VALRUBICIN Drug Interactions: What You Need to Know

INTERACTIONS No drug interaction studies were conducted.

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 to anthracyclines or polyoxyl castor oil. ( 4 )
• Concurrent urinary tract infections. ( 4 )
• Patients with a small bladder capacity unable to tolerate a 75 mL instillation. ( 4 )

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. ( 5.5 , 8.1 , 8.3 )

5.1 Risk of Metastatic Bladder Cancer with Delayed Cystectomy Inform patients that valrubicin intravesical solution has been shown to induce complete response in only about 1 in 5 patients with BCG-refractory CIS, and that delaying cystectomy could lead to development of metastatic bladder cancer, which is lethal. The exact risk of developing metastatic bladder cancer from such a delay may be difficult to assess <span class="opacity-50 text-xs">[see Clinical Studies ( 14 )]</span> but increases the longer cystectomy is delayed in the presence of persisting CIS. If there is not a complete response of CIS to treatment after 3 months or if CIS recurs, reconsider cystectomy.

5.2 Risk in Patients with Perforated Bladder Evaluate the bladder before the intravesical instillation of drug and 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 <span class="opacity-50 text-xs">[see Contraindications ( 4 )]</span> . In case of bladder perforation, delay the administration of valrubicin intravesical solution until bladder integrity has been restored. One patient with a perforated bladder who received 800 mg of valrubicin intravesical solution intravesically developed severe leukopenia and neutropenia approximately two weeks after drug administration <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span> .

5.3 Risk in Patients Undergoing Transurethral Resection of the Bladder (TURB) To avoid systemic exposure to valrubicin intravesical solution for the patients undergoing TURB, evaluate the status of the bladder before the intravesical instillation of drug. Delay administration at least two weeks after transurethral resection and/or fulguration.

5.4 Risk in Patients with Irritable Bladder Symptoms Use valrubicin intravesical solution with caution in patients with severe irritable bladder symptoms. Bladder spasm and spontaneous discharge of the intravesical instillate may occur; clamping of the urinary catheter is not advised.

5.5 Embryo-Fetal Toxicity Based on findings in animal studies and its mechanism of action, valrubicin intravesical solution can cause fetal harm when administered to a pregnant woman <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.1 and 12.3 )]</span> . 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. Advise females who might become pregnant of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with valrubicin intravesical solution and for 6 months following the final dose <span class="opacity-50 text-xs">[see Use in Specific Populations ( 8.1 and 8.3 )]</span> .