JELMYTO® is indicated for the treatment of adult patients with low-grade Upper Tract Urothelial Cancer (LG-UTUC).

For pyelocalyceal solution: A kit containing the following:

• Two 40 mg (each) single-dose vials of sterile, lyophilized, grey to greyish-purple, cake or powder of mitomycin for pyelocalyceal solution
• One single-dose vial of 20 mL of sterile, clear, colorless gel with or without bubbles at room temperature or clear, colorless liquid at 2°C to 8°C (36°F to 46°F), to be used as a vehicle for reconstitution

JELMYTO is contraindicated in patients with perforation of the bladder or upper urinary tract.

The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling:

• Ureteric Obstruction [see Warnings and Precautions (5.1)]
• Bone Marrow Suppression [see Warnings and Precautions (5.2)]

Mitomycin (also known as mitomycin-C) is an alkylating drug isolated from the broth of Streptomyces. Mitomycin is a blue-violet crystalline powder with a molecular formula of C15H18N4O5, and a molecular weight of 334.33. Its chemical name is 7-amino-9α-methoxymitosane, and it has the following structural formula:

Mitomycin is heat stable, has a high melting point, and is freely soluble in organic solvents.

JELMYTO is supplied in a kit containing two vials of sterile lyophilized mitomycin for pyelocalyceal solution, 40 mg each, and one vial of 20 mL of sterile hydrogel, to be used as a vehicle for reconstitution.

Mitomycin for pyelocalyceal solution is a sterile, lyophilized, grey to greyish-purple, cake or powder that contains mitomycin 40 mg and mannitol 80 mg in each vial.

Sterile hydrogel is a sterile, clear, colorless gel with or without bubbles at room temperature or clear, colorless liquid at 2°C to 8°C (36°F to 46°F), which contains 0.04 g hydroxypropyl methylcellulose, 5.67 g poloxamer, 0.21 g polyethylene glycol, and water for injection in each vial.

Once reconstituted, JELMYTO is a clear, purple, viscous liquid at 2°C to 8°C (36°F to 46°F) or semisolid gel at room temperature with a concentration of 4 mg per mL of mitomycin, which may contain a few visible particles and have a pH between 6.0 and 8.0.

The efficacy of JELMYTO is based on the results of the OLYMPUS study (NCT02793128), an open-label, single-arm, multicenter trial that enrolled 71 patients with treatment-naïve or recurrent non-invasive low-grade upper tract urothelial cancer (LG-UTUC) with at least one measurable papillary tumor 5 to ≤ 15 mm located above the ureteropelvic junction; patients who had larger tumors could have had tumor debulking prior to treatment, in order to meet the criteria. Patients were excluded from the trial for a history of carcinoma in situ (CIS) in the urinary tract, invasive urothelial carcinoma within 5 years, high grade papillary urothelial carcinoma within 2 years; or for BCG treatment within 6 months of JELMYTO treatment. Following biopsy and prior to treatment, patients were required to have at least one remaining visible tumor with a diameter of at least 5 mm.

Patients received JELMYTO 4 mg per mL via ureteral catheter or nephrostomy tube with total instillation volume based on individualized volumetric measurements using pyelography with the intent to fill the renal pelvis. Patients were treated with 6 instillations once a week. Patients who maintained a complete response (CR) after the initial treatment period were allowed to proceed to the follow-up period. During the initial treatment period, 71 patients were treated with JELMYTO, of whom 41 were subsequently continued in the follow-up period. During the follow-up period, 29 patients received at least one dose of maintenance therapy.

The baseline demographic and disease characteristics for the trial population were: median age 71 years (range: 42-87 years); 68% male; 87% White; 90% Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1 and 10% ECOG PS 2. The median number of papillary lesions subsequent to debulking and/or biopsy and prior to treatment was 1 lesion (range: 1, 5), the median diameter of the largest lesion was 8.0 mm (range: 5.0, 15.0), and the median total visible tumor burden was 10.0 mm (range: 5.0, 25.0). Twenty-six (37%) patients underwent tumor debulking during the six weeks preceding enrollment. Of 71 enrolled patients, 48% had tumors located in regions not amenable to endoscopic resection. General anesthesia was used in 37% of patients for at least one instillation during the treatment period and for 83% of patients for at least one instillation during the follow-up period.

The major efficacy outcome measures were CR and durability of CR at 12 months after determination of CR based on ureteroscopic and local pathology assessment. CR was defined as complete absence of tumor lesions in the ipsilateral pyelocalyceal system at 3 months after initiation of JELMYTO by urine cytology and ureteroscopy. Biopsy was performed if warranted. Durability of response in patients with a CR was evaluated at 3, 6, 9 and 12 months following the initial assessment. Assessment of durability of CR subsequent to these evaluations was performed per local standards of care.

Forty-one patients (58%) achieved CR in the study (95% CI: 45%, 69%). Of the 41 patients who achieved CR, 23 (56%) of the patients remained at CR at the 12-month time point for assessment of durability, 8 (20%) experienced recurrence of disease, and 10 (24%) were unable to be evaluated (died, discontinued from the study, or were indeterminate for ongoing response). The median duration of response was not reached (range: 0, 18.8 months and ongoing). One patient, who achieved 6 months of durable CR, was diagnosed with metastatic urothelial carcinoma approximately 4.5 months after the last dose of study medication and died from the disease.

1. "OSHA Hazardous Drugs." OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Distributed by:
UroGen Pharma, Inc.
Princeton, NJ 08540

JELMYTO® and UroGen® are registered trademarks of UroGen Pharma, Ltd.
U.S. Patent Nos. 9,040,074 and 9,950,069
Copyright© 2024 UroGen Pharma, Inc.
All rights reserved.

JEL-PI-004

Purpose of this Instructions for Pharmacy

This Instructions for Pharmacy contains information on how to prepare JELMYTO using pharmacy supplies and a Chilling Block.

Intended Use of JELMYTO

JELMYTO (mitomycin) for pyelocalyceal solution is indicated for the treatment of adult patients with low-grade Upper Tract Urothelial Cancer (LG-UTUC).

Important Information You Need to Know Before Reconstituting JELMYTO

Once reconstituted with sterile hydrogel, JELMYTO will appear as a semisolid gel. Once chilled, JELMYTO will convert to a viscous liquid.

Reconstituted JELMYTO must be prepared under chilled conditions. A Chilling Block can be used for this purpose. JELMYTO cannot be prepared without the Chilling Block or other means of chilling.

Preparation of JELMYTO must be performed under aseptic conditions.

Storage Conditions and Handling

Instill the JELMYTO solution as soon as possible after reconstitution. Store reconstituted JELMYTO at 20°C to 25°C (68°F to 77°F) for up to 96 hours (4 days). Protect from light.

JELMYTO is a cytotoxic anti-cancer drug. Procedures for Proper Handling and Disposal of anti-cancer drugs should be followed.

Supplies Needed:

JELMYTO Kit containing: 2 Vials of Mitomycin for Pyelocalyceal Solution, 40 mg/vial 1 Vial Sterile Hydrogel, 20 mL/vial 1 JELMYTO Admixture Label JELMYTO Full Prescribing Information (PI) JELMYTO Instructions for Pharmacy (IFP) JELMYTO Instructions for Administration (IFA)
Pharmacy Supplies (Provided by Your Facility) Do not substitute any of these components. 3 × TEVADAPTOR® or OnGuard®2 CSTD Vial Adaptors 3 × TEVADAPTOR® or OnGuard®2 CSTD Syringe Adaptors 1 × Luer Lock connector 2 × 10 mL Luer Lock syringes 1 × 20 mL Luer Lock syringe 1 × 20-25G needle (for drawing up sterile water) 2 mL sterile water 70% Isopropyl alcohol or equivalent 1 × Light protective bag 1 × Chilling Block (device design may vary) Note: The day before your preparation, put the Chilling Block in the freezer at -20°C to -12°C (-4°F to 10.4°F) overnight. Please refer to the Chilling Block Instructions for Use for more information.

Steps to Prepare JELMYTO Admixture

A.

Freeze Chilling Block
The day before preparation, put the Chilling Block in the freezer at -20°C to -12°C (-4°F to 10.4°F) overnight.
Note: Please refer to the Chilling Block Instructions for Use for additional information.

B.

Prepare Supplies

1. Remove the Chilling Block from the freezer.
2. Disinfect the Chilling Block with 70% Isopropyl alcohol or equivalent, as per your pharmacy's policy. Allow it to air dry, and then place it upright inside the hood or isolator.
3. Wait 20 minutes before continuing.
4. Connect vial adaptors to all three vials.
5. Connect a syringe adaptor to one of the 10 mL syringes.
6. Connect a syringe adaptor to the 20 mL syringe.
7. Place the three vials, the 10 mL syringe, and the 20 mL syringe into the Chilling Block for at least 10 minutes.
8. While the vials and syringes are in the Chilling Block, withdraw 2 mL of sterile water into the other 10 mL syringe and set aside for later use.

C.

Create Pre-Wetting Solution (PWS)

1. Slowly fill the chilled 20 mL syringe with 14 mL of sterile hydrogel.
2. Recap the chilled 20 mL syringe and place it in the Chilling Block.
3. Slowly fill the chilled 10 mL syringe with 4 mL of sterile hydrogel.
4. Discard the unused portion of sterile hydrogel.
5. Replace the needle on 2 mL sterile water syringe with the Luer Lock connector.
6. Remove the syringe adaptor from the 4 mL sterile hydrogel syringe.
7. Connect the 4 mL sterile hydrogel syringe to the other side of the Luer Lock connector on the 2 mL sterile water syringe.
8. Gently mix the sterile water with the sterile hydrogel by pushing the plungers back and forth at least 25 times to create the "pre-wetting solution" (PWS).
9. Transfer the 6 mL PWS into one of the syringes.
10. Replace the Luer Lock connector on the 6 mL PWS syringe with a new syringe adaptor.
11. Place the 6 mL PWS syringe in the Chilling Block.

D.

Mix the Admixture

1. Remove both JELMYTO vials from the Chilling Block.
2. Gently tap the bottom of each vial on the table to ensure all the mitomycin powder is at the bottom of the vials.
3. Remove the chilled 6 mL PWS syringe from the Chilling Block.
4. Inject 3 mL of PWS into each JELMYTO vial.
   Note: To ensure accurate dosing, the contents of each vial must be the same.
5. Discard the empty PWS syringe.
6. Gently swirl each JELMYTO vial upright at least 15 times, ensuring all powder and admixture is contained at the bottom of the vial.
   Note: Do not invert or shake the vials.
7. Immediately remove the chilled 14 mL sterile hydrogel syringe from the Chilling Block.
8. Immediately inject 7 mL of sterile hydrogel into each JELMYTO vial.
   Note: To ensure accurate dosing, the contents of each vial must be the same.
9. Gently swirl each JELMYTO vial upright at least 15 times, ensuring all admixture is contained at the bottom of the vial.
   Note: Do not invert or shake the vials.
10. Recap and place the 20 mL syringe in the Chilling Block.
11. Mix the JELMYTO admixture vials:
    • Recap and place both JELMYTO vials in the Chilling Block for five minutes.
    • Remove both vials and vigorously swirl them upright at least 15 times, ensuring all admixture is contained at the bottom of the vials.
    • Place both vials back in the Chilling Block.
    • Repeat these steps every five minutes for a total of 30 minutes.
    Note: Do not invert or shake the vials.

E.

Prepare Admixture Vial

1. Remove one JELMYTO vial from the Chilling Block.
2. Vigorously swirl the vial upright at least 15 times.
   Note: Do not invert or shake the vial.
3. Using the chilled 20 mL syringe, slowly withdraw 7 mL of admixture from the vial.
   Note: If you are having difficulty withdrawing the admixture, place the components back in the Chilling Block until the admixture liquifies again.
4. Discard the empty JELMYTO vial.
5. Remove the remaining JELMYTO vial from the Chilling Block.
6. Inject the contents of the 20 mL syringe into that vial. Now all the admixture is contained in one vial.
7. Recap the vial adaptor.
8. Vigorously swirl the vial upright at least 15 times.
   Note: Do not invert or shake the vial.
9. Your JELMYTO admixture vial is now complete, with a resultant concentration of 4 mg of mitomycin per mL following reconstitution.

F.

Dispense Admixture Vial

1. Write the "Discard after" date and time on the supplied admixture label and apply to the prepared JELMYTO admixture vial. You may also substitute your pharmacy's label for dispensing the admixture.
   Note: The "Discard after" date and time is 96 hours (4 days) from the completion of the preparation at room temperature.
2. Place the JELMYTO admixture vial in a light-protective bag.
3. Transport to the treatment facility along with the JELMYTO Instructions for Administration.

  Important to Remember

• All components must be kept cold during the preparation process by placing them in the Chilling Block when they are not in use.
• If you have difficulty pushing the solution or withdrawing the solution at any time, put the components back in the Chilling Block until the product liquifies.

Frequently Asked Questions:

How do I connect the vial adaptor? Place the vial adaptor over the vial and press down firmly. You will hear a snap which confirms successful attachment.
How do I connect the syringe adaptor? Screw the Luer Lock end of the syringe adaptor onto the syringe hub until it is finger tight.
How do I connect the syringe adaptor to the vial adaptor? Place the syringe adaptor over the vial adaptor and align the tabs, then press down firmly. You will hear a snap which confirms successful attachment.
How do I disconnect the syringe adaptor from the vial adaptor? Pinch the tabs on the syringe adaptor to separate it from the vial adaptor.
Do I need to put the caps on the syringes and vials before placing them back into the chilling block? YES, the chilling block inserts are not sterile. It is important to maintain aseptic technique.
Do I have to keep the vials upright when mixing? If so, why? YES, the vials should be upright during all mixing to ensure the contents are fully mixed at the bottom of the vial.
I am having difficulty working with the drug product. It seems to be solidifying. If you are having difficulty pushing the solution or withdrawing the solution, place the components back into the Chilling Block until the product liquifies.

This "Instructions for Pharmacy" has been approved by the U.S. Food and Drug Administration.

Distributed by:

UroGen Pharma, Inc.
Princeton, NJ 08540
www.JELMYTO.com

JELMYTO® and UroGen® are registered trademarks of UroGen Pharma, Ltd.
TEVADAPTOR® is a registered trademark of Simplivia Healthcare Ltd.
OnGuard® is a registered trademark of B. Braun Medical Inc.

Copyright© 2022 UroGen Pharma, Inc.
All rights reserved.

JEL-IFP-003

IFP-0002025/Ver. 4

Read and follow this Instructions for Administration prior to each JELMYTO instillation.

Purpose of this Instructions for Administration

This Instructions for Administration contains information on how to instill JELMYTO using the reconstituted JELMYTO vial which you received from the pharmacy and the devices listed under Supplies Needed, obtained by your facility.

Intended Use of JELMYTO

JELMYTO (mitomycin) for pyelocalyceal solution is indicated for the treatment of adult patients with low-grade Upper Tract Urothelial Cancer (LG-UTUC).

Important Information You Need to Know Before Instilling JELMYTO

JELMYTO must be reconstituted by a healthcare professional prior to instillation. Reconstituted JELMYTO will appear as a semisolid gel. Once chilled, JELMYTO will convert to a viscous liquid for instillation.

Once instilled into the patient's pyelocalyceal system, JELMYTO will fill and conform to the cavity and become a gel, thereby exposing the tissue to mitomycin over a prolonged period of time.

JELMYTO is viscous, even when it is a liquid in a chilled state. Therefore, you will need a Uroject12 Syringe Lever to instill JELMYTO into the patient. You cannot instill JELMYTO without the Uroject12 device.

Reconstituted JELMYTO should be instilled as soon as possible after reconstitution. Store reconstituted JELMYTO at 20°C to 25°C (68°F to 77°F) for up to 96 hours (4 days). Protect from light.

When ready to instill, chill JELMYTO to 27°F to 41°F (-3°C to 5°C) for at least 10 minutes, but no longer than one hour, to revert it to a liquid form. See the Steps A through E for complete administration instructions.

JELMYTO is a cytotoxic anti-cancer drug. Procedures for Proper Handling and Disposal of anti-cancer drugs should be followed.

Supplies Needed:

One vial of reconstituted JELMYTO, with a resultant concentration of 4 mg of mitomycin per mL following reconstitution.

(prepared and provided by the pharmacy)

JELMYTO vial

Ancillary Supplies:

(to be provided by your facility)

Do not substitute any of these components.

• TEVADAPTOR® Syringe Adaptor or OnGuard®2 CSTD Syringe Adaptor
• MEDALLION® COP or MEDALLION® Luer Lock syringe, 20 mL
• Ureteral Catheter with molded Luer lock port (5 Fr or 7 Fr)
• Uroject12 Syringe Lever
  Note: The Uroject12 Syringe Lever is a multi-use device and must be sterilized or disinfected before use. Please follow the sterilization or disinfection instructions detailed in the Uroject12 Syringe Lever Instructions for Use.
• An ice bath to chill the vial of JELMYTO prior to instillation.

TEVADAPTOR® or OnGuard®2 CSTD Syringe Adaptor	MEDALLION® COP or MEDALLION® Luer Lock syringe, 20 mL	Ureteral Catheter with molded Luer lock port
Uroject12 Syringe Lever	Ice Bath

Instillation Instructions

A.

Measure the Kidney Volume
The Instillation Volume will be equal to the patient's kidney volume. If the kidney volume is already known, proceed to Section B.
If the kidney volume is NOT known, or needs to be reassessed, use the following steps:

1. Perform a retrograde pyelogram using diluted contrast (50%) so that the entire renal pelvis and calyces are observed and contrast starts to flow below the ureteropelvic junction (UPJ).
2. Record the volume of contrast injected at this point.
3. Allow the contrast to drain from the kidney. This may take about five minutes.
   Note: Do not withdraw contrast back into the syringe.
4. Repeat Steps 1 through 3 two more times, for a total of three measurements to improve accuracy.
5. Average the three volume measurements and round to the nearest whole number. This is the patient's kidney volume.

B.

Select the Instillation Volume
Select the kidney volume OR 15 mL, whichever is lower, as the Instillation Volume.
Note: Maximum Instillation Volume is 15 mL. Record this volume for future instillations.

C.

Chill the JELMYTO

Place the JELMYTO vial in the ice bath for at least 10 minutes, but no longer than one hour. After at least 10 minutes, advance the ureteral catheter over the guidewire towards the target anatomy in the pyelocalyceal system.

D.

Prepare the Administration Syringe

Once the vial is removed from the ice bath, you have 4 minutes to draw JELMYTO into the administration syringe before it solidifies. After 4 minutes, recap and place the components back in the ice bath for no more than 15 minutes to liquify the JELMYTO.

1. Remove the JELMYTO vial from the ice bath and dry it off.
2. Swirl the vial upright to ensure that JELMYTO is uniformly mixed.
3. Connect the syringe adaptor to the 20 mL Luer Lock syringe. This will be the administration syringe.
4. Slowly withdraw the calculated Instillation Volume of JELMYTO into the administration syringe.
5. Press the "Clutch" button on the Uroject12 and pull the knob out.
   

   

6. Insert the administration syringe into the Uroject12 Syringe Lever and rotate it clockwise until it locks in place.
   

   

7. While pressing the "Clutch" button, advance the lever to just above the administration syringe's plunger.
   

   

   Immediately proceed with the instillation steps in Section E to avoid JELMYTO solidification.

E.

Instill JELMYTO

1. Remove the syringe adaptor from the administration syringe.
   Note: If JELMYTO gets on to the syringe tip or the catheter's Luer Lock port, wipe it off immediately with sterile gauze so it does not solidify and prevent a secure connection. (Refer to Frequently Asked Questions for further details.)
2. Connect the administration syringe to the ureteral catheter's Luer Lock port, by rotating the syringe only.
3. Using fluoroscopy, ensure the ureteral catheter is in the desired anatomical position.
4. Gradually instill the JELMYTO into the patient by turning the knob at a rate of 1-2 seconds per stroke. The entire syringe must be emptied within one minute.
   

   

5. Remove the ureteral catheter from the urinary tract.
6. Remove the administration syringe from the Uroject12 by rotating the syringe barrel counter-clockwise.
7. Discard the administration ancillaries according to your facility's disposal procedures.
8. Send the Uroject12 to be reprocessed according to your facility's procedures and the Uroject12 Syringe Lever Instructions for Use.

Frequently Asked Questions:

How do I connect the syringe adaptor? Screw the Luer Lock end of the syringe adaptor onto the syringe hub until it is finger tight.
How do I connect the syringe adaptor to the vial adaptor? Place the syringe adaptor over the vial adaptor and align the tabs; then press down firmly. You will hear a snap which confirms successful attachment.
How do I disconnect the syringe adaptor from the vial adaptor? Pinch the tabs on the syringe adaptor to separate it from the vial adaptor.
I am having a hard time working with reconstituted JELMYTO. It seems to be solidifying. If you are having difficulty pushing or withdrawing JELMYTO, recap and place the components back into the ice bath until JELMYTO liquifies.
What should I do if there is JELMYTO spillage from the syringe tip? You will need to clean JELMYTO off the syringe tip and the Luer Lock port of the catheter to ensure the two components can connect securely. To clean the syringe tip, fold a sterile gauze pad in half twice, and push it into the inside of the Luer Lock port to wipe any JELMYTO off the threads. To clean the Luer Lock port on the catheter, use a sterile gauze pad to wipe off any JELMYTO. Verify that the connectors are clean to ensure a secure connection between the syringe and the catheter.

This "Instructions for Administration" has been approved by the U.S. Food and Drug Administration.

Distributed by:

UroGen Pharma, Inc.
Princeton, NJ 08540
www.JELMYTO.com

JELMYTO® and UroGen® are registered trademarks of UroGen Pharma, Ltd.
TEVADAPTOR® is a registered trademark of Simplivia Healthcare Ltd.
OnGuard® is a registered trademark of B. Braun Medical Inc.
MEDALLION® is a registered trademark of Merit Medical Systems, Inc.

Copyright© 2022 UroGen Pharma, Inc.
All rights reserved.

JEL-IFU-003

IFU-Phy-0006722/Ver. 5

NDC 72493-103-03

Jelmyto®
(mitomycin) for pyelocalyceal solution

Attention Pharmacist: Reconstitution
is required prior to dispensing.
See the Instructions for Pharmacy
before proceeding.

SINGLE-DOSE KIT

Warning: For Pyelocalyceal Use Only

Rx Only

Contents of Kit:

• 2 Vials of JELMYTO® (mitomycin) for pyelocalyceal solution, 40 mg per Vial
• 1 Vial Sterile Hydrogel, 20 mL per Vial
• 1 Admixture Label
• Full Prescribing Information
• Instructions for Pharmacy
• Instructions for Administration

Warning: Hazardous Drug

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F).
Avoid excessive heat over 40°C (104°F). Protect from light.

Reconstituted JELMYTO should be instilled as soon as possible after reconstitution.
Store reconstituted JELMYTO at 20°C to 25°C (68°F to 77°F) for up to 96 hours (4 days).
Protect reconstituted JELMYTO from light.

When ready to instill, chill JELMYTO to -3°C to 5°C (27°F to 41°F) for at least 10 minutes,
but no longer than one hour, to revert it to a liquid form.

UroGen®
Pharma

NDC 72493-101-40

Single-Dose Vial
Sterile

Jelmyto®
(mitomycin) for pyelocalyceal solution
40 mg per Vial

See Instructions for Pharmacy for preparation instructions
Must be Reconstituted with Sterile Hydrogel Before Use
Warning: For Pyelocalyceal Use Only

Store at 20°C to 25°C (68°F to 77°F); excursions permitted
between 15°C and 30°C (59°F and 86°F). Avoid excessive heat
over 40°C (104°F). Protect from light.

Warning: Hazardous Drug

Rx Only

NDC 72493-102-20

Single-Dose Vial

Sterile Hydrogel

For use in preparation of JELMYTO™
(mitomycin) for pyelocalyceal solution

Not for Direct Administration

See Instructions for Pharmacy for
preparation instructions

Store at 20°C to 25°C (68°F to 77°F); excursions
permitted between 15°C and 30°C (59°F and 86°F).
Avoid excessive heat over 40°C (104°F).

Rx Only

20 mL per Vial