Topotecan Hydrochloride (3 brand names, 3 dosage forms, 3 routes)
Available dosage forms: SOLUTION, INJECTABLE, CAPSULE.
Routes of administration: INTRAVENOUS, INJECTION, ORAL.
Brand Names
- HYCAMTIN
- TOPOTECAN
- TOPOTECAN HYDROCHLORIDE
Boxed Warning
Topotecan hydrochloride can cause severe myelosuppression. Administer first cycle only to patients with baseline neutrophil counts of greater than or equal to 1,500/mm3 and platelet counts greater than or equal to 100,000/mm3. Monitor blood cell counts [see Warnings and Precautions (5.1)].
Contraindications
Topotecan hydrochloride is contraindicated in patients who have a history of severe hypersensitivity reactions to topotecan. Reactions have included anaphylactoid reactions [see Adverse Reactions (6.2)].
Adverse Reactions
The following serious adverse reactions are described elsewhere in the labeling: •Myelosuppression [see Warnings and Precautions (5.1)] •Interstitial Lung Disease (ILD) [see Warnings and Precautions (5.2)] •Extravasation and Tissue Injury [see Warnings and Precautions (5.3)]
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.
Overdosage
Overdoses (up to 10-fold of the recommended dose) have occurred in patients receiving intravenous topotecan. The primary complication of overdosage is myelosuppression. Elevated hepatic enzymes, mucositis, gastrointestinal toxicity, and skin toxicity have occurred with overdosages. If an overdose is suspected, monitor the patient closely for myelosuppression and institute supportive-care measures as appropriate.