TOPOTECAN HYDROCHLORIDE

(toe-po-tee'can)

Hycamtin
Classifications: antineoplastic; camptothecin agent; topoisomerase i inhibitor;
Therapeutic: antineoplastic; topoisomerase i inhibitor
Pregnancy Category: D

Availability

4 mg injection

Action

Antitumor mechanism is related to inhibition of the activity of topoisomerase I, an enzyme required for DNA replication. Topoisomerase I is essential for the relaxation of supercoiled double-stranded DNA that enables replication and transcription to proceed.

Therapeutic Effect

Topotecan binds to the DNA-topoisomerase I complex. This permits uncoiling but prevents recoiling of the two strands of DNA, resulting in a permanent break in the DNA strands.

Uses

Metastatic ovarian cancer, small cell lung cancer.

Contraindications

Previous hypersensitivity to topotecan, irinotecan, or other camptothecin analogs; acute infection; severe bone marrow depression; severe thrombocytopenia; pregnancy (category D), lactation.

Cautious Use

Myelosuppression; severe renal impairment or renal failure; history of bleeding disorders; previous cytotoxic or radiation therapy.

Route & Dosage

Metastatic Ovarian Cancer and Small Cell Lung Cancer
Adult: IV 1.5 mg/m² daily for 5 d starting on day 1 of a 21 d course. Four courses of therapy recommended. Subsequent doses can be adjusted by 0.25 mg/m² depending on toxicity.

Renal Impairment
Cl_cr 20–39 mL/min: use 0.75 mg/m²
Hemodialysis: Supplementation not needed

Administration

Intravenous

Initiate therapy only if baseline neutrophil count ≥1500/mm³ and platelet count ≥100,000/mm³. Do not give subsequent doses until neutrophils ≥1000/mm³, platelets ≥100,000/mm³, and Hgb >9.0 mg/dL.
Note: Dosage adjustments to 0.75 mg/m² are recommended with moderate renal impairment.

PREPARE: IV Infusion: Reconstitute each 4-mg vial with 4 mL sterile water for injection to yield 1 mg/mL. Withdraw the required dose and inject into 50–100 mL of NS or D5W. If skin contacts drug during preparation, wash immediately with soap and water.

ADMINISTER: IV Infusion: Give over 30 min immediately after preparation.

INCOMPATIBILITIES Y-site: Dexamethasone, fluorouracil, mitomycin.

Store vials at 20°–25° C (68°–77° F); protect from light. Reconstituted vials are stable for 24 h.

Adverse Effects (≥1%)

Body as a Whole: Asthenia, fever, fatigue. GI: Nausea, vomiting, diarrhea, constipation, abdominal pain, stomatitis, anorexia, transient elevations in liver function tests. Hematologic: Leukopenia, neutropenia, anemia, thrombocytopenia. Respiratory: Dyspnea. Skin: Alopecia.

Interactions

Drug: Increased risk of bleeding with anticoagulants, nsaids, salicylates, antiplatelet agents.

Pharmacokinetics

Distribution: 35% bound to plasma proteins. Metabolism: Undergoes pH-dependent hydrolysis. Elimination:

30% in urine. Half-Life: 2–3 h.

Nursing Implications

Assessment & Drug Effects

Lab tests: Obtain CBC counts with differential frequently; periodically monitor ALT.
Assess for GI distress, respiratory distress, neurosensory symptoms, and S&S of infection throughout therapy.

Patient & Family Education

Learn common adverse effects and measures to control or minimize when possible. Immediately report any distressing adverse effects to physician.
Avoid pregnancy during therapy.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

(31)