VUMON

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

VUMON
For I.V. infusion.

COMPOSITION:
Each ampoule contains 50mg teniposide, benzyl alcohol 150mg as preservative and dehydrated ethanol 42,7% (v/v) per 5mL.

PHARMACOLOGICAL CLASSIFICATION:
A26 Cytostatic agents.

PHARMACOLOGICAL ACTION:
VUMON (also known as VM-26) is a semisynthetic derivative of podophyllotoxin used in the treatment of certain neoplastic diseases. It is 4'-0-demethyl-1-0 (4,6-0-2 thenylidene-beta-D-glucopyranosyl) epipodophyllotoxin.
VUMON is a phase-specific cytotoxic drug, acting in the late S2 or G2 phase of the cell cycle by preventing cells from entering mitosis. VUMON also produces single-strand breaks in DNA. The mechanism of action appears to be due to inhibition of typeII topoisomerases.
Cells resistant to etoposide were fully cross resistant to teniposide and vice versa in both in vivo and in vitro studies, although there have been occasional clinical reports suggesting a lack of complete cross-resistance.
Pharmacokinetics
The pharmacokinetics of teniposide appear to be linear over a range of doses. Accumulation does not occur after daily administration for 3days. No major differences in the disposition of the agent in adults and children have been identified.
Following intravenous infusion, initial clearance from the central compartment is rapid with a distribution half-life of approximately 1hour. Teniposide is highly protein bound, >99%, which may limit its distribution within the body. Levels of teniposide in CSF are low relative to simultaneously measured plasma levels. Mean terminal half-life has ranged from approximately 6 to 20hours with renal clearance accounting for only about 10% of total clearance. While metabolic pathways for teniposide have not been characterised, agents such as phenobarbital and phenytoin that induce hepatic metabolism have been shown to increase the clearance of teniposide.

INDICATIONS:
VUMON is indicated in the following:
Malignant lymphomas
Hodgkin's disease
Relapsed and resistant acute lymphocytic leukaemia, as combination therapy in children and adults.
Intracranial malignant tumours; i.e. glioblastoma, ependymoma, astrocytoma.
Urinary bladder carcinoma.
Refractory neuroblastoma as single or combination therapy.

CONTRA-INDICATIONS:
VUMON should not be given to individuals who have demonstrated a previous hypersensitivity to teniposide or to any component of the formulation.
VUMON is contra-indicated in patients who have severe leukopenia or thrombocytopenia.
Pregnancy:
VUMON may cause foetal harm when administered to a pregnant women. Embryotoxic and teratogenic effects have been seen in pregnant rats given teniposide. No studies in pregnant women have been conducted.
Contra-indicated in lactation.

WARNINGS:
VUMON is a potent medicine and should be used only by physicians experienced with cancer chemotherapeutic medicines. Blood counts as well as renal and hepatic function tests must be done regularly. Discontinue the medicine if abnormal depression of bone marrow or abnormal renal or hepatic function is seen.
Life threatening anaphylactic reactions have occurred following teniposide administration.

DOSAGE AND DIRECTIONS FOR USE:
Monotherapy:
The following dosage schedules are recommended:
Malignant lymphomas and urinary bl