dactinomycin (actinomycin D; ACT)
Cosmegen

Available forms
Available by prescription only
Lyophilized powder for injection: 500-mcg vial

Indications and dosages
Dosage and indications may vary. Check current literature for recommended protocols.
 Uterine cancer, testicular cancer, Wilms’ tumor, rhabdomyosarcoma, Ewing’s sarcoma, sarcoma botryoides, Kaposi’s sarcoma ◇, acute organ (kidney or heart) rejection ◇, malignant melanoma ◇, acute lymphocytic leukemia ◇, advanced tumors of breast or ovary ◇, Paget’s disease of bone ◇. Adults: 500 mcg (0.5 mg) I.V. daily for a maximum of 5 days. Maximum dose is 15 mcg/kg/day or 400 to 600 mcg/m²/day for 5 days. After bone marrow recovery, course may be repeated.
 Dose should be based on body surface area in obese or edematous patients.
Children: 15 mcg/kg (0.015 mg/kg) I.V. daily for a maximum of 5 days. Or, give a total dosage of 2,500 mcg/m² I.V. over a 1-week period. Maximum dose is 15 mcg/kg/day or 400 to 600 mcg/m²/day. After bone marrow recovery, course may be repeated.
 For isolation-perfusion, use 50 mcg/kg for leg or pelvis; 35 mcg/kg for arm. For second course, wait at least 3 weeks, provided all signs of toxicity have subsided.

Pharmacodynamics
Antineoplastic action: Dactinomycin exerts its cytotoxic activity by intercalating between DNA base pairs and inhibiting messenger RNA synthesis and uncoiling the DNA helix. The result is inhibition of DNA synthesis and DNA-dependent RNA synthesis. Drug is cell cycle nonspecific.

Pharmacokinetics
Absorption: Administered I.V.
Distribution: Widely distributed into body tissues, with highest levels found in the bone marrow and nucleated cells. Drug doesn’t cross the blood-brain barrier to a significant extent.
Metabolism: Only minimally metabolized in the liver.
Excretion: Excreted in the urine and bile. Plasma elimination half-life of drug is 36 hours.

Contraindications and precautions
Contraindicated in patients with chickenpox or herpes zoster.

Interactions
Drug-drug. Bone marrow suppressants: May cause additive toxicity. Monitor patient closely.
Vitamin K derivatives: Decreases drug effectiveness. Monitor patient closely.

Adverse reactions
CNS: malaise, fatigue, lethargy, fever.
GI: anorexia, nausea, vomiting, abdominal pain, diarrhea, stomatitis, ulceration, proctitis.
Hematologic: anemia, leukopenia, thrombocytopenia, pancytopenia, aplastic anemia, agranulocytosis.
Hepatic: hepatotoxicity.
Metabolic: increased blood and urine levels of uric acid, hypocalcemia.
Musculoskeletal: myalgia.
Skin: erythema; desquamation; hyperpigmentation of skin, especially in previously irradiated areas; acnelike eruptions; reversible alopecia, extravasation and phlebitis and severe damage to soft tissue at injection site.

Effects on lab test results
• May increase uric acid levels. May decrease calcium levels.
• May decrease hemoglobin, hematocrit, and WBC, RBC, granulocyte, and platelet counts.

Overdose and treatment
Signs and symptoms of overdose include myelosuppression, nausea, vomiting, glossitis, and oral ulceration.
 Treatment is generally supportive and includes antiemetics and transfusion of blood components.

Special considerations
• To reduce nausea, give an antiemetic before administering. Nausea usually occurs within 30 minutes of a dose.
• Use body surface area calculation in obese or edematous patients.
• Use gloves when preparing and administering this drug.
• To reconstitute for I.V. administration, add 1.1 ml of preservative-free sterile water for injection to drug to yield 0.5 mg/ml. Don’t use a preserved diluent because precipitation may occur.
• Drug is highly toxic; avoid inhalation of powder or vapors and contact with skin or mucous membranes.
• If contact with eyes occurs, irrigate eyes with copious amounts of water and contact ophthalmologist immediately. If contact with skin occurs, irrigate area with copious amounts of water for at least 15 minutes.
• For direct I.V. injection, use 2 needle technique: Withdraw dose from vial with one needle and use another needle to inject into the vein.
• Drug may be diluted further with D₅W or normal saline solution for administration by I.V. infusion.
• Discard unused solution because it doesn’t contain preservatives.
• Drug may be administered by I.V. push injection into the tubing of a freely flowing I.V. infusion. Don’t administer through an in-line I.V. filter.
• Drug is a vesicant; treatment of extravasation includes topical administration of dimethyl sulfoxide and cold compresses.
• Patients who have received other cytotoxic drugs or radiation within 6 weeks of dactinomycin may exhibit erythema followed by hyperpigmentation, edema, or both; desquamation; vesiculation; and rarely necrosis.
• Drug may interfere with bioassay procedures for determination of antibacterial drug levels.
• Monitor CBC daily and platelet counts every third day. Leukocyte and platelet nadirs usually occur 14 to 21 days after completion of course of therapy. Observe for signs of bleeding.
• Monitor renal and hepatic functions.
Breast-feeding patients
• It isn’t known whether drug appears in breast milk. However, because of risks of serious adverse reactions, mutagenicity, and carcinogenicity in infants, breast-feeding isn’t recommended.
Pediatric patients
• Restrict use of drug in infants age 6 months and younger; adverse reactions are more frequent in infants younger than age 6 months.

Patient education
• Advise patient to avoid exposure to people with infections.
• Warn patient that alopecia may occur but is usually reversible.
• Tell patient to report sore throat, fever, or signs of bleeding promptly.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use