Generic Name: etoposide phosphate
Dosage Form: injection, powder, lyophilized, for solution
Etopophos®
(etoposide phosphate)
for INJECTION
Warnings
Etopophos® (etoposide phosphate) for Injection should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. Severe myelosuppression with resulting infection or bleeding may occur.
Etopophos Description
Etopophos (etoposide phosphate) for Injection is an antineoplastic agent which is available for intravenous infusion as a sterile lyophile in single-dose vials containing etoposide phosphate equivalent to 100 mg etoposide, 32.7 mg sodium citrate USP, and 300 mg dextran 40.
Etoposide phosphate is a water soluble ester of etoposide (commonly known as VP-16), a semi-synthetic derivative of podophyllotoxin. The water solubility of etoposide phosphate lessens the potential for precipitation following dilution and during intravenous administration.
The chemical name for etoposide phosphate is:
4'-Demethylepipodophyllotoxin 9-[4,6-O-(R)-ethylidene-β-D-glucopyranoside], 4'-(dihydrogen phosphate).
Etoposide phosphate has the following structure:
Etopophos - Clinical Pharmacology
The in vitro cytotoxicity observed for etoposide phosphate is significantly less than that seen with etoposide which is believed due to the necessity for conversion in vivo to the active moiety, etoposide, by dephosphorylation. The mechanism of action is believed to be the same as that of etoposide. Etoposide has been shown to cause metaphase arrest in chick fibroblasts. Its main effect, however, appears to be at the G2 portion of the cell cycle in mammalian cells. 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 (0.3-10 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.
Etopophos Bioequivalence
Following intravenous administration of Etopophos, etoposide phosphate is rapidly and completely converted to etoposide in plasma. A direct comparison of the pharmacokinetic parameters [area under the concentration time curve (AUC) and the maximum plasma concentration (Cmax)] of etoposide following intravenous administration of molar equivalent doses of Etopophos and VePesid® was made in two randomized crossover studies in patients with a variety of malignancies. In the first study of 41 eva luable patients, the etoposide mean ± S.D. AUC values were 168.3 ± 48.2 µg•hr/mL and 156.7 ± 43.4 µg•hr/mL following administration of molar equivalent doses of 150 mg/m2 Etopophos or VePesid with a 3.5-hour infusion time; the corresponding mean ± S.D. Cmax values were 20.0 ± 3.7 µg/mL and 19.6 ± 4.2 µg/mL, respectively. The point estimate (90% confidence interval) for the bioavailability of etoposide from Etopophos, relative to VePesid, was 107% (105%, 110%) for AUC and 103% (99%, 106%) for Cmax. In the second study of 29 eva luable patients following intravenous administration of 90, 100, and 110 mg/m2 molar equivalents of Etopophos or VePesid with a 60-min