April 29, 2017
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Reports indicate an increased incidence of second primary tumors (including leukemia) following treatment with radiation and antineoplastic agents, such as COSMEGEN. Multi-modal therapy creates the need for careful, long-term observation of cancer survivors.

Pregnancy Category D

COSMEGEN may cause fetal harm when administered to a pregnant woman. COSMEGEN has been shown to cause malformations and embryotoxicity in rat, rabbit, and hamster when given in doses of 50-100 mcg/kg (approximately 0.5 - 2 times the maximum recommended daily human dose on a body surface area basis). If this drug is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential must be warned to avoid becoming pregnant.



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).

As with all antineoplastic agents, COSMEGEN is a toxic drug and very careful and frequent observation of the patient for adverse reactions is necessary. These reactions may involve any tissue of the body, most commonly the hematopoietic system resulting in myelosuppression. As such, live virus vaccines should not be administered during therapy with COSMEGEN. The possibility of an anaphylactoid reaction should be borne in mind.

It is extremely important to observe the patient daily for toxic side effects when combination chemotherapy is employed, since a full course of therapy occasionally is not tolerated. If stomatitis, diarrhea, or severe hematopoietic depression appear during therapy, these drugs should be discontinued until the patient has recovered.

Veno-occlusive Disease

Veno-occlusive disease (primarily hepatic) may result in fatality, particularly in children younger than 48 months. (See ADVERSE REACTIONS, Hepatic.)

COSMEGEN (dactinomycin for injection) and Radiation Therapy

An increased incidence of gastrointestinal toxicity and marrow suppression has been reported with combined therapy incorporating COSMEGEN and radiation. Moreover, the normal skin, as well as the buccal and pharyngeal mucosa, may show early erythema. A smaller than usual radiation dose administered in combination with COSMEGEN causes erythema and vesiculation, which progress more rapidly through the stages of tanning and desquamation. Healing may occur in four to six weeks rather than two to three months. Erythema from previous radiation therapy may be reactivated by COSMEGEN alone, even when radiotherapy was administered many months earlier, and especially when the interval between the two forms of therapy is brief. This potentiation of radiation effect represents a special problem when the radiotherapy involves the mucous membrane. When irradiation is directed toward the nasopharynx, the combination may produce severe oropharyngeal mucositis. Severe reactions may ensue if high doses of both COSMEGEN and radiation therapy are used or if the patient is particularly sensitive to such combined therapy.

Particular caution is necessary when administering COSMEGEN within two months of irradiation for the treatment of right-sided Wilms' tumor, since hepatomegaly and elevated AST levels have been noted. In general, COSMEGEN should not be concomitantly administered with radiotherapy in the treatment of Wilms' tumor unless the benefit outweighs the risk.

COSMEGEN (dactinomycin for injection) and Regional Perfusion Therapy

Complications of the perfusion technique are related mainly to the amount of drug that escapes into the systemic circulation and may consist of hematopoietic depression, absorption of toxic products from massive destruction of neoplastic tissue, increased susceptibility to infection, impaired wound healing, and superficial ulceration of the gastric mucosa. Other side effects may include edema of the extremity involved, damage to soft tissues of the perfused area, and (potentially) venous thrombosis.

Laboratory Tests

Many abnormalities of renal, hepatic, and bone marrow function have been reported in patients with neoplastic diseases receiving COSMEGEN. Renal, hepatic, and bone marrow functions should be assessed frequently.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Reports indicate an increased incidence of second primary tumors (including leukemia) following treatment with radiation and antineoplastic agents, such as COSMEGEN. Multi-modal therapy creates the need for careful, long-term observation of cancer survivors.

The International Agency on Research on Cancer has judged that dactinomycin is a positive carcinogen in animals. Local sarcomas were produced in mice and rats after repeated subcutaneous or intraperitoneal injection. Mesenchymal tumors occurred in male F344 rats given intraperitoneal injections of 50 mcg/kg, 2 to 5 times per week for 18 weeks. The first tumor appeared at 23 weeks.

Dactinomycin has been shown to be mutagenic in a number of test systems in vitro and in vivo including human fibroblasts and leukocytes, and HeLa cells. DNA damage and cytogenetic effects have been demonstrated in the mouse and the rat.

Adequate fertility studies have not been reported, although, reports suggest an increased incidence of infertility following treatment with other antineoplastic agents.


Pregnancy Category D


Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from COSMEGEN, a decision should be made as to discontinuation of nursing and/or drug, taking into account the importance of the drug to the mother.

Pediatric Use

The greater frequency of toxic effects of COSMEGEN in infants suggest that this drug should be administered to infants only over the age of 6 to 12 months.

Geriatric Use

Clinical studies of COSMEGEN did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. However, a published meta-analysis of all studies performed by the Eastern Cooperative Oncology Group (ECOG) over a 13-year period suggests that administration of COSMEGEN to elderly patients may be associated with an increased risk of myelosuppression compared to younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

This monograph has been modified to include the generic and brand name in many instances.

Last reviewed on RxList: 3/20/2017


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