Overview
11 DESCRIPTION Topotecan is a semi-synthetic derivative of camptothecin and a topoisomerase inhibitor. The chemical name for topotecan hydrochloride 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 1.25 hydrochloride. It has the molecular formula C 23 H 23 N 3 O 5 ∙xHCl (x=1.25) and a molecular weight of 467.02.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Topoisomerase I relieves torsional strain in DNA by inducing reversible single-strand breaks. Topotecan binds to the topoisomerase I-DNA complex and prevents re-ligation of these single-strand breaks. The cytotoxicity of topotecan is thought to be due to double-strand DNA damage produced during DNA synthesis, when replication enzymes interact with the ternary complex formed by topotecan, topoisomerase I, and DNA. Mammalian cells cannot efficiently repair these double-strand breaks. 12.3 Pharmacokinetics Following administration of topotecan at doses of 0.5 to 1.5 mg/m 2 (0.3 to 1 times the recommended dose) administered as a 30-minute infusion, area under the curve (AUC) increases approximately proportional with dose.
Indications
- 1 INDICATIONS AND USAGE Topotecan Injection is indicated for the treatment of patients with small cell lung cancer (SCLC) with platinum-sensitive disease who progressed at least 60 days after initiation of first-line chemotherapy. Topotecan Injection is a topoisomerase inhibitor indicated for treatment of small cell lung cancer (SCLC) platinum-sensitive disease in patients who progressed at least 60 days after initiation of first-line chemotherapy. ( 1 )
Common Doses
- 1.5 mg
- 39 mL
- 4 mg
- 9 g
Dosage
2 DOSAGE AND ADMINISTRATION Recommended dosage : 1.5 mg/m 2 by intravenous infusion over 30 minutes daily for 5 consecutive days, starting on Day 1 of a 21-day cycle. ( 2.2 ) Renal impairment : Reduce dose for creatinine clearance (CLcr) of 20 to 39 mL/min. ( 2.4 ) 2.1 Important Safety Information Verify dosage using body surface area. Do not exceed a single dose of 4 mg intravenously. 2.2 Recommended Dosage for Small Cell Lung Cancer The recommended dosage of Topotecan Injection is 1.
Black Box Warning
WARNING: MYELOSUPPRESSION Topotecan can cause severe myelosuppression. Administer first cycle only to patients with baseline neutrophil counts of greater than or equal to 1,500/mm 3 and platelet counts greater than or equal to 100,000/mm 3 . Monitor blood cell counts [see Warnings and Precautions (5.1) ] . WARNING: MYELOSUPPRESSION See full prescribing information for complete boxed warning. Topotecan can cause severe myelosuppression.
Contraindications
- 4 CONTRAINDICATIONS Topotecan Injection is contraindicated in patients who have a history of severe hypersensitivity reactions to topotecan. Reactions have included anaphylactoid reactions [see Adverse Reactions (6.2) ] . History of severe hypersensitivity reactions to topotecan. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Myelosuppression [see Warnings and Precautions (5.1) ] Interstitial Lung Disease [see Warnings and Precautions (5.2) ] Extravasation and Tissue Injury [see Warnings and Precautions (5.3) ] The most common Grade 3 or 4 hematologic adverse reactions (incidence >5%) were: neutropenia , anemia , thrombocytopenia, and febrile neutropenia. ( 6.1 ) The most common non-hematologic adverse reactions (incidence >5%) (all grades) were asthenia, dyspnea, nausea, pneumonia, abdominal pain, and fatigue. ( 6.
Interactions
- No major interactions listed on the FDA label. Always consult a healthcare professional.