VePesid (etoposide, USP) (also commonly known as VP-16) is a semisynthetic derivative of podophyllotoxin used in the treatment of certain neoplastic diseases. It is 4’- demethylepipodophyllotoxin 9-[4,6-O-(R)-ethylidene-β-D-glucopyranoside]. It is very soluble in methanol and chloroform, slightly soluble in ethanol, and sparingly soluble in water and ether. It is made more miscible with water by means of organic solvents. It has a molecular weight of 588.56 and a molecular formula of C 29 H 32 O 13 . VePesid is administered orally. VePesid is available as 50 mg pink capsules. Each liquid- filled, soft gelatin capsule contains 50 mg of etoposide, USP in a vehicle consisting of citric acid anhydrous, polyethylene glycol 400, glycerol anhydrous, purified water, gelatin, glycerol anhydrous, sorbitol liquid partially dehydrated, titanium dioxide, red iron oxide, and Glycerol 85%. The capsules are printed with black edible ink, containing isopropyl alcohol, purified water, hypromellose, propylene glycol, FD&C red #40, FD& C blue #1. The structural formula is: chem structure

VePesid (etoposide) is indicated in the management of: Small Cell Lung Cancer— VePesid Capsules in combination with other approved chemotherapeutic agents as first line treatment in patients with small cell lung cancer.

For recommended dosing adjustments in patients with renal impairment see PRECAUTIONS section. Chemotherapy courses are repeated at 3- to 4-week intervals after adequate recovery from any toxicity. VePesid Capsules In small cell lung cancer, the recommended dose of VePesid Capsules is two times the IV dose rounded to the nearest 50 mg (i.e., two times 35 mg/m 2 /day for 4 days to 50 mg/m 2 /day for 5 days). The dosage should be modified to take into account the myelosuppressive effects of other drugs in the combination or the effects of prior x-ray therapy or chemotherapy which may have compromised bone marrow reserve. Administration Precautions To minimize the risk of dermal exposure, always wear impervious gloves when handling blister packs of individually labeled blisters containing VePesid capsules. This includes all handling activities in clinical settings, pharmacies, storerooms, and home healthcare settings, including during unpacking and inspection, transport within a facility, and dose preparation and administration. Stability VePesid Capsules must be stored under refrigeration 2°C to 8°C (36°F to 46°F). The capsules are stable for 24 months under such refrigeration conditions. Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published. 1-8 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

Patients being treated with VePesid must be frequently observed for myelosuppression both during and after therapy. Myelosuppression resulting in death has been reported. Dose-limiting bone marrow suppression is the most significant toxicity associated with VePesid therapy. Therefore, the following studies should be obtained at the start of therapy and prior to each subsequent cycle of VePesid: platelet count, hemoglobin, white blood cell count, and differential. The occurrence of a platelet count below 50,000/mm 3 or an absolute neutrophil count below 500/mm 3 is an indication to withhold further therapy until the blood counts have sufficiently recovered. Pregnancy VePesid can cause fetal harm when administered to a pregnant woman. Etoposide has been shown to be teratogenic in mice and rats. In rats, an intravenous etoposide dose of 0.4 mg/kg/day (about 1/20th of the human dose on a mg/m 2 basis) during organogenesis caused maternal toxicity, embryotoxicity, and teratogenicity (skeletal abnormalities, exencephaly, encephalocele, and anophthalmia); higher doses of 1.2 and 3.6 mg/kg/day (about 1/7th and 1/2 of human dose on a mg/m 2 basis) resulted in 90 and 100% embryonic resorptions. In mice, a single 1.0 mg/kg (1/16th of human dose on a mg/m 2 basis) dose of etoposide administered intraperitoneally on days 6, 7, or 8 of gestation caused embryotoxicity, cranial abnormalities, and major skeletal malformations. An I.P. dose of 1.5 mg/kg (about 1/10th of human dose on a mg/m 2 basis) on day 7 of gestation caused an increase in the incidence of intrauterine death and fetal malformations and a significant decrease in the average fetal body weight. Women of childbearing potential should be advised to avoid becoming pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be warned of the potential hazard to the fetus. VePesid should be considered a potential carcinogen in humans. The occurrence of acute leukemia with or without a preleukemic phase has been reported in rare instances in patients treated with etoposide alone or in association with other neoplastic agents. The risk of development of a preleukemic or leukemic syndrome is unclear. Carcinogenicity tests with VePesid have not been conducted in laboratory animals.

Drug Interactions High-dose cyclosporin A resulting in concentrations above 2,000 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.