Valrubicin

Valrubicin is an anthracycline that affects a variety of interrelated biological functions, most of which involve nucleic acid metabolism. In cells, it inhibits the incorporation of nucleosides into nucleic acids, causes chromosomal damage, and arrests the cell cycle in G 2 .

• VALSTAR 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. VALSTAR 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.

• VALSTAR 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.contraindicated

For Intravesical Use Only. ( 2.1 ) VALSTAR is recommended at a dose of 800 mg administered intravesically once a week for six weeks. ( 2.1 ) Delay administration at least two weeks after transurethral resection and/or fulguration. ( 2.1 ) Warm VALSTAR slowly to room temperature, but do not heat. ( 2.1 ) Use caution when handling and preparing the solution of VALSTAR. ( 2.2 ) 2.1 Recommended Dosing For Intravesical Use Only. Do NOT administer by intravenous or intramuscular routes. VALSTAR is recommended at a dose of 800 mg administered intravesically once a week for six weeks. Delay administration at least two weeks after transurethral resection and/or fulguration [ see Warnings and Precautions ( 5.2 , 5.3 )]. 2.2 Preparation, Handling, and Administration Handle and dispose of VALSTAR in a manner consistent with other cytotoxic drugs. 1 The use of goggles, gloves, and protective gowns is recommended during preparation and administration of the drug. VALSTAR contains polyoxyl castor oil, which has been known to cause leaching of di(2-ethylhexyl) phthalate (DEHP) a hepatotoxic plasticizer, from polyvinyl chloride (PVC) bags and intravenous tubing. VALSTAR should be prepared and stored in glass, polypropylene, or polyolefin containers and tubing. It is recommended that non-DEHP containing administration sets, such as those that are polyethylene-lined, be used. VALSTAR is a sterile, clear red solution. Visually inspect for particulate matter and discoloration prior to administration. At temperatures below 4°C (39°F), polyoxyl castor oil may begin to form a waxy precipitate.

Delaying cystectomy can lead to development of metastatic bladder cancer, which is lethal. ( 5.1 ) Do not administer VALSTAR 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 VALSTAR. ( 5.3 ) Use with caution in patients with severe irritable bladder symptoms. ( 5.4 ) Embryo-Fetal Toxicity: VALSTAR 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 VALSTAR 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 [see Clinical Studies ( 14 )] 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 VALSTAR to patients with a perforated bladder or to those in whom the integrity of the bladder mucosa has been compromised [see Contraindications ( 4 )] .

The most frequently reported adverse reactions ( > 5%) after administration of VALSTAR 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 Endo at 1-800-462-3636 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. The safety of VALSTAR was assessed in 230 patients with transitional cell carcinoma of the bladder, including 205 patients who received multiple weekly doses. One hundred seventy-nine of the 205 patients received the approved dose and schedule of 800 mg weekly for multiple weeks. Approximately 84% of patients who received intravesical VALSTAR in clinical studies experienced local adverse reactions. The local adverse reactions associated with VALSTAR usually occur during or shortly after instillation and resolve within 1 to 7 days after the instillate is removed from the bladder. Seven out of 143 patients (5%) who were scheduled to receive six doses of VALSTAR failed to receive all of the planned doses because of the occurrence of local bladder symptoms.

Lactation: Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on findings in animal studies and its mechanism of action, VALSTAR 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] . Advise females who are or might become pregnant of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically-recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Daily intravenous administration of valrubicin to pregnant rats during the period of organogenesis at doses ≥ 12 mg/kg (about 0.2 times the recommended human intravesical dose on a mg/m 2 basis) was embryo-fetal toxic and teratogenic. Administration of 12 mg/kg resulted in fetal malformations. A dose of 24 mg/kg (about 0.3 times the recommended human intravesical dose on a mg/m 2 basis) caused numerous, severe alterations in the skull and skeleton of the developing fetuses.

Metabolism

When 800 mg VALSTAR was administered intravesically to patients with carcinoma in situ , VALSTAR penetrated into the bladder wall. The mean total anthracycline concentration measured in bladder tissue exceeded the levels causing 90% cytotoxicity to human bladder cells cultured in vitro .

There is no known antidote for overdoses of VALSTAR. The primary anticipated complications of overdosage associated with intravesical administration would be consistent with irritable bladder symptoms. Myelosuppression is possible if VALSTAR is inadvertently administered systemically or if significant systemic exposure occurs following intravesical administration (e.g., in patients with bladder rupture/perforation). Under such inadvertent exposures in the peritoneal cavity, the expected toxicities include leukopenia and neutropenia, beginning within 1 week of dose administration, with nadirs by the second week, and recovery generally by the third week. If VALSTAR is administered when bladder rupture or perforation is suspected, weekly monitoring of complete blood counts should be performed for 3 weeks.

• Sep 25, 1998NDANDA020892Endo Operations
• Apr 19, 2019ANDAANDA206430Hikma

1. 1Underdose2615%
2. 2Bladder Instillation Procedure2414%
3. 3Accidental Exposure To Product2313%
4. 4Urge Incontinence2011%
5. 5Bladder Spasm137.3%
6. 6Urinary Incontinence116.2%
7. 7Pain95.1%
8. 8Dysuria84.5%
9. 9Burning Sensation74.0%
10. 10Drug Ineffective74.0%
11. 11Arthralgia63.4%
12. 12Fatigue63.4%
13. 13Pollakiuria63.4%
14. 14Rash63.4%
15. 15Drug Intolerance52.8%

The 9 most recently updated of 9 ClinicalTrials.gov registrations naming Valrubicin as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Chemotherapy in Treating Patients With Early-Stage Bladder Cancer
  Completed · Phase 2 · Interventional · 75 enrolled · Eastern Cooperative Oncology Group
  NCT00003129updated 2023-06-22
• Efficacy Study of Recombinant Adenovirus for Non Muscle Invasive Bladder Cancer
  Terminated · Phase 2 · Phase 3 · Interventional · 22 enrolled · CG Oncology, Inc.
  NCT01438112updated 2021-04-14
• Multi-center Study to Evaluate the Efficacy and Safety of Maintenance Therapy With Valrubicin Versus no Maintenance, in Subjects Treated With Valrubicin Induction for Carcinoma in Situ (CIS) of the Bladder
  Terminated · Phase 3 · Interventional · 1 enrolled · Endo USA Inc., a Keenova Therapeutics Company
  NCT01310803updated 2017-10-05
• Phase I Study of Percutaneous Valrubicin for Upper Tract Urothelial Carcinoma
  Completed · Phase 1 · Interventional · 4 enrolled · H. Lee Moffitt Cancer Center and Research Institute
  NCT01606345updated 2016-04-22
• A Prospective Registry to Assess the Effectiveness and Local Tolerability of Intravesical Valrubicin in Subjects With Non-muscle Invasive Bladder Cancer (NMIBC)
  Terminated · Observational · 15 enrolled · Endo USA Inc., a Keenova Therapeutics Company
  NCT01314664updated 2015-06-12
• Intravesical AD 32 (Valrubicin) in Patients With Carcinoma in Situ (CIS) of the Bladder Who Have Failed or Have Recurrence Following Treatment With Bacillus Calmette-guerin (BCG)
  Completed · Phase 2 · Phase 3 · Interventional · 90 enrolled · Endo USA Inc., a Keenova Therapeutics Company
  NCT01316874updated 2015-06-12
• Retrospective Chart Review of Valstar
  Completed · Observational · 113 enrolled · Endo USA Inc., a Keenova Therapeutics Company
  NCT01304173updated 2014-02-19
• Surgery With or Without Chemotherapy in Treating Patients With Newly Diagnosed or Recurrent Bladder Cancer
  Unknown · Phase 3 · Interventional · 300 enrolled · Anthra Pharmaceuticals
  NCT00003725updated 2013-11-06
• AD 32 With or Without BCG After Surgery in Treating Patients With Newly Diagnosed or Recurrent Superficial Bladder Cancer
  Completed · Phase 2 · Interventional · Anthra Pharmaceuticals
  NCT00003759updated 2013-01-31

Frequently asked questions

How does Valrubicin work?

Valrubicin is an anthracycline that affects a variety of interrelated biological functions, most of which involve nucleic acid metabolism. In cells, it inhibits the incorporation of nucleosides into nucleic acids, causes chromosomal damage, and arrests the cell cycle in G 2 .

What is Valrubicin used for?

According to FDA labeling, Valrubicin carries indications including: VALSTAR 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. VALSTAR 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.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Valrubicin?

Valrubicin is classified as Anthracyclines and related substances, Topoisomerase Inhibitors, Decreased DNA Integrity, Decreased DNA Replication.

What are the brand names for Valrubicin?

Valrubicin is marketed under brand names including Valstar.

What are the contraindications for Valrubicin?

Valrubicin labeling lists contraindications including: VALSTAR 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.. Always consult the full prescribing information and a clinician.