Aminocamptothecin

PHARMACOLOGIC CATEGORY Antineoplastic Agent, DNA Binding AgentEnzyme Inhibitor, Topoisomerase I Inhibitor
DOSING: ADULTS — I.V.: 45-59 mcg/m2/hour for 72 hours as a continuous infusion; repeat every 2 weeks or 35 mcg/m2/hour as a 72-hour continuous infusion
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection: 5 mg ampul
DOSAGE FORMS: CONCISE Injection: 5 mg ampul [not available in the U.S.; investigational]
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer by continuous I.V. infusion.
USE - UNLABELED / INVESTIGATIONAL — Phase II trials: Relapsed lymphoma, refractory breast cancer, nonsmall cell lung cancer, untreated colorectal carcinoma
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Central nervous system: Fatigue
Dermatologic: Alopecia
Gastrointestinal: Nausea, vomiting, diarrhea, mucositis, anorexia
Hematologic: Neutropenia (may be dose limiting), thrombocytopenia (reversible, but may be dose limiting), anemia
CONTRAINDICATIONS — Hypersensitivity to aminocamptothecin or any component of the formulation
WARNINGS / PRECAUTIONS Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.
RESTRICTIONS — Not available in U.S./Investigational
DRUG INTERACTIONS — Patients taking anticonvulsants that induce hepatic enzymes have less toxicity and can tolerate higher doses of aminocamptothecin.
MONITORING PARAMETERS — WBC with differential, platelet count
MECHANISM OF ACTION — Aminocamptothecin binds to topoisomerase I, stabilizing the cleavable DNA-topoisomerase I complex, resulting in arrest of the replication fork and inhibition of DNA synthesis.
PHARMACODYNAMICS / KINETICS — Ratio of lactone to total drug is 8.7% +/- 4.7% because of instability of aminocamptothecin lactone in plasma.
Distribution: Vd: 46-92 L
Metabolism: None identified
Half-life elimination: Terminal: 8-17 hours for total aminocamptothecin
Excretion: Urine (32% of total drug delivered)