Hycamtin (Topotecan Hydrochloride) - Indications and Dosage

INDICATIONS AND USAGE

HYCAMTIN is indicated for the treatment of:

• metastatic carcinoma of the ovary after failure of initial or subsequent chemotherapy.
• 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).

DOSAGE AND ADMINISTRATION

Prior to administration of the first course of HYCAMTIN, patients must have a baseline neutrophil count of >1,500 cells/mm³ and a platelet count of >100,000 cells/mm³. The recommended dose of HYCAMTIN is 1.5 mg/m² 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 3 ovarian clinical trials was 9 to 12 weeks, and median time to response in 4 small cell lung cancer trials was 5 to 7 weeks. In the event of severe neutropenia during any course, the dose should be reduced by 0.25 mg/m² for subsequent courses. Doses should be similarly reduced if the platelet count falls below 25,000 cells/mm³. Alternatively, in the event of severe neutropenia, G-CSF may be administered following the subsequent course (before resorting to dose reduction) starting from day 6 of the course (24 hours after completion of topotecan administration).

Adjustment of Dose in Special Populations: Hepatic Impairment:    No dosage adjustment appears to be required for treating patients with impaired hepatic function (plasma bilirubin >1.5 to <10 mg/dL).

Renal Functional Impairment:    No dosage adjustment appears to be required for treating patients with mild renal impairment (Cl_cr 40 to 60 mL/min.). Dosage adjustment to 0.75 mg/m² 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.

Elderly Patients:    No dosage adjustment appears to be needed in the elderly other than adjustments related to renal function (see CLINICAL PHARMACOLOGY and PRECAUTIONS).

PREPARATION FOR ADMINISTRATION

Precautions:    HYCAMTIN is a cytotoxic anticancer drug. As with other potentially toxic compounds, HYCAMTIN should be prepared under a vertical laminar flow hood while wearing gloves and protective clothing. If HYCAMTIN solution contacts the skin, wash the skin immediately and thoroughly with soap and water. If HYCAMTIN contacts mucous membranes, flush thoroughly with water.

Preparation for Intravenous Administration:    Each HYCAMTIN 4-mg vial is reconstituted with 4 mL Sterile Water for Injection. Then the appropriate volume of the reconstituted solution is diluted in either 0.9% Sodium Chloride Intravenous Infusion or 5% Dextrose Intravenous Infusion prior to administration.

Because the lyophilized dosage form contains no antibacterial preservative, the reconstituted product should be used immediately.

STABILITY

Unopened vials of HYCAMTIN are stable until the date indicated on the package when stored between 20° and 25°C (68° and 77°F) [see USP] and protected from light in the original package. Because the vials contain no preservative, contents should be used immediately after reconstitution.

Reconstituted vials of HYCAMTIN diluted for infusion are stable at approximately 20° to 25°C (68° to 77°F) and ambient lighting conditions for 24 hours.

HOW SUPPLIED

HYCAMTIN for Injection is supplied in 4-mg (free base) single-dose vials.

NDC 0007-4201-01 (package of 1)

NDC 0007-4201-05 (package of 5)

Storage: Store the vials protected from light in the original cartons at controlled room temperature between 20° and 25°C (68° and 77°F) [see USP].

Handling and Disposal: Procedures for proper handling and disposal of anticancer drugs should be used. Several guidelines on this subject have been published. ^1-8 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.