Miturox

Package leaflet: Information for the user

Miturox 40 mg, powder and solvent for intravesical solution

mitomycin
Equivalent medicine
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, please inform your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Miturox is and what it is used for

Miturox is a medicinal product used in the treatment of cancer, i.e. a medicine that prevents or significantly slows down the division of actively proliferating cells by affecting their metabolism in various ways (cytostatic agent). The therapeutic use of cytostatic agents in cancer therapy is based on the fact that one of the differences between cancer cells and normal cells is the higher rate of cell division in cancer cells, as their growth cannot be controlled.

Therapeutic indications
Miturox is instilled into the urinary bladder (intravesical administration) to prevent recurrence of superficial bladder cancer following removal of the cancerous tissue via the urethra (transurethral resection).

2. What you should know before using Miturox

Mitomycin may be administered only under strict indication and by physicians experienced in this type of therapy.
Do not use Miturox

• if you are allergic to mitomycin or to any of the other ingredients of this medicine (listed in section 6)
• during breastfeeding: you must not breastfeed during treatment with mitomycin
• if you have a perforation of the bladder wall
• if you suffer from inflammation of the urinary bladder (cystitis).

Warnings and precautions
Talk to your doctor or pharmacist before using Miturox.
Particular caution is required when using Miturox

• if you are in poor general health
• if you have impaired pulmonary, renal, or hepatic function
• if you are undergoing radiotherapy
• if you are being treated with other cytostatic agents (substances that inhibit cell growth/division)
• if you have been told that you have bone marrow depression (your bone marrow is unable to produce the blood cells you need). This condition may worsen (especially in elderly patients and during long-term treatment with mitomycin); infection due to low blood cell count may worsen and could be fatal
• if you are of reproductive age, as mitomycin may impair your ability to have children in the future.

Immediately inform your doctor if you experience abdominal or pelvic pain immediately after administration of Miturox into the bladder, or even weeks or months later. Your doctor may need to perform an abdominal ultrasound to determine the cause of your pain.
Mitomycin is a substance that may cause significant heritable genetic alterations and may potentially cause cancer in humans.
Avoid contact with the skin and mucous membranes.
Read the general hygiene instructions to follow after intravesical (endovesical) instillation:
It is recommended to urinate in a sitting position to avoid urine dispersion, and to wash your hands and genital area after urination. This is particularly important the first time you urinate after administration of mitomycin.
Children and adolescents
The use of Miturox in children and adolescents is not recommended.
Other medicines and Miturox
No interactions with other medicines are known in the case of intravesical (endovesical) administration of mitomycin.
Possible interactions during injection or infusion into a blood vessel (intravenous administration)
When administered concomitantly with other treatments (particularly other anticancer drugs, radiotherapy), all of which have a harmful effect on the bone marrow, the intensity of the bone marrow toxicity of mitomycin may increase.
Combination with vinca alkaloids or bleomycin (medicines belonging to the group of cytostatics) may increase the severity of lung toxicity.
An increased risk of a particular kidney disease (hemolytic-uremic syndrome) has been observed in patients treated with intravenous mitomycin concomitantly with 5-fluorouracil or tamoxifen.
Animal experiments have documented a loss of effect of mitomycin when administered together with vitamin B.
You must not receive live vaccines during treatment with mitomycin, as this may expose you to a higher risk of infection from the live vaccine.
Mitomycin may increase the intensity of the harmful effect of Adriamycin (doxorubicin, a medicine belonging to the group of cytostatics) on the heart.
Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Mitomycin may cause heritable genetic alterations and adverse effects on embryonic development.
You must avoid pregnancy during treatment with mitomycin: in case of pregnancy, genetic counseling should be provided.
You must not use mitomycin during pregnancy.
Your doctor must evaluate the benefit versus the risk of harmful effects on the unborn child if treatment with mitomycin becomes necessary during pregnancy.
Breastfeeding
Mitomycin is probably excreted in breast milk. Breastfeeding must be discontinued during treatment with Miturox.
Fertility/Contraception in men and women
Sexually mature patients must use contraceptive measures or practice sexual abstinence during chemotherapy and for 6 months thereafter.
Mitomycin may cause heritable genetic alterations. If you are a man undergoing mitomycin therapy, you must not father children during treatment and for 6 months after treatment ends, and you should seek information about sperm preservation before starting therapy, as mitomycin may cause irreversible infertility.
Driving and using machines
Even when used according to instructions, this medicine may cause nausea and vomiting, thereby prolonging reaction times to an extent that may impair your ability to drive vehicles or operate machinery. This is particularly relevant in case of concomitant alcohol use.

3. How to use Miturox

Miturox is administered only by trained healthcare professionals.
This medicinal product is intended for use by instillation into the urinary bladder (intravesical instillation) after reconstitution.
Your doctor will prescribe the dose suitable for you.
Miturox is introduced under low pressure into the empty bladder via a catheter. The healthcare professional will empty the bladder with a catheter before treatment. Do not go to the toilet immediately before the healthcare professional's visit. The medicine must remain in the bladder for a period of 1–2 hours. To achieve this, you should not drink excessive amounts of liquid before, during, or after treatment. While the solution remains in the bladder, it should be in adequate contact with the entire mucosal surface: moving around may help promote this contact. After 2 hours, you must empty the bladder while sitting down, to avoid spreading urine.

If you use more Miturox than you should
If you have accidentally received a higher dose, you may experience symptoms such as fever, nausea, vomiting, and blood disorders. Your doctor may prescribe supportive therapy for any symptoms that may occur.

If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Possible side effects after instillation into the bladder (intravesical use)

Tell your doctor immediately if you notice any of the following reactions (which have been observed very rarely after instillation into the bladder), as treatment with mitomycin must be stopped:

• severe allergic reaction with symptoms such as feeling faint, skin rash or hives, itching, swelling of lips, face and airways with difficulty breathing, loss of consciousness,
• severe lung disease presenting with shortness of breath, dry cough and crackling sounds when breathing in (interstitial pneumonia),
• severe kidney dysfunction: kidney disease with reduced or absent urination.

Common: may affect up to 1 in 10 people

• inflammation of the bladder (cystitis), which may be accompanied by blood in the bladder/urine
• pain during urination (dysuria)
• frequent urination during the night (nocturia)
• excessive frequency of urination (pollakiuria)
• blood in the urine (haematuria)
• local irritation of the bladder wall
• localized skin rash (localised exanthema)
• allergic skin rash
• skin rash caused by contact with mitomycin (contact dermatitis)
• numbness, swelling and painful redness of the palms of the hands and soles of the feet (palmar-plantar erythema)

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

• skin rash all over the body (generalised exanthema)

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

• inflammation of the bladder with damage to bladder tissue (necrotising cystitis)
• allergic-type inflammation of the bladder (eosinophilic cystitis)
• narrowing (stenosis) of the urinary tract
• reduced bladder capacity
• calcium deposits in the bladder wall (bladder wall calcification)
• partial transformation of bladder wall tissue into connective tissue (bladder wall fibrosis)
• decrease in the number of white blood cells (leucopenia), leading to increased risk of infection
• decrease in the number of platelets (thrombocytopenia), causing bruising and bleeding
• systemic allergic reactions
• lung disorder presenting with shortness of breath, dry cough and crackling sounds when breathing in (interstitial lung disease)
• increased levels of liver enzymes (increased transaminases)
• hair loss (alopecia)
• nausea and vomiting
• diarrhoea
• kidney disease (renal dysfunction) with reduced or absent urination
• fever

Not known (frequency cannot be estimated from the available data)
If mitomycin accidentally reaches areas other than the bladder:

• damage to the bladder
• pus-filled pocket in the abdomen (abscess)
• death (necrosis) of surrounding tissue (fat)
• bladder fistula

Possible side effects after injection or infusion into a blood vessel (intravenous administration)

Very common: may affect more than 1 in 10 people

• suppression of blood cell production in the bone marrow (bone marrow suppression)
• decrease in the number of white blood cells (leucopenia), leading to increased risk of infection
• decrease in the number of platelets (thrombocytopenia), causing bruising and bleeding
• nausea and vomiting

Common: may affect up to 1 in 10 people

• lung disorder presenting with shortness of breath, dry cough and crackling sounds when breathing in (interstitial pneumonia)
• difficulty breathing (dyspnoea), cough, shortness of breath
• skin rash (exanthema)
• allergic skin rash
• skin rash caused by contact with mitomycin (contact dermatitis)
• numbness, swelling and painful redness of the palms of the hands and soles of the feet (palmar-plantar erythema)
• kidney disorders (renal dysfunction, nephrotoxicity, glomerulopathy, increased blood creatinine levels) with reduced or absent urination

In case of injection or leakage of mitomycin into surrounding tissue (extravasation):

• inflammation of connective tissue (cellulitis)
• tissue death (tissue necrosis)

Uncommon: may affect up to 1 in 100 people

• inflammation of mucous membranes (mucositis)
• inflammation of the mucous membranes of the mouth (stomatitis)
• diarrhoea
• hair loss (alopecia)
• fever
• loss of appetite

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

• potentially fatal infection
• blood poisoning (sepsis)
• decrease in the number of red blood cells due to abnormal destruction of these cells (haemolytic anaemia)
• bruising (purpura) and red or purple spots on the skin (petechiae) (thrombotic thrombocytopenic purpura)
• heart failure following previous treatment with anticancer medicines (anthracyclines)
• increased blood pressure in the lungs causing, for example, shortness of breath, dizziness and fainting (pulmonary hypertension)
• disease with blockage of veins in the lungs (pulmonary veno-occlusive disease, PVOD)
• liver disease (liver dysfunction)
• increased levels of liver enzymes (transaminases)
• yellowing of the skin and whites of the eyes (jaundice)
• disease with blockage of veins in the liver (hepatic veno-occlusive disease, VOD)
• skin rash all over the body (generalised exanthema)
• a particular form of kidney failure (haemolytic-uraemic syndrome, HUS) characterised by destruction of red blood cells at a faster rate than bone marrow can produce them (haemolytic anaemia), acute kidney failure and low platelet count
• a type of haemolytic anaemia caused by factors in small blood vessels (microangiopathic haemolytic anaemia, MAHA)

Not known (frequency cannot be estimated from the available data)

• infection
• reduction in red blood cell count (anaemia)

Reporting of side effects

If you get any side effects, including ones 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 Miturox

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label and the carton after
Exp. The expiry date refers to the last day of that month.
This medicine does not require any special storage temperature conditions.
Keep the vial in the outer packaging to protect the medicine from light.
The physical and chemical stability during use has been demonstrated for 48 hours when stored protected
from light at room temperature (15 °C – 25 °C) and for 72 hours when stored protected from light at
2 °C – 8 °C in the refrigerator.
From a microbiological point of view, the medicine should be used immediately.
If not used immediately, the times and conditions of storage prior to use are the responsibility of the
user and normally should not exceed 24 hours at 2 °C – 8 °C, protected from light, unless
reconstitution has taken place under controlled and validated aseptic conditions.
Protect the reconstituted solution from light.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What Miturox contains

• The active substance is mitomycin. One vial of powder for solution for intravesical use contains 40 mg of mitomycin. After reconstitution with 40 ml of solvent, 1 ml of solution for intravesical use contains 1 mg of mitomycin.
• The other components are:

Powder for solution for intravesical use:
urea
Solvent for intravesical solution:
sodium chloride, water for injections, pH-adjusting agents (sodium hydroxide 1 M, hydrochloric acid 1 M).

Description of the appearance of Miturox and contents of the pack
Miturox is a powder ranging in colour from grey to grey-blue.
The solvent is a clear, colourless solution.
Miturox powder and solvent for intravesical solution (instillation set) is available in packs containing 1, 4 or 5 glass vials (50 ml) with rubber stoppers and aluminium seals. The intravesical instillation sets also contain 1, 4 or 5 APP* bags with a volume of 40 ml, containing a 9 mg/ml (0.9%) sodium chloride injectable solution.
The sets are available with or without catheters and/or connectors (Luer-Lock to conical).
* APP = advanced polypropylene (polyolefin/polystyrene/polystyrene block copolymer).
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
medac Gesellschaft für klinische Spezialpräparate mbH
Theaterstr. 6
22880 Wedel
Germany
Tel.: +49 4103 8006-0
Fax: +49 4103 8006-100

This medicinal product is authorised in the European Economic Area Member States under the following names:
Austria, Belgium, Denmark, Estonia, Finland, Ireland, Iceland, Latvia, Lithuania, Norway, Netherlands, Poland, Sweden, Slovakia:
Mitomycin medac
Germany:
mito-extra
Italy:
Miturox
Portugal:
Mitomicina medac
Slovenia:
Mitomicin medac
United Kingdom:
Mitomycin medac

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The following information is intended exclusively for physicians or healthcare professionals:
Important information on the use of Miturox
Miturox may only be used by appropriately trained healthcare professionals.
Ensure proper storage (see section 5) and integrity of the packaging.

Treatment regimens
There are several intravesical mitomycin regimens differing in dose, instillation frequency and duration of therapy.
Unless otherwise specified, the dose of mitomycin is 40 mg instilled into the bladder once weekly. Regimens with instillation every 2 weeks, monthly or every 3 months may also be used.
The specialist must determine the optimal regimen, frequency and duration of therapy on an individual basis.
It is recommended to use this medicine at its optimal pH (urinary pH > 6). Reducing fluid intake before, during and after instillation may reduce the dilution effect on the concentration of mitomycin in the urinary bladder. The bladder must be emptied prior to instillation. Mitomycin is instilled into the bladder via a catheter under low pressure.
After removal of the catheter, the solution must remain in the bladder for 1–2 hours. During this period, the solution must be in sufficient contact with the entire bladder mucosal surface. Patients should therefore be advised to change position every 15 minutes. After 2 hours, the patient should empty the instilled solution, preferably while sitting.

General principles and protective measures for the use of Miturox
In general, direct contact with Miturox must be avoided. Miturox is a cytotoxic drug that poses risks to people and the environment. Penetration of the drug into the body through unprotected wounds or softened skin, inhalation via aerosols, contact of droplets with eyes or mucous membranes, or ingestion may be hazardous. Eating, drinking, smoking or storing food, beverages or tobacco is not permitted in work areas.
Personal protective equipment should include a closed, splash-resistant protective gown, disposable gloves, appropriate protective masks and safety goggles with side shields during handling. Miturox may only be transported in closed containers (for storage conditions after reconstitution, see section 5).
After completion of procedures and in case of skin contact, wash hands thoroughly with plenty of water and use skin care products.

Preparation of the reconstituted intravesical solution
Before use, the medicine must be dissolved under aseptic conditions using a sterile 0.9% (9 mg/ml) sodium chloride solution (see instructions for use, step 7). Dissolve the contents of one vial of Miturox (equivalent to 40 mg of mitomycin) in 40 ml of sterile 0.9% (9 mg/ml) sodium chloride solution. The vial contents should dissolve within 2 minutes to form a clear, blue-violet solution. Use only clear, blue-violet solutions.
To reduce the risk of traumatic catheterisation and to make the procedure more comfortable, the use of a lubricant is recommended. Women may require less lubricant than men. Before administering Miturox, drain the bladder after catheterisation to reduce the amount of potentially introduced lubricant.
The vial contents are for single use only and intended for a single dose. Discard any unused solution.
Unused medicine and waste materials derived from this medicine must be disposed of in accordance with local regulations.
For further information on the catheter, refer to the corresponding instructions for use.

Instructions for users of Miturox
Components and use of the instillation set <with catheter, with connector>
Main components of the instillation set

Connecting the vial to the solvent bag

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

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

3. Open the protective overwrap (B) of the solvent bag (C) and completely remove it.

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

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

Mixing the powder with the solvent

6. Bend the break seal inside the vial connector tube (C1) repeatedly upwards and downwards to break it.

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 solution back into the solvent bag. Some solvent may remain in the bag.
Gently shake the vial to dissolve the medicinal product with the solvent.
The contents of the vial should dissolve within 2 minutes to form a clear, blue-violet solution.

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 should be used immediately.
If not used immediately, refer to section 5 “How to store Miturox”.
Use only clear, blue-violet solutions. The solution must not be administered refrigerated to prevent the patient from feeling the urge to urinate, which would reduce exposure time.

Catheterization

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

Empty the urinary bladder using the catheter.
Note for use with a user-selected catheter with conical connector:
To connect the bag to a catheter with a conical connector (not shown), the provided Luer-Lock to conical connector (F) must be used.
For this purpose, the following additional steps must be performed:

• Remove the protective cap from the catheter connector (C2, see step 10).
• Attach the Luer-Lock to conical connector (F) to the catheter connector (C2) of the bag.
• Carefully connect the bag with the Luer-Lock to conical connector (F) to the patient's indwelling catheter.
• Proceed then to step 11.

Connecting the catheter to the solvent bag

10. Rotate and agitate the bag before connecting it.

Do not administer the solution refrigerated.
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. Bend the break seal inside the catheter connector tube (C2) repeatedly upwards and downwards to break it.

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

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

Gently squeeze the solvent bag with the other hand to slowly instill the medicinal product into the patient's urinary 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 backflow of liquid into the catheter and minimizes the risk of contamination. Alternatively, steps 15 and 16 may be performed while keeping gentle pressure on the solvent bag.

15. Immediately and carefully remove the catheter from the bladder without disconnecting the solvent bag from the catheter, after emptying the instillation set. Once the catheter is removed, the solution should remain in the bladder for 1–2 hours. Avoid contamination from droplet splashes.

Note for use with a user-selected catheter with conical connector:
Separate the bag, including the Luer-Lock to conical connector, from the indwelling catheter.
Close the indwelling catheter, for example by using a cap or catheter clamp, to ensure the medicinal product remains active in the bladder for the intended duration.

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

The vial contents are intended for single use/single dose only. Any residual solution must be discarded.

Instructions for users of Miturox
Components and use of the instillation set < with catheter, without connector >
Main components of the instillation set

Main component Description
A Vial with powder
B Protective overwrap
C Solvent bag containing 0.9% sodium chloride solution (9 mg/ml)
C1 Vial connector with protective cap and break seal
C2 Luer-Lock catheter connector with protective cap and break 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 set after instillation to avoid contamination.

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

3. Open the protective overwrap (B) of the solvent bag (C) and completely remove it.

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

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

Mixing the powder with the solvent

6. Bend the break seal inside the vial connector tube (C1) repeatedly upwards and downwards to break it.

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

Shake the vial slowly to dissolve the medicine with the solvent.

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.

Catheterization

9. Catheterize the patient in accordance with 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 urinary bladder using the catheter.
Connecting the catheter to the solvent bag

10. Rotate and shake the bag before connecting.

Do not administer the solution 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) on the solvent bag.

Instillation

11. Bend the break seal inside the catheter connector tube (C2) repeatedly upwards and downwards to break it.

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

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

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

13. Squeeze any remaining air out of the solvent bag to empty the catheter as much as possible.

After instillation

14. Closing the pressure clamp (C3) prevents backflow of liquid into the catheter and minimizes the risk of contamination. Alternatively, steps 15 and 16 may be performed while keeping the solvent bag pressed.

15. Immediately and carefully remove the catheter from the bladder without disconnecting the solvent bag from the catheter after emptying the instillation set. Once the catheter is removed, the solution should remain in the bladder for 1–2 hours. Avoid contamination from droplet splashes.

16. Dispose of the product in accordance with current national regulations, using the disposal bag.

The vial contents are intended for single use/single dose only. Any residual solution must be discarded.

Instructions for Miturox Users
Components and use of the instillation set < without catheter, with connector >
Main components of the instillation set

Main component Description
A Vial with powder
B Protective envelope
C Solvent bag containing 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
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 set after instillation to avoid contamination.

2. Remove the flip-off cap from the vial (A) and disinfect the stopper in accordance with local regulations.

3. Open the protective envelope (B) of the solvent bag (C) and completely remove it.

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

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

Mixing the powder with the solvent

6. Bend the break seal inside the vial connector tube (C1) repeatedly upwards and downwards to break it.

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 solution back into the solvent bag. Some solvent may remain inside the bag.
Gently shake the vial to dissolve the medication with the solvent.
The vial contents should dissolve within 2 minutes to form a clear, blue-violet solution.

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 should be used immediately.
If the product is not used immediately, refer to section 5 “How to store Miturox”.
Use only clear, blue-violet solutions. The solution must not be administered at refrigerator temperature to prevent the patient from feeling the urge to urinate, which would reduce the exposure time.

Catheterization

9. Catheterize the patient in accordance with local regulations and instructions for use, using an appropriate catheter and lubricant.

Empty the urinary bladder using the catheter.
Note for use with a user-selected catheter with conical connector:
This package does not include a catheter. Use the provided Luer-Lock to conical connector (F) to connect the bag to the patient’s indwelling catheter at the beginning of instillation (action not illustrated).
To do so, the following additional steps must be performed:

• Remove the protective cap from the catheter connector (C2, see step 10).
• Connect the Luer-Lock to conical connector (F) to the catheter connector (C2) on the bag.
• Carefully connect the bag with the Luer-Lock to conical connector (F) to the patient’s indwelling catheter.
• Proceed then to step 11.

Connecting the catheter to the solvent bag

10. Rotate and shake the bag before connecting.

Do not administer the solution at refrigerator temperature.
Remove the protective cap from the catheter connector (C2).
Connect the patient's catheter to the catheter connector (C2) on the solvent bag.

Instillation

11. Bend the break seal inside the catheter connector tube (C2) repeatedly upwards and downwards to break it.

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

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

Continue squeezing until the solvent bag and the vial are completely empty.

13. Squeeze the remaining air out of the solvent bag to empty the catheter as much as possible.

After instillation

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

15. Immediately and carefully remove the catheter from the bladder without disconnecting the solvent bag from the catheter after emptying the instillation set. Once the catheter is removed, the solution must remain in the bladder for 1–2 hours. Avoid contamination from splashing droplets.

Note for use with a user-selected catheter with conical connector:
Separate the bag, including the conical Luer-Lock connector, from the permanent catheter.
Close the permanent catheter, for example using a cap or catheter clamp, to ensure that the medicinal product remains in the bladder for the intended duration.

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

The contents of the vial are intended for single use/single dose only. Any residual solution must be discarded.

Instructions for Miturox users
Components and use of the instillation set < without catheter, without connector>
Main components of the instillation set

Main component Description
A Vial with powder
B Protective pouch
C Solvent bag containing 0.9% sodium chloride solution (9 mg/ml)
C1 Vial connector with protective cap and tamper-evident seal
C2 Catheter Luer-Lock connector with protective cap and tamper-evident 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 set after instillation to avoid contamination.

2. Remove the flip-off seal from the vial (A) and disinfect the stopper according to current local regulations.

3. Open the protective pouch (B) of the solvent bag (C) and completely remove it.

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

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

Mixing the powder with the solvent

6. Bend the break seal inside the vial connector tube (C1) repeatedly upwards and downwards to break it.

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 solution back into the solvent bag. Some solvent may remain inside the bag.
Gently shake the vial to dissolve the medicinal product in the solvent.
The contents of the vial should dissolve into a clear, blue-violet solution within 2 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 in the vial, repeat steps 7 and 8.
From a microbiological standpoint, the medicinal product should be used immediately.
If the product is not used immediately, refer to section 5 “How to store Miturox”.
Use only clear, blue-violet solutions. The solution must not be administered refrigerated to prevent the patient from feeling the urge to urinate, which would reduce the exposure time.

Catheterization

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

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

10. Rotate and agitate the bag before connecting it.

Do not administer the solution refrigerated.
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. Bend the break seal inside the catheter connector tube (C2) repeatedly upwards and downwards to break it.

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

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

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

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

After instillation

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

15. Immediately and carefully remove the catheter from the bladder without disconnecting the solvent bag from the catheter after emptying the instillation set. Once the catheter is removed, the solution must remain in the bladder for 1–2 hours. Avoid contamination from splashing droplets.

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

The contents of the vial are intended for single use/single dose only. Any residual solution must be discarded.