VUMON® PARENTERAL
Bristol
Teniposide
Antineoplastic
Action And Clinical Pharmacology: Teniposide is a semi-synthetic derivative of podophyllotoxin.
In vitro, teniposide exerts a powerful cytostatic effect by first arresting cells in metaphase. Its main effect, however, is preventing cells from entering mitosis (arrest of G2 phase of cell cycle) within 1 to 2 hours after drug addition. At higher concentrations, a third effect can be observed, disintegration of part of interphase cells (those preparing for mitosis). Unlike other podophyllum compounds and spindle poisons such as colchicine, the effect of teniposide on fibroblasts is virtually irreversible.
Teniposide produces a dose dependent inhibition of thymidine uptake after 2.5 hours. This, however, is not accompanied by a comparable reduction in DNA synthesis.
An i.v. dose of 67 to 90 mg/mgiven over 1/2 to 1 hour in man, showed the mean volume of distribution to be 28.45% of body weight. An i.v. dose of 67 mg/madministered over 1/2 hour produced a triexponential plasma decay with a terminal phase half-life of 21.2 hours in adults and 9.6 hours in children. Urinary recovery was 44.45% after 72 hours of which 21.3% was unchanged drug. Recovery in feces was variable (0 to 10.05%) over a 3-day period. Studies in rats show the major route of excretion to be the bile.
Indications And Clinical Uses: Neuroblastoma: Second-line single agent or combination therapy in patients who have not responded or who have relapsed on other chemotherapeutic regimens.
Non-Hodgkin’s Lymphoma: Second-line combination or as a single agent in patients who are or have become refractory to other chemotherapeutic regimens.
Acute Lymphocytic Leukemia: Second-line combination therapy with cytosine arabinoside in patients who have not responded or relapsed on other chemotherapeutic regimens.
Contra-Indications: Teniposide should not be given to individuals who have demonstrated a previous hypersensitivity to it. Also, it is contraindicated in patients having severe leukopenia, thrombocytopenia and severe hepatic and/or renal impairment.
Manufacturers’ Warnings In Clinical States: Teniposide is a potent drug and should be used only by physicians experienced with cancer chemotherapeutic drugs (see Precautions). Blood counts as well as renal and hepatic function tests must be done regularly. Discontinue the drug if abnormal depression of bone marrow or abnormal renal or hepatic function is seen.
Teniposide should be given cautiously to individuals with pre-existing hepatic and/or renal impairment.
Bacterial infection must be brought under control before therapy due to the risk of septicemia. Near fatal anaphylactic reactions have occurred following teniposide administration.
Pregnancy: Use in pregnancy is not recommended.
Conception Control: It is also recommended that patients with childbearing or conceiving potential, who are receiving teniposide, exercise adequate conception control.
Although embryotoxic and teratogenic effects have not been seen in pregnant rats given teniposide, the possibility of these effects cannot be ruled out. Teniposide has caused reduced spermiogenesis in monkeys and dogs, and reduced testicular and ovarian weights in dogs.
As with any potent antineoplastic drug, the benefit to patient versus the risk of toxicity must be carefully weighed. Chronic toxicity studies in dogs have shown teniposide to have an oncogenetic potential.
Precautions: Teniposide should be administered by individuals experienced in the use of antineoplastic therapy.
Since leukopenia and thrombocytopenia have been reported, platelets and white blood cell counts should be performed prior to each subsequent cycle.
A white blood cell count of between 2 000 to 3 000 cells/mmsuggests that the dose should be reduced by 50%. Platelet counts between 75 000 to 100 000 cells/mmrequire a dosage reduction of 50%. Should the white blood cell count fall below 2 000 cells/mmor the platelet count fall below 75 000 cells/mmconsideration should be given to discontinuation of treatment until bone marrow recovery occurs. Leukopenia and thrombocytopenia are at their lowest level between 7 and 14 days after initial therapy. Bone marrow recovery requires 2 to 3 weeks.
Liver and renal function should be regularly monitored.
Care should be taken to ensure infusions are given i.v. with indwelling catheter in proper position prior to infusion, as extravasation necrosis and/or thrombophlebitis may result with improper administration.
Instances of hypotension have been reported during infusion. Therefore, vital signs should be monitored during first 30 minutes.
Adverse Reactions: The most serious toxicity is bone marrow depression, notably leukopenia and thrombocytopenia, which occurs 7 to 14 days after treatment.
The most frequently reported side effects were immunosuppression, alopecia and nausea and/or vomiting. Gastrointestinal: nausea and vomiting (11%), vomiting (10%), nausea (4%), anorexia (1%), diarrhea (1%), pain
Skin: alopecia (31%), stomatitis (3%), skin (2%).
Hematopoietic System: leukopenia (39%), thrombocytopenia (32%), low hemoglobin (9%), neutropenia (8%), pancytopenia (3%), sepsis (2%) and granulocytopenia (1%).
Cardiac: hypotension (1%), tachycardia (1%), heart failure (1%), tachypnea (
Hepatotoxicity: 2%.
Nephrotoxicity: 2%.
Miscellaneous: fever and/or chills (3%), oral ulceration (2%), anaphylaxis (1%), and the following less than one percent: cystitis, lethargy, flushing, burning sensation in mouth, oesophagitis, aphasia, confusion and agitation, microscopic hematuria, peripheral neuropathy and asthenia.
Symptoms And Treatment Of Overdose: Symptoms and Treatment: No overdosage occurred during clinical trials, but should it occur, symptomatic measures should be taken to sustain the patient through any period of toxicity that might occur. The anticipated complications would be hematotoxicity, nephrotoxicity, hepatotoxicity, and cardiotoxicity. Patients should be monitored for 3 to 4 weeks in case of delayed toxicity.
Dosage And Administration: Doses should be adjusted according to individual patient variability and toxicity when employed as a single agent or in combination with other antineoplastic agents.
Teniposide has been employed in combinations with other antineoplastic agents as discussed in the medical literature. References are available from the manufacturer.
To avoid the possibility of hypotensive reactions, it should not be administered by bolus injection or rapid infusion.
Preparation of I.V. Solutions: Add required dose of teniposide in normal saline or 5% dextrose in water at a concentration not exceeding 0.2 mg/mL. Contact with buffered aqueous solutions above pH 8 should be avoided. Reconstitution results in a clear, colorless solution which is stable for 4 hours at room temperature at concentrations of 0.1 to 0.2 mg/mL. Vumon mixed with normal saline or 5% dextrose in water should be administered immediately by the i.v. route over a period of not less than 30 minutes. It should not be mixed with other antineoplastic drugs.
Handling and Disposal: Preparation should be done in a vertical laminar flow hood (Biological Safety Cabinet – Class II).
Personnel preparing solutions should wear PVC gloves, safety glasses, disposable gowns, and masks.
All needles, syringes, vials and other materials which have come in contact with the drug should be segregated and incinerated at 1 000°C or more. Sealed containers may explode. Intact vials should be returned to the manufacturer for destruction. Proper precautions should be taken in packaging these materials for transport.
Personnel regularly involved in the preparation and handling of teniposide should have bi-annual blood examinations.
Availability And Storage: Each 5 mL clear, glass ampul contains: teniposide 50 mg (10 mg/mL). Nonmedicinal ingredients: benzyl alcohol 3% w/v, ethanol, maleic acid, N.N. dimethylacetamide and polyoxyethylated castor oil.
VUMON® PARENTERAL Bristol Teniposide Antineoplastic
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