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Topotecan Hydrochloride 4 mg/4mL Injection, Powder, Lyophilized, For Solution — NDC 63323-0762-94 package photo

Topotecan Hydrochloride 4 mg/4mL Injection, Powder, Lyophilized, For Solution

by Fresenius Kabi USA, LLC · 1 VIAL in 1 BOX (63323-762-94) / 4 mL in 1 VIAL
NDC 63323-0762-94
🏷️ FDA NDC (as labeled) 63323-762-94 billing pads the product segment with a zero
This package
Contains4 mL in 1 vial Pack sizes2 compare ↓
Also comes in: 4 mL 63323-0762-10
Rx only Generic Discontinued Non-controlled ⚠ Discontinued by firm
🗂️ 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 →

This page is curated, coded, and maintained by

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

⚠️
Excluded from the active FDA NDC Directory. The labeler reported this product as discontinued, so it is excluded from the active NDC Directory. The listing was last certified through Mar 2016. A label may still appear on DailyMed, but the NDC is no longer in the current FDA NDC Directory. Search the FDA NDC Directory ↗

🆔 Identity & classification

FDA NDC (as labeled) 63323-762-94
Product NDC 63323-762
11-digit billing NDC 63323076294
NCPDP billing unit EA — each (per item)
RxCUI 1799416
UNII 956S425ZCY
UPC 0363323762100
Application # ANDA091089
SPL Set ID b6019088-cd94-43b4-b5ce-ba20b6b8021e
Established class (EPC) Topoisomerase Inhibitor
Mechanism of action Topoisomerase Inhibitors
DEA schedule Non-controlled
Marketing category ANDA
Marketing status Discontinued
FDA listing status Discontinued by firm (certified through Mar 2016)
Marketing start 2010-11-30
Route INTRAVENOUS
Dosage form INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION
Substance TOPOTECAN HYDROCHLORIDE
GPI-14 21550080102120
GPI class Topotecan HCl
GCN Seq No 026807
GCN 22661
HICL code 011381
Ingredient (HICL) Topotecan Hcl
HIC1 code V
Therapeutic class — broad (HIC1) Neoplasms
HIC2 code V3
Therapeutic class — intermediate (HIC2) Antineoplastic Drugs (Continued 1)
HIC3 code V3E
Therapeutic class — specific (HIC3) Antineoplastic - Topoisomerase I Inhibitors
AHFS code 10:00.00.00
AHFS class Antineoplastic Agents
FDB label name TOPOTECAN HCL 4 MG VIAL
FDB brand name Topotecan Hcl
Legend status F — Federal legend — prescription drug or device
TE code (Orange Book) AP · RLD · RS
Why two NDCs? The FDA registers this code as 63323-762-94 — 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 → 63323-0762-94. 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 Topoisomerase Inhibitor class.

Pharmacologic class Topoisomerase Inhibitor
Drug family (ATC) Topoisomerase 1 (TOP1) inhibitors
How it works Topoisomerase Inhibitors
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

LabelerFresenius Kabi USA, LLC
Application holderFRESENIUS KABI USA LLC
FDA applicationANDA091089 (ANDA)
Labeler code63323
First marketedNov 2010
Product typeHuman Prescription Drug
Portfolio554 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 TOPOTECAN HCL 4 MG VIAL Ingredient Topotecan Hcl
📗 Our plain-language guide HelloPharmacist
  • Topotecan is a chemotherapy used for three types of cancer: small cell lung cancer (SCLC), metastatic ovarian cancer, and advanced cervical cancer. The IV form covers all three, de...
  • What exactly is topotecan used to treat?
  • The most common effects are drops in blood counts — low white blood cells, red blood cells, and platelets — along with nausea, vomiting, hair loss, fatigue, and bowel changes. Most...
  • What side effects should I expect, and which ones should make me call someone right away?
📖 Read our full Topotecan 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.

🧪 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.

Loading inactive ingredients from the official FDA label in the background. No external source is being called by this page request.
Where does this data come from?
Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

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.
ℹ️
No price is published for this exact package yet. CMS surveys NADAC per package size, so a different pack of the same drug often has one.
Try another pack size: 4 mL
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.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Hycamtin 4 mg/4mL 00078-0674-61 Novartis 1 vial — AP FDA listed —
topotecan hydrochloride 4 mg/4mL 16729-0151-31 Accord 1 vial — AP FDA listed —
Topotecan hydrochloride 4 mg/4mL 45963-0615-56 Actavis 1 vial — AP FDA listed —
Topotecan Hydrochloride 4 mg/4mLthis 63323-0762-94 Fresenius 1 vial — AP Discontinued —
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

🏛️
2010
On the market since
Nov 2010
📍
2026
Currently FDA-listed
16 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.

💊 Medicaid utilization by pack size

Medicaid (SDUD) totals over the four most recent reported quarters for every package size of this drug — handy when a specific package (e.g. a starter/titration pack) carries little or no Medicaid volume on its own.
1 vial63323-0762-10 218 Rx · $11,732
1 vial this page63323-0762-94 No Medicaid data
Drug total (last 4 qtrs): 218 Rx · 150 units · $11,732 gross reimbursed
Tap a pack size to open its page. Source: CMS State Drug Utilization Data, last 4 quarters.

🔬 Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for Topotecan hydrochloride — the ingredient across all brands.

Top reported reactions

Death384
Febrile Neutropenia257
Anaemia235
White Blood Cell Count Decreased204
Pyrexia202
Nausea188
Platelet Count Decreased184

Age at onset

Neonate1
Infant6
Child32
Adolescent7
Adult46
Elderly11

Reporter sex

2,410 reports
Male · 41%
Female · 57%
Unknown · 1%

Serious outcomes

Hospitalization921
Death720
Life-threatening151
Disabling58
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 160 0
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
63323-0762-94 You're viewing this 1 VIAL in 1 BOX (63323-762-94) / 4 mL in 1 VIAL 2010-11-30 Discontinued by firm
63323-0762-10 1 VIAL in 1 BOX (63323-762-10) / 4 mL in 1 VIAL 2010-11-30 Active

This pack shows little to no recent Medicaid volume — a different pack size carries most fills. See all packs ↓

Pack size FAQ

What quantity is in NDC 63323-0762-94?
NDC 63323-0762-94 is listed by the FDA — 1 vial in 1 box / 4 ml in 1 vial.
What NDC number is used to bill for this package of Topotecan Hydrochloride 4 mg/4mL Injection, Powder, Lyophilized, For Solution?
Bill NDC 63323-0762-94 — the 11-digit billing format is 63323076294. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

🧭 About this NDC listing & data coverage

Finished prescription product No longer marketed (per FDA listing data)
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) — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is 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 — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
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.
What does the discontinued status mean for this NDC?
The labeler reported a marketing end date (or the listing was delisted), so this specific package is no longer actively marketed. Remaining stock may still be dispensed for a time, and the NDC stays valid for historical records and claims — but data feeds (pricing, labeling) typically stop updating for it. Other package sizes or other manufacturers' versions of the same medication may still be marketed — see the equivalents section where available.
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 63323-762-94, 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: 63323-0762-94, written without dashes as 63323076294. 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 63323-0762-94, the first segment (63323) is the labeler code FDA assigned to Fresenius Kabi USA, LLC; the middle segment (0762) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (94) identifies this exact package size and type. Together they name one specific package of one specific product.
Does this product come in other package sizes?
Yes — the FDA directory lists 1 other package presentation of this same product, including 1 vial (63323-0762-10). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
Fresenius Kabi USA, LLC 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.
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.
🚨 Boxed Warning 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📦 Storage and Handling 📋 Description 💬 Information for Patients
🚨 Boxed Warning 101 words ▾

WARNING: MYELOSUPPRESSION Topotecan hydrochloride can cause severe myelosuppression. Administer first cycle only to patients with baseline neutrophil counts of greater than or equal to 1,500/mm 3 and platelet counts greater than or equal to 100,000/mm 3 . Monitor blood cell counts [see Warnings and Precautions ( 5.1 )].

WARNING: MYELOSUPPRESSION See full prescribing information for complete boxed warning. Topotecan hydrochloride can cause severe myelosuppression. Administer first cycle only to patients with baseline neutrophil counts greater than or equal to 1,500/mm 3 and platelet counts greater than or equal to 100,000/mm 3 .

Monitor blood cell counts. ( 2.4 , 5.1 )

🎯 Indications and Usage 194 words ▾

1 INDICATIONS AND USAGE Topotecan hydrochloride for injection is a topoisomerase inhibitor indicated for treatment of: • Patients with metastatic ovarian cancer after disease progression on or after initial or subsequent chemotherapy, as a single agent. ( 1.1 ) • Patients with small cell lung cancer (SCLC) platinum-sensitive disease who progressed at least 60 days after initiation of first-line chemotherapy, as a single agent. ( 1.2 ) • Patients with Stage IV-B, recurrent, or persistent cervical cancer which is not amenable to curative treatment, in combination with cisplatin.

( 1.3 )

1.1Ovarian Cancer Topotecan hydrochloride for injection, as a single agent, is indicated for the treatment of patients with metastatic ovarian cancer after disease progression on or after initial or subsequent chemotherapy.

1.2Small Cell Lung Cancer Topotecan hydrochloride for injection, as a single agent, is indicated for the treatment of patients with small cell lung cancer (SCLC) with platinum-sensitive disease who progressed at least 60 days after initiation of first-line chemotherapy.

1.3Cervical Cancer Topotecan hydrochloride for injection in combination with cisplatin is indicated for the treatment of patients with Stage IV-B, recurrent, or persistent cervical cancer not amenable to curative treatment.

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION • Ovarian cancer and small cell lung cancer: 1.5 mg/m 2 by intravenous infusion over 30 minutes daily for 5 consecutive days, starting on Day 1 of a 21-day cycle. ( 2.2 , 2.3 ) • Cervical cancer: 0.75 mg/m 2 by intravenous infusion over 30 minutes on Days 1, 2, and 3 with cisplatin 50 mg/m 2 on Day 1, of a 21-day cycle. ( 2.4 ) • Renal impairment: Reduce dose if creatinine clearance (CLcr) 20 to 39 mL/min. ( 2.6 )

2.1Important Safety Information Verify dosage using body surface area. Do not exceed a single dose of 4 mg intravenously.

2.2Recommended Dosage for Ovarian Cancer The recommended dosage of topotecan hydrochloride is 1.5 mg/m 2 by intravenous infusion over 30 minutes daily for 5 consecutive days, starting on Day 1 of a 21-day cycle until disease progression or unacceptable toxicity.

2.3Recommended Dosage for Small Cell Lung Cancer (SCLC) The recommended dosage of topotecan hydrochloride is 1.5 mg/m 2 by intravenous infusion over 30 minutes daily for 5 consecutive days, starting on Day 1 of a 21-day cycle.

2.4Recommended Dosage for Cervical Cancer The recommended dosage of topotecan hydrochloride is 0.75 mg/m 2 by intravenous infusion over 30 minutes daily on Days 1, 2, and 3 in combination with cisplatin 50 mg/m 2 on Day 1, of a 21-day cycle.

2.5Dosage Modifications for Adverse Reactions Hematologic Do not administer subsequent cycles of topotecan hydrochloride for injection until neutrophils recover to greater than 1,000/mm 3 , platelets recover to greater than 100,000/mm 3 , and hemoglobin levels recover to greater than or equal to 9 g/dL (with transfusion if necessary). For topotecan hydrochloride as a single agent, reduce the dose to 1.25 mg/m 2 /day for : • neutrophil counts of less than 500/mm 3 , or administer granulocyte-colony stimulating factor (GCSF) starting no sooner than 24 hours following the last dose. • platelet counts less than 25,000/mm 3 during previous cycle.

For topotecan hydrochloride in combination with cisplatin, reduce the dose to 0.60 mg/m 2 /day (and further to 0.45 mg/m 2 if necessary) for : • febrile neutropenia (defined as neutrophil counts less than 1,000/mm 3 with temperature of greater than or equal to 38.0°C (100.4°F), or administer G-CSF starting no sooner than 24 hours following the last dose. • platelet counts less than 25,000/mm 3 during previous cycle.

2.6Dosage Modification for Renal Impairment For topotecan hydrochloride as a single agent, reduce the dose to 0.75 mg/m 2 /day for patients with creatinine clearance (CLcr) of 20 to 39 mL/min (calculated with the Cockcroft-Gault method using ideal body weight) [see Clinical Pharmacology ( 12.3 )] .

2.7Preparation and Intravenous Administration Visually inspect for particulate matter and discoloration prior to administration, whenever solution and container permit. Preparation Reconstitute each 4 mg vial of topotecan hydrochloride with 4 mL Sterile Water for Injection, USP. Dilute the appropriate volume of the reconstituted solution in either 0.9% Sodium Chloride Intravenous Infusion, USP or 5% Dextrose in Water Injection, USP.

Stability Because the vials contain no preservative, use contents immediately after reconstitution. Discard any unused portion. Store reconstituted product diluted for infusion at approximately 20°C to 25°C (68°F to 77°F) protected from light for no more than 24 hours.

Discard after 24 hours. Topotecan hydrochloride is a cytotoxic drug. Follow applicable handling and disposal procedures.

1

💊 Dosage Forms and Strengths 40 words ▾

3 DOSAGE FORMS AND STRENGTHS For injection: 4 mg (topotecan free base) lyophilized powder in a single-dose vial for reconstitution; light yellow to greenish powder. For injection: 4 mg (free base) lyophilized powder in a single-dose vial. ( 3 )

⛔ Contraindications 40 words ▾

4 CONTRAINDICATIONS Topotecan hydrochloride is contraindicated in patients who have a history of severe hypersensitivity reactions to topotecan. Reactions have included anaphylactoid reactions [see Adverse Reactions ( 6.2 )] . History of severe hypersensitivity reactions to topotecan. ( 4 )

⚠️ Warnings and Cautions ~2 min read ▾

5 WARNINGS AND PRECAUTIONS • Interstitial lung disease (ILD): Fatal cases have occurred. Permanently discontinue if ILD confirmed. ( 5.2 ) • Extravasation and tissue injury: Severe cases have occurred.

If extravasation occurs, immediately stop administration and institute recommended management procedures. ( 5.3 ) • Embryo-Fetal toxicity: Can cause fetal harm. Advise patients of potential risk to the fetus and to use effective contraception.

( 5.4 , 8.1 , 8.3 )

5.1Myelosuppression Topotecan hydrochloride can cause severe myelosuppression. Single Agent Grade 4 neutropenia occurred in 78% of 879 patients, with a median duration of 7 days and was most common during Cycle 1 (58% of patients). Grade 4 neutropenia associated with infection occurred in 13% and febrile neutropenia occurred in 5%.

Sepsis occurred in 4% of patients and was fatal in 1%. Grade 4 thrombocytopenia occurred in 27%, with a median duration of 5 days. Grade 3 or 4 anemia occurred in 37% of patients.

Combination with cisplatin Grade 4 neutropenia occurred in 48% and Grade 4 thrombocytopenia occurred in 7% of 147 patients. Grade 3 or 4 anemia occurred in 40% of patients. Topotecan can cause fatal typhlitis (neutropenic enterocolitis).

Consider the possibility of typhlitis in patients presenting with fever, neutropenia, and abdominal pain. Administer the first cycle of topotecan hydrochloride for injection only to patients with a baseline neutrophil count of greater than or equal to 1,500/mm 3 and a platelet count greater than or equal to 100,000/mm 3 . Monitor blood counts frequently during treatment.

Withhold and reduce dose of topotecan hydrochloride based on neutrophil counts, platelet counts and hemoglobin levels [see Dosage and Administration ( 2.5 ) ].

5.2Interstitial Lung Disease Interstitial lung disease (ILD), including fatalities, can occur with topotecan hydrochloride. Underlying risk factors include history of ILD, pulmonary fibrosis, lung cancer, thoracic radiation, and use of pneumotoxic drugs or colony stimulating factors. Monitor for pulmonary symptoms indicative of ILD. Permanently discontinue topotecan hydrochloride for injection if ILD is confirmed.

5.3Extravasation and Tissue Injury Extravasation, including severe cases, can occur with topotecan hydrochloride. If signs or symptoms of extravasation occur, immediately stop administration of topotecan hydrochloride and institute recommended management procedures [see Adverse Reactions ( 6.1 )].

5.4Embryo-Fetal Toxicity Based on animal data, topotecan hydrochloride can cause fetal harm when administered to a pregnant woman. Topotecan caused embryolethality, fetotoxicity, and teratogenicity in rats and rabbits when administered during organogenesis. Advise women of the potential risk to a fetus.

Advise females of reproductive potential to use effective contraception during treatment and for 6 months after the last dose of topotecan hydrochloride for injection. Advise males with a female partner of reproductive potential to use effective contraception during treatment with topotecan hydrochloride for injection and for 3 months after the last dose [see Use in Specific Populations ( 8.1 , 8.3 ), Nonclinical Toxicology ( 13.1 )].

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: • Myelosuppression [see Warnings and Precautions ( 5.1 )] • Interstitial Lung Disease (ILD) [see Warnings and Precautions ( 5.2 )] • Extravasation and Tissue Injury [see Warnings and Precautions ( 5.3 )] Ovarian cancer: • The most common Grade 3 or 4 hematologic adverse reactions (incidence > 5%) were: neutropenia, anemia, thrombocytopenia, and febrile neutropenia. ( 6.1 ) • The most common (incidence > 5%) non-hematologic adverse reactions (all Grades) were: nausea, vomiting, fatigue, diarrhea, and dyspnea.

( 6.1 ) SCLC: • The most common Grade 3 or 4 hematologic adverse reactions were (incidence > 5%): neutropenia, anemia, thrombocytopenia, and febrile neutropenia. ( 6.1 ) • The most common (incidence > 5%) non-hematologic adverse reactions (all Grades) were: asthenia, dyspnea, nausea, pneumonia, abdominal pain, and fatigue. ( 6.1 ) Cervical cancer: • The most common Grade 3 or 4 hematologic adverse reactions were (incidence > 5%): neutropenia, anemia, and thrombocytopenia.

( 6.1 ) • The most common (incidence > 25% and ≥ 2% higher than cisplatin alone) non-hematologic adverse reactions were: pain, vomiting, and infection/febrile neutropenia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials 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 with rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data in Warnings and Precautions reflect exposure to topotecan hydrochloride for injection from eight trials in which 879 patients with ovarian cancer or small cell lung cancer (SCLC) received topotecan hydrochloride for injection 1.5 mg/m 2 by intravenous infusion daily for 5 consecutive days, starting on Day 1 of a 21 day cycle and from one trial (Study GOG 0179) in which 147 patients with cervical cancer received topotecan hydrochloride for injection 0.75 mg/m 2 by intravenous infusion daily on Days 1, 2, and 3, with cisplatin 50 mg/m 2 by intravenous infusion on Day 1, of a 21-day cycle.

Ovarian Cancer The safety of topotecan hydrochloride for injection was evaluated in a randomized trial conducted in 226 patients with metastatic ovarian cancer (Study 039) [see Clinical Studies ( 14.1 )] . Table 1 shows the incidence of Grade 3 and 4 hematologic and non-hematologic adverse reactions that occurred in patients receiving topotecan hydrochloride for injection. Table 1.

Adverse Reactions Occurring in Greater than or Equal to 5% of Patients With Ovarian Cancer in Study 039 a Death related to sepsis occurred in 2% of patients receiving topotecan hydrochloride and 0% of patients receiving paclitaxel. b Pain includes body pain, skeletal pain, and back pain. Adverse Reactions Topotecan Hydrochloride (n=112) Paclitaxel (n=114) Grade 3-4 (%) Grade 3-4 (%) Hematologic Grade 4 neutropenia (< 500/mm 3 ) 80 21 Grade 3 or 4 anemia (Hgb < 8 g/dL) 41 6 Grade 4 thrombocytopenia (< 25,000/mm 3 ) 27 3 Febrile neutropenia 23 4 Non-Hematologic Infections Sepsis a 5 2 Respiratory, thoracic, and mediastinal Dyspnea 6 5 Gastrointestinal Vomiting 10 3 Nausea 10 2 Diarrhea 6 1 Abdominal pain 5 4 Intestinal obstruction 5 4 Constipation 5 0 General and administrative site conditions Fatigue 7 6 Pain b 5 7 Asthenia 5 3 Small Cell Lung Cancer (SCLC) The safety of topotecan hydrochloride for injection was evaluated in randomized, comparative trial in patients with recurrent or progressive SCLC (Study 090) [see Clinical Studies ( 14.2 )].

Table 2 shows the Grade 3 or 4 hematologic and non-hematologic adverse reactions in patients with SCLC. Table 2. Adverse Reactions Occurring in Greater than or Equal to 5% of Patients With Small Cell Lung Cancer in Study 090 a Death related to…

👥 Use in Specific Populations ~3 min read ▾

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

8.1Pregnancy Risk Summary Based on animal data and its mechanism of action, topotecan hydrochloride can cause fetal harm when administered to a pregnant woman. There are no available clinical data on the use of topotecan hydrochloride in pregnancy. Topotecan caused embryolethality, fetotoxicity, and teratogenicity in rats and rabbits when administered during organogenesis at doses similar to the clinical dose (see Data ).

Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the background risk of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. Data Animal Data: In rabbits, an intravenous dose of 0.10 mg/kg/day [about equal to the 1.5 mg/m 2 clinical dose based on body surface area (BSA)] given on Days 6 through 20 of gestation caused maternal toxicity, embryolethality, and reduced fetal body weight.

In the rat, an intravenous dose of 0.23 mg/kg/day (about equal to the 1.5 mg/m 2 clinical dose based on BSA) given for 14 days before mating through gestation Day 6 caused fetal resorption, microphthalmia, pre-implant loss, and mild maternal toxicity. Administration of an intravenous dose of 0.10 mg/kg/day (about half the 1.5 mg/m 2 clinical dose based on BSA) given to rats on Days 6 through 17 of gestation caused an increase in post-implantation mortality. This dose also caused an increase in total fetal malformations.

The most frequent malformations were of the eye (microphthalmia, anophthalmia, rosette formation of the retina, coloboma of the retina, ectopic orbit), brain (dilated lateral and third ventricles), skull, and vertebrae.

8.2Lactation Risk Summary There are no data on the presence of topotecan or its metabolites in human milk or their effects on the breastfed infant or on milk production. Lactating rats excrete high concentrations of topotecan in milk (see Data ) . Because of the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment with topotecan hydrochloride for injection and for 1 week after the last dose.

Data Following intravenous administration of topotecan to lactating rats at a dose of 4.72 mg/m 2 (about twice the 1.5 mg/m 2 clinical dose based on BSA), topotecan was excreted into milk at concentrations up to 48-fold higher than those in plasma.

8.3Females and Males of Reproductive Potential Pregnancy Testing Verify pregnancy status of females of reproductive potential prior to initiating topotecan hydrochloride for injection [see Use in Specific Populations ( 8.1 )] . Contraception Topotecan hydrochloride can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations ( 8.1 )] . Females: Advise females of reproductive potential to use effective contraception during treatment with topotecan hydrochloride for injection and for six months after the last dose.

Males: Topotecan hydrochloride may damage spermatozoa, resulting in possible genetic and fetal abnormalities. Advise males with a female partner of reproductive potential to use effective contraception during treatment with topotecan hydrochloride for injection and for three months after the last dose [see Nonclinical Toxicology ( 13.1 )] . Infertility Females: Topotecan hydrochloride can have both acute and long-term effects on fertility [see Nonclinical Toxicology ( 13.1 )] .

Males: Effects on spermatogenesis occurred in animals administered topotecan hydrochloride [see Nonclinical Toxicology ( 13.1 )] .

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

8.5Geriatric Use Of the 879 patients with metastatic ovarian cancer or small cell lung cancer in clinical trials of topotecan hydrochloride for injection, 32% were aged 65 years and older, while 3.8% were aged 75 years and older. Of the 140 patients with Stage IV-B, relapsed, or refractory cervical cancer in clinica…

🤰 Pregnancy ~1 min read ▾

8.1Pregnancy Risk Summary Based on animal data and its mechanism of action, topotecan hydrochloride can cause fetal harm when administered to a pregnant woman. There are no available clinical data on the use of topotecan hydrochloride in pregnancy. Topotecan caused embryolethality, fetotoxicity, and teratogenicity in rats and rabbits when administered during organogenesis at doses similar to the clinical dose (see Data ).

Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the background risk of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. Data Animal Data: In rabbits, an intravenous dose of 0.10 mg/kg/day [about equal to the 1.5 mg/m 2 clinical dose based on body surface area (BSA)] given on Days 6 through 20 of gestation caused maternal toxicity, embryolethality, and reduced fetal body weight.

In the rat, an intravenous dose of 0.23 mg/kg/day (about equal to the 1.5 mg/m 2 clinical dose based on BSA) given for 14 days before mating through gestation Day 6 caused fetal resorption, microphthalmia, pre-implant loss, and mild maternal toxicity. Administration of an intravenous dose of 0.10 mg/kg/day (about half the 1.5 mg/m 2 clinical dose based on BSA) given to rats on Days 6 through 17 of gestation caused an increase in post-implantation mortality. This dose also caused an increase in total fetal malformations.

The most frequent malformations were of the eye (microphthalmia, anophthalmia, rosette formation of the retina, coloboma of the retina, ectopic orbit), brain (dilated lateral and third ventricles), skull, and vertebrae.

🧒 Pediatric Use 13 words ▾

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

🧓 Geriatric Use 117 words ▾

8.5Geriatric Use Of the 879 patients with metastatic ovarian cancer or small cell lung cancer in clinical trials of topotecan hydrochloride for injection, 32% were aged 65 years and older, while 3.8% were aged 75 years and older. Of the 140 patients with Stage IV-B, relapsed, or refractory cervical cancer in clinical trials of topotecan hydrochloride for injection who received topotecan hydrochloride with cisplatin in the randomized clinical trial, 6% were aged 65 years and older, while 3% were aged 75 years and older.

No overall differences in effectiveness or safety were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients.

🆘 Overdosage 54 words ▾

10 OVERDOSAGE Overdoses (up to 10-fold of the recommended dose) have occurred in patients receiving intravenous topotecan. The primary complication of overdosage is myelosuppression. Elevated hepatic enzymes, mucositis, gastrointestinal toxicity, and skin toxicity have occurred with overdosages. If an overdose is suspected, monitor the patient closely for myelosuppression and institute supportive-care measures as appropriate.

🧬 Clinical Pharmacology ~2 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Topoisomerase I relieves torsional strain in DNA by inducing reversible single-strand breaks. Topotecan binds to the topoisomerase I-DNA complex and prevents re-ligation of these single-strand breaks. The cytotoxicity of topotecan is thought to be due to double-strand DNA damage produced during DNA synthesis, when replication enzymes interact with the ternary complex formed by topotecan, topoisomerase I, and DNA.

Mammalian cells cannot efficiently repair these double-strand breaks.

12.3Pharmacokinetics Following administration of topotecan hydrochloride for injection at doses of 0.5 to 1.5 mg/m 2 (0.1 to 0.3 times the recommended single agent dose) administered as a 30-minute infusion, area under the curve (AUC) increases proportionally with dose. Distribution Protein binding of topotecan is approximately 35%. Elimination The terminal half-life of topotecan is 2 to 3 hours following intravenous administration.

Metabolism Topotecan undergoes a reversible pH-dependent hydrolysis of its pharmacologically active lactone moiety. At pH less than or equal to 4, the lactone is exclusively present, whereas the ring-opened hydroxy-acid form predominates at physiologic pH. Topotecan is metabolized to an N-demethylated metabolite in vitro.

The mean metabolite: parent AUC ratio was about 3% for total topotecan and topotecan lactone following intravenous administration. Excretion The overall recovery of total topotecan and its N-desmethyl metabolite in urine and feces over 9 days averaged 73.0% ± 2.0% following an intravenous dose. Mean values of 51.0% ± 3.0% as total topotecan and 3.0% ± 1.0% as N-desmethyl topotecan were excreted in the urine.

Fecal elimination of total topotecan accounted for 18.0% ± 4.0% while fecal elimination of N-desmethyl topotecan was 1.7% ± 0.6%. An O-glucuronidation metabolite of topotecan and N-desmethyl topotecan has been identified in the urine. Specific Populations No clinically significant differences in the pharmacokinetics of topotecan were observed based on age, sex, or hepatic impairment following intravenous administration.

Patients with Renal Impairment: Compared to patients with CLcr (calculated by the Cockcroft-Gault method using ideal body weight) greater than 60 mL/min, plasma clearance of topotecan lactone decreased by 33% in patients with CLcr 40-60 mL/min and decreased 65% in patients with CLcr 20-39 mL/min. The effect on topotecan pharmacokinetics in patients with CLcr less than 20 mL/min is unknown [see Dosage and Administration ( 2.6 )] . Drug Interaction Studies Clinical Studies No clinically significant changes in topotecan pharmacokinetics were observed when coadministered cisplatin.

No clinically significant changes in the pharmacokinetics of free platinum were observed in patients coadministered cisplatin with topotecan. In Vitro Studies Topotecan does not inhibit CYP1A2, CYP2A6, CYP2C8/9, CYP2C19, CYP2D6, CYP2E, CYP3A, or CYP4A or dihydropyrimidine dehydrogenase.

🧬 Mechanism of Action 70 words ▾

12.1Mechanism of Action Topoisomerase I relieves torsional strain in DNA by inducing reversible single-strand breaks. Topotecan binds to the topoisomerase I-DNA complex and prevents re-ligation of these single-strand breaks. The cytotoxicity of topotecan is thought to be due to double-strand DNA damage produced during DNA synthesis, when replication enzymes interact with the ternary complex formed by topotecan, topoisomerase I, and DNA.

Mammalian cells cannot efficiently repair these double-strand breaks.

📦 How Supplied / Storage and Handling 114 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1How Supplied Topotecan hydrochloride for injection, USP is supplied as a sterile, lyophilized, buffered, light yellow to greenish powder. Topotecan hydrochloride for injection, USP is supplied as follows: Product No. Unit of Sale Strength Each 760210 NDC 63323-762-10 Individually packaged 4 mg (base) per vial NDC 63323-762-10 Single Dose Vial The container closure is not made with natural rubber latex

16.2Storage and Handling Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from light; product is light-sensitive. Retain in carton. Handle and dispose of topotecan hydrochloride for injection, USP consistent with recommendations for the handling and disposal of hazardous drugs 1 .

📦 Storage and Handling 48 words ▾

16.2Storage and Handling Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from light; product is light-sensitive. Retain in carton. Handle and dispose of topotecan hydrochloride for injection, USP consistent with recommendations for the handling and disposal of hazardous drugs 1 .

📋 Description 150 words ▾

11 DESCRIPTION Topotecan is a topoisomerase inhibitor. The chemical name for topotecan hydrochloride is ( S ) - 10-[(dimethylamino)methyl]-4-ethyl-4,9-dihydroxy-1 H -pyrano[3',4':6,7] indolizino [1,2- b ]quinoline-3,14-(4 H ,12 H )-dione 1.25 hydrochloride. It is soluble in water and melts with decomposition at 213° to 218°C.

Topotecan hydrochloride has the following structural formula: C 23 H 23 N 3 O 5 • 1.25HCl M.W. 467.02 Topotecan hydrochloride for injection, USP is supplied as a sterile, lyophilized, buffered, light yellow to greenish powder available in single-dose vials. Each vial contains topotecan hydrochloride equivalent to 4 mg of topotecan as free base.

The reconstituted solution ranges in color from yellow to yellow green and is intended for administration by intravenous infusion. Inactive ingredients are mannitol, 48 mg, and tartaric acid, 20 mg. Hydrochloric acid and sodium hydroxide may be used to adjust the pH.

The solution pH ranges from 2.5 to 3.5. Structural Formula

💬 Information for Patients ~1 min read ▾

17 PATIENT COUNSELING INFORMATION • Myelosuppression Inform patients that topotecan hydrochloride decreases blood cell counts such as white blood cells, platelets, and red blood cells. Advise patients to notify their healthcare provider promptly for fever, other signs of infection, or bleeding [see Warnings and Precautions ( 5.1 )] . • Interstitial Lung Disease (ILD) Inform patients of the risks of severe ILD. Advise patients to contact their healthcare provider immediately to report new or worsening respiratory symptoms [see Warnings and Precautions ( 5.2 )] . • Embryo-Fetal Toxicity Advise females of reproductive potential and males with female partners of reproductive potential of the potential risk to a fetus.

Advise women to contact their healthcare provider if they become pregnant, or if pregnancy is suspected during treatment with topotecan hydrochloride for injection [see Warnings and Precautions ( 5.4 ), Use in Specific Populations ( 8.1 , 8.3 )] . Advise females of reproductive potential to use effective contraception during treatment and for 6 months after the last dose of topotecan hydrochloride for injection [see Use in Specific Populations ( 8.1 , 8.3 )] . Advise males with a female partner of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of topotecan hydrochloride for injection [see Use in Specific Populations ( 8.1 , 8.3 ), Nonclinical Toxicology ( 13.1 )] . • Lactation Advise women to discontinue breastfeeding during treatment and for 1 week after the last dose of topotecan hydrochloride for injection [see Use in Specific Populations ( 8.2 )] . • Infertility Advise male and female patients of the potential risk for impaired fertility [see Use in Specific Populations ( 8.3 ), Nonclinical Toxicology ( 13.1 )] . • Asthenia and Fatigue Advise patients that topotecan hydrochloride for injection may cause asthenia or fatigue.

These symptoms may impair the ability to safely drive or operate machinery. Lake Zurich, IL 60047 www.fresenius-kabi.com/us 451171G Revised: March 2024 Logo

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