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Black Box Warning
ConditionName:
See full prescribing information for complete Boxed Warning.
ConditionName:
COSMEGEN® (dactinomycin for injection) should be administered only under the supervision of a physician who is experienced in the use of cancer chemotherapeutic agents.
This drug is HIGHLY TOXIC and both powder and solution must be handled and administered with care. Inhalation of dust or vapors and contact with skin or mucous membranes, especially those of the eyes, must be avoided. Avoid exposure during pregnancy. Due to the toxic properties of dactinomycin (e.g., corrosivity, carcinogenicity, mutagenicity, teratogenicity), special handling procedures should be reviewed prior to handling and followed diligently. Dactinomycin is extremely corrosive to soft tissue. If extravasation occurs during intravenous use, severe damage to soft tissues will occur. In at least one instance, this has led to contracture of the arms.
Overview
Dactinomycin is a Antibiotic and a antineoplastic Agent that is FDA approved for the treatment of Wilms’ tumor, childhood rhabdomyosarcoma, Ewing’s sarcoma and metastatic, nonseminomatous testicular cancer, gestational trophoblastic neoplasia, and adjunctive treatment of locally recurrent or locoregional solid malignancies.. There is a Black Box Warning for this drug as shown here. Common adverse reactions include Diarrhea, Nausea and vomiting.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Indications
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.
COSMEGEN, as a component of regional perfusion, is indicated for the palliative and/or adjunctive treatment of locally recurrent or locoregional solid malignancies.
Dosage
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.
Intravenous Use
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.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
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Developed by:
Class of Recommendation:
Strength of Evidence:
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Guideline-Supported Use of Dactinomycin in adult patients.
Non–Guideline-Supported Use
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Non–Guideline-Supported Use of Dactinomycin in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding FDA-Labeled Use of Dactinomycin in pediatric patients.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
Condition1
Developed by:
Class of Recommendation:
Strength of Evidence:
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Guideline-Supported Use of Dactinomycin in pediatric patients.
Non–Guideline-Supported Use
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Non–Guideline-Supported Use of Dactinomycin in pediatric patients.
Contraindications
Condition1
Warnings
ConditionName:
See full prescribing information for complete Boxed Warning.
ConditionName:
COSMEGEN® (dactinomycin for injection) should be administered only under the supervision of a physician who is experienced in the use of cancer chemotherapeutic agents.
This drug is HIGHLY TOXIC and both powder and solution must be handled and administered with care. Inhalation of dust or vapors and contact with skin or mucous membranes, especially those of the eyes, must be avoided. Avoid exposure during pregnancy. Due to the toxic properties of dactinomycin (e.g., corrosivity, carcinogenicity, mutagenicity, teratogenicity), special handling procedures should be reviewed prior to handling and followed diligently. Dactinomycin is extremely corrosive to soft tissue. If extravasation occurs during intravenous use, severe damage to soft tissues will occur. In at least one instance, this has led to contracture of the arms.
Description
Precautions
Description
Adverse Reactions
Clinical Trials Experience
There is limited information regarding Clinical Trial Experience of Dactinomycin in the drug label.
Body as a Whole
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous
Postmarketing Experience
There is limited information regarding Postmarketing Experience of Dactinomycin in the drug label.
Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Dactinomycin in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Dactinomycin during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Dactinomycin with respect to nursing mothers.
Pediatric Use
There is no FDA guidance on the use of Dactinomycin with respect to pediatric patients.
Geriatic Use
There is no FDA guidance on the use of Dactinomycin with respect to geriatric patients.
Gender
There is no FDA guidance on the use of Dactinomycin with respect to specific gender populations.
Race
There is no FDA guidance on the use of Dactinomycin with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Dactinomycin in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Dactinomycin in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Dactinomycin in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Dactinomycin in patients who are immunocompromised.
Administration and Monitoring
Administration
Intravenous
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. 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.
Monitoring
There is limited information regarding Monitoring of Dactinomycin in the drug label.
Description
IV Compatibility
There is limited information regarding IV Compatibility of Dactinomycin in the drug label.
Overdosage
Acute Overdose
Signs and Symptoms
Description
Management
Description
Chronic Overdose
There is limited information regarding Chronic Overdose of Dactinomycin in the drug label.
Pharmacology
There is limited information regarding Dactinomycin Pharmacology in the drug label.
