[.
]
Action/Kinetics:
An inhibitor of topoisomerase I. Topoisomerase I relieves torsional strain in DNA by causing reversible single-strand breaks. Topotecan binds to the topoisomerase I-DNA complex and prevents religation of single-strand breaks. Cytotoxicity thought to be caused by double-strand DNA damage produced during DNA synthesis when replication enzymes interact with the ternary complex formed by topotecan, topoisomerase I, and DNA. Hydrolyzed to the active lactone form of the drug. About 30% of the drug is excreted in the urine.
t
1/2, terminal: 2 to 3 hr.
Uses:
Metastatic cancer of the ovary after failure of initial or subsequent chemotherapy. Small cell lung cancer sensitive disease after failure of first-line chemotherapy.
Contraindications:
Pregnancy, lactation. Severe bone marrow depression, including those with baseline neutrophil counts less than 1,500 cells/mm
3.
Special Concerns:
Safety and efficacy have not been determined in children.
Side Effects:
Hematologic: Bone marrow suppression, including neutropenia, thrombocytopenia, anemia, sepsis or fever/infection with grade 4 neutropenia, platelet or RBC infusions.
GI: N&V;, abdominal pain, constipation, diarrhea, intestinal obstruction, stomatitis.
CNS: Asthenia, headache, pain, paresthesias.
Musculoskeletal: Arthralgia, myalgia.
Body as a whole: Anorexia, fatigue, malaise, fever, pain.
Respiratory: Dyspnea, coughing.
Dermatologic: Total alopecia, rash, servere dermatitis, severe pruritus.
Miscellaneous: Chest pain, allergic reactions,
anaphylaxis, angioedema.
Laboratory Test Alterations:
AST, ALT, bilirubin.
Drug Interactions:
-
Cisplatin / More severe myelosuppression
-
Filgrastim / Prolonged duration of neutropenia
How Supplied:
Powder for injection: 4 mg
Dosage
?IV Infusion
Metastatic ovarian cancer, small cell lung cancer.
Adults: 1.5 mg/m
2 by IV infusion over 30 min daily for 5 consecutive days, starting on day 1 of a 21-day course of therapy. A minimum of four courses is recommended. If severe neutropenia occurs, reduce the dose by 0.25 mg/m
2 for subsequent courses. Also, for severe neutropenia, filgrastim may be given following the subsequent course and before dosage reduction starting from day 6 of the course (i.e., 24 hr after completion of topotecan administration).
Reduce the dose to 0.75 mg/m
2 for clients with a C
CR of 20-39 mL/min. No dosage reduction is required if the C
CR is 40-60 mL/min.
