VUMON (teniposide injection)
VUMON(teniposide injection) is a cytotoxic drug which should be administered underthe supervision of a qualified physician experienced in the use of cancerchemotherapeutic agents. Appropriate management of therapy and complicationsis possible only when adequate treatment facilities are readily available.

Severemyelosuppression with resulting infection or bleeding may occur. Hypersensitivityreactions, including anaphylaxis-like symptoms, may occur with initial dosingor at repeated exposure to VUMON. Epinephrine, with or without corticosteroidsand antihistamines, has been employed to alleviate hypersensitivity reactionsymptoms.

VUMON (teniposideinjection) (also commonly known as VM-26), is supplied as a sterile nonpyrogenicsolution in a nonaqueous medium intended for dilution with a suitable parenteralvehicle prior to intravenous infusion. VUMON is available in 50 mg (5 mL)ampules. Each mL contains 10 mg teniposide, 30 mg benzyl alcohol, 60 mg N,N-dimethylacetamide,500 mg purified Cremophor EL (polyoxyethylatedcastor oil)*, and 42.7% (v/v) dehydrated alcohol. The pH of the clear solutionis adjusted to approximately 5 with maleic acid.

Teniposide is a semisyntheticderivative of podophyllotoxin. The chemical name for teniposide is 4′-demethylepipodophyllotoxin9-[4,6-O-(R)-2-thenylidene-β-D-glucopyranoside]. Teniposide differs from etoposide,another podophyllotoxin derivative, by the substitution of a thenylidene groupon the glucopyranoside ring.

Teniposide has the following structural formula:

Teniposideis a white to off-white crystalline powder with the empirical formula CHOS and a molecular weight of 656.66. It is a lipophilic compound with a partitioncoefficient value (octanol/water) of approximately 100. Teniposide is insolublein water and ether. It is slightly soluble in methanol and very soluble inacetone and dimethylformamide.

Teniposide is a phase-specific cytotoxicdrug, acting in the late S or early G phase of thecell cycle, thus preventing cells from entering mitosis.

Teniposidecauses dose-dependent single- and double-stranded breaks in DNA and DNA-proteincross-links. The mechanism of action appears to be related to the inhibitionof type II topoisomerase activity since teniposide does not intercalate intoDNA or bind strongly to DNA. The cytotoxic effects of teniposide are relatedto the relative number of double-stranded DNA breaks produced in cells, whichare a reflection of the stabilization of a topoisomerase II-DNA intermediate.

Teniposidehas a broad spectrum of in vivo antitumor activity againstmurine tumors, including hematologic malignancies and various solid tumors.Notably, teniposide is active against sublines of certain murine leukemiaswith acquired resistance to cisplatin, doxorubicin, amsacrine, daunorubicin,mitoxantrone, or vincristine.

Plasma drug levels declinedbiexponentially following intravenous infusion (155 mg/m over1 to 2.5 hours) of VUMON given to 8 children (4-11 years old) with newly diagnosedacute lymphoblastic leukemia (ALL). The observed average pharmacokinetic parametersand associated coefficients of variation (CV%) based on a two-compartmentalmodel analysis of the data are as follows:

There appears to be some association between an increasein serum alkaline phosphatase or gamma glutamyl-transpeptidase and a decreasein plasma clearan