Dose

The recommended dose of ADSTILADRIN is 75 mL at a concentration of 3 x 1011 viral particles (vp)/mL instilled once every three (3) months into the bladder via a urinary catheter [see Dosage and Administration (2.2)].

Premedication with an anti-cholinergic is recommended before each instillation of ADSTILADRIN.

Preparation and Handling

ADSTILADRIN is a non-replicating adenoviral vector-based gene therapy. Follow universal biosafety precautions for handling.

Individuals who are immunosuppressed or immune-deficient, should not prepare, administer, or come into contact with ADSTILADRIN [see Warnings and Precautions (5)].

ADSTILADRIN is provided as a sterile frozen suspension.

Thaw four (4) vials of ADSTILADRIN at room temperature (20°C to 25°C [68°F to 77°F]) until ADSTILADRIN is liquid. Do not expose the vials to higher temperatures. Protect from light.

ADSTILADRIN must be brought to room temperature (20°C to 25°C [68°F to 77°F]) prior to use.

The time for thawing and bringing ADSTILADRIN to room temperature is approximately 8-10 h when thawing in the cardboard nest and approximately 3-5 h when thawing the vials outside the cardboard nest. DO NOT Refreeze.

Once the vial thawing procedure is initiated, the vials may be stored for up to 24 hours at room temperature or refrigerated at 2°C to 8°C (36°F to 46°F). Visually inspect all 4 vials 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.

Items required for instillation:

• Four (4) thawed vials of ADSTILADRIN

• Four (4) vented vial adaptors suitable for a standard 20 mLvial

• 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 adapter.
- Use only catheters made of vinyl/PVC (uncoated or coated with hydrogel), red rubber latex or silicone to instill ADSTILADRIN. Do not use catheters coated or embedded with silver or antibiotics.

1. Using aseptic technique, remove the cap from an ADSTILADRIN vial and attach a vented vial adapter 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 universal precautions.

• Use ADSTILADRIN within 1 hour of drawing into syringe.

Treat any ADSTILADRIN spills with a virucidal agent (such as sodium hypochlorite with 0.5% active chlorine or 6% hydrogen peroxide solution) for 30 minutes. Disposable materials that have come into contact with ADSTILADRIN should be placed in biohazard containers for destruction. Non-disposable equipment may be decontaminated according to the facility’s standard operating procedures. [see Patient Counseling Information (17)].

Bladder instillation of ADSTILADRIN

1. Premedication with an anticholinergic before each instillation of ADSTILADRIN is recommended.
2. ADSTILADRIN must be brought to room temperature before administration. Use ADSTILADRIN within 24 hours after taking it out from the freezer.
3. Before administering ADSTILADRIN to the patient, insert one straight, or intermittent, urinary catheter with a proximal funnel opening that will accommodate the Luer lock adapter.
4. Use only catheters made of vinyl/PVC (uncoated or coated with hydrogel), red rubber latex or silicone to instill ADSTILADRIN. Do not use catheters coated or embedded with silver or antibiotics.
5. Use the catheter to completely empty the patient’s bladder before instillation of ADSTILADRIN. Do not remove the catheter.
6. Attach the Luer lock end of the same catheter adaptor to the syringe containing ADSTILADRIN and insert the tapered end of the catheter adaptor into the funnel opening of the catheter.
7. Slowly instill 75 mL of ADSTILADRIN into the bladder through the catheter, ensuring that the complete volume is administered.
8. After the instillation, ADSTILADRIN should be retained in the bladder for 1 hour. During the 1 hour dwell time, the patient should reposition approximately every 15 minutes from left to right, back and abdomen to maximize bladder surface exposure. If, during the dwell time, the patient exhibits bladder cramping or premature voiding, repositioning of the patient may be adjusted or discontinued.
9. Evacuate ADSTILADRIN from the bladder as part of routine emptying of the bladder, or the patient may void and completely empty the bladder after 1 hour has elapsed.
10. Voided urine should be disinfected for 30 minutes with an equal volume of virucidal agent before flushing of the toilet. [see Patient Counseling Information (17)].