Lastet - General Information:A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Lastet inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Lastet acts primarily in the G2 and S phases of the cell cycle. [PubChem]
Pharmacology:Lastet is an antineoplastic agent and an epipodophyllotoxin (a semisynthetic derivative of the podophyllotoxins). It inhibits DNA topoisomerase II, thereby inhibiting DNA synthesis. Lastet 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.
Lastet for patients
Patients are generally advised to call their doctor in case of fever, symptoms of infection or painful injection sites, as these may progress severely without adequate medical attention. It is advised to drink lots of fluids after treatment to prevent damage to the bladder and kidneys, typically 1.5 to 3.5 litres of water on the day of treatment and for several days after.
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.
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.
Additional information about LastetLastet Indication: 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.
Mechanism Of Action: Lastet inhibits DNA topoisomerase II, thereby inhibiting DNA synthesis at the premitotic stage of cell division. Lastet is cell cycle dependent and phase specific, affecting mainly the S and G2 phases of cell division.
Drug Interactions: Aprepitant Aprepitant may change levels of chemotherapy agent
Cyclosporine Cyclosporine increases the effect of etoposide
Quinupristin This combination presents an increased risk of toxicity
Food Interactions: Grapefruit and grapefruit juice should be avoided throughout treatment as grapefruit can decrease serum levels of this product.
Generic Name: Etoposide
Synonyms: (-)-Etoposide; Etoposidum [INN-Latin]; trans-Etoposide
Drug Category: Antineoplastic Agents, Phytogenic; Nucleic Acid Synthesis Inhibitors
Drug Type: Small Molecule; Approved
Other Brand Names containing Etoposide: Eposin; Etopophos; Lastet; Toposar; Vepesid; Vepesid J; Zuyeyidal;
Absorption: Absorbed well, time to peak plasma concentration is 1-1.5 hrs. Mean bioavailability is 50%.
Toxicity (Overdose): Side effects include alopecia, constipation, diarrhea, nausea and vomiting and secondary malignancies (leukemia).
Protein Binding: 97%
Biotransformation: Primarily hepatic (through O-demethylation via the CYP450 3A4 isoenzyme pathway) with 40% excreted unchanged in the urine.
Half Life: 4-12 hours
Dosage Forms of Lastet: Solution Intravenous
Chemical IUPAC Name: 4'-demethyl-epipodophyllotoxin 9-[4,6-O-(R)-ethylidene-beta-D-glucopyranoside], 4'-(dihydrogen phosphate)
Chemical Formula: C29H32O13
Etoposide on Wikipedia: http://en.wikipedia.org/wiki/Etoposide
Organisms Affected: Humans and other mammals
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