No

Antineoplastic Agent, Miscellaneous

Treatment of acute lymphocytic leukemia, small cell lung cancer

D

Hypersensitivity to teniposide or Cremophor EL (polyoxyethylated castor oil) any component

The U.S. Food and Drug Administration (FDA) currently recommends that procedures for proper handling and disposal of antineoplastic agents be considered. Administer I.V. infusions over a period of at least 30-60 minutes, must be diluted, do not administer IVP. Teniposide contains benzyl alcohol, which has been associated with a fatal "gasping" syndrome in premature infants.

>10%:

Gastrointestinal: Mucositis, nausea, vomiting, diarrhea

Hematologic: Myelosuppression, leukopenia, neutropenia, thrombocytopenia

Miscellaneous: Infection

1% to 10%:

Cardiovascular: Hypotension

Central nervous system: Fever

Dermatologic: Alopecia, rash

Hematologic: Hemorrhage

Miscellaneous: Hypersensitivity

<1%: Metabolic abnormalities, hepatic dysfunction, peripheral neurotoxicity, renal dysfunction

Symptoms of overdose include bone marrow suppression, leukopenia, thrombocytopenia, nausea, vomiting

Treatment is supportive

CYP3A3/4 enzyme substrate; CYP2C19 enzyme inhibitor

Methotrexate: Alteration of MTX transport has been found as a slow efflux of MTX and its polyglutamated form out of the cell, leading to intercellular accumulation of MTX

Sodium salicylate, sulfamethizole, tolbutamide: displace teniposide from protein-binding sites - could cause substantial increases in free drug levels, resulting in potentiation of toxicity

Store ampuls in refrigerator at 2°C to 8°C (36°F to 46°F); reconstituted solutions are stable at room temperature for up to 24 hours after preparation. Teniposide must be diluted with either D₅W or 0.9% sodium chloride solutions to a final concentration of 0.1, 0.2, 0.4 or 1 mg/mL. In order to prevent extraction of the plasticizer DEHP, solutions should be prepared in non-DEHP-containing containers such as glass or polyolefin containers. The use of polyvinyl chloride (PVC) containers is not recommended. Administer 1 mg/mL solutions within 4 hours of preparation to reduce the potential for precipitation. Precipitation may occur at any concentration. Incompatible with heparin.

Inhibits mitotic activity; inhibits cells from entering mitosis

Distribution: V_d: 0.28 L/kg; distributed mainly into liver, kidneys, small intestine, and adrenals; crosses blood-brain barrier to a limited extent

V_d: 3-11 L (children); 8-44 L (adults)

Protein binding: 99.4%

Metabolism: Extensively in the liver

Half-life: 5 hours

Elimination: In urine (21% as unchanged drug); renal (44%) and fecal ( less than or equal to 10%)

I.V.:

Adults: 50-180 mg/m² once or twice weekly for 4-6 weeks or 20-60 mg/m²/day for 5 days

Acute lymphoblastic leukemia (ALL): 165 mg/m² twice weekly for 8-9 doses or 250 mg/m² weekly for 4-8 weeks

Small cell lung cancer: 80-90 mg/m²/day for 5 days

Dosage adjustment in renal/hepatic impairment: Data is insufficient, but dose adjustments may be necessary in patient with significant renal or hepatic impairment

Dosage adjustment in Down syndrome patients: Reduce initial dosing; administer the first course at half the usual dose. Patients with both Down syndrome and leukemia may be especially sensitive to myelosuppressive chemotherapy.

None reported

Myelosuppression is common; avoid clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

This drug can only be administered I.V. You will require regular blood tests to assess response to therapy. For nausea or vomiting, small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help, antiemetics may be prescribed. You may experience hair loss or loss of appetite (maintaining adequate nutrition is important). Report unusual bleeding or bruising, persistent fever or chills, sore throat, sores in mouth or vagina, or difficulty breathing. Pregnancy/breast-feeding precautions: Do not get pregnant while taking this medication; use appropriate barrier contraceptive measures. Breast-feeding is not recommended.

Monitor blood pressure during infusion; observe for chemical phlebitis at injection site

Injection: 10 mg/mL (5 mL)

Clark PI and Slevin ML, "The Clinical Pharmacology of Etoposide and Teniposide," Clin Pharmacokinet, 1987, 12(4):223-52.

Jeffrey LP, Chairman, National Study Commission on Cytotoxic Exposure. Position Statement. "The Handling of Cytotoxic Agents by Women Who Are Pregnant, Attempting to Conceive, or Breast-Feeding," January 12, 1987.

Muggia FM, "Teniposide: Overview of Its Therapeutic Potential in Adult Cancers," Cancer Chemother Pharmacol, 1994, 34(Suppl):S127-33.

O'Dwyer PJ, Alonso MT, Leyland-Jones B, et al, "Teniposide: A Review of 12 Years of Experience," Cancer Treat Rep, 1984, 68(12):1455-66.

Rivera GK and Evans WE, "Clinical Trials of Teniposide (VM-26) in Childhood Acute Lymphocytic Leukemia," Semin Oncol, 1992, 19(2 Suppl 6):51-8.

Sonneveld P, "Teniposide in Lymphomas and Leukemias," Semin Oncol, 1992, 19(2 Suppl 6):59-64.