Get your patient on Etoposide
Etoposide prescribing information
Warnings
VePesid (etoposide) 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.
INDICATIONS AND USAGE
VePesid (etoposide) is indicated in the management of: Small Cell Lung Cancer —Etoposide capsules in combination with other approved chemotherapeutic agents as first line treatment in patients with small cell lung cancer.
DOSAGE AND ADMINISTRATION
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 etoposide capsules is two times the IV dose rounded to the nearest 50 mg (i.e., two times 35 mg/m2/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.
CONTRAINDICATIONS
VePesid is contraindicated in patients who have demonstrated a previous hypersensitivity to etoposide or any component of the formulation.
ADVERSE REACTIONS
The following data on adverse reactions are based on both oral and intravenous administration of VePesid as a single agent, using several different dose schedules for treatment of a wide variety of malignancies.
Hematologic Toxicity
Myelosuppression is dose related and dose limiting, with granulocyte nadirs occurring 7 to 14 days after drug administration and platelet nadirs occurring 9 to 16 days after drug administration. Bone marrow recovery is usually complete by day 20, and no cumulative toxicity has been reported. Fever and infection have also been reported in patients with neutropenia. Death associated with myelosuppression has been reported. The occurrence of acute leukemia with or without a preleukemic phase has been reported rarely in patients treated with VePesid in association with other antineoplastic agents. ( See WARNINGS .)
Gastrointestinal Toxicity
Nausea and vomiting are the major gastrointestinal toxicities. The severity of such nausea and vomiting is generally mild to moderate with treatment discontinuation required in 1% of patients. Nausea and vomiting can usually be controlled with standard antiemetic therapy. Mild to severe mucositis/esophagitis may occur. Gastrointestinal toxicities are slightly more frequent after oral administration than after intravenous infusion.
Allergic Reactions
Anaphylactic-like reactions characterized by chills, fever, tachycardia, bronchospasm, dyspnea, and/or hypotension have been reported to occur in 0.7% to 2% of patients receiving intravenous VePesid and in less than 1% of the patients treated with the oral capsules. These reactions have usually responded promptly to the cessation of the infusion and administration of pressor agents, corticosteroids, antihistamines, or volume expanders as appropriate; however, the reactions can be fatal. Hypertension and/or flushing have also been reported. Blood pressure usually normalizes within a few hours after cessation of the infusion. Anaphylactic-like reactions have occurred during the initial infusion of VePesid. Facial/tongue swelling, coughing, diaphoresis, cyanosis, tightness in throat, laryngospasm, back pain, and/or loss of consciousness have sometimes occurred in association with the above reactions. In addition, an apparent hypersensitivity-associated apnea has been reported rarely. Rash, urticaria, and/or pruritus have infrequently been reported at recommended doses. At investigational doses, a generalized pruritic erythematous maculopapular rash, consistent with perivasculitis, has been reported.
Alopecia
Reversible alopecia, sometimes progressing to total baldness, was observed in up to 66% of patients.
Other Toxicities
The following adverse reactions have been infrequently reported: abdominal pain, aftertaste, constipation, dysphagia, asthenia, fatigue, malaise, somnolence, transient cortical blindness, optic neuritis, interstitial pneumonitis/pulmonary fibrosis, fever, seizure (occasionally associated with allergic reactions), Stevens-Johnson syndrome, and toxic epidermal necrolysis, pigmentation, and a single report of radiation recall dermatitis. Hepatic toxicity, generally in patients receiving higher doses of the drug than those recommended, has been reported with VePesid. Metabolic acidosis has also been reported in patients receiving higher doses. The incidences of adverse reactions in the table that follows are derived from multiple data bases from studies in 2,081 patients when VePesid was used either orally or by injection as a single agent.
| ADVERSE DRUG EFFECT | PERCENT RANGE OF REPORTED INCIDENCE |
| Hematologic toxicity | |
| Leukopenia (less than 1,000 WBC/mm 3 ) | 3 to 17 |
| Leukopenia (less than 4,000 WBC/mm 3 ) | 60 to 91 |
| Thrombocytopenia (less than 50,000 platelets/mm 3 ) | 1 to 20 |
| Thrombocytopenia (less than 100,000 platelets/mm 3 ) | 22 to 41 |
| Anemia | 0 to 33 |
| Gastrointestinal toxicity | |
| Nausea and vomiting | 31 to 43 |
| Abdominal pain | 0 to 2 |
| Anorexia | 10 to 13 |
| Diarrhea | 1 to 13 |
| Stomatitis | 1 to 6 |
| Hepatic | 0 to 3 |
| Alopecia | 8 to 66 |
| Peripheral neurotoxicity | 1 to 2 |
| Hypotension | 1 to 2 |
| Allergic reaction | 1 to 2 |
DESCRIPTION
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:
CLINICAL PHARMACOLOGY
VePesid has been shown to cause metaphase arrest in chick fibroblasts. Its main effect, however, appears to be at the G 2 portion of the cell cycle in mammalian cells. Two different dose-dependent responses are seen. At high concentrations (10 mcg/mL or more), lysis of cells entering mitosis is observed. At low concentrations (0.3 to 10 mcg/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.
How Supplied
VePesid® (Etoposide Capsules, USP), 50 mg, are supplied as pink capsules with “V3545” printed in black and are available in blister packs of 20 individually labeled blisters, each containing one capsule (NDC 83270-451-05). Capsules are to be stored under refrigeration, between 2°C to 8°C (36°F to 46°F). DO NOT FREEZE.
References 1. ONS Clinical Practice Committee. Cancer Chemotherapy Guidelines and Recommendations for Practice. Pittsburgh, PA: Oncology Nursing Society; 1999:32- 41. 2. Recommendations for the safe handling of parenteral antineoplastic drugs. Washington, DC: Division of Safety, Clinical Center Pharmacy Department and Cancer Nursing Services, National Institutes of Health; 1992. US Dept of Health and Human Services, Public Health Service Publication NIH 92-2621. 3. AMA Council on Scientific Affairs. Guidelines for handling parenteral antineoplastics. JAMA. 1985;253:1590-1592. 4. National Study Commission on Cytotoxic Exposure. Recommendations for handling cytotoxic agents. 1987. Available from Louis P. Jeffrey, ScD, Chairman, National Study Commission on Cytotoxic Exposure. Massachusetts College of Pharmacy and Allied Health Sciences, 179 Longwood Avenue, Boston, MA 02115. 5. Clinical Oncological Society of Australia. Guidelines and recommendations for safe handling of antineoplastic agents. Med J Aust. 1983;1:426-428. 6. Jones RB, Frank R, Mass T. Safe handling of chemotherapeutic agents: a report from The Mount Sinai Medical Center. CA Cancer J Clin. 1983;33:258-263. 7. American Society of Hospital Pharmacists. ASHP technical assistance bulletin on handling cytotoxic and hazardous drugs. Am J Hosp Pharm. 1990;47:1033-1049. 8. Controlling occupational exposure to hazardous drugs. (OSHA Work-Practice Guidelines.) Am J Health-Syst Pharm. 1996;53:1669-1685.
Manufactured by: Eirgen Pharma Ltd Westside Business Park, Waterford, X91 YV67, Ireland Rev. 05-2026-00
