Zusduri Drug Information

ZUSDURI™ is indicated for the treatment of adult patients with recurrent low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC). ZUSDURI is an alkylating drug indicated for the treatment of adult patients with recurrent low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC).

Important

Administration Instructions Administer ZUSDURI by intravesical instillation only. Do not administer by pyelocalyceal instillation or by any other route.

Recommended Dose

The recommended dose of ZUSDURI is 75 mg (56 mL) instilled once weekly for six weeks into the bladder via a urinary catheter.

Preparation Instructions See the Instructions for Pharmacy enclosed in the carton for

complete information on preparation. ZUSDURI must be reconstituted with sterile hydrogel under chilled conditions. Reconstituted ZUSDURI has reverse thermal properties with a gelation point of approximately 19°C (66°F) and will appear as a viscous liquid under chilled conditions and a semisolid gel at room temperature.

Storage Instructions for Reconstituted ZUSDURI: Instill reconstituted ZUSDURI as soon as possible. If not used immediately, store reconstituted ZUSDURI: under refrigeration at 2℃ to 8℃ (36°F to 46°F) for up to 7 days; or under refrigeration at 2℃ to 8℃ (36°F to 46°F) for up to 6 days followed by no more than 24 hours at room temperature, 20°C to 25°C (68°F to 77°F). Discard 7 days after reconstitution. Protect from light.

Avoid excessive heat over 40°C (104°F). ZUSDURI is a hazardous drug. Follow applicable special handling and disposal procedures. 1

Bladder Instillation of

ZUSDURI See the Instructions for Administration enclosed in the carton for complete information on bladder instillation. ZUSDURI must be chilled at -3°C to 5°C (27°F to 41°F) to convert to a viscous liquid prior to instillation. When instilling ZUSDURI, each syringe must be emptied within thirty seconds to avoid gelation.

Instillation of ZUSDURI requires syringes and a urinary catheter with fixed Luer Lock connectors. Advise patients that ZUSDURI may discolor urine to a violet to blue color following the instillation procedure. Advise patients for at least 24 hours post-instillation to avoid urine contact with skin, to void urine sitting on a toilet, to wash hands and genital area with water and soap after each urination, and to flush the toilet several times after use.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect rates observed in practice. The safety of ZUSDURI was evaluated in ENVISION, a single-arm, multicenter study in 240 patients with recurrent LG-IR-NMIBC. Patients received 75 mg ZUSDURI instilled once a week for 6 consecutive weeks. The median number of doses of ZUSDURI administered to patients was 6 (range 1-6) doses and 228 patients (95%) received all six scheduled doses.

Serious adverse reactions occurred in 12% of patients who received ZUSDURI, including urinary retention (0.8%) and urethral stenosis (0.4%). A fatal adverse reaction of cardiac failure occurred in 1 patient (0.4%) receiving ZUSDURI. Permanent discontinuation of ZUSDURI due to an adverse reaction occurred in 2.9% of patients, including 1.7% who discontinued due to a renal or urinary disorder. Dosage interruption of ZUSDURI due to adverse reactions occurred in 10% of patients. Adverse reactions (≥ 2%) which required dosage interruption were urinary tract infection (2.5%) and dysuria (2.5%). The most common (≥ 10%) adverse reactions, including laboratory abnormalities, that occurred in patients were increased creatinine, increased potassium, dysuria, decreased hemoglobin, increased aspartate aminotransferase, increased alanine aminotransferase, increased eosinophils, decreased lymphocytes, urinary tract infection, decreased neutrophils, and hematuria.

Table 1 summarizes the adverse reactions in ENVISION. Table 1: Adverse Reactions (≥ 10% All Grades Graded per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. ) in Patients Who Received ZUSDURI in ENVISION Adverse Reaction ZUSDURI N = 240 All Grades (%) Grade 3 or 4 Only includes Grade 3 adverse reactions (%) Renal and urinary disorders Dysuria 23

Hematuria Includes multiple related terms 10 0 Infections and infestations Urinary tract

infection 12

Clinically relevant adverse reactions occurring in < 10% of patients receiving

ZUSDURI in ENVISION included increased urinary frequency, fatigue, urinary incontinence, urinary retention, urethral stenosis, genital pain, urinary urgency, genital edema, genital pruritus, genital rash, urethritis, acute kidney injury, balanoposthitis, and nocturia. Table 2 summarizes laboratory abnormalities in ENVISION. Table 2: Laboratory Abnormalities (≥ 10% All Grades Graded per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. ) That Worsened From Baseline in Patients Who Received ZUSDURI in ENVISION Laboratory Abnormality ZUSDURI The denominator used to calculate the rate varied from 227 to 238 based on the number of patients with a baseline value and at least one post-treatment value All Grades (%) Grade 3 or 4 Only includes Grade 3 laboratory abnormalities (%) Hematology Hemoglobin Decreased 17

Eosinophils Increased 15 0 Lymphocytes Decreased 14 0.4 Neutrophils Decreased 10 0.4

Chemistry Creatinine Increased 29

Potassium Increased 26 2.2 Aspartate Aminotransferase (AST) Increased 15 0.4 Alanine Aminotransferase

(ALT) Increased 15 0.4

Pregnancy Risk Summary Based on findings in animals and mechanism of action, ZUSDURI can cause fetal harm when administered to a pregnant woman . There are no available data on ZUSDURI use in pregnant women to inform the drug-associated risk. In animal reproduction studies, administration of mitomycin resulted in teratogenicity (see Data ). Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% - 4% and 15% - 20%, respectively. Data Animal Data Teratological changes have been noted with mitomycin in animal studies.

Pediatric Use Safety and efficacy in pediatric patients have not been established.

is contraindicated in patients with: Perforation of the bladder, Prior hypersensitivity reactions to mitomycin or any component of the product. Perforation of the bladder, Prior hypersensitivity reaction to mitomycin or any component of the product.