No

Antineoplastic Agent, Natural Source (Plant) Derivative

Treatment of metastatic carcinoma of the ovary after failure of initial or subsequent chemotherapy; second-line treatment of small cell lung cancer

D

Hypersensitivity to any component, pregnancy, breast-feeding

The U.S. Food and Drug Administration (FDA) currently recommends that procedures for proper handling and disposal of antineoplastic agents be considered; monitor bone marrow function

>10%:

Central nervous system: Headache

Dermatologic: Alopecia (reversible)

Gastrointestinal: Nausea, vomiting, diarrhea

Emetic potential: Moderately low (10% to 30%)

Hematologic: Myelosuppressive: Principle dose-limiting toxicity; white blood cell count nadir is 8-11 days after administration and is more frequent than thrombocytopenia (at lower doses); recover is usually within 21 days and cumulative toxicity has not been noted

WBC: Mild to severe

Platelets: Mild (at low doses)

Nadir (days): 8-11

Recovery (days): 14-21

1% to 10%:

Neuromuscular & skeletal: Paresthesia

Respiratory: Dyspnea

<1%: Mild erythema and bruising

Increased toxicity: Filgrastim (G-CSF): Prolonged/severe neutropenia and thrombocytopenia; concomitant administration with other antineoplastics has been associated with increased morbidity/mortality - not recommended (eg, cisplatin)

Store intact vials of lyophilized powder for injection at room temperature and protected from light. Topotecan should be initially reconstituted with 4 mL SWI. This solution is stable for 24 hours at room temperature. Topotecan should be further diluted in 100 mL D₅W. This solution is stable for 24 hours at room temperature.

Standard I.V. dilution: Dose/100 mL D₅W; stability is pH dependent; although topotecan may be further diluted in 0.9% NaCl, stability is longer in D₅W

Inhibits topoisomerase I (an enzyme which relaxes torsionally strained-coiled duplex DNA) to prevent DNA replication and translocation; topotecan acts in S phase

Absorption: Oral: ~30%

Distribution: V_dss of the lactone is high (mean: 87.3 L/mm²; range: 25.6-186 L/mm²), suggesting wide distribution and/or tissue sequestering

Metabolism: Topotecan (TPT) undergoes a rapid, pH-dependent opening of the lactone ring to yield a relatively inactive hydroxy acid in plasma.

Half-life: 3 hours

Protein binding: 35%

Elimination: Primarily renal, with 30% of dose eliminated within 24 hours

Refer to individual protocols:

Metastatic ovarian cancer and small cell lung cancer: IVPB: 1.5 mg/m²/day for 5 days; repeated every 21 days (neutrophil count should be >1500/mm³ and platelet count should be >100,000/mm³)

Dosage adjustment for hematological effects: If neutrophil count <1500/mm³, reduce dose by 0.25 mg/m²/day for 5 days for next cycle

Dosing adjustment in renal impairment:

Cl_cr 20-39 mL/minute: Administer 50% of normal dose

Cl_cr <20 mL/minute: Do not use, insufficient data available

Hemodialysis: Supplemental dose is not necessary

CAPD effects: Unknown

CAVH effects: Unknown

Dosing adjustment in hepatic impairment: Bilirubin 1.5-10 mg/dL: Adjustment is not necessary

CBC with differential and platelet count and renal function tests

None known

None reported

May cause myelosuppression; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

This medication can only be administered I.V. and frequent blood tests may be necessary to monitor effects of the drug. Report pain, swelling, or irritation at infusion site. Do not use alcohol and prescription or OTC medications without consulting prescriber. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake); maintain good oral hygiene (use soft toothbrush or cotton applicators several times a day and rinse mouth frequently). You may experience nausea, vomiting, or loss of appetite (frequent small meals, frequent mouth care, sucking lozenges, or chewing gum may help, or consult prescriber). Hair loss may occur (reversible). You will be susceptible to infection; avoid crowds and infected persons and do not receive any vaccinations unless approved by prescriber. Report persistent fever or chills, unhealed sores, oral or vaginal sores, foul-smelling urine, painful urination, easy bruising or bleeding, yellowing of eyes or skin, and change in color of urine or stool. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Do not breast-feed.

Powder for injection, as hydrochloride, lyophilized: 4 mg (base)