ADSTILADRIN Intravesical suspension Ref.[116667] Active ingredients: Nadofaragene firadenovec

Treatment should be initiated and administered in clinical centres and supervised by a physician experienced in the management of patients with NMIBC.

Posology

The recommended dose of ADSTILADRIN is 75 mL at a concentration of 3 × 10¹¹ viral particles (vp)/mL administered by intravesical instillation every three (3) months.

The maximum duration of treatment should be determined based on the individual patient's clinical response and tolerability. Response should be reassessed prior to each instillation, and the medicinal product discontinued in case of high-grade (HG) recurrence or unacceptable toxicity.

Anticholinergic pretreatment

Premedication with a single dose of an anticholinergic medicinal product before each instillation is recommended (see section 4.4).

Special populations

Elderly

No dose adjustment is recommended in patients aged 65 years or older.

Hepatic or renal impairment

The safety and efficacy of ADSTILADRIN have not been established in patients with hepatic or renal impairment. No dose adjustment is recommended in these patients.

Paediatric population

There is no relevant use of ADSTILADRIN in the paediatric population for the indication of treatment of BCG-unresponsive NMIBC with CIS with or without papillary tumours.

Method of administration

ADSTILADRIN is for intravesical instillation only.

Precautions to be taken before handling or administering the medicinal product

ADSTILADRIN must be thawed and prepared for intravesical instillation prior to administration. For instructions on preparation and administration, see section 6.6.

Intravesical instillation:

• Insert a straight or intermittent urinary catheter with a proximal funnel opening that will accommodate the Luer lock adaptor into the bladder under aseptic conditions. Use only catheters made of vinyl/PVC (uncoated or coated with hydrogel), red rubber latex or silicone to instil ADSTILADRIN. Do not use catheters coated or embedded with silver or antibiotics.
• Use the catheter to completely empty the bladder before instillation. Do not remove the catheter, it should be left in place for instillation of the product.
• Attach the Luer lock end of the catheter adaptor to the syringe containing ADSTILADRIN and insert the tapered end of the catheter adaptor into the funnel opening of the catheter.
• Instil 75 mL of ADSTILADRIN slowly into the bladder through the catheter, ensuring that the complete volume is administered.
• Remove the catheter after instillation.
• Retain ADSTILADRIN in the bladder for 1 hour. During the 1-hour dwell time, reposition the patient from left to right, back and abdomen to maximise bladder surface exposure. Reposition the patient approximately every 15 minutes. If, during the dwell time, the patient exhibits bladder cramping or premature voiding, turning of the patient may be adjusted or discontinued.
• Evacuate ADSTILADRIN from the bladder via urinary catheter, or the patient may void and completely empty the bladder after 1 hour has elapsed.
• Disinfect voided urine for 15 minutes with 2 cups of virucidal agent (e.g. household bleach) before flushing the toilet. Instruct the patient to do this after every voiding for the first 2 days after each treatment (see also section 4.4.).

There has been no experience with overdose of ADSTILADRIN in clinical studies. In the event of a suspected overdose, the patient should be closely monitored for signs or symptoms of adverse reactions, treated symptomatically, and supportive measures instituted as required.

4 years.

Temporary storage conditions for unopen vials:

The product can be stored at -20 ± 5°C for a maximum period of three months without exceeding the original expiry date printed on the vial and carton.

When stored at -20 ± 5°C the date of placement at -20 ± 5°C should be noted. In addition, the date for when the medicinal product should be discarded if not used, must be written on the carton. These dates should be three months apart but should not pass the original expiry date. This discard date supersedes the original expiry date.

Once the vial thawing procedure is initiated ADSTILADRIN can be stored:

• refrigerated at 2-8°C for a total of seven days and
• at room temperature for a maximum of 24 hours, all including thawing time.
• do not refreeze vials once thawing has been initiated.

The vials may be moved between refrigerator and room temperature if the allowed total storage time at each condition is not exceeded (24 hours at room temperature and 7 days refrigerated including thawing time).

In use stability after withdrawal from the vial:

If unable to administer the suspension shortly after withdrawal, the solution may be stored in syringes for up to 6 hours at room temperature (20-25oC), protected from light.

From a microbiological point of view, unless the method of opening precludes the risk of microbial contamination, the product should be used immediately.

If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user.

Store below -60°C.

Protect the vials from light. Keep vials in outer carton.

For storage conditions of unopened vials and after withdrawal from the vial, see section 6.3.

20 mL of intravesical suspension in a single-dose clear Type 1 glass vial with a bromobutyl rubber stopper sealed with a tamper-evident aluminium crimp.

Each carton contains four vials.

Precautions to be taken before handling or administering the medicinal product

This medicinal product contains genetically modified organisms (GMOs).

• Any ADSTILADRIN spills should be treated with a virucidal agent (such as 5% sodium hypochlorite or hydrogen peroxide disinfectant) for 30 minutes. Disinfectant should be present in the preparation area and patient room in case of spill.
• Personal protective equipment (including gloves, safety glasses, apron or protective clothing) should be worn while handling or administering ADSTILADRIN.
• Healthcare professionals who are immunocompromised, immune deficient, or pregnant should not prepare, administer, or come into contact with ADSTILADRIN.

Thawing and thawing time

When thawing at room temperature: Frozen vials will thaw in approximately 3-5 hours outside the cardboard nest when placed at room temperature (20-25°C) (8-10 hours inside the nest). Protect the vials from light, even if thawed outside the cardboard nest.

When thawing in refrigerator: Frozen ADSTILADRIN vials will thaw in approximately 4-5 hours outside the cardboard nest when placed in the refrigerator (up to 8°C) (11-13 hours inside the nest). Subsequent time for bringing thawed ADSTILADRIN to room temperature is approximately 2 hours 30 minutes outside of the cardboard nest (6 hours inside the nest).

Do not expose the vials to higher temperatures.

All four vials should be inspected for visible particles and discoloration. The suspension is clear to slightly opalescent and may contain opalescent flecks. Do not use if visible particles or discoloration are observed. Mix gently. Do not shake.

Once the thawing procedure is initiated (at 2-8°C and/or at room temperature), the date and time for placing and removing the product from the specified storage condition, should be noted on the carton. When removing the product, the time remaining at the specific storage condition should be noted on the carton.

Items required for instillation

• Four (4) thawed vials of ADSTILADRIN
• Four (4) vented vial adaptors (20 mm) suitable for a 30R vial
• Two (2) standard 50 or 60 mL polypropylene Luer lock syringes or one (1) Luer lock syringe equal to or greater than 75 mL (max 100 mL)
• Two (2) Luer lock adaptors:
  • One (1) straight, or intermittent, urethral catheter with a proximal funnel opening that will accommodate the Luer lock adaptor.
  • Use only catheters made of vinyl/PVC (uncoated or coated with hydrogel), red rubber latex or silicone to instil ADSTILADRIN. Do not use catheters coated or embedded with silver or antibiotics.

Follow universal biohazard precautions for handling. Healthcare professionals who are immunocompromised, immune-deficient, or pregnant should not prepare, administer, or come into contact with ADSTILADRIN.

Preparation

1. Using aseptic technique, remove the cap from an ADSTILADRIN vial and attach a vented vial adaptor according to manufacturer's instructions.

2. Connect the syringe to the vial adaptor and withdraw the contents of the vial into the syringe. Repeat steps 1-2 for the remaining three (3) vials until 75 mL has been withdrawn into one (1) or two (2) syringes. The volumes in the syringes do not have to be equal.

3. Discard any remaining volume according to the facility's standard operating procedures (see below Precautions to be taken for the disposal of the medicinal product).

4. Use ADSTILADRIN within 6 hours of drawing into syringe.

Bladder instillation of ADSTILADRIN

• Premedication with an anticholinergic agent before each instillation of ADSTILADRIN is recommended.
• ADSTILADRIN must be brought to room temperature before administration.
• Before administering ADSTILADRIN to the patient, insert one straight, or intermittent, urinary catheter with a proximal funnel opening that will accommodate the Luer lock adaptor into the bladder under aseptic conditions.
• Use only catheters made of vinyl/PVC (uncoated or coated with hydrogel), red rubber latex or silicone to instil ADSTILADRIN. Do not use catheters coated or embedded with silver or antibiotics.
• Use the catheter to completely empty the patient's bladder before instillation. Do not remove the catheter.
• Attach the Luer lock end of the catheter adaptor to the syringe containing ADSTILADRIN and insert the tapered end of the catheter adaptor into the funnel opening of the catheter.
• Instil 75 mL of ADSTILADRIN slowly into the bladder through the catheter, ensuring that the complete volume is administered.
• Remove the catheter after instillation.
• Retain ADSTILADRIN in the bladder for 1 hour. During the 1-hour dwell time, reposition the patient approximately every 15 minutes from left to right, back and abdomen to maximize bladder surface exposure. If the patient exhibits bladder cramping or premature voiding during the dwell time, repositioning of the patient may be adjusted or discontinued.
• Evacuate ADSTILADRIN from the bladder via urinary catheter, or the patient may void and completely empty the bladder after 1 hour has elapsed.
• Voided urine should be disinfected for 15 minutes with 2 cups of virucidal agent (e.g. household bleach) before flushing of the toilet. Instruct the patient to do this after every voiding for the first 2 days after each treatment.

Measures to take in case of accidental exposure

Accidental exposure to nadofaragene firadenovec, including contact with skin, eyes and mucous membranes, is to be avoided.

• In case of accidental exposure to skin, the affected area must be thoroughly cleaned with soap and water for at least 15 minutes.
• In case of accidental exposure to eyes, the affected area must be thoroughly flushed with water for at least 15 minutes.
• In case of accidental ingestion, immediately rinse the mouth and drink plenty of water.
• Precautions to be taken for the disposal of the medicinal product

Unused medicinal product and disposable materials that have come into contact with ADSTILADRIN should be placed in biohazard containers for destruction. Non-disposable equipment must be decontaminated according to the facility's biohazard standard operating procedures.