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(DAK-tih-no-MY-sin)
Cosmegen
Lyophilized powder for reconstitution
500 mcg vial with 20 mg of mannitol.
Class: Antineoplastic antibiotic

 Actions Dactinomycin is the pricipal component of the mixture of actinomycins produced by Streptomyces parvullus. It inhibits messenger RNA synthesis. Dactinomycin is minimally metabolized. Plasma half-life is about 36 hr.

 Indications

Adult

Wilms tumor, rhabdomyosarcoma, metastatic nonseminomatous testicular carcinoma, Ewing sarcoma, sarcoma botryides, trophoblastic tumor, metastatic and nonmetastatic choriocarcinoma; radiation therapy.

Pediatric

Wilms tumor, rhabdomyosarcoma, metastatic nonseminomatous testicular carcinoma, Ewing sarcoma, sarcoma botryides, trophoblastic tumor, metastatic choriocarcinoma.

Osteosarcoma, malignant melanoma, Paget disease of the bone.

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

 Route/Dosage Adults: IV Administer the drug in short courses. Base dose on BSA in obese or edematous patients. Dose should not exceed 15 mcg/kg or 400 to 600 mcg/m2 daily for 5 days. Repeat in 3 wk if necessary. Usual dose is 500 mcg/day for a max of 5 days.

Pediatric: IV Administer the drug in short courses. Base dose on BSA in obese or edematous patients. Do not exceed 15 mcg/kg/day or 400 to 600 mcg/m2/day for 5 days. Repeat in 3 to 4 wk if necessary. Usual dose is 0.015 mg/kg/day for 5 days. Alternative schedule is a total dosage of 2.5 mg/m2 over 1 wk.

Interactions No specific drug interactions reported.

Lab Test Interferences Bioassay procedures for the determination of antibacterial drug levels.

 Adverse Reactions

CNS: Malaise; fatigue; lethargy. DERMATOLOGIC: Alopecia; hyperpigmentation; radiation recal; folliculitis. GI: Nausea; vomiting; severe mucositis; pharyngitis; abdominal pain; peptic ulcer; proctitis; hepatic veno-occlusive disease; hepatic necrosis. HEMATOLOGIC: Bone marrow suppression. OTHER: Second primary tumors.

 Precautions

Pregnancy: Category C. Lactation: Decide whether to discontinue nursing or to discontinue the drug. Infants: Toxicity is increased in infants. Avoid use in infants younger than 6 to 12 mo. Chicken pox or herpes zoster: Do not give at or about the time of infection with chicken pox or herpes zoster; severe generalized disease may occur. Extravasation risk: Local irritation or phlebitis may occur. Refer to the institution’s specific protocol. GI toxicity and marrow suppression: Increased incidence. Radiation: With combined dactinomycin-radiation therapy, the normal skin, as well as the buccal and pharyngeal mucosa, 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.

PATIENT CARE CONSIDERATIONS

 Administration/Storage

  • Store at room temperature (59° to 86°F). Protect from light.
  • Reconstitute with Sterile Water for Injection. Add directly to infusion solutions of 5% Dextrose or Sodium Chloride Injection or to the tubing of a running IV infusion. Diluents with preservatives can cause precipitation of dactinomycin.
  • The product does not contain a preservative; discard unused portion within 24 hr.
  • Administer by IV injection.
  • In-line membrane filters made of cellulose ester can remove dactinomycin.
  • Give by IV push injection or by IV side arm.
  • Use “2-needle technique” if given directly into the vein without use of an infusion. Reconstitute and withdraw dose from vial with 1 sterile needle. Use another needle for direct injection into vein.
  • Handle and administer powder and solution with care. Avoid inhalation of dust or vapors and contact with skin or mucous membranes, especially those of the eyes.

Radiation therapy

  • Dactinomycin may be tried in radiosensitive tumors not responding to x-ray therapy. Objective improvement in tumor size and activity may be observed when lower, better tolerated doses of both types of therapy are employed.

Perfusion technique

  • Dactinomycin alone or with other antineoplastics has been given by the isolation-perfusion technique. Administer 0.05 mg/kg for lower extremity or pelvis; 0.035 mg/kg for upper extremity. Use lower doses in obese patients, or when previous therapy has been employed. Some tumors resistant to chemotherapy and radiation therapy may respond. The drug is in continuous contact with the tumor for the duration of treatment. The dose may be increased well over that used by the systemic route, usually without added toxicity.

 Assessment/Interventions

  • Nausea and vomiting caused by dactinomycin necessitates intermittent administration. Observe the patient daily for toxic side effects when multiple chemotherapy is used. If stomatitis, diarrhea, or severe hematopoietic depression appear, discontinue use until the patient has recovered.
  • Toxic effects usually do not become apparent until 2 to 4 days after a course of therapy and may not be maximal before 1 to 2 wk. Adverse reactions are usually reversible with discontinuation of therapy.
  • Alleviate nausea and vomiting occurring during the first few hours after use by giving antiemetics.
  • Perform platelet and white cell counts daily. If either count markedly decreases, withhold drug until marrow recovery occurs; this often takes up to 3 wk.
  • Use caution in the first 2 mo after irradiation for the treatment of right-sided Wilms tumor because hepatomegaly and elevated AST levels have been noted.

 Patient/Family Education

  • Explain name, action, and potential side effects of drug.
  • Advise patient, family, or caregiver that medication will be prepared and administered by health care provider in a health care setting.
  • Advise patient, family, or caregiver that medication may be used in combination with other agents to achieve maximum benefit possible.
  • Review dosing schedule with patient, family, or caregiver.
  • Advise patient, family, or caregiver to immediately report any of the following to health care provider: rash; hives; difficulty breathing; fever, chills, or other signs of infection; sores in mouth; unusual bleeding or bruising; 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.
  • Instruct patient to not take any prescription or otc medications or dietary supplements unless advised by health care provider.
  • Caution women of childbearing potential to avoid becoming pregnant while being treated.
  • Instructwomen of childbearing potential to notify health care provider if becoming pregnant, planning on becoming pregnant, or are breastfeeding.
  • Advise patient that frequent follow-up visits and laboratory tests will be required to monitor therapy and to keep appointments.

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