Valrubicin Intravesical Solution

1 INDICATIONS AND USAGE Valrubicin intravesical solution is an anthracycline topoisomerase inhibitor indicated for intravesical therapy of BCG-refractory carcinoma in situ (CIS) of the urinary bladder in patients for whom immediate cystectomy would be associated with unacceptable morbidity or mortality. • Valrubicin intravesical solution is an anthracycline topoisomerase inhibitor indicated for intravesical therapy of BCG-refractory carcinoma in situ (CIS) of the urinary bladder in patients for whom immediate cystectomy would be associated with unacceptable morbidity or mortality. ( 1 )

6 ADVERSE REACTIONS The most frequently reported adverse reactions ( > 5%) after administration of valrubicin intravesical solution are urinary frequency, dysuria, urinary urgency, bladder spasm, hematuria, bladder pain, urinary incontinence, cystitis, urinary tract infection, nocturia, local burning symptoms, abdominal pain, and nausea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Hikma at us.hikma@primevigilance.com or call 1-877-845-0689 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

8.1 Pregnancy Risk Summary Based on findings in animal studies and its mechanism of action, valrubicin intravesical solution can cause fetal harm when administered to a pregnant females [see Clinical Pharmacology ( 12.1 and 12.3 )] . There are no available data in pregnant females to inform the drug-associated risk. In animal reproduction studies, intravenous administration of valrubicin to pregnant rats during the period of organogenesis at a dose about 0.2 times the recommended human intravesical dose caused embryo-fetal malformations and increased resorptions [see Data] .

5 WARNINGS AND PRECAUTIONS • Delaying cystectomy can lead to development of metastatic bladder cancer, which is lethal. ( 5.1 ) • Do not administer valrubicin intravesical solution to patients with a perforated bladder or to those in whom the integrity of the bladder mucosa has been compromised. ( 5.2 , 12.3 ) • Evaluate the status of the bladder before the intravesical instillation of valrubicin intravesical solution. ( 5.3 ) • Use with caution in patients with severe irritable bladder symptoms. ( 5.4 ) • Embryo-Fetal Toxicity: Valrubicin intravesical solution can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. 4 CONTRAINDICATIONS Valrubicin intravesical solution is contraindicated in patients with: • Perforated bladder [see Warnings and Precautions ( 5.2 )] • Known hypersensitivity to anthracyclines or polyoxyl castor oil • Active urinary tract infection • Small bladder capacity and unable to tolerate a 75 mL instillation • Perforated bladder or compromised bladder mucosa ( 4 , 5.2 ) • Hypersensitivity...