Action

Damages DNA before mitosis by inhibiting topoisomerase II enzyme. This action impairs DNA synthesis and inhibits selected cancer cell growth. Cell-cycle-phase specific.

Availability

Capsules: 50 mg

Injection: 20 mg/ml

Powder for injection (phosphate): 100 mg in single-dose vials

Indications and dosages

➣ Testicular cancer

Adults: 50 to 100 mg/m² I.V. daily for 5 days. Or 100 mg/m² I.V. on days 1,3, and 5, with course repeated q 3 to 4 weeks.

➣ Small-cell carcinoma of lung

Adults: 70 mg/m² (rounded up or down to nearest 50 mg) P.O. daily for 4 days, then a maximum of 100 mg/m² (rounded up or down to nearest 50 mg) P.O. daily for 5 days every 3 to 4 weeks. Alternatively, 35 mg/m² I.V. daily for 4 days, then a maximum of 50 mg/m² I.V. daily for 5 days q 3 to 4 weeks.

Dosage adjustment

• Renal impairment

Off-label uses

• AIDS-related Kaposi's sarcoma

• Wilms' tumor

• Neuroblastoma

• Malignant lymphoma

• Hodgkin's disease

• Ovarian neoplasms

Contraindications

• Hypersensitivity to drug or its components

Precautions

Use cautiously in:

• active infections, decreased bone marrow reserve, renal or hepatic impairment

• pregnant patients and patients with childbearing potential

• breastfeeding patients

• children (safety and efficacy not established).

Administration

• For I.V. concentrations above 0.4 mg/ml, mix each 100 mg with 250 to 500 ml of dextrose 5% in water or normal saline solution, to help prevent crystallization.

• Give I.V. infusion over 30 to 60 minutes. Don't use in-line filter.

See Avoid rapid infusion, which may cause severe hypotension and bronchospasm.

• Administer with antiemetics, as prescribed.

• Wear disposable gloves when handling. If drug comes into contact with skin, wash thoroughly with soap and water.

• Be aware that drug is given with other chemotherapeutic agents.

Adverse reactions

CNS: drowsiness, fatigue, headache, vertigo, peripheral neuropathy

CV: hypotension (with I.V. use), heart failure, myocardial infarction

GI: nausea, vomiting, stomatitis

GU: sterility

Hematologic: anemia, leukopenia, thrombocytopenia, bone marrow depression

Hepatic: hepatotoxicity

Metabolic: hyperuricemia

Musculoskeletal: muscle cramps

Respiratory: pulmonary edema, bronchospasm

Other: alopecia, fever, phlebitis at I.V. site, allergic reactions including anaphylaxis

Interactions

Drug-drug. Live-virus vaccines: increased risk of adverse reactions

Other antineoplastics: additive bone marrow depression

Drug-diagnostic tests. Hemoglobin, neutrophils, platelets, red blood cells, white blood cells: decreased values

Uric acid: increased level

Patient monitoring

See Monitor blood pressure during and after infusion. Stop infusion if severe hypotension occurs.

• With I.V. use, monitor infusion rate closely to prevent infusion reactions.

• Throughout infusion, check I.V. site for extravasation, which may cause thrombophlebitis.

See Keep diphenhydramine, hydrocortisone, epinephrine, and artificial airway at hand in case anaphylaxis occurs.

• Assess for CNS adverse effects. Assist patient during ambulation as needed.

See Monitor for signs and symptoms of bone marrow depression.

• Monitor CBC, liver function tests, and blood urea nitrogen and creatinine levels. Report platelet count below 50,000/mm³ or neutrophil count below 500/mm³.

Patient teaching

• Instruct patient to inspect mouth daily for ulcers and bleeding gums.

See Tell patient to immediately report difficulty breathing or signs and symptoms of allergic reaction.

See Caution female of childbearing age to avoid pregnancy and breastfeeding during drug therapy.

• Instruct patient to move slowly when sitting up or standing, to avoid lightheadedness or dizziness from sudden blood pressure decrease.

• Tell patient drug may cause hair loss.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.