Topotecan

What it is and how it works

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.

Indications

Topotecan Hydrochloride for injection is a topoisomerase inhibitor indicated for treatment of: Patients with metastatic ovarian cancer after disease progression on or after initial or subsequent chemotherapy, as a single agent Patients with small cell lung cancer (SCLC) platinum-sensitive disease who progressed at least 60 days after initiation of first-line chemotherapy, as a single agent Patients with Stage IV-B, recurrent, or persistent cervical cancer which is not amenable to curative treatment, in combination with cisplatin Ovarian Cancer Topotecan hydrochloride for injection, as a single agent, is indicated for the treatment of patients with metastatic ovarian cancer after disease progression on or after initial or subsequent chemotherapy. Small Cell Lung Cancer Topotecan hydrochloride for injection, as a single agent, 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.

Dosage and administration (summary)

Ovarian Cancer and Small Cell Lung Cancer: 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 ( 2.1 , 2.2 ) Cervical Cancer: 0.75 mg/m 2 by intravenous infusion over 30 minutes on Days 1, 2, and 3, with cisplatin 50 mg/m 2 on Day 1, of a 21-day cycle Renal Impairment: Reduce dose if creatinine clearance (CLcr) 20 to 39 mL/min Important Safety Information Verify dosage using body surface area. Do not exceed a single dose of 4 mg intravenously.

Contraindications

Topotecan Hydrochloride for Injection is contraindicated in patients who have a history of severe hypersensitivity reactions to topotecan. Reactions have included anaphylactoid reactions . History of severe hypersensitivity reactions to topotecan

Warnings and precautions

Interstitial Lung Disease (ILD): Fatal cases have occurred. Permanently discontinue if ILD confirmed. Extravasation and Tissue Injury: Severe cases have occurred. If extravasation occurs, immediately stop administration and institute recommended management procedures. Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of potential risk to the fetus and to use effectives contraception. ( 5.4 , 8.1 , 8.3 ) Myelosuppression Topotecan hydrochloride for injection can cause severe myelosuppression.

Pregnancy

Pregnancy Risk Summary Based on animal data and its mechanism of action, topotecan hydrochloride for injection can cause fetal harm when administered to a pregnant woman. There are no available clinical data on the use of topotecan hydrochloride for injection in pregnancy.

Storage and supply

Topotecan hydrochloride for injection is supplied as a sterile, lyophilized, yellow powder for reconstitution in 4-mg (free base) single-dose vials. NDC 16729-151-31 (package of 1) Store between 20°C and 25°C (68°F and 77°F) in original carton. Protect from light. Topotecan Hydrochloride for injection is a cytotoxic drug.

Source: Topotecan Hydrochloride (Topotecan Hydrochloride) — US FDA prescribing information, 2024-10-04, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.