Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravesical [preservative free]:
Valstar: 40 mg/mL (5 mL) [contains alcohol, usp, cremophor el]
Generic: 40 mg/mL (5 mL)
Pharmacology
Mechanism of Action
Blocks function of DNA topoisomerase II; inhibits DNA synthesis, causes extensive chromosomal damage, and arrests cell development (G2 phase); unlike other anthracyclines, does not appear to intercalate DNA; readily penetrates cells.
Pharmacokinetics/Pharmacodynamics
Absorption
Intravesical: Penetrates into bladder wall; negligible systemic absorption (dependent on bladder wall condition; trauma to mucosa may increase absorption, bladder wall perforation may significantly increase absorption and systemic myelotoxicity).
Metabolism
Negligible after intravesical instillation and 2-hour retention
Excretion
Urine (post 2-hour retention): 98.6% as intact drug; 0.4% as N-trifluoroacetyladriamycin)
Use: Labeled Indications
Bladder cancer: Intravesical treatment of BCG-refractory bladder carcinoma in situ of the urinary bladder when cystectomy would be associated with unacceptable morbidity or mortality.
Contraindications
Known hypersensitivity to anthracyclines, polyoxyl castor oil, or any component of the formulation; perforated bladder; concurrent urinary tract infection; small bladder capacity (unable to tolerate a 75 mL instillation)
Dosage and Administration
Dosing: Adult
Note: Delay for at least 2 weeks after transurethral resection and/or fulguration.
Bladder cancer: Intravesical: 800 mg once weekly (retain for 2 hours) for 6 weeks
Dosing: Geriatric
Refer to adult dosing.
Dosing: Adjustment for Toxicity
In clinical trials (Steinberg 2000), treatment was delayed for 1 week for the following adverse events: Grade 3 dysuria (not controlled with phenazopyridine), frequency/urgency lasting >24 hours, grade 2 gross hematuria (without clots) lasting >48 hours, grade 3 hematuria (with clots) lasting >48 hours. For local toxicities <grade 4 (eg, dysuria [not controlled with phenazopyridine] or severe bladder spasm), anticholinergic therapy (systemic or topical) or topical anesthesia was administered prior to subsequent instillations.
Reconstitution
Allow vials to slowly warm to room temperature (do not heat) prior to use. A waxy precipitate (due to polyoxyl castor oil) may form at temperatures <4°C, warm vial in the hand until solution is clear (do not use vial if particulate still present). Dilute 800 mg (20 mL) with 55 mL NS (total volume of 75 mL). Use non-PVC containers (glass, polyolefin, or polypropylene) and administration sets to avoid leaching of DEHP plasticizers. Stable for 12 hours at room temperature when diluted in 0.9% sodium chloride. Do not mix with other drugs.
Administration
For intravesical use only; not for IV or IM use.
Intravesicular bladder instillation: Insert urinary catheter, empty bladder prior to instillation, slowly by gravity flow, instill 800 mg/75 mL (in 0.9% sodium chloride injection), remove catheter. Retain in the bladder for 2 hours, then void. Administer through non-PVC tubing due to the polyoxyl castor oil component. Maintain adequate hydration following treatment.
Storage
Store intact vials at 2°C to 8°C (36°F to 48°F). Do not freeze. Solutions diluted in 0.9% sodium chloride are stable for 12 hours at room temperature.
Drug Interactions
There are no known significant interactions.
Adverse Reactions
In general, local adverse reactions occur during or shortly after instillation and resolve within 1 to 7 days.
>10%: Genitourinary: Irritable bladder (88%), urinary frequency (61%), urinary urgency (57%), dysuria (56%), bladder spasm (31%), hematuria (29%; microscopic: 3%; gross hematuria: 1%), bladder pain (28%), urinary incontinence (22%), cystitis (15%), urinary tract infection (15%), red urine discoloration
1% to 10%:
Cardiovascular: Chest pain (3%), vasodilation (2%), peripheral edema (1%)
Central nervous system: Localized burning (5%), headache (4%), malaise (4%), dizziness (3%)
Dermatologic: Skin rash (3%)
Endocrine & metabolic: Hyperglycemia (1%)
Gastrointestinal: Abdominal pain (5%), nausea (5%), diarrhea (3%), vomiting (2%), flatulence (1%)
Genitourinary: Nocturia (7%), urinary retention (4%), urethral pain (3%), pelvic pain (1%)
Hematologic & oncologic: Anemia (2%)
Neuromuscular & skeletal: Weakness (4%), back pain (3%), myalgia (1%)
Respiratory: Pneumonia (1%)
Miscellaneous: Fever (2%)
<1%, postmarketing, and/or case reports: Ageusia, increased nonprotein nitrogen, pruritus, reduced urine flow, skin irritation (local), tenesmus, urethritis
Warnings/Precautions
Concerns related to adverse effects:
- Bladder irritation: Irritable bladder symptoms may occur during instillation and retention, and for a brief time after voiding. Use with caution in patients with severe irritable bladder symptoms;. Prolonged symptoms should prompt contact with the physician.
- Red-tinged urine: May occur in first 24 hours after instillation. Prolonged discoloration should prompt contact with the physician.
Disease-related concerns:
- Bladder perforation: Evaluate bladder status prior to instillation. Do not administer if mucosal integrity of bladder has been compromised or bladder perforation is present; delay treatment until restoration of bladder integrity.
- Bladder procedures: Delay valrubicin therapy for at least 2 weeks after transurethral resection and/or fulguration.
Other warnings/issues:
- Administration: Use aseptic technique to prevent urinary tract infection or traumatizing urinary mucosa. Although clamping of the urinary catheter after administration is not recommended, use caution and appropriate medical supervision if performed.
- Appropriate use: Delaying cystectomy for intravesical treatment may lead to metastatic bladder cancer; the risk for metastatic disease increases with delay duration; reconsider cystectomy for recurrence or if complete response to treatment does not occur within 3 months.
- Polyoxyl castor oil: Contains polyoxyl castor oil which may be associated with hypersensitivity reactions. Use is contraindicated in patients with hypersensitivity to polyoxyl castor oil.
Monitoring Parameters
Cystoscopy, biopsy, and urine cytology every 3 months for recurrence or progression
Pregnancy
Pregnancy Risk Factor
C
Pregnancy Considerations
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to valrubicin may cause fetal harm.
Systemic exposure (eg, with bladder perforation) during human pregnancy may result in fetal harm. Females of reproductive potential should use effective contraception during treatment and for 6 months after the final valrubicin dose. Males with female partners of reproductive potential should use effective contraception during treatment and for 3 months after the last valrubicin dose.
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience bladder irritation, passing a lot of urine, leaking of urine, abdominal pain, nausea, or urine discoloration. Have patient report immediately to prescriber painful urination, blood in the urine, change in amount of urine passed, or unable to pass urine (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
