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 Prior to administration of the first course of Hycamtin, patients must have the following:
Ovarian Cancer and Small Cell Lung CancerThe 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.
In the event of severe neutropenia during any course, the dose should be reduced by 0.25 mg/m² (to 1.25 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). Cervical CancerThe recommended dose of Hycamtin is 0.75 mg/m² by intravenous infusion over 30 minutes daily on days 1, 2, and 3; followed by cisplatin 50 mg/m² by intravenous infusion on day 1 repeated every 21 days (a 21-day course). Dosage adjustments for subsequent courses of Hycamtin in combination with cisplatin are specific for each drug.
Adjustments for Special Populations Preparation for Administration Stability How Supplied Adjustments for Special PopulationsHepatic 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 (CLcr 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. Hycamtin in combination with cisplatin for the treatment of cervical cancer should be initiated only 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 Hycamtin after cisplatin discontinuation in patients with cervical cancer. Elderly Patients: No dosage adjustment appears to be needed in the elderly other than adjustments related to renal function. Preparation for AdministrationPrecautions: 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 4-mg vial of Hycamtin is reconstituted with 4 mL Sterile Water for Injection. The appropriate volume of the reconstituted solution is then 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. StabilityUnopened vials of Hycamtin are stable until the date indicated on the package when stored between 20°C and 25°C (68°F 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°C to 25°C (68°F to 77°F) and ambient lighting conditions for 24 hours. How SuppliedHycamtin 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°C and 25°C (68°F 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. There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate. Important Safety InformationIndicationsHycamtin is indicated for the treatment of metastatic carcinoma of the ovary after failure of initial or subsequent chemotherapy.Hycamtin is indicated for the treatment of small cell lung cancer sensitive disease after failure of first-line chemotherapy.*
Hycamtin in combination with cisplatin is indicated for the treatment of histologically confirmed Stage IV-B, recurrent, or persistent carcinoma of the cervix which is not amenable to curative treatment with surgery and/or radiation therapy. ContraindicationsHycamtin is contraindicated in patients who have a history of hypersensitivity reactions to topotecan or to any of its ingredients. Hycamtin should not be used in patients who are pregnant or breast-feeding, or those with severe bone marrow depression.WarningsHycamtin should be used only in patients with adequate bone marrow reserves, including baseline neutrophil counts of at least 1,500 cells/mm³ and platelet counts of at least 100,000/mm³. Frequent monitoring of blood counts should be instituted during treatment with Hycamtin.Patients should not be treated with subsequent courses of Hycamtin until neutrophils recover to >1,000 cells/mm³, platelets recover to >100,000 cells/mm³, and hemoglobin levels recover to 9.0 g/dL (with transfusion if necessary). Severe myelotoxicity has been reported when 5-day dosing of Hycamtin is used in combination with cisplatin. Hycamtin may cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised to avoid becoming pregnant during therapy with Hycamtin. Drug InteractionsConcomitant administration of G-CSF can prolong the duration of neutropenia, so if G-CSF is to be used, it should not be initiated until 24 hours after completion of treatment with Hycamtin.Myelosuppression was more severe when Hycamtin, at a dose of 1.25 mg/m²/day x 5 days, was given in combination with cisplatin at a dose of 50 mg/m² in phase I studies. In one study, 1 of 3 patients had severe neutropenia for 12 days, and a second patient died with neutropenic sepsis. Dosing for Ovarian Cancer/Small Cell Lung CancerPrior 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 (to 1.25 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 24 hours after completion of administration of Hycamtin. Dosing for Cervical CancerPrior to administration of the first course of Hycamtin, patients must have a baseline absolute neutrophil count of >1,500 cells/mm³ and a platelet count of >100,000 cells/mm³. The recommended dose of Hycamtin is 0.75 mg/m² by intravenous infusion over 30 minutes daily on days 1, 2, and 3; followed by cisplatin 50 mg/m² by intravenous infusion on day 1 repeated every 21 days (a 21-day course).Dosage adjustments for subsequent courses of a regimen of Hycamtin in combination with cisplatin are specific for each drug. In the event of severe febrile neutropenia (defined as <1,000 cells/mm³ with temperature of 38.0°C or 100.4°F), the dose of Hycamtin should be reduced by 20% to 0.60 mg/m² for subsequent courses. Doses of Hycamtin should be similarly reduced (by 20% to 0.60 mg/m²) if the platelet count falls below 10,000 cells/mm³. Alternatively, in the event of severe febrile neutropenia, G-CSF may be administered following the subsequent course (before resorting to dose reduction) starting from day 4 of the course (24 hours after completion of topotecan administration). If febrile neutropenia occurs despite the use of G-CSF, the dose of Hycamtin should be reduced by another 20% to 0.45 mg/m² for subsequent courses. Adverse Events for Ovarian Cancer/Small Cell Lung CancerThe most common serious adverse event is myelosuppression.Severe neutropenia, the dose-limiting toxicity for Hycamtin, occurred in 78% of 879 ovarian and small cell lung cancer patients treated. Other hematologic adverse events reported include severe leukopenia (32%), severe thrombocytopenia (27%), and severe anemia (37%). Frequently reported nonhematologic adverse events associated with use of Hycamtin included nausea (64%), vomiting (45%), diarrhea (32%), alopecia (49%), fatigue (29%), and dyspnea (22%). Most nonhematologic toxicities were grade 1 or 2. Adverse Events for Cervical CancerThe most common serious adverse event is myelosuppression.Frequently reported grade 3/4 adverse events associated with use of Hycamtin/cisplatin included neutropenia (74%), leukopenia (66%), anemia (40%), thrombocytopenia (33%), pain (22%), vomiting (15%), nausea (14%), other GI (14%), metabolic/laboratory (14%), and genitourinary (12%). See manufacturer’s Prescribing Information for cisplatin administration and hydration guidelines, and for cisplatin dosage adjustment in the event of hematologic toxicity. |
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