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Topotecan 1 mg/mL Injection — NDC 16729-0243-31 package photo
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Topotecan 1 mg/mL Injection — NDC 16729-243-31 (Billing 16729-0243-31)

by Accord Healthcare Inc. · 1 VIAL, MULTI-DOSE in 1 CARTON / 4 mL in 1 VIAL, MULTI-DOSE

This is a package of Topotecan 1 mg/mL Injection from Accord Healthcare Inc., marketed since Jul 2020 and currently FDA-listed. It is this product's only package size.

NDC 16729-0243-31
🏷️ FDA NDC (as labeled) 16729-243-31 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

NDC database record

One package, one record: these facts belong to NDC 16729-243-31 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
16729 labeler · 243 product · 31 package
Package marketed since
Jul 8, 2020
Sample package
No — commercial package
Listing certified through
Dec 31, 2026
Barcode (UPC)
0316729243308
Medicaid fills, this package
21 prescriptions in the last four reported quarters
FDA record last changed
Jul 24, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 16729-243-31
Product NDC 16729-243
11-digit billing NDC 16729024331
NCPDP billing unit ML — per mL (volume)
RxCUI 637549
UNII 7M7YKX2N15
UPC 0316729243308
Application # ANDA204406
SPL Set ID 7636bc1e-77b6-46ad-9df0-c8bb1c5e503f
Established class (EPC) Topoisomerase Inhibitor
Mechanism of action Topoisomerase Inhibitors
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2020-07-08
Route INTRAVENOUS
Dosage form INJECTION
Substance TOPOTECAN

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

GPI-14 21550080102020
GPI class Topotecan HCl
GCN Seq No 067043
GCN 29519
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/4 ML VIAL
FDB brand name Topotecan Hcl
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 067043
  • GCN: 29519
  • GPI-14 (Medi-Span): 21550080102020
  • HICL (First Databank): 011381
  • AHFS class code: 10:00.00.00
  • RxCUI (RxNorm): 637549
Why two NDCs? The FDA registers this code as 16729-243-31 — 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 → 16729-0243-31. 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.

Clinical

Label name TOPOTECAN HCL 4 MG/4 ML VIAL Ingredient Topotecan Hcl
📖 What it is MedlinePlus · NLM

Topotecan injection is used to treat ovarian cancer (cancer that begins in the female reproductive organs where eggs are formed) and small cell lung cancer (a type of cancer that begins in the lungs) that have spread and did not improve after treatment with other medications. It is also used together with other medications to treat cervical cancer (cancer that begins in the opening of the uterus [womb]) that has not improved or has come back after other treatments. Topotecan is in a class of medications called topoisomerase type I inhibitors. It works by killing cancer cells.

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • It’s a chemotherapy medicine. Depending on the product, it treats small cell lung cancer, metastatic ovarian cancer, and, with cisplatin, advanced or recurrent cervical cancer. Hyc...
  • The injection is given into a vein by your care team over about 30 minutes, in repeated 21-day courses. Hycamtin capsules are taken by mouth. Your team sets the schedule, so follow...
  • Low blood counts are the most common, along with nausea, vomiting, hair loss, diarrhea or constipation, tiredness and fever. Your blood will be checked often to keep an eye on this...
  • Call right away for fever, chills or other signs of infection, since low white blood cells can lead to serious infection. Also call for severe belly pain or diarrhea, new cough or...
📖 Read our full Topotecan guide →
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 eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo $19.82 $19.82 / 1 vial
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
Medicare Part B allowsASP · J9351 $2.759 / J9351 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)16729-243-31
11-digit billing NDC16729-0243-31
Format5-3-2 as registered → padded to 5-4-2 for billing (zero added to the product segment)
HCPCS J-codeJ9351
DescriptorINJECTION, TOPOTECAN, 0.1 MG
Billing units / pkg10 units
How the units are derivedThis package is 4 ML; the HCPCS unit is 0.1 MG, so one package = 10 billing units.
Medicare Part B spend (2026 (Q1))$32,436 · 553 claims · $58.65 per claim (all NDCs under J9351)
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
16729-0243-31 You're viewing this Main listing 1 VIAL, MULTI-DOSE in 1 CARTON / 4 mL in 1 VIAL, MULTI-DOSE 2020-07-08 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Topotecan 1 mg/mLthis 16729-0243-31 Accord 1 vial — — 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

🏛️
2020
On the market since
Jul 2020
📍
2026
Currently FDA-listed
6 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.

🧪 Avoiding an ingredient? See Topotecan inactive ingredients by manufacturer: every current product's list side by side, so you can ask your pharmacy for the version that does not list it.

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

  • UNII QTT17582CB
    A strong acid used to adjust and maintain the proper pH level in liquid medicines, ensuring stability and preventing breakdown of active ingredients.
  • UNII 55X04QC32I
    A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during storage.
  • 5 mg / 1 mL UNII W4888I119H
    Tartaric acid is a natural organic acid found in grapes and tamarinds. In medicines, it works as a buffer to control acidity, an antioxidant to prevent spoilage, and sometimes a flavoring or binding agent.
  • UNII 059QF0KO0R
    Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.

4 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

LabelerAccord Healthcare Inc.
Application holderACCORD HEALTHCARE INC
FDA applicationANDA204406 (ANDA)
Labeler code16729
First marketedJul 2020
Product typeHuman Prescription Drug
Portfolio143 products on file

More NDCs from Accord Healthcare Inc. labeler code 16729

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. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). 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 🔄 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 🍼 Nursing Mothers 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📚 References 📄 Package Label / Principal Display Panel
🚨 Boxed Warning 128 words ▾

WARNING: BONE MARROW SUPPRESSION Do not give Topotecan Injection to patients with baseline neutrophil counts less than 1,500 cells/mm 3 . In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection and death, monitor peripheral blood counts frequently on all patients receiving Topotecan Injection . [see Warnings and Precautions ( 5.1 ) ] WARNING: BONE MARROW SUPPRESSION See full prescribing information for complete boxed warning Do not give Topotecan to patients with baseline neutrophil counts less than 1,500 cells/mm 3 .

In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection and death, monitor peripheral blood cell counts frequently on all patients receiving Topotecan Injection. ( 5.1 )

🎯 Indications and Usage 154 words ▾

1 INDICATIONS AND USAGE Topotecan Injection is indicated for the treatment of: small cell lung cancer sensitive disease after failure of first-line chemotherapy. In clinical studies submitted to support approval, sensitive disease was defined as disease responding to chemotherapy but subsequently progressing at least 60 days (in the Phase 3 study) or at least 90 days (in the Phase 2 studies) after chemotherapy [see Clinical Studies ( 14 ) ] . Topotecan Injection in combination with cisplatin is indicated for the treatment of: stage IV-B, recurrent, or persistent carcinoma of the cervix which is not amenable to curative treatment with surgery and/or radiation therapy.

Topotecan is a topoisomerase inhibitor indicated for: small cell lung cancer sensitive disease after failure of first-line chemotherapy. ( 1 ) combination therapy with cisplatin for stage IV-B, recurrent, or persistent carcinoma of the cervix which is not amenable to curative treatment with surgery and/or radiation therapy. ( 1 )

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Verify dose using body surface area prior to dispensing. Recommended dosage should not exceed 4 mg [see Overdosage 10 ]. Prior to administration of the first course of Topotecan Injection, patients must have a baseline neutrophil count of >1,500 cells/mm 3 and a platelet count of >100,000 cells/mm 3 .

Small cell lung cancer: 1.5 mg/m 2 by intravenous infusion over 30 minutes daily for 5 consecutive days, starting on day one of a 21-day course. ( 2.1 ) Cervical cancer: 0.75 mg/m 2 by intravenous infusion over 30 minutes on days 1, 2, and 3 followed by cisplatin 50 mg/m 2 by intravenous infusion on day 1 repeated every 21 days. ( 2.2 ) See Dosage Modification Guidelines for patients with neutropenia or reduced platelets.( 2.1 , 2.2 ) See Dosage Adjustment in Renal Impairment.

( 2.3 )

2.1Small Cell Lung Cancer Recommended Dosage The recommended dose of topotecan 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 course. In the absence of tumor progression, a minimum of 4 courses is recommended because tumor response may be delayed. The median time to response in 4 small cell lung cancer trials was 5 to 7 weeks.

Dosage Modification Guidelines In the event of severe neutropenia (defined as <500 cells/mm 3 ) during any course, reduce the dose by 0.25 mg/m 2 (to 1.25 mg/m 2 ) for subsequent courses. Alternatively, in the event of severe neutropenia, administer G-CSF (granulocyte-colony stimulating factor) following the subsequent course (before resorting to dose reduction) starting from day 6 of the course (24 hours after completion of topotecan administration). In the event the platelet count falls below 25,000 cells/mm 3 , reduce doses by 0.25 mg/m 2 (to 1.25 mg/m 2 ) for subsequent courses.

2.2Cervical Cancer Recommended Dosage The recommended dose of Topotecan Injection is 0.75 mg/m 2 by intravenous infusion over 30 minutes daily on days 1, 2, and 3; followed by cisplatin 50 mg/m 2 by intravenous infusion on day 1 repeated every 21 days (a 21-day course). Dosage Modification Guidelines Dosage adjustments for subsequent courses of Topotecan Injection in combination with cisplatin are specific for each drug. See manufacturer’s prescribing information for cisplatin administration and hydration guidelines and for cisplatin dosage adjustment in the event of hematologic toxicity In the event of severe febrile neutropenia (defined as <1000 cells/mm 3 with temperature of 38°C or 100.4°F), reduce the dose of Topotecan Injection to 0.60 mg/m 2 for subsequent courses.

Alternatively, in the event of severe febrile neutropenia, administer G-CSF following the subsequent course (before resorting to dose reduction) starting from day 4 of the course (24 hours after completion of administration of Topotecan Injection). If febrile neutropenia occurs despite the use of G-CSF, reduce the dose of Topotecan Injection to 0.45 mg/m 2 for subsequent courses. In the event the platelet count falls below 25,000 cells/mm 3 , reduce doses to 0.60 mg/m 2 for subsequent courses.

2.3Dosage Adjustment in Specific Populations Renal Impairment No dosage adjustment of Topotecan Injection appears to be required for patients with mild renal impairment (Cl cr 40 to 60 mL/min.). Dosage adjustment of Topotecan Injection to 0.75 mg/m 2 is recommended for patients with moderate renal impairment (20 to 39 mL/min.). Insufficient data are available in patients with severe renal impairment to provide a dosage recommendation for Topotecan Injection. [see Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.3 ) ] Topotecan Injection in combination with cisplatin for the treatment of cervical cancer should only be initiated in patients with serum creatinine ≤1.5 mg/dL.

In the clinical trial, cisplatin was discontinued for a serum creatinine >1.5 mg/dL. Insufficient data are available regarding continuing monotherapy with Topotecan Injection after cisplatin discontinuation in… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 71 words ▾

3 DOSAGE FORMS AND STRENGTHS Topotecan Injection is available in the following strengths: 1 mg/mL Multiple Dose Vial 4 mg/4 mL (1 mg/mL) Multiple Dose Vial Each mL contains topotecan hydrochloride equivalent to 1 mg of topotecan free base for intravenous infusion only following dilution. 1 mg/mL Multiple Dose Vial 4 mg/4 mL (1 mg/mL) Multiple Dose Vial Each mL contains topotecan hydrochloride equivalent to 1 mg of topotecan free base.

⛔ Contraindications 65 words ▾

4 CONTRAINDICATIONS Topotecan Injection is contraindicated in patients who have a history of severe hypersensitivity reactions (e.g., anaphylactoid reactions) to topotecan or to any of its ingredients. Topotecan Injection should not be used in patients with severe bone marrow depression. History of severe hypersensitivity reactions (e.g., anaphylactoid reactions) to topotecan or any of its ingredients ( 4 ) Severe bone marrow depression ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Bone marrow suppression: Administer Topotecan Injection only to patients with adequate bone marrow reserves. Monitor peripheral blood counts and adjust the dose if needed. ( 5.1 ) Topotecan-induced neutropenia can lead to neutropenic colitis.

( 5.2 ) Interstitial lung disease: topotecan has been associated with reports of interstitial lung disease. Monitor patients for symptoms and discontinue Topotecan Injection if the diagnosis is confirmed. ( 5.3 ) Pregnancy: Can cause fetal harm.

Advise women of potential risk to the fetus. ( 5.4 , 8.1 )

5.1Bone Marrow Suppression Bone marrow suppression (primarily neutropenia) is the dose-limiting toxicity of Topotecan Injection. Neutropenia is not cumulative over time. In the comparative study, in small cell lung cancer, the treatment-related death rates were 5% for topotecan and 4% for CAV (cyclophosphamide-doxorubicin-vincristine).

Neutropenia From a combined experience of patients receiving topotecan which included patients treated for small cell lung cancer: Grade 4 neutropenia (<500 cells/mm 3 ) was most common during course 1 of treatment (60% of patients) and occurred in 39% of all courses, with a median duration of 7 days. The nadir neutrophil count occurred at a median of 12 days. Therapy-related sepsis or febrile neutropenia occurred in 23% of patients, and sepsis was fatal in 1%.

Pancytopenia has been reported. Cervical cancer experience: Grade 3 and grade 4 neutropenia affected 26 % and 48 % of patients, respectively. Thrombocytopenia From a combined experience of patients receiving topotecan which included patients treated for small cell lung cancer: Grade 4 thrombocytopenia (<25,000/mm 3 ) occurred in 27% of patients and in 9% of courses, with a median duration of 5 days and platelet nadir at a median of 15 days.

Platelet transfusions were given to 15% of patients in 4% of courses. Cervical cancer experience: Grade 3 and grade 4 thrombocytopenia affected 26 % and 7 % of patients, respectively. Anemia From a combined experience of patients receiving topotecan which included patients treated for small cell lung cancer: Grade 3/4 anemia (<8 g/dL) occurred in 37% of patients and in 14% of courses.

Median nadir was at day 15. Transfusions were needed in 52% of patients in 22% of courses. Cervical cancer experience: Grade 3 and grade 4 anemia affected 34 % and 6 % of patients, respectively.

Monitoring of Bone Marrow Function Administer Topotecan Injection only in patients with adequate bone marrow reserves, including baseline neutrophil count of at least 1,500 cells/mm 3 and platelet count at least 100,000/mm 3 . Monitor peripheral blood counts frequently during treatment with Topotecan Injection. Do not treat patients with subsequent courses of Topotecan Injection until neutrophils recover to >1,000 cells/mm 3 , platelets recover to >100,000 cells/mm 3 , and hemoglobin levels recover to 9 g/dL (with transfusion if necessary).Severe myelotoxicity has been reported when Topotecan Injection is used in combination with cisplatin [see Drug Interactions ( 7 ) ]

5.2Neutropenic Colitis Topotecan-induced neutropenia can lead to neutropenic colitis. Fatalities due to neutropenic colitis have been reported in clinical trials with Topotecan Injection. In patients presenting with fever, neutropenia, and a compatible pattern of abdominal pain, consider the possibility of neutropenic colitis.

5.3Interstitial Lung Disease Topotecan Injection has been associated with reports of interstitial lung disease (ILD), some of which have been fatal [see Adverse Reactions ( 6.2 ) ]. Underlying risk factors include history of ILD, pulmonary fibrosis, lung cancer, thoracic exposure to radiation, and use of pneumotoxic drugs and/or colony stimulating factors. Monitor patients for pulmonary symptoms indicative of interstitial lung disease (e.g., cough, fever, dyspnea, and/or hypoxia), and discontinue Topotecan Injection if a new diagnosis of ILD is confirmed.

5.4Pregnancy Pregna… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS Small cell lung cancer: The most common hematologic adverse reactions were: neutropenia (97%), leukopenia (97%), anemia (89%), and thrombocytopenia (69%). ( 6.1 ) The most common (>25%) non-hematologic adverse reactions (all grades) were: nausea, alopecia, vomiting, sepsis or pyrexia/infection with neutropenia, diarrhea, constipation, fatigue, and pyrexia. ( 6.1 ) Cervical cancer (Topotecan Injection plus cisplatin): The most common hematologic adverse reactions (all grades) were: anemia (94%), leukopenia (91%), neutropenia (89%), and thrombocytopenia (74%).

( 6.1 ) The most common (>25%) non-hematologic adverse reactions (all grades) were: pain, nausea, vomiting, and infection/febrile neutropenia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Accord Healthcare Inc. at 1-866-941-7875 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 to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Small Cell Lung Cancer Data in the following section are based on the combined experiences of the 879 patients studied, including 426 patients with small cell lung cancer treated with topotecan. Table 1 lists the principle hematologic adverse reactions and Table 2 lists non-hematologic adverse reactions occurring in at least 15% of patients.

Table 1. Hematologic Adverse Reactions Experienced in ≥15% of Patients, Including 426 Patients With Small Cell Lung Cancer, Receiving Topotecan Hematologic Adverse Reaction Patients (n=879) % Incidence Neutropenia <1,500 cells/mm 3 <500 cells/mm 3 97 78 Leukopenia <3,000 cells/mm 3 <1,000 cells/mm 3 97 32 Thrombocytopenia <75,000/mm 3 <25,000/mm 3 69 27 Anemia <10 g/dL <8 g/dL 89 37 Table 2. Non-hematologic Adverse Reactions Experienced by ≥15% of 879 Patients, Including 426 Patients With Small Cell Lung Cancer, Receiving Topotecan Non-hematologic Adverse Reaction Percentage of Patients with Adverse Reaction (879 Patients) All Grades Grade 3 Grade 4 Infections and infestations Sepsis or pyrexia/infection with neutropenia a 43 NR 23 Metabolism and nutrition disorders Anorexia 19 2 <1 Nervous system disorders Headache 18 1 <1 Respiratory, thoracic, and mediastinal disorders Dyspnea 22 5 3 Coughing 15 1 0 Gastrointestinal disorders Nausea 64 7 1 Vomiting 45 4 1 Diarrhea 32 3 1 Constipation 29 2 1 Abdominal pain 22 2 2 Stomatitis 18 1 <1 Skin and subcutaneous tissue disorders Alopecia 49 NA NA Rash b 16 1 0 General disorders and administrative site conditions Fatigue 29 5 0 Pyrexia 28 1 <1 Pain c 23 2 1 Asthenia 25 4 2 NA = Not applicable NR = Not reported separately a Does not include Grade 1 sepsis or pyrexia b Rash also includes pruritus, rash erythematous, urticaria, dermatitis, bullous eruption, and maculopapular rash. c Pain includes body pain, back pain, and skeletal pain.

Nervous System Disorders Paresthesia occurred in 7% of patients but was generally grade 1. Hepatobiliary Disorders Grade 1 transient elevations in hepatic enzymes occurred in 8% of patients. Greater elevations, grade 3/4, occurred in 4%.

Grade 3/4 elevated bilirubin occurred in <2% of patients. Table 3 shows the grade 3/4 hematologic and major non-hematologic adverse reactions in the topotecan/CAV comparator trial in small cell lung cancer. Table 3.

Adverse Reactions Experienced by ≥5% of Small Cell Lung Cancer Patients Randomized to Receive Topotecan or CAV Adverse Reaction Topotecan (n=107) CAV (n=104) Hematologic Grade 3/4 % % Grade 4 neutropenia (<500 cells/mm 3 ) 70 72 Grade 3/4 anemia (Hgb <8 g dL) 42 20 Grade 4 thrombocytopenia (<25,000 plts/mm 3 ) 29 5 Pyrexia/Grade 4 neutropenia 28 26 Non-hematologic Grade 3/4 % % Infections and infestations Documented sepsis a 5 5 Respiratory, thoracic, and mediastinal disorders Dyspnea 9 14 Pneumonia 8 6 Gastrointestinal disorde… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~1 min read ▾

7 DRUG INTERACTIONS G-CSF: Concomitant administration of G-CSF can prolong the duration of neutropenia, so if G-CSF is to be used, do not initiate it until day 6 of the course of therapy, 24 hours after completion of treatment with Topotecan Injection. Platinum and Other Cytotoxic Agents: Myelosuppression was more severe when topotecan, at a dose of 1.25 mg/m 2 /day for 5 days, was given in combination with cisplatin at a dose of 50 mg/m 2 in Phase 1 studies. In one study, 1 of 3 patients had severe neutropenia for 12 days and a second patient died with neutropenic sepsis.

Greater myelosuppression is also likely to be seen when Topotecan Injection is used in combination with other cytotoxic agents, thereby necessitating a dose reduction. However, when combining topotecan with platinum agents (e.g., cisplatin or carboplatin), a distinct sequence-dependent interaction on myelosuppression has been reported. Coadministration of a platinum agent on day 1 of dosing with topotecan required lower doses of each agent compared to co-administration on day 5 of the dosing schedule for topotecan.

For information on the pharmacokinetics, efficacy, safety, and dosing of Topotecan Injection at a dose of 0.75 mg/m 2 /day on days 1, 2, and 3 in combination with cisplatin 50 mg/m 2 on day 1 for cervical cancer [see Dosage and Administration ( 2 ) , Adverse Reactions ( 6 ), Clinical Pharmacology ( 12.3 ) and Clinical Studies ( 14 ) ] . Do not initiate G-CSF until 24 hours after completion of treatment with Topotecan Injection. Concomitant administration can prolong duration of neutropenia.

( 7 ) Greater myelosuppression is likely to be seen when used in combination with other cytotoxic agents. ( 7 )

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Nursing Mothers: Discontinue nursing when receiving Topotecan Injection. ( 8.3 )

8.1Pregnancy Pregnancy Category D [see Warnings and Precautions ( 5.4 ) ]. Topotecan Injection can cause fetal harm when administered to a pregnant woman. In rabbits, a dose of 0.1 mg/kg/day (about equal to the clinical dose of 1.5 mg/m 2 ) given on days 6 through 20 of gestation caused maternal toxicity, embryolethality, and reduced fetal body weight.

In the rat, a dose of 0.23 mg/kg/day (about equal to the clinical dose of 1.5 mg/m 2 ) given for 14 days before mating through gestation day 6 caused fetal resorption, microphthalmia, pre-implant loss, and mild maternal toxicity. A dose of 0.1 mg/kg/day (about half the clinical dose of 1.5 mg/m 2 ) 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. There are no adequate and well controlled studies of Topotecan Injection in pregnant women. If this drug is used during pregnancy, or if a patient becomes pregnant while receiving Topotecan Injection, the patient should be apprised of the potential hazard to the fetus. [see Warnings and Precautions ( 5.4 ) ]

8.3Nursing Mothers Rats excrete high concentrations of topotecan into milk. Lactating female rats given 4.72 mg/m 2 IV (about three times the clinical dose of 1.5 mg/m 2 ) excreted topotecan into milk at concentrations up to 48-fold higher than those in plasma. It is not known whether the drug is excreted in human milk.

Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Topotecan Injection, discontinue breastfeeding when women are receiving Topotecan Injection.

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

8.5Geriatric Use Of the 879 patients in a combined experience of topotecan which included patients with small cell lung cancer, 32% (n=281) were 65 years of age and older, while 3.8% (n=33) were 75 years of age and older. Of the 140 patients with stage IV-B, relapsed, or refractory cervical cancer in clinical studies of Topotecan Injection who received Topotecan Injection plus cisplatin in the randomized clinical trial, 6% (n = 9) were 65 years of age and older, while 3% (n = 4) were 75 years of age and older. No overall differences in effectiveness or safety were observed between these patients and younger adult patients, and other reported clinical experience has not identified differences in responses between the elderly and younger adult patients, but greater sensitivity of some older individuals cannot be ruled out.

There were no apparent differences in the pharmacokinetics of topotecan in elderly patients, once the age-related decrease in renal function was considered [see Clinical Pharmacology ( 12.3 ) ]. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see Dosage and Administration ( 2.3 ) ].

8.6Renal Impairment No dosage adjustment of Topotecan Injection appears to be required for patients with mild renal impairment (Cl cr 40 to 60 mL/min.). Dosage reduction is recommended for patients with moderate renal impairment (Cl cr 20 to 39 mL/min.). Insufficient data are available in patients with severe renal impairment to provide a dosage recommendation for Topotecan Injection. [see Dosage and Administration ( 2.3 ) and Clinical Pharmacology ( 12.3 ) ].

🤰 Pregnancy ~1 min read ▾

8.1Pregnancy Pregnancy Category D [see Warnings and Precautions ( 5.4 ) ]. Topotecan Injection can cause fetal harm when administered to a pregnant woman. In rabbits, a dose of 0.1 mg/kg/day (about equal to the clinical dose of 1.5 mg/m 2 ) given on days 6 through 20 of gestation caused maternal toxicity, embryolethality, and reduced fetal body weight.

In the rat, a dose of 0.23 mg/kg/day (about equal to the clinical dose of 1.5 mg/m 2 ) given for 14 days before mating through gestation day 6 caused fetal resorption, microphthalmia, pre-implant loss, and mild maternal toxicity. A dose of 0.1 mg/kg/day (about half the clinical dose of 1.5 mg/m 2 ) 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. There are no adequate and well controlled studies of Topotecan Injection in pregnant women. If this drug is used during pregnancy, or if a patient becomes pregnant while receiving Topotecan Injection, the patient should be apprised of the potential hazard to the fetus. [see Warnings and Precautions ( 5.4 ) ]

🧒 Pediatric Use 13 words ▾

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

🧓 Geriatric Use ~1 min read ▾

8.5Geriatric Use Of the 879 patients in a combined experience of topotecan which included patients with small cell lung cancer, 32% (n=281) were 65 years of age and older, while 3.8% (n=33) were 75 years of age and older. Of the 140 patients with stage IV-B, relapsed, or refractory cervical cancer in clinical studies of Topotecan Injection who received Topotecan Injection plus cisplatin in the randomized clinical trial, 6% (n = 9) were 65 years of age and older, while 3% (n = 4) were 75 years of age and older. No overall differences in effectiveness or safety were observed between these patients and younger adult patients, and other reported clinical experience has not identified differences in responses between the elderly and younger adult patients, but greater sensitivity of some older individuals cannot be ruled out.

There were no apparent differences in the pharmacokinetics of topotecan in elderly patients, once the age-related decrease in renal function was considered [see Clinical Pharmacology ( 12.3 ) ]. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see Dosage and Administration ( 2.3 ) ].

🆘 Overdosage 143 words ▾

10 OVERDOSAGE Overdoses (up to 10-fold of the prescribed dose) occurred in patients treated with intravenous topotecan. The primary complication of overdosage is bone marrow suppression. The observed signs and symptoms of overdose are consistent with the known adverse reactions associated with Topotecan Injection for intravenous use [see Adverse Reactions ( 6.1 , 6.2 ) ].

In addition, elevated hepatic enzymes and mucositis have been reported following overdose. One patient received a single dose of 40 mg/m 2 of intravenous topotecan and developed gastrointestinal toxicity, skin toxicity, and myelosuppression leading to septic shock. Another patient received a single dose of 35 mg/m 2 and experienced severe, reversible neutropenia.

There is no known antidote for overdosage with Topotecan Injection. If an overdose is suspected, monitor the patient for bone marrow suppression and institute supportive-care measures (such as prophylactic G-CSF and antibiotic therapy) as appropriate.

🧬 Clinical Pharmacology ~3 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 religation 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.

12.2Pharmacodynamics The dose-limiting toxicity of topotecan is leukopenia. White blood cell count decreases with increasing topotecan dose or topotecan AUC. When topotecan is administered at a dose of 1.5 mg/m 2 /day for 5 days, an 80% to 90% decrease in white blood cell count at nadir is typically observed after the first cycle of therapy.

12.3Pharmacokinetics The pharmacokinetics of topotecan have been evaluated in cancer patients following doses of 0.5 to 1.5 mg/m 2 administered as a 30-minute infusion. Topotecan exhibits multiexponential pharmacokinetics with a terminal half-life of 2 to 3 hours. Total exposure (AUC) is approximately dose-proportional.

Distribution: Binding of topotecan to plasma proteins is about 35%. Metabolism: Topotecan undergoes a reversible pH dependent hydrolysis of its lactone moiety; it is the lactone form that is pharmacologically active. At pH ≤ 4, the lactone is exclusively present, whereas the ring-opened hydroxy-acid form predominates at physiologic pH.

In vitro studies in human liver microsomes indicate topotecan is metabolized to an N-demethylated metabolite. The mean metabolite:parent AUC ratio was about 3% for total topotecan and topotecan lactone following IV administration. Excretion: Renal clearance is an important determinant of topotecan elimination.

In a mass balance/excretion study in 4 patients with solid tumors, the overall recovery of total topotecan and its N-desmethyl metabolite in urine and feces over 9 days averaged 73.4 ± 2.3% of the administered IV dose. Mean values of 50.8 ± 2.9% as total topotecan and 3.1 ± 1.0% as N-desmethyl topotecan were excreted in the urine following IV administration. Fecal elimination of total topotecan accounted for 17.9 ± 3.6% 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. These metabolites, topotecan-O-glucuronide and N-desmethyl topotecan-O-glucuronide, were less than 2% of the administered dose. Effect of Gender: The overall mean topotecan plasma clearance in male patients was approximately 24% higher than that in female patients, largely reflecting difference in body size.

Effect of Age: Topotecan pharmacokinetics have not been specifically studied in an elderly population, but population pharmacokinetic analysis in female patients did not identify age as a significant factor. Decreased renal clearance, which is common in the elderly, is a more important determinant of topotecan clearance [see Dosage and Administration ( 2.3 ) and Use in Specific Populations ( 8.5 ) ]. Effect of Race: The effect of race on topotecan pharmacokinetics has not been studied.

Effect of Renal Impairment: In patients with mild renal impairment (creatinine clearance of 40 to 60 mL/min.), topotecan plasma clearance was decreased to about 67% of the value in patients with normal renal function. In patients with moderate renal impairment (Cl cr of 20 to 39 mL/min.), topotecan plasma clearance was reduced to about 34% of the value in control patients, with an increase in half-life. Mean half-life, estimated in 3 renally impaired patients, was about 5.0 hours.

Dosage adjustment is recommended for these patients [see Dosage and Administration ( 2.3 ) ]. Effect of Hepatic Impairment: Plasma clearance in patients with hepatic impairment (serum bilirubin levels between 1.7 and 15.0 mg/dL) was decreased to about 67% of the va… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 74 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 religation 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 129 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Topotecan Injection is supplied in the following: 1 mg/mL Multiple Dose Vial NDC 16729-243-30 (package of 1) 4 mg/4 mL (1 mg/mL) Multiple Dose Vial NDC 16729-243-31 (package of 1) Unopened vials of Topotecan Injection are stable until the date indicated on the package when stored at controlled room temperature between 20ºC and 25°C (68°F and 77°F) with excursions allowed from 15°C to 30°C (59°F to 86°F). Retain in carton to protect from light. Topotecan Injection is supplied as a multiple dose vial.

Studies have shown the product is stable for 28 days after initial puncture when stored at room temperature. Topotecan Injection diluted for infusion is stable for 4 hours at room temperature or 24 hours at refrigerated temperature in ambient lighting conditions.

📋 Description 218 words ▾

11 DESCRIPTION Topotecan is a semi-synthetic derivative of camptothecin and is an anti-tumor drug with topoisomerase I-inhibitory activity. The chemical name for topotecan free base 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. It has the molecular formula C 23 H 23 N 3 O 5 and a molecular weight of 421.45.

Topotecan has three pKa values: pKa 1 = 10.50 corresponding to the benzyldimethylamino group, pKa 2 = 6.99 corresponding to the phenol group and pKa 3 = 0.60 corresponding to the quinoline group. As formulated in Topotecan Injection, topotecan has the following structural formula: where n is >1, corresponding to HCl added to adjust the pH to approximately 1.5 to 2.5. Topotecan Injection is supplied as a sterile, non-pyrogenic, clear, yellow solution at a topotecan free base concentration of 4 mg/4 mL (1 mg/mL) and 1 mg/mL available in multiple dose vials.

Each mL of Topotecan Injection contains topotecan hydrochloride equivalent to 1 mg of topotecan as free base, 5 mg tartaric acid, NF, and water for injection, USP. Hydrochloric acid and/or sodium hydroxide may be used to adjust the pH.. The hydrochloride salt of topotecan is soluble in water and melts with decomposition at 213 ° C to 218°C.

The solution must be diluted before administration by intravenous infusion. structural formula

💬 Information for Patients 171 words ▾

17 PATIENT COUNSELING INFORMATION

17.1Bone Marrow Suppression Inform patients that Topotecan Injection decreases blood cell counts such as white blood cells, platelets, and red blood cells. Patients who develop fever, other signs of infection (e.g., chills, cough, or burning pain on urination), or bleeding while on therapy should notify their physician promptly. Inform patients that frequent blood tests will be performed while taking Topotecan Injection to monitor for the occurrence of bone marrow suppression.

17.2Pregnancy and Breastfeeding Advise patients to use effective contraceptive measures to prevent pregnancy and to avoid breastfeeding during treatment with Topotecan Injection.

17.3Asthenia and Fatigue Inform patients that Topotecan Injection may cause asthenia or fatigue. If these symptoms occur, caution should be observed when driving or operating machinery. Rx only Manufactured for: Accord Healthcare, Inc., 8041 Arco Corporate Drive, Suite 200, Raleigh, NC 27617, USA.

Manufactured by: Intas Pharmaceuticals Limited, Plot No.: 457, 458, Village – Matoda, Bavla Road, Ta.- Sanand, Dist.- Ahmedabad – 382 210, INDIA. 10 7121 0 6027367 Issued December 2023

🍼 Nursing Mothers 87 words ▾

8.3Nursing Mothers Rats excrete high concentrations of topotecan into milk. Lactating female rats given 4.72 mg/m 2 IV (about three times the clinical dose of 1.5 mg/m 2 ) excreted topotecan into milk at concentrations up to 48-fold higher than those in plasma. It is not known whether the drug is excreted in human milk.

Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Topotecan Injection, discontinue breastfeeding when women are receiving Topotecan Injection.

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics The pharmacokinetics of topotecan have been evaluated in cancer patients following doses of 0.5 to 1.5 mg/m 2 administered as a 30-minute infusion. Topotecan exhibits multiexponential pharmacokinetics with a terminal half-life of 2 to 3 hours. Total exposure (AUC) is approximately dose-proportional.

Distribution: Binding of topotecan to plasma proteins is about 35%. Metabolism: Topotecan undergoes a reversible pH dependent hydrolysis of its lactone moiety; it is the lactone form that is pharmacologically active. At pH ≤ 4, the lactone is exclusively present, whereas the ring-opened hydroxy-acid form predominates at physiologic pH.

In vitro studies in human liver microsomes indicate topotecan is metabolized to an N-demethylated metabolite. The mean metabolite:parent AUC ratio was about 3% for total topotecan and topotecan lactone following IV administration. Excretion: Renal clearance is an important determinant of topotecan elimination.

In a mass balance/excretion study in 4 patients with solid tumors, the overall recovery of total topotecan and its N-desmethyl metabolite in urine and feces over 9 days averaged 73.4 ± 2.3% of the administered IV dose. Mean values of 50.8 ± 2.9% as total topotecan and 3.1 ± 1.0% as N-desmethyl topotecan were excreted in the urine following IV administration. Fecal elimination of total topotecan accounted for 17.9 ± 3.6% 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. These metabolites, topotecan-O-glucuronide and N-desmethyl topotecan-O-glucuronide, were less than 2% of the administered dose. Effect of Gender: The overall mean topotecan plasma clearance in male patients was approximately 24% higher than that in female patients, largely reflecting difference in body size.

Effect of Age: Topotecan pharmacokinetics have not been specifically studied in an elderly population, but population pharmacokinetic analysis in female patients did not identify age as a significant factor. Decreased renal clearance, which is common in the elderly, is a more important determinant of topotecan clearance [see Dosage and Administration ( 2.3 ) and Use in Specific Populations ( 8.5 ) ]. Effect of Race: The effect of race on topotecan pharmacokinetics has not been studied.

Effect of Renal Impairment: In patients with mild renal impairment (creatinine clearance of 40 to 60 mL/min.), topotecan plasma clearance was decreased to about 67% of the value in patients with normal renal function. In patients with moderate renal impairment (Cl cr of 20 to 39 mL/min.), topotecan plasma clearance was reduced to about 34% of the value in control patients, with an increase in half-life. Mean half-life, estimated in 3 renally impaired patients, was about 5.0 hours.

Dosage adjustment is recommended for these patients [see Dosage and Administration ( 2.3 ) ]. Effect of Hepatic Impairment: Plasma clearance in patients with hepatic impairment (serum bilirubin levels between 1.7 and 15.0 mg/dL) was decreased to about 67% of the value in patients without hepatic impairment. Topotecan half-life increased slightly, from 2.0 hours to 2.5 hours, but these hepatically impaired patients tolerated the usual recommended topotecan dosage regimen.

Drug Interactions: Pharmacokinetic studies of the interaction of topotecan with concomitantly administered medications have not been formally investigated. In vitro inhibition studies using marker substrates known to be metabolized by human P450 CYP1A2, CYP2A6, CYP2C8/9, CYP2C19, CYP2D6, CYP2E, CYP3A, or CYP4A or dihydropyrimidine dehydrogenase indicate that the activities of these enzymes were not altered by topotecan. Enzyme inhibition by topotecan has not been evaluated in vivo .

Cisplatin: No pharmacokinetic data are available following topotecan (0.75 mg/m 2 /day for 3 consecutive days) and cisplatin (50 mg/m 2 /day on day 1) in patients with cervical cance… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics 57 words ▾

12.2Pharmacodynamics The dose-limiting toxicity of topotecan is leukopenia. White blood cell count decreases with increasing topotecan dose or topotecan AUC. When topotecan is administered at a dose of 1.5 mg/m 2 /day for 5 days, an 80% to 90% decrease in white blood cell count at nadir is typically observed after the first cycle of therapy.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES

14.1Small Cell Lung Cancer Topotecan was studied in 426 patients with recurrent or progressive small cell lung cancer in 1 randomized, comparative study and in 3 single-arm studies. Randomized Comparative Study In a randomized, comparative, Phase 3 trial, 107 patients were treated with topotecan (1.5 mg/m 2 /day x 5 days starting on day 1 of a 21-day course) and 104 patients were treated with CAV (1,000 mg/m 2 cyclophosphamide, 45 mg/m 2 doxorubicin, 2 mg vincristine administered sequentially on day 1 of a 21-day course).

All patients were considered sensitive to first-line chemotherapy (responders who then subsequently progressed ≥60 days after completion of first-line therapy). A total of 77% of patients treated with topotecan and 79% of patients treated with CAV received platinum/etoposide with or without other agents as first-line chemotherapy. Response rates, response duration, time to progression, and survival are shown in Table 6 .

Table 6. Efficacy of Topotecan Versus CAV (cyclophosphamide-doxorubicin-vincristine) in Small Cell Lung Cancer Patients Sensitive to First-Line Chemotherapy Parameter Topotecan (n = 107) CAV (n = 104) Complete response rate Partial response rate Overall response rate 0% 24% 24% 1% 17% 18% Difference in overall response rates 95% Confidence interval of the difference 6% (–6 to 18%) Response duration a (weeks) Median 95% Confidence interval Hazard-ratio n = 26 14.4 13.1 to 18 n = 19 15.3 13.1 to 23.1 (Topotecan:CAV) (95% CI) ( P -value) 1.42 (0.73 to 2.76) (0.30) Time to progression (weeks) Median 95% Confidence interval Hazard ratio 13.3 11.4 to 16.4 12.3 11 to 14.1 (Topotecan:CAV) (95% CI) ( P -value) 0.92 (0.69 to 1.22) (0.55) Survival (weeks) Median 95% Confidence interval Hazard ratio 25 20.6 to 29.6 24.7 21.7 to 30.3 (Topotecan:CAV) (95% CI) ( P -value) 1.04 (0.78 to 1.39) (0.8) a The calculation for duration of response was based on the interval between first response and time to progression.

The time to response was similar to both arms: topotecan median of 6 weeks (range 2.4 to 15.7) versus CAV median 6 weeks (range 5.1 to 18.1). Changes on a disease-related symptom scale in patients who received topotecan or who received CAV are presented in Table 7 . It should be noted that not all patients had all symptoms, nor did all patients respond to all questions.

Each symptom was rated on a 4-category scale with an improvement defined as a change in 1 category from baseline sustained over 2 courses. Limitations in interpretation of the rating scale and responses preclude formal statistical analysis. Table 7.

Percentage of Patients with Symptom Improvement a : Topotecan Versus CAV in Patients with Small Cell Lung Cancer Symptom Topotecan Injection (n=107) CAV (n=104) n b (%) n b (%) Shortness of breath 68 (28) 61 (7) Interference with daily activity 67 (27) 63 (11) Fatigue 70 (23) 65 (9) Hoarseness 40 (33) 38 (13) Cough 69 (25) 61 (15) Insomnia 57 (33) 53 (19) Anorexia 56 (32) 57 (16) Chest pain 44 (25) 41 (17) Hemoptysis 15 (27) 12 (33) a Defined as improvement sustained over at least 2 courses compared to baseline. b Number of patients with baseline and at least 1 post-baseline assessment.

Single-Arm Studies Topotecan was also studied in 3 open-label, non-comparative trials in a total of 319 patients with recurrent or progressive small cell lung cancer after treatment with first-line chemotherapy. In all 3 studies, patients were stratified as either sensitive (responders who then subsequently progressed ≥90 days after completion of first-line therapy) or refractory (no response to first-line chemotherapy or who responded to first-line therapy and then progressed within 90 days of completing first-line therapy).

Response rates ranged from 11% to 31% for sensitive patients and 2% to 7% for refractory patients. Median time to progression and median survival were similar in all 3 studies and the comparative study.

14.2Cervical Cancer In a comparative trial, 147 eligible wom… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology 164 words ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity testing of topotecan has not been performed. Topotecan is known to be genotoxic to mammalian cells and is a probable carcinogen. Topotecan was mutagenic to L5178Y mouse lymphoma cells and clastogenic to cultured human lymphocytes with and without metabolic activation.

It was also clastogenic to mouse bone marrow. Topotecan did not cause mutations in bacterial cells. Topotecan given to female rats prior to mating at a dose of 1.4 mg/m 2 IV (about equal to the clinical dose of 1.5 mg/m 2 ) caused superovulation possibly related to inhibition of follicular atresia.

This dose given to pregnant female rats also caused increased pre-implantation loss. Studies in dogs given 0.4 mg/m 2 IV (about 1/4th the clinical dose of 1.5 mg/m 2 ) of topotecan daily for a month suggest that treatment may cause an increase in the incidence of multinucleated spermatogonial giant cells in the testes. Topotecan may impair fertility in women and men.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 161 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity testing of topotecan has not been performed. Topotecan is known to be genotoxic to mammalian cells and is a probable carcinogen. Topotecan was mutagenic to L5178Y mouse lymphoma cells and clastogenic to cultured human lymphocytes with and without metabolic activation.

It was also clastogenic to mouse bone marrow. Topotecan did not cause mutations in bacterial cells. Topotecan given to female rats prior to mating at a dose of 1.4 mg/m 2 IV (about equal to the clinical dose of 1.5 mg/m 2 ) caused superovulation possibly related to inhibition of follicular atresia.

This dose given to pregnant female rats also caused increased pre-implantation loss. Studies in dogs given 0.4 mg/m 2 IV (about 1/4th the clinical dose of 1.5 mg/m 2 ) of topotecan daily for a month suggest that treatment may cause an increase in the incidence of multinucleated spermatogonial giant cells in the testes. Topotecan may impair fertility in women and men.

📚 References 81 words ▾

15 REFERENCES 1. Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in Health Care Settings. NIOSH Alert 2004-165.

2.OSHA Technical Manual, TED 1-0.15A, Section VI: Chapter 2. Controlling Occupational Exposure to Hazardous Drugs. OSHA, 1999. http://www.osha.gov/ dts/osta/otm/otm_vi/otm_vi_2.html 3.

American Society of Health-System Pharmacists. ASHP Guidelines on Handling Hazardous Drugs. Am J Health-Syst Pharm .

2006;63:1172-1193. 4. Polovich M, White JM, Kelleher LO (eds.) 2005.

Chemotherapy and Biotherapy Guidelines and Recommendations for Practice. (2 nd ed) Pittsburgh, PA: Oncology Nursing Society.

📄 Package Label / Principal Display Panel 40 words ▾

Principal Display Panel - 1 mg/mL Container Label Principal Display Panel - 1 mg/mL Carton image 1 image 2

Principal Display Panel - 4 mg/4 mL Container Label Principal Display Panel - 4 mg/4 mL Carton image 3 image 4

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

Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for this package alone, not the drug overall. Other pack sizes report separately.
💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.
📅 Q1 2025 – Q1 2026 · 5 quarters of data
ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.
Prescriptions last 4 qtrs
21
Units reimbursed last 4 qtrs
50
Gross reimbursed last 4 qtrs
$990.90
Avg / prescription
$47.19
Avg / unit
$20.0182
Latest quarter Q1 2026
21Rx
Fee-for-service vs managed care ⓘ
100% MCO
Fee-for-service · 0 Rx Managed care · 21 Rx
State Medicaid map
Alaska: no data reported AK Maine: no data reported ME Washington: no data reported WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: no data reported MN Wisconsin: no data reported WI Michigan: no data reported MI New York: no data reported NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: 50 units · 1.2 per 100k residents OR Nevada: no data reported NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: no data reported IA Illinois: no data reported IL Indiana: no data reported IN Ohio: no data reported OH Pennsylvania: no data reported PA New Jersey: no data reported NJ Massachusetts: no data reported MA California: no data reported CA Utah: no data reported UT Colorado: no data reported CO Nebraska: no data reported NE Missouri: no data reported MO Kentucky: no data reported KY West Virginia: no data reported WV Virginia: no data reported VA Maryland: no data reported MD Connecticut: no data reported CT Rhode Island: no data reported RI Arizona: no data reported AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: no data reported AR Tennessee: no data reported TN North Carolina: no data reported NC South Carolina: no data reported SC Delaware: no data reported DE Oklahoma: no data reported OK Louisiana: no data reported LA Mississippi: no data reported MS Alabama: no data reported AL Georgia: no data reported GA D.C.: no data reported DC Hawaii: no data reported HI Texas: no data reported TX Florida: no data reported FL
Units reimbursed · per 100k residents
1.21.2
gray = no data reported ⓘ
Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.
Tap or hover a state
…for its Medicaid breakdown
🏆 Top states by units · per 100k residents
1 Oregon 1.2 /100k
National units — by quarter
💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

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 — the ingredient across all brands.

Top reported reactions

Febrile Neutropenia602
Anaemia576
Death567
Neutropenia557
Nausea459
Disease Progression453
Thrombocytopenia447

Age at onset

Neonate12
Infant100
Child314
Adolescent35
Adult241
Elderly83

Reporter sex

6,852 reports
Male · 39%
Female · 60%
Unknown · 1%

Serious outcomes

Hospitalization2,590
Death1,640
Life-threatening437
Disabling121
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 490 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.

About this NDC listing & data coverage

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

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The 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.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Accord Healthcare Inc.. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Accord Healthcare Inc. is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
Does this product have a billing J-code?
Yes — this NDC cross-references HCPCS code J9351 for medical-claim billing (typically used when a product is administered in a clinical setting rather than dispensed at a retail pharmacy). See the Billing section on this page.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 16729-0242-31 · Accord 16729-0244-38 · Accord →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.