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Topotecan

TOPOTECAN

Standard Dose

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 ) 2.1 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 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.

Max Dose

See official label

Primary Use

1 INDICATIONS AND USAGE Topotecan Injection is indicated for the treatment of: small cell lung cancer sensitive disease after failure of first-line chemotherapy.

Summary

Indications and usage 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 ) ] .

Structured Monograph

Clinical summary

Indications and usage 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 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 ) 2.1 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 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. Warnings and cautions 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 ) 5.1 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 ( 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 ) ] 5.2 Neutropenic

Boxed Warning

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 )

Monitoring

• 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.

Interaction Notes

• 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.