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Valrubicin

Medically reviewed by Drugs.com. Last updated on May 31, 2020.

Pronunciation

(val ROO bi sin)

Index Terms

  • N-trifluoroacetyladriamycin-14-valerate
  • AD32

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)

Brand Names: U.S.

  • Valstar

Pharmacologic Category

  • Antineoplastic Agent, Anthracycline
  • Antineoplastic Agent, Topoisomerase II Inhibitor

Pharmacology

Valrubicin blocks function of DNA topoisomerase II; it inhibits DNA synthesis, causes extensive chromosomal damage, and arrests cell development (G2 phase). Unlike other anthracyclines, valrubicin does not appear to intercalate DNA.

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; active urinary tract infection; small bladder capacity (unable to tolerate a 75 mL instillation).

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 (Dinney 2013; Steinberg 2000), treatment was delayed for 1 week for the following adverse events: grade 3 dysuria (not controlled with phenazopyridine), frequency or urgency on treatment day or lasting >24 hours, or grade 2 or 3 hematuria on treatment day or lasting >48 hours, or for bladder infection. For local toxicities < grade 4 (eg, dysuria [not controlled with phenazopyridine] or 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 (39°F), 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. Do not mix with other medications.

Administration

For intravesical use only; not for IV or IM use. Administer through non-PVC tubing due to the polyoxyl castor oil component.

Intravesicular bladder instillation: Insert urinary catheter under aseptic conditions and drain bladder. Instill 800 mg/75 mL (in NS) slowly by gravity flow over several minutes, then remove catheter. Retain in the bladder for 2 hours, then void (some patients may be unable to retain for the full 2 hours). Patients should maintain adequate hydration following treatment.

Storage

Store intact vials at 2°C to 8°C (36°F to 48°F). Do not freeze. Store in original carton. Solutions diluted in NS are stable for 12 hours at temperatures ≤25°C (77°F).

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 (spasm or spontaneous emptying) may occur during instillation and retention, and for a brief time after voiding. Clamping of the urinary catheter is not recommended. Use with caution in patients with severe irritable bladder symptoms.

• Urine discoloration: Red-tinged urine may occur for first 24 hours after instillation. Prolonged discoloration should prompt contact with the physician.

Disease-related concerns:

• Bladder perforation: Evaluate bladder status prior to intravesical instillation. Do not administer valrubicin 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 ≥2 weeks after transurethral resection and/or fulguration.

Other warnings/issues:

• Appropriate use: Valrubicin induces complete response in ~20% of patients with BCG-refractory carcinoma in situ. Delaying cystectomy for intravesical treatment may lead to the development of metastatic bladder cancer. While the precise risk for metastatic bladder cancer is unknown, the risk increases the longer cystectomy is delayed. Reconsider cystectomy for recurrence or if complete response to treatment does not occur within 3 months.

• Polyoxyl castor oil: Valrubicin contains polyoxyl castor oil, which may be associated with hypersensitivity reactions. Use is contraindicated in patients with hypersensitivity to polyoxyl castor oil.

Monitoring Parameters

Evaluate bladder status prior to administration. Monitor cystoscopy, biopsy, and urine cytology every 3 months for recurrence or progression. Monitor for hematuria and for bladder irritation symptoms.

Reproductive Considerations

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.

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.

Patient Education

What is this drug used for?

• It is used to treat bladder cancer.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Bladder irritation

• Passing a lot of urine

• Leaking of urine

• Abdominal pain

• Nausea

• Urine discoloration

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Painful urination

• Blood in the urine

• Change in amount of urine passed

• Unable to pass urine

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.