openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
Warnings sections page 1 of 1 · 1 matching rows.
warnings and cautions
5 WARNINGS AND PRECAUTIONS Risks in Patients with Perforated Bladder : Evaluate the bladder before the intravesical instillation of ZUSDURI. Do not administer to patients with a perforated bladder or in whom the integrity of the bladder mucosa has been compromised. ( 4 , 5.1 ). Embryo-Fetal Toxicity : Can cause fetal harm. Advise of potential risk to a fetus and to use effective contraception. ( 5.2 , 8.1 , 8.3 ) 5.1 Risks in Patients with Perforated Bladder ZUSDURI may lead to systemic exposure to mitomycin and severe adverse reactions if administered to patients with a perforated bladder or to those in whom the integrity of the bladder mucosa has been compromised. Evaluate the bladder before the intravesical instillation of ZUSDURI and do not administer to patients with a perforated bladder or mucosal compromise until bladder integrity has been restored [see Contraindications (4) ]. 5.2 Embryo-Fetal Toxicity Based on findings in animals and mechanism of action, ZUSDURI can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of mitomycin resulted in teratogenicity. Advise females of reproductive potential to use effective contraception during treatment with ZUSDURI and for 6 months following the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ZUSDURI and for 3 months following the last dose [see Use in Specific Populations (8.1 , 8.3) and Clinical Pharmacology (12.1) ].
6 ADVERSE REACTIONS 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. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact UroGen Pharma at 1-855-987-6436 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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 [see Clinical Studies (14) ]. 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 0.4 Hematuria Includes multiple related terms 10 0 Infections and infestations Urinary tract infection 12 0.8 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 0.8 Eosinophils Increased 15 0 Lymphocytes Decreased 14 0.4 Neutrophils Decreased 10 0.4 Chemistry Creatinine Increased 29 1.3 Potassium Increased 26 2.2 Aspartate Aminotransferase (AST) Increased 15 0.4 Alanine Aminotransferase (ALT) Increased 15 0.4
adverse reactions table
<table width="80%"><caption>Table 1: Adverse Reactions (≥ 10% All Grades<footnote ID="t1a">Graded per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.</footnote>) in Patients Who Received ZUSDURI in ENVISION</caption><col width="50%" align="left" valign="top"/><col width="25%" align="center" valign="top"/><col width="25%" align="center" valign="top"/><thead><tr styleCode="botrule"><th styleCode="Lrule Rrule" valign="middle" rowspan="2">Adverse Reaction</th><th styleCode="Rrule" colspan="2">ZUSDURI N = 240</th></tr><tr><th styleCode="Lrule Rrule" align="center">All Grades (%)</th><th styleCode="Rrule">Grade 3 or 4<footnote ID="t1c">Only includes Grade 3 adverse reactions</footnote> (%)</th></tr></thead><tbody><tr styleCode="botrule"><td styleCode="Lrule Rrule bold" colspan="3">Renal and urinary disorders</td></tr><tr styleCode="botrule"><td styleCode="Lrule Rrule"> Dysuria</td><td styleCode="Rrule">23</td><td styleCode="Rrule">0.4</td></tr><tr styleCode="botrule"><td styleCode="Lrule Rrule"> Hematuria<footnote ID="t1b">Includes multiple related terms</footnote></td><td styleCode="Rrule">10</td><td styleCode="Rrule">0</td></tr><tr styleCode="botrule"><td styleCode="Lrule Rrule bold" colspan="3">Infections and infestations</td></tr><tr styleCode="botrule"><td styleCode="Lrule Rrule"> Urinary tract infection<footnoteRef IDREF="t1b"/></td><td styleCode="Rrule">12</td><td styleCode="Rrule">0.8</td></tr></tbody></table>
adverse reactions table
<table width="80%"><caption>Table 2: Laboratory Abnormalities (≥ 10% All Grades<footnote ID="t21">Graded per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.</footnote>) That Worsened From Baseline in Patients Who Received ZUSDURI in ENVISION</caption><col width="50%" align="left" valign="top"/><col width="25%" align="center" valign="top"/><col width="25%" align="center" valign="top"/><thead><tr styleCode="botrule"><th styleCode="Lrule Rrule" valign="middle" rowspan="2">Laboratory Abnormality</th><th styleCode="Rrule" colspan="2">ZUSDURI<footnote ID="t2b">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</footnote></th></tr><tr><th styleCode="Lrule Rrule" align="center">All Grades (%)</th><th styleCode="Rrule">Grade 3 or 4<footnote ID="t2c">Only includes Grade 3 laboratory abnormalities</footnote> (%)</th></tr></thead><tbody><tr styleCode="botrule"><td styleCode="Lrule Rrule bold" colspan="3">Hematology</td></tr><tr styleCode="botrule"><td styleCode="Lrule Rrule"> Hemoglobin Decreased</td><td styleCode="Rrule">17</td><td styleCode="Rrule">0.8</td></tr><tr styleCode="botrule"><td styleCode="Lrule Rrule"> Eosinophils Increased</td><td styleCode="Rrule">15</td><td styleCode="Rrule">0</td></tr><tr styleCode="botrule"><td styleCode="Lrule Rrule"> Lymphocytes Decreased</td><td styleCode="Rrule">14</td><td styleCode="Rrule">0.4</td></tr><tr styleCode="botrule"><td styleCode="Lrule Rrule"> Neutrophils Decreased</td><td styleCode="Rrule">10</td><td styleCode="Rrule">0.4</td></tr><tr styleCode="botrule"><td styleCode="Lrule Rrule bold" colspan="3">Chemistry</td></tr><tr styleCode="botrule"><td styleCode="Lrule Rrule"> Creatinine Increased</td><td styleCode="Rrule">29</td><td styleCode="Rrule">1.3</td></tr><tr styleCode="botrule"><td styleCode="Lrule Rrule"> Potassium Increased</td><td styleCode="Rrule">26</td><td styleCode="Rrule">2.2</td></tr><tr styleCode="botrule"><td styleCode="Lrule Rrule"> Aspartate Aminotransferase (AST) Increased</td><td styleCode="Rrule">15</td><td styleCode="Rrule">0.4</td></tr><tr><td styleCode="Lrule Rrule"> Alanine Aminotransferase (ALT) Increased</td><td styleCode="Rrule">15</td><td styleCode="Rrule">0.4</td></tr></tbody></table>