DrugindexOnline^{2nd edition}

Pronouncation: (DAK-tih-no-MY-sin)
Class: Antineoplastic agent

Trade Names:
Cosmegen
- Lyophilized powder for reconstitution 500 mcg vial with 20 mg of mannitol

Mechanism of Action

Pharmacology

Dactinomycin is the principal component of the mixture of actinomycins produced by Streptomyces parvulus . It inhibits messenger RNA synthesis.

Pharmacokinetics

Distribution

Concentrated in nucleated cells. Does not penetrate blood-brain barrier.

Metabolism

Minimally metabolized.

Elimination

Approximately 30% recovered in urine and feces in 1 wk; t _½ approximately 36 h.

Indications and Usage

Treatment of Wilms tumor, childhood rhabdomyosarcoma, Ewing sarcoma, and metastatic nonseminomatous testicular cancer as part of combination chemotherapy and/or multi-modality treatment regimen; palliative and/or adjunctive treatment of locally recurrent or locoregional solid malignancies as a component of regional perfusion; treatment of gestational trophoblastic neoplasia as a single agent or as part of a combination chemotherapy regimen.

Contraindications

If given at or about the time of infection with chickenpox or herpes zoster, a severe generalized disease may occur, which could result in death.

Dosage and Administration

Adults and Children

IV The dosage varies depending on the tolerance of the patient, the size and location of the neoplasm, and the use of other forms of therapy. The dose intensity per 2-wk cycle for adults and children should not exceed 15 mcg/kg/day or 400 to 600 mcg/m ² /day for 5 days. Calculate the dosage for obese or edematous patients on the basis of surface area to more closely relate dosage to lean body mass.

General Advice

• For IV or regional perfusion only.
• Dactinomycin is highly toxic. Handle and administer powder and reconstituted solution with extreme care. Diligently follow institutional and NIH procedures for handling, administration, and disposal of anticancer drugs. Wear appropriate protective equipment when preparing and administering dactinomycin. Avoid inhalation of dust or vapors and contact with skin, mucous membranes, and eyes.
• If accidental skin or mucous membrane contact occurs, immediately irrigate affected area with copious amounts of water for at least 15 minutes while removing contaminated clothing and shoes. Destroy contaminated clothing and thoroughly clean shoes before reuse.
• If accidental eye contact occurs, immediately institute irrigation with copious amounts of water, normal saline or a balanced salt ophthalmic irrigating solution for at least 15 minutes. Prompt ophthalmic evaluation should follow irrigation.
• Reconstitute powder for injection with 1.1 mL sterile water for injection (without preservative). Mix thoroughly to obtain complete dissolution. Resulting solution contains 500 mcg/mL (0.5 mg/mL) of dactinomycin.
• Do not reconstitute powder for injection using diluents with preservatives that can cause precipitation of dactinomycin.
• Reconstituted solution should be a clear, golden-colored solution.
• Add prescribed dose or reconstituted solution directly to infusion solution of dextrose 5% or sodium chloride injection or to the tubing of a running IV infusion.
• If medication is to be given directly into a vein without the use of an infusion, use the “2-needle technique” to reduce risk of tissue damage. Reconstitute and withdraw the calculated dose from the vial with one sterile needle. Use another sterile needle for direct injection into the vein.
• Do not use inline filters made of cellulose which can remove dactinomycin.

Storage/Stability

Store powder for injection at room temperature (59° to 86°F). Protect from light and humidity. Dactinomycin is stable after reconstitution but does not contain a preservative. Use reconstituted solution as soon as possible. Discard any unused solution. Do not save any unused solution for future use.

Drug Interactions

No specific drug interactions reported.

Laboratory Test Interactions

Bioassay procedures for the determination of antibacterial drug levels.

Adverse Reactions

CNS

Fatigue; lethargy; malaise.

Dermatologic

Acne; alopecia; edema; epidermolysis; erythema; extravasation; flare-up of erythema; skin eruptions; increased pigmentation of previously irradiated skin.

EENT

Pharyngitis.

GI

Abdominal pain; anorexia; cheilitis; diarrhea; dysphagia; esophagitis; GI ulceration; nausea; ulcerative stomatitis; vomiting.

Genitourinary

Proctitis.

Hepatic

Hepatomegaly; hepatic veno-occlusive disease; hepatitis; abnormal LFTs; liver toxicity including ascites.

Hematologic-Lymphatic

Agranulocytosis; anemia; aplastic anemia; leukopenia; pancytopenia; reticulocytopenia; thrombocytopenia.

Lab Tests

Hypercalcemia.

Metabolic

Growth retardation.

Musculoskeletal

Myalgia.

Respiratory

Pneumonitis.

Miscellaneous

Fever; infection.

Precautions

Warnings Dactinomycin is extremely corrosive to soft tissue. If extravasation occurs during IV use, severe damage to soft tissues will occur. In at least one instance, this has led to contracture of the arms. Avoid use in pregnancy. Dactinomycin is also carcinogenic, mutagenic, and teratogenic.

Monitor Ensure liver function (ie, transaminases, bilirubin) and renal function (ie, Scr, BUN) are evaluated before starting therapy and frequently thereafter during treatment. Notify health care provider if abnormalities develop. Ensure CBC with differential and platelet count are evaluated daily. Monitor patient for signs or symptoms of infection or bleeding. Monitor patient closely for toxic adverse reactions of therapy, especially when multiple chemotherapy is being used. Monitor IV injection site for signs or symptoms of extravasation.

Pregnancy

Category D .

Lactation

Undetermined.

Children

Toxicity is increased in infants. Avoid use in infants younger than 6 to 12 mo of age.

Elderly

Use with caution because of the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy.

Chickenpox or herpes zoster

Do not give at or about the time of infection with chickenpox or herpes zoster; severe generalized disease may occur.

GI toxicity and marrow suppression

Increased incidence.

Radiation

With combined dactinomycin-radiation therapy, the normal skin, as well as the buccal and pharyngeal mucosa, may show early erythema. A smaller than usual x-ray dose, when given with dactinomycin, causes erythema and vesiculation, which progress more rapidly through the tanning and desquamation stages. Erythema from previous x-ray therapy may be reactivated by dactinomycin alone, even when irradiation occurred many months earlier, and especially when the interval between the 2 forms of therapy is brief. When the nasopharynx is irradiated, the combination may produce severe oropharyngeal mucositis. Severe reactions may appear if high doses are used or if the patient is particularly sensitive to such combined therapy.

Second primary tumors

Increased incidence.

Toxic effects

Note that toxic effects (with exception of nausea and vomiting) usually do not become apparent until 2 to 4 days after a course of therapy is stopped, and may not peak until 1 to 2 wk have elapsed.

Patient Information

• Review the treatment regimen including dosing schedule, duration of treatment, and monitoring that will be required.
• Review benefits of therapy and risks, including reactivation of erythema from previous radiation therapy, and potential of developing secondary primary tumors.
• Advise patient, family, or caregiver that medication will be prepared and administered by health care professionals in a health care setting.
• Advise patient, family, or caregiver that medication may be used in combination with other agents to achieve max benefit possible.
• Advise patient, family, or caregiver that medication may cause hair loss but that this is reversible when therapy is stopped.
• Advise patient, family, or caregiver to immediately report any of the following to health care provider: rash; hives; difficulty breathing or unexplained shortness of breath; fever, chills, or other signs of infection; sores in mouth; pain, redness, or swelling at injection site.
• Advise patient, family, or caregiver to report any of the following to health care provider: persistent nausea, vomiting, or appetite loss; persistent or worsening general body weakness; skin changes; nail changes.
• Caution women of childbearing potential to avoid becoming pregnant during therapy.