Topotecan

TOPOTECAN- topotecan injection
Accord Healthcare Inc.

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) ]

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.

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.

2.1 Small 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.

2.2 Cervical 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.

2.3 Dosage 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 patients with cervical cancer.

2.4 Instructions for Handling, Preparation and Intravenous Administration

Handling

Topotecan is a cytotoxic anticancer drug. Prepare Topotecan Injection under a vertical laminar flow hood while wearing gloves and protective clothing. If Topotecan Injection solution contacts the skin, wash the skin immediately and thoroughly with soap and water. If Topotecan Injection contacts mucous membranes, flush thoroughly with water.

Use procedures for proper handling and disposal of anticancer drugs. Several guidelines on this subject have been published. 1-4

Preparation and Administration

The appropriate volume of the Topotecan Injection is diluted in a minimum of 50 mL of 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP prior to administration. Infuse over 30 minutes. Topotecan Injection diluted for infusion is stable for 4 hours at room temperature or 24 hours at refrigerated temperature in ambient lighting conditions.

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.

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.

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.

5 WARNINGS AND PRECAUTIONS

5.1 Bone 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) ]

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2024. All Rights Reserved.