Brands, Medical Use, Clinical Data
Drug Category
- Antineoplastic Agents, Phytogenic
- Nucleic Acid Synthesis Inhibitors
Dosage Forms
Brands / Synonyms
(-)-Etoposide; Eposin; Etopophos; Etopophos Preservative Free; Etoposide (JAN/USP); Etoposide USP26; Etoposidum [INN-Latin]; Lastet; Teniposide; Toposar; trans-Etoposide
; Vepesid; VePESID (TN); Vepesid J; Zuyeyidal
Indications
For use in combination with other chemotherapeutic agents in the treatment of refractory testicular tumors and as first line treatment in patients with small cell lung cancer. Also used to treat other malignancies such as lymphoma, non-lymphocytic leukemia, and glioblastoma multiforme.
Pharmacology
Etoposide is an antineoplastic agent and an epipodophyllotoxin (a semisynthetic derivative of the podophyllotoxins). It inhibits DNA topoisomerase II, thereby inhibiting DNA synthesis. Etoposide is cell cycle dependent and phase specific, affecting mainly the S and G2 phases. Two different dose-dependent responses are seen. At high concentrations (10 µg/mL or more), lysis of cells entering mitosis is observed. At low concentrations (0.3 to 10 µg/mL), cells are inhibited from entering prophase. It does not interfere with microtubular assembly. The predominant macromolecular effect of etoposide appears to be the induction of DNA strand breaks by an interaction with DNA-topoisomerase II or the formation of free radicals.
Mechanism of Action
Etoposide inhibits DNA topoisomerase II, thereby inhibiting DNA synthesis at the premitotic stage of cell division. Etoposide is cell cycle dependent and phase specific, affecting mainly the S and G2 phases of cell division.
Absorption
Absorbed well, time to peak plasma concentration is 1-1.5 hrs. Mean bioavailability is 50%.
Toxicity
Side effects include alopecia, constipation, diarrhea, nausea and vomiting and secondary malignancies (leukemia).
Biotrnasformation / Drug Metabolism
Primarily hepatic (through O-demethylation via the CYP450 3A4 isoenzyme pathway) with 40% excreted unchanged in the urine.
Contraindications
ETOPOPHOS (etoposide phosphate) for Injection is contraindicated in patients who have demonstrated a previous
hypersensitivity to etoposide, etoposide phosphate, or any other component of the formulations.
Drug Interactions
Caution should be exercised when administering ETOPOPHOS with drugs that are known to inhibit phosphatase
activities (e.g., levamisole hydrochloride). High-dose cyclosporin A resulting in concentrations above 2000 ng/mL
administered with oral etoposide has led to an 80% increase in etoposide exposure with a 38% decrease in total body
clearance of etoposide compared to etoposide alone.
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