging is intact.
BCG-medac must be administered under the same conditions required for endovesical endoscopy.
BCG-medac must not be administered subcutaneously, intradermally, intramuscularly,
intravenously, or for vaccination against tuberculosis.
The Luer-Lock connector on the solvent bag catheter may be used solely for endovesical instillation!
General principles and protective measures for the use of BCG-medac
Direct contact with BCG-medac should generally be avoided. BCG-medac is a medicinal product that can cause infections in humans and poses a risk to healthcare workers. Penetration of the medicinal product into the body through damaged skin, inhalation of aerosols, contact of droplets with eyes or mucous membranes, or ingestion may present a hazard. Eating, drinking, smoking, or storing food, beverages, or tobacco products must not be permitted in work areas. BCG-medac must not be handled in rooms used for the preparation of cytotoxic drugs for intravenous use, nor by personnel preparing cytotoxic drugs for intravenous use.
The medicinal product must not be handled by individuals with known immunodeficiency.
Personal protective equipment should include closed, splash-resistant protective gowns, disposable gloves, FFP2 face masks, and safety goggles with side shields during handling. BCG-medac must be transported exclusively in closed containers (for storage conditions after reconstitution, see section 5).
After completion of procedures, clean work surfaces with an appropriate disinfectant solution.
After procedures and in case of skin contact, disinfect hands with a hand disinfectant, allow them to dry, wash them, and use skin care products.
Tuberculin skin test
Endovesical treatment with BCG-medac may induce sensitivity to tuberculin and consequently alter the interpretation of the tuberculin skin test for diagnosing mycobacterial infection. Therefore, the tuberculin reactivity test should be performed prior to administration of BCG-medac.
Preparation of the reconstituted endovesical suspension
Prior to use, the medicinal product must be resuspended under aseptic conditions using sterile 0.9% sodium chloride solution (9 mg/mL) (see instructions for use, step 7). The catheter must be inserted with particular care to avoid injury to the urethral and bladder epithelium, which could lead to systemic BCG infection. To reduce the risk of traumatic catheterization and to make the procedure more comfortable, the use of a lubricant is recommended. In women, a smaller amount of lubricant may be required compared to men. No adverse effect of the lubricant’s potential antiseptic properties on the product’s efficacy has been observed. Before administering BCG-medac, drain the bladder after catheterization to reduce the amount of lubricant potentially introduced. Mix the suspension by gently shaking before use. Visible macroscopic particles do not affect the efficacy and safety of the medicinal product.
The vial content is for single use/single dose only. Any residual suspension must be discarded.
Unused medicinal product and waste materials derived from its use must be disposed of in accordance with local regulations.
Procedures in case of emergencies and BCG-medac spills
Wear protective clothing and avoid raising dust.
Cover spilled BCG-medac suspension with cellulose and moisten it with a disinfectant proven effective against mycobacteria. After cleaning up the spilled BCG-medac suspension, clean the surface again with a disinfectant solution and allow it to dry. Skin contact must be treated using an appropriate disinfectant.
First aid
Always consult a physician in case of contamination.
In case of skin contact: remove contaminated clothing. Disinfect and clean the skin and check for contamination of wounds.
In case of eye contact: rinse the affected eye with a sufficient amount of eye wash solution or, alternatively, with water. Remove contact lenses, if applicable.
In case of ingestion: rinse mouth thoroughly with abundant water.
In case of inhalation: ensure adequate supply of fresh air.
For further information on the catheter, refer to the corresponding instructions for use.
Instructions for users of BCG-medac
Components and use of the instillation kit |
Main components of the instillation kit

Active component	Description
A	Vial with powder
B	Protective wrapper
C	Solvent bag with 0.9% sodium chloride solution (9 mg/mL)
C1	Vial connector with protective cap and opening seal
C2	Luer-Lock catheter connector with protective cap and opening seal
C3	Pressure clamp
C4	Filling port without application function
D	Luer-Lock catheter
D1	Lubricant
E	Disposal bag

Connecting the vial to the solvent bag

1. Prepare the disposal bag (E) for direct disposal of the kit after instillation to avoid contamination.

2. Remove the snap-off cap from the vial (A) and disinfect the stopper according to local regulations.

3. Open the protective wrapper (B) of the solvent bag (C) by pulling it away, and remove it completely.

4. Remove the protective cap from the vial connector (C1).

5. Press the connector onto the vial until it stops.

Mixing powder and solvent

6. Break the opening seal inside the tube of the vial connector (C1) by bending it several times up and down.

7. Hold the solvent bag so that the vial is positioned below it.

Squeeze the solvent bag several times to transfer a sufficient amount of solvent into the vial.
Ensure not to completely fill the vial to allow for subsequent transfer of the suspension back into the solvent bag. Some solvent may remain in the bag.
Shake the vial gently to minimize foam formation during mixing of the medicinal product with the solvent. If excessive foaming occurs, allow the vial to rest briefly (a few minutes).
The contents of the vial should form a homogeneous suspension. This may take several minutes.

8. Invert the solvent bag and hold it so that the vial is positioned above it.

Hold the vial.
Squeeze the solvent bag several times until the vial is completely empty.
If any powder remains inside the vial, repeat steps 7 and 8.
From a microbiological standpoint, the medicinal product must be used immediately.
If not used immediately, refer to section 5 “How to store BCG‑medac”.
The suspension must not be instilled at refrigerator temperature to avoid inducing the urge to urinate in the patient, which would reduce the exposure time.

Catheterization

9. Catheterize the patient according to local regulations and instructions for use, using the provided Luer-Lock catheter (D) and lubricant (D1), or another appropriate catheter and/or lubricant.

Empty the bladder using the catheter.
Connecting the catheter to the solvent bag

10. To resuspend any sediment, rotate and agitate the bag before connecting.

Do not administer the suspension at refrigerator temperature.
Remove the protective cap from the catheter connector (C2).
Connect the patient’s Luer-Lock catheter (D) to the catheter connector (C2) of the solvent bag.

Instillation

11. Break the opening seal inside the tube of the catheter connector (C2) by bending it several times up and down.

While doing so, hold the patient’s catheter steady.

12. Hold the solvent bag with the inverted vial above the bag.

Gently squeeze the solvent bag with the other hand to slowly instill the medicinal product into the patient’s bladder.
Continue squeezing until both the solvent bag and the vial are completely empty.

13. Squeeze out the remaining air from the solvent bag to empty the catheter as completely as possible.

After instillation

14. Closing the pressure clamp (C3) prevents fluid from flowing back into the catheter and minimizes the risk of contamination. Alternatively, steps 15 and 16 may be performed while keeping the solvent bag compressed.

15. Carefully remove the catheter from the bladder without disconnecting the solvent bag from the catheter. Avoid contamination from splashing droplets.

16. Dispose of the product according to national regulations using the disposal bag.

The contents of the vial are for single use only (single dose). Any residual suspension must be discarded.

Instructions for users of BCG‑medac
Components and use of the instillation kit
Main components of the instillation kit

Main component Description
A Vial with powder
B Protective wrapper
C Solvent bag containing 0.9% sodium chloride solution (9 mg/mL)
C1 Vial connector with protective cap and opening seal
C2 Catheter Luer-Lock connector with protective cap and opening seal
C3 Pressure clamp
C4 Filling port without application function
D Luer-Lock catheter
D1 Lubricant
E Disposal bag
F Luer-Lock to conical connector
Connecting the vial to the solvent bag

1. Prepare the disposal bag (E) for direct disposal of the kit after instillation to avoid contamination.

2. Remove the snap-off closure cap from the vial (A) and disinfect the stopper according to local regulations.

3. Open the protective wrapper (B) of the solvent bag (C) by pulling it away, and remove it completely.

4. Remove the protective cap from the vial connector (C1).

5. Press the connector onto the vial until it stops.

Mixing powder and solvent

6. Break the opening seal inside the tube of the vial connector (C1) by bending it several times up and down.

7. Hold the solvent bag so that the vial is positioned below it.

Squeeze the solvent bag several times to transfer a sufficient amount of solvent into the vial.
Ensure not to completely fill the vial to allow for subsequent transfer of the suspension back into the solvent bag. Some solvent may remain in the bag.
Shake the vial gently to minimize foam formation during mixing of the medicinal product with the solvent. If excessive foaming occurs, allow the vial to rest briefly (a few minutes).
The contents of the vial should form a homogeneous suspension. This may take several minutes.

8. Invert the solvent bag and hold it so that the vial is positioned above it.

Hold the vial.
Squeeze the solvent bag several times until the vial is completely empty.
If any powder remains inside the vial, repeat steps 7 and 8.
From a microbiological standpoint, the medicinal product must be used immediately.
If not used immediately, refer to section 5 “How to store BCG‑medac”.
The suspension must not be instilled at refrigerator temperature to avoid inducing the urge to urinate in the patient, which would reduce the exposure time.

Catheterization

9. Catheterize the patient according to local regulations and instructions for use, using the provided Luer-Lock catheter (D) and lubricant (D1), or another appropriate catheter and/or lubricant.

Empty the bladder using the catheter.
Note for use with a self-selected catheter with conical connector:
To connect the bag to a self-selected catheter (not shown), the provided Luer-Lock to conical connector (F) must be used.
To do so, complete the following additional steps:

• Remove the protective cap from the catheter connector (C2, see step 10).
• Rotate and agitate the bag before connecting to resuspend any sediment.
• Connect the Luer-Lock to conical connector (F) to the catheter connector (C2) of the solvent bag.

Instillation

11. Break the opening seal inside the tube of the catheter connector (C2) by bending it several times up and down.

While doing so, hold the patient’s catheter steady.

12. Hold the solvent bag with the inverted vial above the bag.

Gently squeeze the solvent bag with the other hand to slowly instill the medicinal product into the patient’s bladder.
Continue squeezing until both the solvent bag and the vial are completely empty.

13. Squeeze out the remaining air from the solvent bag to empty the catheter as completely as possible.

After instillation

14. Closing the pressure clamp (C3) prevents fluid from flowing back into the catheter and minimizes the risk of contamination. Alternatively, steps 15 and 16 may be performed while keeping the solvent bag compressed.

15. Carefully remove the catheter from the bladder without disconnecting the solvent bag from the catheter. Avoid contamination from splashing droplets.

16. Dispose of the product according to national regulations using the disposal bag.

The contents of the vial are for single use only (single dose). Any residual suspension must be discarded.

Instructions for users of BCG‑medac
Components and use of the instillation kit
Main components of the instillation kit

Main component Description
A Vial with powder
B Protective wrapper
C Solvent bag containing 0.9% sodium chloride solution (9 mg/mL)
C1 Vial connector with protective cap and opening seal
C2 Catheter Luer-Lock connector with protective cap and opening seal
C3 Pressure clamp
C4 Filling port without application function
E Disposal bag
Connecting the vial to the solvent bag

1. Prepare the disposal bag (E) for direct disposal of the kit after instillation to avoid contamination.

2. Remove the snap-off closure cap from the vial (A) and disinfect the stopper according to local regulations.

3. Open the protective wrapper (B) of the solvent bag (C) by pulling it away, and remove it completely.

4. Remove the protective cap from the vial connector (C1).

5. Press the connector onto the vial until it stops.

Mixing powder and solvent

6. Break the opening seal inside the tube of the vial connector (C1) by bending it several times up and down.

7. Hold the solvent bag so that the vial is positioned below it.

Squeeze the solvent bag several times to transfer a sufficient amount of solvent into the vial.
Ensure not to completely fill the vial to allow for subsequent transfer of the suspension back into the solvent bag. Some solvent may remain in the bag.
Shake the vial gently to minimize foam formation during mixing of the medicinal product with the solvent. If excessive foaming occurs, allow the vial to rest briefly (a few minutes).
The contents of the vial should form a homogeneous suspension. This may take several minutes.

8. Invert the solvent bag and hold it so that the vial is positioned above it.

Hold the vial.
Squeeze the solvent bag several times until the vial is completely empty.
If any powder remains inside the vial, repeat steps 7 and 8.
From a microbiological standpoint, the medicinal product must be used immediately.
If not used immediately, refer to section 5 “How to store BCG‑medac”.
The suspension must not be instilled at refrigerator temperature to avoid inducing the urge to urinate in the patient, which would reduce the exposure time.

Catheterization

9. Catheterize the patient according to local regulations and instructions for use, using an appropriate catheter and lubricant.

Empty the bladder using the catheter.
Connecting the catheter to the solvent bag

10. To resuspend any sediment, rotate and agitate the bag before connecting.

Do not administer the suspension at refrigerator temperature.
Remove the protective cap from the catheter connector (C2).
Connect the patient’s catheter to the catheter connector (C2) of the solvent bag.

Instillation

11. Break the opening seal inside the tube of the catheter connector (C2) by bending it several times up and down.

While doing so, hold the patient’s catheter steady.

12. Hold the solvent bag with the inverted vial above the bag.

Gently squeeze the solvent bag with the other hand to slowly instill the medicinal product into the patient’s bladder.
Continue squeezing until both the solvent bag and the vial are completely empty.

13. Squeeze out the remaining air from the solvent bag to empty the catheter as completely as possible.

After instillation

14. Closing the pressure clamp (C3) prevents fluid from flowing back into the catheter and minimizes the risk of contamination. Alternatively, steps 15 and 16 may be performed while keeping the solvent bag compressed.

15. Carefully remove the catheter from the bladder without disconnecting the solvent bag from the catheter. Avoid contamination from splashing droplets.

16. Dispose of the product according to national regulations using the disposal bag.

The contents of the vial are for single use only (single dose). Any residual suspension must be discarded.

Instructions for users of BCG‑medac
Components and use of the instillation kit
Main components of the instillation kit

Main component Description
A Vial with powder
B Protective wrapper
C Solvent bag containing 0.9% sodium chloride solution (9 mg/mL)
C1 Vial connector with protective cap and opening seal
C2 Catheter Luer-Lock connector with protective cap and opening seal
C3 Pressure clamp
C4 Filling port without application function
E Disposal bag
F Luer-Lock to conical connector
Connecting the vial to the solvent bag

1. Prepare the disposal bag (E) for direct disposal of the kit after instillation to avoid contamination.

2. Remove the snap-off closure cap from the vial (A) and disinfect the stopper according to local regulations.

3. Open the protective wrapper (B) of the solvent bag (C) by pulling it away, and remove it completely.

4. Remove the protective cap from the vial connector (C1).

5. Press the connector onto the vial until it stops.

Mixing powder and solvent

6. Break the opening seal inside the tube of the vial connector (C1) by bending it several times up and down.

7. Hold the solvent bag so that the vial is positioned below it.

Squeeze the solvent bag several times to transfer a sufficient amount of solvent into the vial.
Ensure not to completely fill the vial to allow for subsequent transfer of the suspension back into the solvent bag. Some solvent may remain in the bag.
Shake the vial gently to minimize foam formation during mixing of the medicinal product with the solvent. If excessive foaming occurs, allow the vial to rest briefly (a few minutes).
The contents of the vial should form a homogeneous suspension. This may take several minutes.

8. Invert the solvent bag and hold it so that the vial is positioned above it.

Hold the vial.
Squeeze the solvent bag several times until the vial is completely empty.
If any powder remains inside the vial, repeat steps 7 and 8.
From a microbiological standpoint, the medicinal product must be used immediately.
If not used immediately, refer to section 5 “How to store BCG‑medac”.
The suspension must not be instilled at refrigerator temperature to avoid inducing the urge to urinate in the patient, which would reduce the exposure time.

Catheterization

9. Catheterize the patient according to local regulations and instructions for use, using an appropriate catheter and lubricant.

Empty the bladder using the catheter.
This package does not include a catheter. Use the provided connector (F) to connect the bag to the patient’s catheter with a conical connector (not shown).
To do so, complete the following additional steps:

• Remove the protective cap from the catheter connector (C2, see step 10).
• Connect the connector (F) to the catheter connector (C2) of the bag.
• Carefully connect the bag to the patient’s catheter via connector (F).
• Then proceed to step 11.

Connecting the catheter to the solvent bag

10. To resuspend any sediment, rotate and agitate the bag before connecting.

Do not administer the suspension at refrigerator temperature.
Remove the protective cap from the catheter connector (C2).
Connect the patient’s catheter to the catheter connector (C2) of the solvent bag.

Instillation

11. Break the opening seal inside the tube of the catheter connector (C2) by bending it several times up and down.

While doing so, hold the patient’s catheter steady.

12. Hold the solvent bag with the inverted vial above the bag.

Gently squeeze the solvent bag with the other hand to slowly instill the medicinal product into the patient’s bladder.
Continue squeezing until both the solvent bag and the vial are completely empty.

13. Squeeze out the remaining air from the solvent bag to empty the catheter as completely as possible.

After instillation

14. Closing the pressure clamp (C3) prevents fluid from flowing back into the catheter and minimizes the risk of contamination. Alternatively, steps 15 and 16 may be performed while keeping the solvent bag compressed.

15. Carefully remove the catheter from the bladder without disconnecting the solvent bag from the catheter. Avoid contamination from splashing droplets.

16. Dispose of the product according to national regulations using the disposal bag.

The contents of the vial are for single use only (single dose). Any residual suspension must be discarded.