Teniposide

A to Z Drug Facts

Actions Teniposide is a phase-specific cytotoxic drug, acting in the late S or early G₂ phase of the cell cycle, thus preventing cells from entering mitosis. Teniposide causes single- and double-stranded breaks in DNA and DNA: protein cross-links. The mechanism of action appears to be related to the inhibition of type II topoisomerase activity. The terminal half-life is 5 hr. The volume of distribution is 3 to 11 L in children and 8 to 44 L in adults. Renal elimination is 44%, fecal elimination is £ 10%, and 4% to 12% is excreted unchanged in the urine.

 Indications

Adult

Refractory childhood acute lymphoblastic leukemia.

Pediatric

Refractory acute lymphoblastic leukemia.

Adult acute lymphocytic leukemia, non-Hodgkin's lymphoma.

 Contraindications Hypersensitivity to teniposide or Cremophor EL (polyoxyethylated castor oil).

 Route/Dosage

Acute Lymphoblastic Leukemia

ADULTS: IV 165 mg/m² on days 1, 4, 8, and 11 during consolidation on the “Linker” regimen.

DOSAGE ADJUSTMENT: Reduce dose 50% during the first treatment course in patients with Down's syndrome and leukemia. Higher doses may be administered during subsequent courses, depending on the degree of myelosuppression.

Acute Lymphoblastic Leukemia, Combination Therapy

PEDIATRIC: IV 165 mg/m²/dose twice weekly for 8 to 9 doses; or 250 mg/m²/dose once a week for 4 to 8 wk in combination with other chemotherapeutic drugs.

DOSAGE ADJUSTMENT: Reduce dose 50% for the initial course of therapy. Depending on the degree of myelosuppression and mucositis which occur, higher doses may be given during subsequent courses.

Interactions

Methotrexate

Plasma clearance of methotrexate may be slightly increased.

Phenytoin

May increase clearance of teniposide, resulting in decreased therapeutic effects.

Tolbutamide, sodium salicylate, and sulfamethizole

May displace protein bound teniposide.

Lab Test Interferences None well documented.

 Adverse Reactions

CARDIOVASCULAR: Hypotension (with rapid IV administration or large doses). DERMATOLOGIC: Alopecia, rash. GI: Moderate to low potential for nausea and vomiting, mucositis, diarrhea. Mucositis may be more severe in patients with Down's syndrome and leukemia. HEMATOLOGIC: Bone marrow suppression, nadir at 3 to 14 days (usually occurs in 7 days), infection, bleeding. HYPERSENSITIVITY: Acute anaphylactoid reaction (5% frequency), incidence may be higher in brain tumor or neuroblastoma patients. OTHER: The risk of secondary acute non-lymphocytic leukemia was 12 times higher in children treated once or twice weekly for acute lymphoblastic leukemia than with regimens using less frequent administration schedules. Fever.

 Precautions

Pregnancy: Category D. Lactation: Undetermined. Adjustment in hepatic and renal dysfunction: Dosage reduction is advised in patients with impaired renal or hepatic function. Specific recommendations are currently unavailable. Anaphylaxis: Anaphylaxis manifested by chills, fever, tachycardia, bronchospasm, dyspnea, facial flushing, hypertension, or hypotension may occur. Extravasation risk: Local irritation or phlebitis may occur. Refer to your institution specific protocol. Hepatic function impairment: Exercise caution in patients with hepatic dysfunction. Hypersensitivity: Note hypersensitivity reactions to polyoxyethylated castor oil. Hypotension: Administer by slow IV infusion since hypotension may occur with rapid IV injection. Myelosuppression: Dose-limiting bone marrow suppression is the most significant toxicity.

 Administration/Storage

• Refrigerate unopened ampules in original package to protect from light.
• Dilute with 5% Dextrose or 0.9% Sodium Chloride for a final concentration of 0.1 mg/mL, 0.2 mg/mL, 0.4 mg/mL, or 1 mg/mL.
• Diluted solutions may leach DEHP from PVC infusion sets or bags. Use glass, polypropylene, or polyolefin containers.
• Solutions with a final concentration £ 0.4 mg/mL are stable at room temperature for £ 24 hr. Administer solutions with a final concentration of 1 mg/mL within 4 hr of preparation to prevent precipitation. Excessive shaking can cause precipitation. Refrigeration of diluted teniposide is not recommended.
• Administer IV.
• Infuse over ³ 30 to 60 min to decrease risk of hypotension.
• During 24-hr continuous infusion, teniposide can precipitate and obstruct a central venous catheter.
• The use of a non-PVC IV administration set is recommended.
• Heparin can cause precipitation of teniposide. Flush well with heparin-free solutions before and after administration.

 Assessment/Interventions

• Observe patients during and after the infusion for signs of hypersensitivity.
• Perform at the start of therapy and prior to each subsequent dose: Platelet count, hemoglobin, white bood cell count and differential. A platelet count < 50,000/mm³ or an absolute neutrophil count < 500/mm³ is an indication to withhold further therapy until the blood counts have sufficiently recovered.
• Carefully monitor renal and hepatic function tests prior to and during therapy.

 Patient/Family Education

• Contraceptive measures are recommended during treatment.
• Notify health care provider of the following: Fever; chills; rapid heartbeat; difficult breathing.

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