Teniposide

Pronunciation: TEN-i-POE-side
Class: Podophyllotoxin derivative

Trade Names

Vumon
- Injection, concentrate 50 mg per 5 mL

Pharmacology

Teniposide is a phase-specific cytotoxic drug, acting in the late S or early G ₂ 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.

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Pharmacokinetics

Distribution

The volume of distribution is 3 to 11 L in children and 8 to 44 L/m ² in adults. Teniposide is highly protein bound (greater than 99%).

Elimination

Teniposide half-life is about 5 h. Total body Cl is approximately 25%; 44% is recovered in urine within 120 h after dosing, and 0% to 10% is recovered in feces after 72 h.

Special Populations

Exercise caution in patients with hepatic function impairment.

Indications and Usage

In combination with other approved anticancer agents, indicated for induction therapy in patients with refractory childhood lymphoblastic leukemia.

Unlabeled Uses

Adult acute lymphocytic leukemia, non-Hodgkin lymphoma.

Contraindications

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

Dosage and Administration

IV Teniposide 165 mg/m ² and cytarabine 300 mg/m ² twice weekly for 8 to 9 doses or, in patients refractory to vincristine/prednisone-containing regimens, teniposide 250 mg/m ² (in combination with vincristine 1.5 mg/m ² ) IV weekly for 4 to 8 wk and prednisone 40 mg/m ² orally for 28 days.

Dosage adjustments may be necessary in patients with renal or hepatic impairment.

General Advice

• Contact of undiluted teniposide with plastic equipment or devices to prepare solutions for infusions may result in softening or cracking and possible drug product leakage. This has not been reported with diluted solutions.
• Dilute with either dextrose 5% injection or sodium chloride 0.9% injection.
• Administer over at least a 30- to 60-min period.

Storage/Stability

Store refrigerated at 36° to 46°F. Protect form light. Diluted solutions in concentrations of 0.1, 0.2, or 0.4 mg/mL are stable at room temperature for up to 24 hours after preparation. Solutions prepared at a final concentration of 1 mg/mL should be administered within 4 h of preparation.

Drug Interactions

Teniposide plasma concentrations may be reduced, decreasing the efficacy.

Plasma Cl of methotrexate may be slightly increased.

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

May displace protein bound teniposide.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypotension (2%).

Dermatologic

Alopecia (9%); rash (3%).

GI

Mucositis (76%); diarrhea (33%); nausea/vomiting (29%).

Hematologic-Lymphatic

Neutropenia (95%); leukopenia (89%); anemia (88%); thrombocytopenia (85%); nospecified myelosuppression (75%); bleeding (5%).

Hypersensitivity

Hypersensitivity reactions characterized by bronchospasm, chills, dyspnea, fever, flushing, hypertension or hypotension, and tachycardia (5%).

Miscellaneous

Infection (12%); fever (3%).

Precautions

Pregnancy

Category D .

Lactation

Undetermined.

Children

Studies involved 303 patients (age range, 0.5 mo to 20 yr of age) who received teniposide as a single agent.

Hypersensitivity

Hypersensitivity reactions to polyoxyethylated castor oil have been reported.

Renal Function

Dosage reduction is advised in patients with renal function impairment. Specific recommendations are currently unavailable.

Hepatic Function

Exercise caution in patients with hepatic dysfunction. Dosage reduction is advised in patients with hepatic function impairment. Specific recommendations are currently unavailable.

Special Risk Patients

Patients with both Down syndrome and leukemia may be especially sensitive to myelosuppressive chemotherapy; therefore, reduce the initial dose of teniposide in these patients.

Anaphylaxis

Anaphylaxis manifested by chills, fever, tachycardia, bronchospasm, dyspnea, facial flushing, hypertension, or hypotension may occur.

Benzyl alcohol

Injection solution contains benzyl alcohol as a preservative, which has been associated with a fatal gasping syndrome in premature infants.

Extravasation risk

Local irritation or phlebitis may occur. Refer to your institution-specific protocol.

Hypotension

Administer by slow IV infusion because hypotension may occur with rapid IV injection.

Overdosage

Symptoms

Bone marrow suppression.

Patient Information

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

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