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topotecan (Hycamtin, SKF-104864A, Topo, TPT)

Tradename: Hycamtin. Indications: - treatment of metastatic ovarian cancer - after failure of initial therapy - treatment of recurrent & stage IVB cervical cancer in combination with cisplatin - ONLY if patient has NOT previously received cisplatin (NGC NICE) - relapsed small-cell lung cancer - oral topotecan, IV not recommmended - Ewing sarcoma [2] - osteosarcoma [2] Contraindications: 1) pregnant or breast-feeding women 2) severe bone marrow suppression Lyophilized powder: 1) store at room temperature & protect from light 2) reconstitute with 4 mL sterile water for injection (SWI) 3) further dilute in 100 mL D5W 4) 2.5 mg/mL + 50 mg of mannitol, pH = 3.5 when reconstituted with 2 mL sterile water for injection (SWI) 5) 4 mg base/vial (as HCl) Monitor: 1) complete blood count (CBC) 2) renal function tests Adverse effects: 1) common (> 10%) - headache, alopecia (reversible), nausea/vomiting, diarrhea, myelosuppression 2) less common (1-10%) - paresthesia, dyspnea 3) uncommon (< 1%) - mild erythema & bruising 4) other - emetic potential is moderately low (10-30%) - myelosuppression - dose-limiting toxicity - WBC mild to severe, platelets mild at low doses - nadir 8-11 days - recovery 14-21 days - may cause permanent sterility Drug interactions: 1) increased toxicity with filgastim (G-CSF) 2) coadministration with other antineoplastic agents is associated with increased morbidity & mortality (i.e. cisplatin) Laboratory: - topotecan in serum/plasma Mechanism of action: - inhibits topoisomerase-1

General

topoisomerase-1 inhibitor

Properties

MISC-INFO: pregnancy-category D

Database Correlations

PUBCHEM correlations

References

  1. Kaiser Permanente Northern California Regional Drug Formulary, 1998 Health and Clinical Excellence (NICE) ngc-guideline: 15543
  2. Deprecated Reference