Topotecan
Generic Name: topotecan
Brand Names:
Topotecan
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.
Overview
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.
Uses
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.
Dosage
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.
Side Effects
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.
Interactions
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.
Warnings
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 . 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. 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.
Pregnancy
8.1 Pregnancy 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.
Storage
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 excursio...
Frequently Asked Questions
What is Topotecan used for?▼
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.
What are the side effects of Topotecan?▼
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.
Can I take Topotecan during pregnancy?▼
8.1 Pregnancy 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.
What are the important warnings for Topotecan?▼
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 . 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. 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.
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Medical Disclaimer
This drug information is for educational purposes only and should not replace professional medical advice. Drug information is sourced from the FDA National Drug Code Directory and Structured Product Labeling. Always consult with a healthcare provider before starting, stopping, or changing any medication.