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Valstar valrubicin 40 mg/mL Solution, Concentrate — NDC 67979-0001-01 package photo

Valstar valrubicin 40 mg/mL Solution, Concentrate

by Endo USA, Inc. · 4 VIAL in 1 CARTON (67979-001-01) / 5 mL in 1 VIAL
NDC 67979-0001-01
🏷️ FDA NDC (as labeled) 67979-001-01 billing pads the product segment with a zero
Rx only Brand On market Non-controlled
🗂️ Data synced Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

🆔 Identity & classification

FDA NDC (as labeled) 67979-001-01
Product NDC 67979-001
11-digit billing NDC 67979000101
NCPDP billing unit ML — per mL (volume)
RxCUI 262063, 313567
UNII 2C6NUM6878
Application # NDA020892
SPL Set ID e96f30a0-6662-11de-8f80-0002a5d5c51b
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 1998-10-01
Route INTRAVESICAL
Dosage form SOLUTION, CONCENTRATE
Substance VALRUBICIN
GPI-14 21200080002020
GPI class Valstar
GCN Seq No 041003
GCN 94175
HICL code 018864
Ingredient (HICL) Valrubicin
HIC1 code V
Therapeutic class — broad (HIC1) Neoplasms
HIC2 code V1
Therapeutic class — intermediate (HIC2) Antineoplastic Drugs
HIC3 code V1D
Therapeutic class — specific (HIC3) Antibiotic Antineoplastics
AHFS code 10:00.00.00
AHFS class Antineoplastic Agents
FDB label name VALSTAR 40 MG/ML VIAL
FDB brand name Valstar
Legend status F — Federal legend — prescription drug or device
TE code (Orange Book) AO · RLD · RS
Why two NDCs? The FDA registers this code as 67979-001-01 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 67979-0001-01. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

🏷️ RxNorm drug class

This medicine belongs to the Anthracyclines and related substances class.

Drug family (ATC) Anthracyclines and related substances
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

🏭 Manufacturer & labeler

LabelerEndo USA, Inc.
Application holderENDO OPERATIONS LTD
FDA applicationNDA020892 (NDA)
Labeler code67979
First marketedOct 1998
Product typeHuman Prescription Drug
Portfolio101 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

🩺 Clinical

Label name VALSTAR 40 MG/ML VIAL Ingredient Valrubicin
📖 What it is MedlinePlus · NLM

What is cancer chemotherapy? Cancer chemotherapy is a type of cancer treatment. It uses medicines to destroy cancer cells. Normally, your body forms new cells as needed, replacing old cells that die. Cancer cells keep growing without control. New cells grow even when you don't need them, and old cells don't die when they should. These extra cells can form a mass called a tumor. Chemotherapy works by killing the cancer cells, stopping them from spreading, or slowing their growth. Chemotherapy is used to: Treat cancer by curing the cancer, lessening the chance it will return, or stopping or...

Read the full MedlinePlus article ↗
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

🧪 Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • UNII 3K9958V90M
    A liquid solvent derived from fermentation or chemical synthesis. In medicines, alcohol dissolves active ingredients, helps preserve the product, and improves how the body absorbs certain drugs.
  • UNII N762921K75
    A colorless, odorless gas that makes up most of the air we breathe. In medicines, it's used as a packaging gas or propellant to protect products from oxidation and maintain freshness.
  • UNII 6D4M1DAL6O
    Polyoxyl 35 castor oil is a synthetic compound made by chemically treating castor oil. It works as a solubilizer and emulsifier to help dissolve and evenly mix oily and water-based ingredients in medicines.

3 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMedingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

💲 Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer mLPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
Medicare Part B allowsASP · J9357 $1,247.047 / J9357 unit
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

🧾 Billing & reimbursement

FDA NDC (as labeled)67979-001-01
11-digit billing NDC67979-0001-01
Format5-3-2 as registered → padded to 5-4-2 for billing (zero added to the product segment)
HCPCS J-codeJ9357
DescriptorINJECTION, VALRUBICIN, INTRAVESICAL, 200 MG
Billing units / pkg0.2 units
Crosswalk sourcePDAC NDC-HCPCS crosswalk (DME MAC / DMEPOS)
Where does this data come from?
The HCPCS J-code crosswalk comes from the CMS ASP NDC-HCPCS crosswalk and the DMEPDAC (DME MAC) NDC-HCPCS crosswalk — free public CMS data. Billing units are derived from the code’s descriptor and the package amount.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Valrubicin Intravesical Solution 40 mg/mL 24201-0101-04 Hikma 4 vials AO FDA listed
Valstar 40 mg/mLthis 67979-0001-01 Endo 4 vials AO FDA listed
About this product: this is the brand-name version. Some generic versions are approved by the FDA, but we could not confirm current pharmacy availability from our pricing/market data.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
1998
On the market since
Oct 1998
📍
2026
Currently FDA-listed
28 years listed
🔒
·
Generic approved (availability unconfirmed)
see note
🔒Generic approved by FDA, but pharmacy availability is not confirmed

The FDA lists approved generic versions of this medicine, but that does not always mean a pharmacy can get one today. Patent rules, launch agreements, supply and pricing can affect when generics actually arrive.

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
67979-0001-01 You're viewing this 4 VIAL in 1 CARTON (67979-001-01) / 5 mL in 1 VIAL 1998-10-01 Active

🧭 About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) ✓ Available
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk ✓ Available
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The FDA registers it as 67979-001-01, which is what is printed on the packaging and shown on DailyMed. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero: 67979-0001-01, written without dashes as 67979000101. The Identity section at the top of this page lists every form of this code.
What do the three segments of this NDC mean?
In 67979-0001-01, the first segment (67979) is the labeler code FDA assigned to Endo USA, Inc.; the middle segment (0001) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (01) identifies this exact package size and type. Together they name one specific package of one specific product.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Endo USA, Inc.. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Endo USA, Inc. is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
Does this product have a billing J-code?
Yes — this NDC cross-references HCPCS code J9357 for medical-claim billing (typically used when a product is administered in a clinical setting rather than dispensed at a retail pharmacy). See the Billing section on this page.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage 75 words

1 INDICATIONS AND USAGE 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.

( 1 )

⏱️ Dosage and Administration ~2 min read

2 DOSAGE AND ADMINISTRATION 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 )

2.1Recommended 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 )].

2.2Preparation, 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. If this happens, the vial should be warmed in the hand until the solution is clear.

If particulate matter is still seen, do not administer VALSTAR. For each instillation, slowly allow four 5 mL vials (200 mg valrubicin/5 mL vial) to warm to room temperature, but do not heat. Withdraw 20 mL of VALSTAR from the four vials and dilute with 55 mL of 0.9% Sodium Chloride Injection, USP to provide 75 mL of a diluted VALSTAR solution.

VALSTAR diluted in 0.9% Sodium Chloride Injection, USP for administration is stable for 12 hours at temperatures up to 25°C (77°F). Since compatibility data are not available, do not mix VALSTAR with other drugs. Insert a urethral catheter into the patient's bladder under aseptic conditions, drain the bladder, and instill the diluted 75 mL VALSTAR solution slowly via gravity flow over a period of several minutes.

Withdraw the catheter and retain VALSTAR in the bladder for two hours before voiding. At the end of two hours, all patients should void. Some patients may be unable to retain the drug for the full two hours.

Instruct patients to maintain adequate hydration following VALSTAR treatment [see Patient Counseling Information ( 17 )] .

💊 Dosage Forms and Strengths 30 words

3 DOSAGE FORMS AND STRENGTHS 200 mg/5 mL sterile, clear red, solution in single-use vials for intravesical instillation upon dilution. Injection: 200 mg/5 mL in single-use vials ( 3 )

Contraindications 85 words

4 CONTRAINDICATIONS 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. ( 4 ) Patients with a small bladder capacity unable to tolerate a 75 mL instillation.

( 4 )

⚠️ Warnings and Cautions ~2 min read

5 WARNINGS AND PRECAUTIONS 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 )

5.1Risk 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.

5.2Risk 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 )] . In case of bladder perforation, delay the administration of VALSTAR until bladder integrity has been restored. One patient with a perforated bladder who received 800 mg of VALSTAR intravesically developed severe leukopenia and neutropenia approximately two weeks after drug administration [see Clinical Pharmacology ( 12.3 )] .

5.3Risk in Patients Undergoing Transurethral Resection of the Bladder (TURB) To avoid systemic exposure to VALSTAR 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.

5.4Risk in Patients with Irritable Bladder Symptoms Use VALSTAR 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.

5.5Embryo-Fetal Toxicity Based on findings in animal studies and its mechanism of action, VALSTAR can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 and 12.3 )] . 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 VALSTAR and for 6 months following the final dose [see Use in Specific Populations ( 8.1 and 8.3 )] .

🤒 Adverse Reactions ~2 min read

6 ADVERSE REACTIONS 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 .

6.1Clinical 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.

TABLE 1 displays the frequency of the local adverse reactions at baseline and during treatment among 179 patients who received 800 mg doses of VALSTAR in a multiple-cycle treatment regimen. TABLE 1 Local Adverse Reactions Before and During Treatment with VALSTAR (N=179) Adverse Reaction Before Treatment During 6-week Course of Treatment ANY LOCAL BLADDER SYMPTOM 45% 88% Urinary Frequency 30% 61% Dysuria 11% 56% Urinary Urgency 27% 57% Bladder Spasm 3% 31% Hematuria 11% 29% Bladder Pain 6% 28% Urinary Incontinence 7% 22% Cystitis 4% 15% Nocturia 2% 7% Local Burning Symptoms – Procedure Related 0% 5% Urethral Pain 0% 3% Pelvic Pain 1% 1% Hematuria (Gross) 0% 1% TABLE 2 displays the adverse reactions other than local bladder symptoms that occurred in 1% or more of the 230 patients who received at least one dose of VALSTAR in a clinical trial.

TABLE 2 Systemic Adverse Reactions (≥ 1%) Following Intravesical Administration of VALSTAR (N=230) Body System Preferred Term Body as a Whole Abdominal Pain 5% Asthenia 4% Headache 4% Malaise 4% Back Pain 3% Chest Pain 3% Fever 2% Cardiovascular Vasodilation 2% Digestive Nausea 5% Diarrhea 3% Vomiting 2% Flatulence 1% Hemic and Lymphatic Anemia 2% Metabolic and Nutritional Hyperglycemia 1% Peripheral Edema 1% Musculoskeletal Myalgia 1% Nervous Dizziness 3% Respiratory Pneumonia 1% Skin and Appendages Rash 3% Urogenital Urinary Tract Infection 15% Urinary Retention 4% Hematuria (miscroscopic) 3% Adverse reactions other than local reactions that occurred in less than 1% of the patients who received VALSTAR intravesically in clinical trials are listed below.

Digestive System: Tenesmus Metabolic and Nutritional: Nonprotein nitrogen increased Skin and Appendages: Pruritus Special Senses: Taste loss Urogenital System: Local skin irritation, poor urine flow, and urethritis

🔄 Drug Interactions 9 words

7 DRUG INTERACTIONS No drug interaction studies were conducted.

👥 Use in Specific Populations ~2 min read

8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 )

8.1Pregnancy 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. This dose also caused an increase in fetal resorptions and a decrease in viable fetuses.

8.2Lactation Risk Summary There are no data on the presence of valrubicin or its metabolites in human milk, the effects of valrubicin on the breast-fed infant, or its effects on milk production. Because of the potential for serious adverse reactions in breast-fed infants from valrubicin, advise a lactating female not to breastfeed during treatment with VALSTAR and for 2 weeks after the final dose.

8.3Females and Males of Reproductive Potential Contraception Females VALSTAR can cause fetal harm when administered to a pregnant female. Advise females of reproductive potential to use effective contraception during treatment with VALSTAR and for 6 months after the final dose [see Use in Specific Populations ( 8.1 )] . Males Based on genotoxicity findings, advise men with female partners of reproductive potential to use effective contraception during treatment with VALSTAR and for 3 months following the final dose [see Non Clinical Toxicology ( 13.1 )] Infertility Males Studies of the effects of VALSTAR on human male or female fertility have not been done.

Based on findings in animal studies, VALSTAR may impair fertility in males of reproductive potential [see Nonclinical Toxicology ( 13.1 )] .

8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established.

8.5Geriatric Use Because carcinoma in situ of the bladder generally occurs in older individuals, 85% of the patients enrolled in the clinical studies of VALSTAR were more than 60 years of age (49% of the patients were more than 70 years of age). In the primary efficacy studies, the mean age of the population was 69.5 years. There are no specific precautions regarding use of VALSTAR in geriatric patients who are otherwise in good health.

🤰 Pregnancy 219 words

8.1Pregnancy 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. This dose also caused an increase in fetal resorptions and a decrease in viable fetuses.

🧒 Pediatric Use 13 words

8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established.

🧓 Geriatric Use 76 words

8.5Geriatric Use Because carcinoma in situ of the bladder generally occurs in older individuals, 85% of the patients enrolled in the clinical studies of VALSTAR were more than 60 years of age (49% of the patients were more than 70 years of age). In the primary efficacy studies, the mean age of the population was 69.5 years. There are no specific precautions regarding use of VALSTAR in geriatric patients who are otherwise in good health.

🆘 Overdosage 110 words

10 OVERDOSAGE 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.

🧬 Clinical Pharmacology ~2 min read

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action 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 . Although valrubicin does not bind strongly to DNA, valrubicin metabolites interfere with the normal DNA breaking-resealing action of DNA topoisomerase II.

12.3Pharmacokinetics 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 . During the two-hour dose-retention period, the metabolism of VALSTAR to its major metabolites N-trifluoroacetyladriamycin and N-trifluoroacetyladriamycinol in bladder tissue was negligible.

After retention, the drug was almost completely excreted by voiding the instillate. Mean percent recovery of VALSTAR, N-trifluoroacetyladriamycin, and total anthracyclines in 14 urine samples from six patients was 98.6%, 0.4%, and 99.0% of the total administered drug, respectively. During the two-hour dose-retention period, only nanogram quantities of VALSTAR were absorbed into the plasma.

N-trifluoroacetyladriamycin and N-trifluoroacetyladriamycinol were measured in blood. Total systemic exposure to anthracyclines during and after intravesical administration of VALSTAR is dependent upon the condition of the bladder wall. The mean AUC 0-6 hours (total anthracyclines exposure) for an intravesical dose of 900 mg of VALSTAR administered 2 weeks after transurethral resection of bladder tumors (n=6) was 78 nmol/L•hr.

In patients receiving 800 mg of VALSTAR 5 to 51 minutes after typical (n=8) and extensive (n=5) TURB tumors, the mean AUC 0-6 hours values for total anthracyclines were 409 and 788 nmol/L•hr, respectively. The AUC 0-6 hours total exposure to anthracyclines was 18,382 nmol/L•hr in one patient who experienced a perforated bladder following a transurethral resection that occurred 5 minutes before administration of an intravesical dose of 800 mg of VALSTAR. Administration of a comparable intravenous dose of VALSTAR (600 mg/m 2 ; n=2) as a 24-hour infusion resulted in an AUC 0-6 hours for total anthracyclines of 11,975 nmol/L•hr.

These results are shown in FIGURE 2. FIGURE 2. Comparison of Mean AUC 0-6 hours in VALSTAR Clinical Studies (N=number of patients) FIGURE 2.

Comparison of Mean AUC0-6 hours in VALSTAR Clinical Studies (N=number of patients)

🧬 Mechanism of Action 67 words

12.1Mechanism of Action 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 . Although valrubicin does not bind strongly to DNA, valrubicin metabolites interfere with the normal DNA breaking-resealing action of DNA topoisomerase II.

📦 How Supplied / Storage and Handling 61 words

16 HOW SUPPLIED/STORAGE AND HANDLING VALSTAR is a sterile, clear red solution in polyoxyl castor oil/dehydrated alcohol, USP, containing 40 mg valrubicin per mL. VALSTAR is available in single-use, clear glass vials, individually packaged in the following sizes: NDC 67979-001-01 Carton of four 200 mg/5 mL single-use vials Store vials under refrigeration at 2°-8°C (36°-46°F) in the carton. DO NOT FREEZE.

📋 Description 148 words

11 DESCRIPTION VALSTAR contains valrubicin (N-trifluoroacetyladriamycin-14-valerate), which is a semisynthetic analog of the anthracycline doxorubicin as a cytotoxic agent. The chemical name of valrubicin is (2 S - cis )-2-[1,2,3,4,6,11-hexahydro-2,5,12-trihydroxy-7-methoxy-6,11-dioxo-4-[[2,3,6-trideoxy-3-[(trifluoroacetyl)amino]-α-L- lyxo -hexopyranosyl]oxyl]-2-naphthacenyl]-2-oxoethylpentanoate. Valrubicin is an orange or orange-red powder that is highly lipophilic, soluble in methylene chloride, ethanol, methanol and acetone, and relatively insoluble in water.

Its chemical formula is C 34 H 36 F 3 NO 13 and its molecular weight is 723.65. The chemical structure is shown in FIGURE 1. VALSTAR is intended for intravesical administration in the urinary bladder.

It is supplied as a nonaqueous solution that should be diluted before intravesical administration. Each vial of VALSTAR contains 200 mg valrubicin at a concentration of 40 mg/mL in 5 mL of 50% polyoxyl castor oil/50% dehydrated alcohol, USP without preservatives or other additives. The solution is sterile and nonpyrogenic.

FIGURE 1. Chemical Structure of Valrubicin

💬 Information for Patients ~1 min read

17 PATIENT COUNSELING INFORMATION Risk of Metastatic Bladder Cancer with Delayed Cystectomy Inform patients that VALSTAR has been shown to induce complete responses in only about 1 in 5 patients, and that delaying cystectomy could lead to development of metastatic bladder cancer, which is lethal. Discuss the relative risk of cystectomy versus the risk of metastatic bladder cancer [see Clinical Trials ( 14 )] and that the risk increases the longer cystectomy is delayed in the presence of persisting CIS. Local Adverse Reactions Before and During Treatment Inform patients that the major acute toxicities from VALSTAR are related to irritable bladder symptoms that may occur during instillation and retention of VALSTAR and for a limited period following voiding [see Adverse Reactions ( 6.1 )] .

Inform patients that for the first 24 hours following administration, red-tinged urine is typical. Advise patients to report prolonged irritable bladder symptoms or prolonged passage of red-colored urine immediately to their physician. Instruct patients to maintain adequate hydration following VALSTAR treatment.

Embryo-Fetal Toxicity Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment with VALSTAR and for 6 months after the last dose. Advise females to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions ( 5.5 ), Use in Specific Populations ( 8.1 and 8.3 )] . Advise male patients with female partners of reproductive potential to use effective contraception during treatment with VALSTAR and for 3 months after the last dose [see Use in Specific Populations ( 8.3 )] .

Lactation Advise females not to breastfeed during treatment with VALSTAR and for 2 weeks after the last dose [see Use in Specific Populations ( 8.2 )] . Healthcare professionals can telephone Endo (1-800-462-3636) for information on this product. Manufactured for: Endo USA Malvern, PA 19355 Manufactured by: BSP Pharmaceuticals S.p.A Latina Scalo, Italy © 2024 Endo, Inc. or one of its affiliates.

Revised: 07/2024

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗
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