Topotecan HCl

A to Z Drug Facts

Actions Topotecan HCl is an antitumor drug with topoisomerase I-inhibitory activity. The mean volume of distribution at steady state is between 17 to 22 L/m² for topotecan and 26 to 563 L/m² for its active lactone moiety. Topotecan undergoes a reversible pH-dependent hydrolysis of its lactone moiety; it is the lactone form that is pharmacologically active. Topotecan exhibits multiexponential pharamacokinetics with a terminal half-life of 2 to 3 hr. About 30% of the dose is excreted in the urine. Total exposure (AUC) is approximately dose-proportional. Binding of topotecan to plasma proteins is approximately 35%.

 Indications Relapsed or refractory metastatic ovarian cancer; relapsed or refractory small-cell lung cancer.

Non-small-cell lung cancer.

 Contraindications Hypersensitivity to topotecan or to any of its ingredients; patients who are pregnant or breastfeeding; severe bone marrow depression.

 Route/Dosage

Ovarian or Small-Cell Lung Cancer

ADULTS: IV Topotecan 1.5 mg/m²/day over 30 min daily for 5 consecutive days starting on day 1 of a 21-day cycle. Tumor response may be delayed; administer at least 4 cycles provided the tumor is not progressing. Before giving each dose, the patient should have a neutrophil count greater than 1500/mm³ and a platelet count greater than 100,000/mm³.

Dosage Adjustment

ADULTS: IV If neutropenia develops (defined as ANC less than 1500/mm³), reduce the dose 0.25 mg/m² for subsequent doses. Alternately, a course of filgrastim may be started on day 6 of each subsequent cycle; give the first filgrastim dose 24 hr after the final topotecan dose.

Renal Function Impairment

ADULTS: IV Dosage adjustment is recommended in patients with moderate renal impairment for Ccr of 20 to 39 mL/min, give 50% of usual dose, for Ccr less than 20 mL/min reduce dose. Specific recommendations not available.

Interactions

Cisplatin

Myelosuppression is more severe when topotecan is given in combination with cisplatin.

Filgrastim

Coadministration can prolong the duration of neutropenia. If filgrastim is used, do not initiate until day 6 of the course of therapy, 24 hr after completion of treatment with topotecan.

Lab Test Interferences None well documented.

 Adverse Reactions

CNS: Fatigue; headache; paresthesias; neuropathy. DERMATOLOGIC: Alopecia; rashes; pruritus. GI: Nausea; vomiting; diarrhea; constipation, abdominal pain; stomatitis; anorexia; mucositis. GU: Microscopic hematuria. HEMATOLOGIC: Neutropenia; thrombocytopenia; anemia. RESPIRATORY: Dyspnea.

 Precautions

Pregnancy: Category D. Lactation: Discontinue breastfeeding. Children: Safety and efficacy have not been established. Anemia: Severe anemia (grade 3/4, Hgb less than 8 g/dL) occurred. Bone marrow suppression (primary neutropenia): Bone marrow suppression (primary neutropenia) is the dose-limiting toxicity of topotecan. Administer only to patients with adequate bone marrow reserves, including baseline neutrophil counts of at least 1500 cells/mm³ and platelet counts of at least 100,000/mm³. Extravasation: Topotecan is an irritant; inadvertent extravasation may produce mild local reactions such as erythema and bruising. Neutropenia: Grade 4 (less than 500 cells/mm³) neutropenia was most common during course 1 of treatment. Thrombocytopenia: Grade 4 thrombocytopenia (less than 25,000 cells/mm³) occurred.

 Administration/Storage

• Protect vials from light in the original cartons at controlled room temperature 20° to 25°C (68° to 77°F). Reconstituted vials of topotecan diluted for infusion are stable at approximately 20° to 25°C (68° to 77°F) and ambient lighting conditions for 24 hr.
• Reconstitute each vial of powder with 4 mL of Sterile Water for Injection, for a final concentration of 1 mg/mL.
• Further dilute reconstituted solution with 0.9% Sodium Chloride or 5% Dextrose.
• Diluted solutions are chemically stable for up to 4 days at room temperature or for up to 7 days under refrigeration. Refrigerate preservative-free solutions and use within 24 hr. With prolonged storage, the possibility of microbial contamination must be considered.
• Administer by IV infusion over 30 min.

 Assessment/Interventions

• Prior to administration of the first course of topotecan, patients must have a baseline neutrophil count of greater than 1500 cells/mm³ and a platelet count of greater than 100,000 cells/mm³.
• Administer topotecan under the supervision of a health care provider experienced in the use of cancer chemotherapeutic agents.
• Do not give topotecan therapy to patients with baseline neutrophil counts of less than 1500 cells/mm³.
• Perform frequent peripheral blood cell counts on all patients receiving topotecan. Do not treat patients with subsequent courses until neutrophils recover to more than 1000 cells/mm³, platelets recover to more than 100,000 cells/mm³, and hemoglobin levels recover to 9 g/dL (with transfusion if necessary).

 Patient/Family Education

• Explain name, action, and potential side effects of drug.
• Advise patient, family, or caregiver that medication will be prepared and administered by health care provider in a health care setting.
• Review dosing schedule with patient, family, or caregiver.
• Advise patient, family, or caregiver that medication may cause hair loss but that it is reversible when therapy is stopped.
• Advise patient, family, or caregiver to immediately report any of the following to health care provider: fever, chills, or other signs of infection; unusual bleeding or bruising; pain, redness, or swelling at injection site.
• Advise patient, family, or caregiver to report any of the following to health care provider: persistent nausea, vomiting, diarrhea, or appetite loss; persistent or worsening general body weakness.
• Caution patient that medication may cause weakness or fatigue and to use caution when driving or performing other tasks that require mental alertness or coordination.
• Instruct patient not to take any prescription or OTC medications or dietary supplements unless advised to do so by health care provider.
• Caution women of childbearing potential to avoid becoming pregnant during therapy.
• Instruct women of childbearing potential to notify health care provider if pregnant, planning to become pregnant, or breastfeeding.
• Advise patient, family, or caregiver that frequent follow-up visits and laboratory tests will be required to monitor therapy and to keep appointments.

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Copyright © 2003 Facts and Comparisons
David S. Tatro
A to Z Drug Facts