Drug reference

Topotecan

Topoisomerase Inhibitor · Antineoplastic

Topoisomerase InhibitorAntineoplastic

CDSCO approvedSchedule H

EXCRETION

—

not curated

INTERACTIONS

12 major

SEVERE in our sources

PREGNANCY

and reproductive function in

FDA category + note

Top interactionssee all 12 →

AdalimumabSevereDatabaseDDInter
BaricitinibSevereDatabaseDDInter
CarboplatinSevereDatabaseDDInter
CertolizumabSevereDatabaseDDInter

Mechanism

Topotecan is a camptothecin analog that functions as a topoisomerase I inhibitor. It stabilizes the covalent complex formed between topoisomerase I and DNA, preventing the re-ligation of single-strand DNA breaks. This action results in the accumulation of irreversible DNA damage during replication, ultimately leading to G2-M phase cell cycle arrest and subsequent apoptosis in cancerous cells.

Indications

Previously treated ovarian cancerPreviously treated small cell lung cancerCervical cancer (in conjunction with cisplatin)Metastatic carcinoma of ovarySmall cell lung cancerCervical cancer

Dosing

Adult: therapy, for the treatment of adults with persistent, recurrent, or metastatic carcinoma of the cervix. The case for cost-effectiveness has not been proven. l MEDICINAL FORMS There can be variation in the licensing of different medicines containing the same drug.…
Renal adjustment: Reduce dose in patients with moderate renal dysfunction (CLCr of 20–40 mL/min). Should not be administered to patients with severe renal impairment (CLCr <20 mL/min).

Pharmacokinetics

Half-life

3.5 to 4.1 h

Bioavailability

30% to 40% (oral form in development)

Protein binding

7%–35% (low plasma protein binding, may explain greater CNS penetration)

Metabolism

Hepatic metabolism appears to be a relatively minor route of drug elimination.

Excretion

30% to 40% of the administered dose appears in the urine within 24 h.

Contraindications

Severe renal impairment (CLCr <20 mL/min)
Baseline neutrophil count less than 1500 cells/mm3
Platelet count below 100,000

Side effects

Common

Neutropenia (dose-limiting toxicity, with or without thrombocytopenia)NauseaVomitingElevated liver transaminasesFeverFatigueRashPain abdomenAnorexiaDiarrhoea

Serious

Severe neutropenia (up to 81%, with 26% incidence of febrile neutropenia at 1.5 mg/m2 daily for 5 days every 3 weeks)
Mouth sores (mucositis) (in patients with hematological malignancies)
Diarrhea (in patients with hematological malignancies)
Bone marrow depression (especially neutropenia)