Valrubicin

A to Z Drug Facts

Actions Valrubicin, a semisynthetic analog of the anthracycline doxorubicin, readily penetrates into cells, causes extensive chromosomal damage, and arrests the G₂ phase of the cell cycle. During the 2-hr dose retention period, the metabolism of valrubicin to its major metabolites was negligible. After retention, the drug was almost completely excreted by voiding the instillate. Mean percent recovery of total anthracyclines was 99% of the total administered drug.

 Indications Intravesical use for the treatment of BCG-refractory carcinoma in-situ of the urinary bladder when immediate cystectomy is contraindicated.

 Contraindications Concurrent urinary tract infection, perforated bladder, compromised integrity of the bladder wall, bladder capacity < 75 mL, or hypersensitive to anthracyclines or Cremophor EL. Use with caution in patients with severe irritable bladder symptoms.

 Route/Dosage Adults: Urethral catheter 800 mg (contents of 4 vials) instilled in the bladder once weekly for 6 wk starting ³ 14 days after fulguration or transurethral resection. Do not use IV or IM. Insert a urethral catheter into the patient's bladder under aseptic conditions, drain the bladder, and instill the diluted 75 mL solution slowly via gravity flow for several minutes. Withdraw the catheter. The patient should retain the drug for 2 hr before voiding. At the end of 2 hr, all patients should void.

Interactions No specific drug interactions have been reported.

Lab Test Interferences None well documented.

 Adverse Reactions

CNS: Weakness; dizziness. GI: Abdominal pain; very low potential for nausea and vomiting. GU: Urinary frequency and urgency; painful urination; bladder spasm; hematuria; bladder pain; urinary incontinence; urinary tract infection; nocturia; urinary retention; local reactions occur shortly after instillation and resolve within 1 to 7 days. HEMATOLOGIC: Dose-limiting leukopenia and neutropenia in patients with increased systemic exposure. Nadir seen by week 2 and recovery by week 3.

 Precautions

Pregnancy: Category C. Lactation: Women should discontinue nursing before the initiation of valrubicin therapy. Children: Safety and efficacy have not been established. Extravasation risk: Local irritation or phlebitis may occur. Refer to your institution specific protocol. Cystectomy: Inform patients that valrubicin induces complete response in » 20% with BCG-refractory CIS and that delaying cystectomy could lead to development of metastatic bladder cancer, which is lethal. Bladder integrity: Do not administer to patients with a perforated bladder or to those in whom the integrity of the bladder mucosa has been compromised. Irritable bladder symptoms: Use 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; if performed, execute under medical supervision and with caution.

 Administration/Storage

• Refrigerate intravesical solution. Do not freeze. Do not heat vials.
• Allow solution to warm slowly to room temperature. Do not heat or microwave.
• Dilute with 0.9% Sodium Chloride providing 75 mL of a diluted solution.
• Valrubicin may be prepared in glass containers using a non-PVC-containing administration set.
• Solutions diluted with 0.9% Sodium Chloride are chemically stable for 12 hr at room temperature.
• Solutions should be clear and red in color.
• Visually inspect the product for particulate matter prior to administration. Cremophor EL may form a waxy precipitate at temperatures < 4°C (39°F); warm the vial by hand to dissolve the precipitate. If particles remain after warming, discard the dose.
• Do not mix with other drugs.
• Intravesical administration.
• Instill into bladder slowly by gravity via a urethral catheter. During the first hour following installation, the patient should lie for 15 min each in the prone and supine position and also on each side. The patient is then allowed to be up, but retains the suspension for another 60 min (total of 2 hr). All patients should void in the seated position for safety reasons.
• Aseptic techniques must be used during administration of intravesical valrubicin to avoid introducing contaminants into the urinary tract or unduly traumatizing the urinary mucosa.
• Follow Safe Handling procedures.
• Urine voided for 6 hr after instillation should be collected and disposed of as chemotherapy waste.

 Assessment/Interventions

• Valrubicin contains Cremophor EL (polyoxyethylated castor oil) which may cause hypersensitivity reactions. Patients with hypersensitivity reactions to valrubicin who require further therapy should be pretreated with a corticosteroid and an antihistamine.
• Assess bladder status at baseline and prior to instilling each dose. Delay therapy if bladder integrity is compromised.
• Monitor for refractory CIS closely for disease recurrence or progression. Recommended evaluations include cystoscopy, biopsy, and urine cytology every 3 mo.
• Assess patient response after 3 mo or if disease recurs. In the absence of a complete response, reconsider cystectomy.

 Patient/Family Education

• Patients should not drink fluids for 4 hr before administration. They should void before instillation of valrubicin into the bladder.
• Instruct patients to maintain adequate hydration after treatment.
• Inform patients that the major acute toxicities from valrubicin are related to irritable bladder symptoms that may occur during instillation and retention of valrubicin and for a limited period following voiding.
• Valrubicin may cause red discoloration of urine for £ 24 hr after administration.
• Patients should report prolonged irritable bladder symptoms or prolonged passage of red-colored urine immediately to their health care provider.
• Advise women of chilbearing potential not to become pregnant during treatment. Advise men to refrain from engaging in procreative activities while receiving therapy. Advise all patients of reproductive age to use an effective contraception method during the treatment period.

Books@Ovid
Copyright © 2003 Facts and Comparisons
David S. Tatro
A to Z Drug Facts