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Akman pleaded guilty in the U.S. District Court"...
COSMEGEN, as part of a combination chemotherapy and/or multi-modality treatment regimen, is indicated for the treatment of Wilms' tumor, childhood rhabdomyosarcoma, Ewing's sarcoma and metastatic, nonseminomatous testicular cancer.
COSMEGEN is indicated as a single agent, or as part of a combination chemotherapy regimen, for the treatment of gestational trophoblastic neoplasia.
DOSAGE AND ADMINISTRATION
Not for oral administration
Toxic reactions due to COSMEGEN are frequent and may be severe (see ADVERSE REACTIONS), thus limiting in many instances the amount that may be administered. However, the severity of toxicity varies markedly and is only partly dependent on the dose employed.
Careful calculation of the dosage should be performed prior to administration of each dose.
The dosage of COSMEGEN varies depending on the tolerance of the patient, the size and location of the neoplasm, and the use of other forms of therapy. It may be necessary to decrease the usual dosages suggested below when additional chemotherapy or radiation therapy is used concomitantly or has been used previously.
The dosage for COSMEGEN is calculated in micrograms (mcg). The dose intensity per 2-week cycle for adults or children should not exceed 15 mcg/kg/day or 400-600 mcg/m²/day intravenously for five days. Calculation of the dosage for obese or edematous patients should be performed on the basis of surface area in an effort to more closely relate dosage to lean body mass.
A wide variety of single agent and combination chemotherapy regimens with COSMEGEN may be employed. Because chemotherapeutic regimens are constantly changing, dosing and administration should be performed under the direct supervision of physicians familiar with current oncologic practices and new advances in therapy. The following suggested regimens are based upon a review of current literature concerning therapy with COSMEGEN and are on a per cycle basis.
Wilms' Tumor, Childhood Rhabdomyosarcoma and Ewing's Sarcoma
Regimens of 15 mcg/kg intravenously daily for five days administered in various combinations and schedules with other chemotherapeutic agents have been utilized in the treatment of Wilms' tumor, rhabdomyosarcoma and Ewing's sarcoma.
Metastatic Nonseminomatous Testicular Cancer
1000 mcg/m² intravenously on Day 1 as part of a combination regimen with cyclophosphamide, bleomycin, vinblastine, and cisplatin.
Gestational Trophoblastic Neoplasia
12 mcg/kg intravenously daily for five days as a single agent.
500 mcg intravenously on Days 1 and 2 as part of a combination regimen with etoposide, methotrexate, folinic acid, vincristine, cyclophosphamide and cisplatin.
Regional Perfusion in Locally Recurrent and Locoregional Solid Malignancies
The dosage schedules and the technique itself vary from one investigator to another; the published literature, therefore, should be consulted for details. In general, the following doses are suggested:
50 mcg (0.05 mg) per kilogram of body weight for lower extremity or pelvis.
35 mcg (0.035 mg) per kilogram of body weight for upper extremity.
It may be advisable to use lower doses in obese patients, or when previous chemotherapy or radiation therapy has been employed.
Preparation of Solution for Intravenous Administration
This drug is HIGHLY TOXIC and both powder and solution must be handled and administered with care (see BOXED WARNING and HOW SUPPLIED, Special Handling). Since COSMEGEN is extremely corrosive to soft tissues, it is intended for intravenous use. Inhalation of dust or vapors and contact with skin or mucous membranes, especially those of the eyes, must be avoided. Appropriate protective equipment should be worn when handling COSMEGEN. Should accidental eye contact occur, copious irrigation for at least 15 minutes with water, normal saline or a balanced salt ophthalmic irrigating solution should be instituted immediately, followed by prompt ophthalmologic consultation. Should accidental skin contact occur, the affected part must be irrigated immediately with copious amounts of water for at least 15 minutes while removing contaminated clothing and shoes. Medical attention should be sought immediately. Contaminated clothing should be destroyed and shoes cleaned thoroughly before reuse. (See HOW SUPPLIED, Special Handling.)
Reconstitute COSMEGEN by adding 1.1 mL of Sterile Water for Injection (without preservative) using aseptic precautions. The resulting solution of COSMEGEN will contain approximately 500 mcg (0.5 mg) per mL.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. When reconstituted, COSMEGEN is a clear, gold-colored solution.
Once reconstituted, the solution of COSMEGEN can be added to infusion solutions of Dextrose Injection 5 percent or Sodium Chloride Injection either directly or to the tubing of a running intravenous infusion.
Although reconstituted COSMEGEN is chemically stable, the product does not contain a preservative and accidental microbial contamination might result. Any unused portion should be discarded. Use of water containing preservatives (benzyl alcohol or parabens) to reconstitute COSMEGEN for Injection, results in the formation of a precipitate.
Studies conducted on dactinomycin lyophilized powder for injection demonstrate that drug product diluted at concentrations of 10 mcg/mL or higher in WFI, 0.9% saline and 5% dextrose in glass or PVC infusion containers are chemically stable for up to 10 hours when stored at ambient room temperature. Drug product diluted to concentrations lower than 10 mcg/mL and stored at ambient room temperature showed significantly lower recoveries. Therefore, only drug product diluted at concentrations greater than 10 mcg/mL are recommended for administration. Since the product contains no preservatives, the final prepared product (which has undergone reconstitution and dilution) must be used within 4 hours of initial reconstitution when stored at ambient room temperature.
Partial removal of COSMEGEN from intravenous solutions by cellulose ester membrane filters used in some intravenous in-line filters has been reported.
Since dactinomycin is extremely corrosive to soft tissue, precautions for materials of this nature should be observed.
If the drug is given directly into the vein without the use of an infusion, the “two-needle technique” should be used. Reconstitute and withdraw the calculated dose from the vial with one sterile needle. Use another sterile needle for direct injection into the vein.
Discard any unused portion of the COSMEGEN solution.
Management of Extravasation
Care in the administration of COSMEGEN will reduce the chance of perivenous infiltration (see BOXED WARNING and ADVERSE REACTIONS). It may also decrease the chance of local reactions such as urticaria and erythematous streaking. On intravenous administration of COSMEGEN, extravasation may occur with or without an accompanying burning or stinging sensation, even if blood returns well on aspiration of the infusion needle. If any signs or symptoms of extravasation have occurred, the injection or infusion should be immediately terminated and restarted in another vein. If extravasation is suspected, intermittent application of ice to the site for 15 minutes 4 times daily for 3 days may be useful. The benefit of local administration of drugs has not been clearly established. Because of the progressive nature of extravasation reactions, close observation and plastic surgery consultation is recommended. Blistering, ulceration and/or persistent pain are indications for wide excision surgery, followed by split-thickness skin grafting.
COSMEGEN for Injection is a lyophilized powder. In the dry form the compound is an amorphous yellow to orange powder. The solution is clear, gold-colored and essentially free from visible particles. COSMEGEN for Injection is supplied in vials containing 0.5 mg (500 micrograms) of dactinomycin and 20.0 mg of mannitol.
Store at 20-25°C (68-77°F). See USP controlled room temperature. Protect from light and humidity.
Animal studies have shown dactinomycin to be corrosive to skin, irritating to the eyes and mucous membranes of the respiratory tract and highly toxic by the oral route. It has also been shown to be carcinogenic, mutagenic, embryotoxic and teratogenic. Due to the drug's toxic properties, appropriate precautions including the use of appropriate safety equipment are recommended for the preparation of COSMEGEN for parenteral administration. Inhalation of dust or vapors and contact with skin or mucous membranes, especially those of the eyes, must be avoided. Avoid exposure during pregnancy. The National Institutes of Health presently recommends that the preparation of injectable antineoplastic drugs should be performed in a Class II laminar flow biological safety cabinet. Personnel preparing drugs of this class should wear chemical resistant, impervious gloves, safety goggles, outer garments and shoe covers. Additional body garments should be used based upon the task being performed (e.g., sleevelets, apron, gauntlets, disposable suits) to avoid exposed skin surfaces and inhalation of vapors and dust. Appropriate techniques should be used to remove potentially contaminated clothing.
Several other guidelines for proper handling and disposal of antineoplastic drugs have been published and should be considered.1-4
Accidental Contact Measures
Should accidental eye contact occur, copious irrigation for at least 15 minutes with water, normal saline or a balanced salt ophthalmic irrigating solution should be instituted immediately, followed by prompt ophthalmologic consultation. Should accidental skin contact occur, the affected part must be irrigated immediately with copious amounts of water for at least 15 minutes while removing contaminated clothing and shoes. Medical attention should be sought immediately. Contaminated clothing should be destroyed and shoes cleaned thoroughly before reuse (see PRECAUTIONS, General and DOSAGE AND ADMINISTRATION, Preparation of Solution for Intravenous Administration).
1. Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in Health Care Settings. NIOSH Alert 2004-165.
2.OSHA Technical Manual, TED 1-0.15A, Section VI: Chapter 2. Controlling Occupational Exposure to Hazardous Drugs. OSHA, 1999. http://www.osha.gov/ dts/osta/otm/otm_vi/otm_vi_2.html.
3.American Society of Health-System Pharmacists. ASHP Guidelines on Handling Hazardous Drugs. Am J Health-Syst Pharm. 2006;63:1172-1193.
4.Polovich M, White JM, Kelleher LO (eds.) 2005. Chemotherapy and Biotherapy Guidelines and Recommendations for Practice. (2nd ed) Pittsburgh, PA: Oncology Nursing Society.
Manufactured by: Baxter Oncology GmbH, 33790 Halle/Westfalen, Germany. For: Recordati Rare Diseases Inc., Lebanon, NJ 08833 , U.S.A. Revised: February 2013.
Last reviewed on RxList: 9/18/2013
This monograph has been modified to include the generic and brand name in many instances.
Additional Cosmegen Information
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