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Valrubicin Intravesical Solution 40 mg/mL Solution, Concentrate — NDC 24201-101-04 (Billing 24201-0101-04)

by Hikma Pharmaceuticals USA Inc. · 4 VIAL in 1 CARTON / 5 mL in 1 VIAL

This is a package of Valrubicin Intravesical Solution 40 mg/mL Solution, Concentrate from Hikma Pharmaceuticals USA Inc., marketed since Apr 2019 and currently FDA-listed. It is this product's only package size.

NDC 24201-0101-04
🏷️ FDA NDC (as labeled) 24201-101-04 billing pads the product segment with a zero
Rx only Generic On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

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Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 24201-101-04
Product NDC 24201-101
11-digit billing NDC 24201010104
NCPDP billing unit ML — per mL (volume)
RxCUI 313567
UNII 2C6NUM6878
Application # ANDA206430
SPL Set ID 8739ae02-e4c5-0fa2-e053-2a91aa0a1b74
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2019-04-23
Route INTRAVESICAL
Dosage form SOLUTION, CONCENTRATE
Substance VALRUBICIN
TE code (Orange Book) AO · RLD · RS

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GPI-14 21200080002020
GPI class Valrubicin
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 VALRUBICIN 200 MG/5 ML VIAL
FDB brand name Valrubicin
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 041003
  • GCN: 94175
  • GPI-14 (Medi-Span): 21200080002020
  • HICL (First Databank): 018864
  • AHFS class code: 10:00.00.00
  • RxCUI (RxNorm): 313567
Why two NDCs? The FDA registers this code as 24201-101-04 — 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 → 24201-0101-04. 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.

Clinical

Label name VALRUBICIN 200 MG/5 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 ↗
📗 Our plain-language guide HelloPharmacist
  • It treats a type of early bladder cancer called carcinoma in situ that didn’t respond to BCG treatment. It’s used when removing the bladder would be too risky for you.
  • A healthcare professional places it into your bladder through a catheter, about once a week for six weeks. It stays in for two hours, then you empty your bladder. Drink plenty of f...
  • Bladder symptoms are very common. These include frequent or urgent urination, burning, spasms, and sometimes blood in the urine. They usually go away within 1 to 7 days after each...
  • Call for fever, signs of a urinary tract infection, severe pain, or heavy bleeding. Also call for any allergic reaction. Tell your team if you felt the bladder was injured or the t...
📖 Read our full Valrubicin Intravesical guide →

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
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.

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)24201-101-04
11-digit billing NDC24201-0101-04
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
How the units are derivedThis package is 5 ML; the HCPCS unit is 200 MG, so one package = 0.2 billing units.
Medicare Part B spend (2026 (Q1))$159,015 · 28 claims · $5,679.10 per claim (all NDCs under J9357)
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.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
24201-0101-04 You're viewing this Main listing 4 VIAL in 1 CARTON / 5 mL in 1 VIAL 2019-04-23 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Valrubicin Intravesical Solution 40 mg/mLthis 24201-0101-04 Hikma 4 vials — AO FDA listed —
Valstar 40 mg/mL 67979-0001-01 Endo 4 vials — AO FDA listed —
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
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

🏛️
2019
On the market since
Apr 2019
📍
2026
Currently FDA-listed
7 years listed
🔓
·
Generic on the market
this product is a generic
✅This is a generic drug

This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.

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.

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.

  • 0.5 mL / 1 mL 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.
  • 0.5 mL / 1 mL 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 DailyMed — ingredient 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.

Manufacturer & labeler

LabelerHikma Pharmaceuticals USA Inc.
Application holderHIKMA PHARMACEUTICALS USA INC
FDA applicationANDA206430 (ANDA)
Labeler code24201
First marketedApr 2019
Product typeHuman Prescription Drug
Portfolio726 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.

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 ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 🧬 Pharmacokinetics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📚 References 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 80 words ▾

1 INDICATIONS AND USAGE Valrubicin intravesical solution 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. • Valrubicin intravesical solution 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 ) • Valrubicin intravesical solution 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 valrubicin intravesical solution slowly to room temperature, but do not heat. ( 2.1 ) • Use caution when handling and preparing the solution of valrubicin intravesical solution. ( 2.2 )

2.1Recommended Dosing For Intravesical Use Only. Do NOT administer by intravenous or intramuscular routes. Valrubicin intravesical solution 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 valrubicin intravesical solution 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. Valrubicin intravesical solution 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.

Valrubicin intravesical solution 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. Valrubicin intravesical solution is a 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 valrubicin intravesical solution. 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 valrubicin intravesical solution from the four vials and dilute with 55 mL of 0.9% Sodium Chloride Injection, USP to provide 75 mL of a diluted valrubicin intravesical solution.

Valrubicin intravesical solution 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 valrubicin intravesical solution with other drugs. Insert a urethral catheter into the patient's bladder under aseptic conditions, drain the bladder, and instill the diluted 75 mL valrubicin intravesical solution slowly via gravity flow over a period of several minutes.

Withdraw the catheter and retain valrubicin intravesical solution 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 valrubicin intravesical solution treatment [see Patient Counseling Information ( 17 )] .

💊 Dosage Forms and Strengths 32 words ▾

3 DOSAGE FORMS AND STRENGTHS Injection: 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 94 words ▾

4 CONTRAINDICATIONS Valrubicin intravesical solution 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 valrubicin intravesical solution 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 valrubicin intravesical solution.

( 5.3 ) • Use with caution in patients with severe irritable bladder symptoms. ( 5.4 ) • Embryo-Fetal Toxicity: Valrubicin intravesical solution 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 valrubicin intravesical solution 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 valrubicin intravesical solution 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 valrubicin intravesical solution until bladder integrity has been restored. One patient with a perforated bladder who received 800 mg of valrubicin intravesical solution 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 valrubicin intravesical solution 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 valrubicin intravesical solution 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, valrubicin intravesical solution 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 valrubicin intravesical solution 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 valrubicin intravesical solution 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 Hikma at [email protected] or call 1-877-845-0689 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 valrubicin intravesical solution 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 valrubicin intravesical solution in clinical studies experienced local adverse reactions. The local adverse reactions associated with valrubicin intravesical solution 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 valrubicin intravesical solution 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 valrubicin intravesical solution in a multiple-cycle treatment regimen. TABLE 1 Local Adverse Reactions Before and During Treatment with Valrubicin Intravesical Solution (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 valrubicin intravesical solution in a clinical trial.

TABLE 2 Systemic Adverse Reactions (≥ 1%) Following Intravesical Administration of Valrubicin Intravesical Solution (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 valrubicin intravesical solution 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, valrubicin intravesical solution 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 valrubicin intravesical solution and for 2 weeks after the final dose.

8.3Females and Males of Reproductive Potential Contraception Females Valrubicin intravesical solution can cause fetal harm when administered to a pregnant female. Advise females of reproductive potential to use effective contraception during treatment with valrubicin intravesical solution 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 valrubicin intravesical solution and for 3 months following the final dose [see Non Clinical Toxicology ( 13.1 )] Infertility Males Studies of the effects of valrubicin intravesical solution on human male or female fertility have not been done.

Based on findings in animal studies, valrubicin intravesical solution 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 valrubicin intravesical solution 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 valrubicin intravesical solution in geriatric patients who are otherwise in good health.

🤰 Pregnancy ~1 min read ▾

8.1Pregnancy Risk Summary Based on findings in animal studies and its mechanism of action, valrubicin intravesical solution 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 80 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 valrubicin intravesical solution 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 valrubicin intravesical solution in geriatric patients who are otherwise in good health.

🆘 Overdosage 116 words ▾

10 OVERDOSAGE There is no known antidote for overdoses of valrubicin intravesical solution. The primary anticipated complications of overdosage associated with intravesical administration would be consistent with irritable bladder symptoms. Myelosuppression is possible if valrubicin intravesical solution 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 valrubicin intravesical solution 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 valrubicin intravesical solution was administered intravesically to patients with carcinoma in situ , valrubicin intravesical solution 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 valrubicin intravesical solution 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 valrubicin intravesical solution, 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 valrubicin intravesical solution 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 valrubicin intravesical solution 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 valrubicin intravesical solution administered 2 weeks after transurethral resection of bladder tumors (n=6) was 78 nmol/L•hr.

In patients receiving 800 mg of valrubicin intravesical solution 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 valrubicin intravesical solution. Administration of a comparable intravenous dose of valrubicin intravesical solution (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 Valrubicin Intravesical Solution Clinical Studies (N=number of patients) figure-2

🧬 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 77 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Valrubicin Intravesical Solution, USP is a sterile, clear red solution in polyoxyl castor oil/dehydrated alcohol, USP, containing 40 mg valrubicin per mL. Valrubicin Intravesical Solution, USP is available in single-use, clear glass vials, individually packaged in the following sizes: NDC 24201-101-04 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.

The container closure is not made with natural rubber latex.

📋 Description 159 words ▾

11 DESCRIPTION Valrubicin Intravesical Solution, USP 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. FIGURE 1.

Chemical Structure of Valrubicin Valrubicin Intravesical Solution, USP 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 Valrubicin Intravesical Solution, USP contains 200 mg valrubicin at a concentration of 40 mg/mL in 5 mL of 50% polyoxyl castor oil/50% v/v dehydrated alcohol, USP without preservatives or other additives.

The solution is sterile and nonpyrogenic. structure

💬 Information for Patients ~2 min read ▾

17 PATIENT COUNSELING INFORMATION Risk of Metastatic Bladder Cancer with Delayed Cystectomy • Inform patients that valrubicin intravesical solution 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 valrubicin intravesical solution are related to irritable bladder symptoms that may occur during instillation and retention of valrubicin intravesical solution 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 valrubicin intravesical solution treatment.

Embryo-Fetal Toxicity • Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment with valrubicin intravesical solution 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 valrubicin intravesical solution and for 3 months after the last dose [see Use in Specific Populations ( 8.3 )] .

Lactation • Advise females not to breastfeed during treatment with valrubicin intravesical solution and for 2 weeks after the last dose [see Use in Specific Populations ( 8.2 )] . Healthcare professionals can email Hikma at [email protected] or call 1-877-845-0689 for information on this product. Manufactured by: The University of Iowa Pharmaceuticals Iowa City, Iowa 52242 Manufactured for: Hikma Berkeley Heights, NJ 07922 Rev.

June 2022

🧬 Pharmacokinetics ~1 min read ▾

12.3Pharmacokinetics When 800 mg valrubicin intravesical solution was administered intravesically to patients with carcinoma in situ , valrubicin intravesical solution 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 valrubicin intravesical solution 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 valrubicin intravesical solution, 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 valrubicin intravesical solution 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 valrubicin intravesical solution 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 valrubicin intravesical solution administered 2 weeks after transurethral resection of bladder tumors (n=6) was 78 nmol/L•hr.

In patients receiving 800 mg of valrubicin intravesical solution 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 valrubicin intravesical solution. Administration of a comparable intravenous dose of valrubicin intravesical solution (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 Valrubicin Intravesical Solution Clinical Studies (N=number of patients) figure-2

🔬 Clinical Studies ~2 min read ▾

14 CLINICAL STUDIES Valrubicin intravesical solution was administered intravesically to a total of 230 patients with transitional cell carcinoma of the bladder, including 205 patients who received multiple weekly doses ranging from 200 to 900 mg. One hundred seventy-nine of the 205 patients received the approved dose and schedule of 800 mg weekly for multiple weeks. Patients receiving valrubicin intravesical solution for refractory carcinoma in situ were monitored for disease recurrence or progression with cystoscopy, biopsy, and urine cytology every 3 months.

In the 90 study patients with BCG-refractory carcinoma in situ (CIS), 70% had received at least 2 courses of BCG and 30% had received one course of BCG and at least one additional course of treatment with another agent(s) - e.g., mitomycin, thiotepa, or interferon. Valrubicin intravesical solution was administered beginning at least two weeks after transurethral resection and/or fulguration. After intravesical administration of valrubicin intravesical solution, 16 patients (18%) had a complete response documented by bladder biopsies and cytology at 6 months following initiation of therapy.

Median duration of response from start of treatment varied according to the method of analysis (13.5 months if measured to last bladder biopsy without tumor and 21 months if measured until time of documented recurrence). A retrospective analysis in the 16 patients with complete response to valrubicin intravesical solution demonstrated that time to recurrence of their disease after treatment with valrubicin intravesical solution was longer than time to recurrence after previous courses of intravesical therapy. Of the 90 patients with BCG-refractory CIS, 11% (10 patients) developed metastatic or deeply-invasive bladder cancer during follow-up; four of these patients, none who underwent cystectomy, died with metastatic bladder cancer and six were found to have developed stage progression to deeply-invasive disease (T3), with lymph node involvement in one patient, at the time of cystectomy.

It is uncertain to what extent the development of advanced bladder cancer in these patients was due to the delay in cystectomy required to receive treatment with valrubicin intravesical solution (3 months was the time of follow-up to determine response), as cystectomy was often delayed or was never performed despite failure of treatment with valrubicin intravesical solution. In the 10 patients documented to have invasive bladder cancer or metastatic disease, the delay between the time of treatment failure (when cystectomy should have been performed) and cystectomy or documentation of advanced bladder cancer was a median of 17.5 months.

🧪 Nonclinical Toxicology 127 words ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility The carcinogenic potential of valrubicin has not been evaluated. In vitro, valrubicin was mutagenic in the bacterial reverse mutation (Ames) assay and clastogenic in the chromosomal aberration assay in Chinese Hamster Ovary (CHO) cells. Studies in animals evaluating the effects of valrubicin on male or female fertility have not been conducted.

Based on effects on male reproductive organs in general toxicology studies in dogs with intravesical instillation, valrubicin may impair fertility in male patients. When instilled into the bladder of male dogs weekly for 6 weeks, valrubicin caused mild to moderate atrophy of the prostate with inflammation, diffuse decrease in acinar size, epithelial changes. It also caused testicular degeneration, marked germ cell depletion, spermatid giant cells and karyomegaly.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 124 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility The carcinogenic potential of valrubicin has not been evaluated. In vitro, valrubicin was mutagenic in the bacterial reverse mutation (Ames) assay and clastogenic in the chromosomal aberration assay in Chinese Hamster Ovary (CHO) cells. Studies in animals evaluating the effects of valrubicin on male or female fertility have not been conducted.

Based on effects on male reproductive organs in general toxicology studies in dogs with intravesical instillation, valrubicin may impair fertility in male patients. When instilled into the bladder of male dogs weekly for 6 weeks, valrubicin caused mild to moderate atrophy of the prostate with inflammation, diffuse decrease in acinar size, epithelial changes. It also caused testicular degeneration, marked germ cell depletion, spermatid giant cells and karyomegaly.

📚 References 8 words ▾

15 REFERENCES 1. OSHA Hazardous Drugs. OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html.

📄 Package Label / Principal Display Panel 9 words ▾

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL vial-label

Package/Label Display Panel carton-image

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

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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 form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
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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 Hikma Pharmaceuticals USA Inc.. Listing status can change — the directory data on this page refreshes weekly.
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Hikma Pharmaceuticals 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.
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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.
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← 24201-0100-24 · Hikma 24201-0110-24 · Hikma →
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