DACTINOMYCIN

DACTINOMYCIN
(dak-ti-noe-mye'sin)
Cosmegen
Classifications: antineoplastic; antibiotic;
Therapeutic:antineoplastic

Prototype: Doxorubicin
Pregnancy Category: D

Availability

0.5 mg injection

Action

Potent cytotoxic cell cycle nonspecific antibiotic. Complexes with DNA, thereby inhibiting DNA, RNA, and protein synthesis in actively proliferating cells. Causes delayed myelosuppression. Potentiates effects of x-ray therapy and the converse also appears likely.

Therapeutic Effect

Has antineoplastic properties that result from inhibiting DNA and RNA synthesis.

Uses

As single agent or in combination with other antineoplastics or radiation to treat Wilms' tumor, rhabdomyosarcoma, carcinoma of testes and uterus, Ewing's sarcoma, solid malignancies, gestational trophoblastic neoplasia, and sarcoma botryoides.

Unlabeled Uses

Malignant melanoma, Kaposi's sarcoma, osteogenic sarcoma, among others.

Contraindications

Acute infection; pregnancy (category D), lactation, infants <6 mo.

Cautious Use

Previous therapy with antineoplastics or radiation within 3–6 wk, bone marrow depression; infections; history of gout; impairment of kidney or liver function; obesity; chickenpox, herpes zoster, and other viral infections.

Route & Dosage

Neoplasms
Adult/Adolescent/Child/Infant (>6 mo): IV 500 mcg/d for 5 d max, may repeat at 2–4 wk intervals if tolerated (if patient is obese or edematous, give 400–600 mcg/m2/d to relate dosage to lean body mass); monitor for symptoms of toxicity from overdosage

Wilms' Tumor, Childhood Rhabdomyosarcoma, Ewing's Sarcoma, Nephroblastoma
Adult/Child: IV 15 mcg/kg/d x 5 d with other agents

Gestational Trophoblastic Neoplasia
Adult: IV 12 mcg/kg/d x 5 d or 500 mcg x 2 d with other agents

Solid Tumor
Adult/Adolescent/Child/Infant (>6 mo): IV 50 mcg/kg (lower extremity) or 35 mcg/kg (upper extremity)

Administration

Intravenous
  • Use gloves and eye shield when preparing solution. If skin is contaminated, rinse with running water for 10 min; then rinse with buffered phosphate solution. If solution gets into the eyes, wash with water immediately; then irrigate with water or isotonic saline for 10 min.

PREPARE: Direct: Reconstitute 0.5 mg vial by adding 1.1 mL sterile water (without preservative) for injection; the resulting solution will contain approximately 0.5 mg/mL.  IV Infusion: Further dilute in 50 mL of D5W or NS for infusion.  

ADMINISTER: Direct: Use two-needle technique for direct IV: Withdraw calculated dose from vial with one needle, change to new needle to give directly into vein without using an infusion. Give over 2–3 min. Or give directly into an infusing solutions of D5W or NS, or into tubing or side arm of a running IV infusion.  IV Infusion: Give diluted solution as a single dose over 15–30 min.  

INCOMPATIBILITIES Y-site: Filgrastim.

  • Store drug at 15°–30° C (59°–86° F) unless otherwise directed. Protect from heat and light.

Adverse Effects (≥1%)

GI: Nausea, vomiting, anorexia, abdominal pain, diarrhea, proctitis, GI ulceration, stomatitis, cheilitis, glossitis, dysphagia, hepatitis. Hematologic: Anemia (including aplastic anemia), agranulocytosis, leukopenia, thrombocytopenia , pancytopenia, reticulopenia. Skin: Acne, desquamation, hyperpigmentation and reactivation of erythema especially over previously irradiated areas, alopecia (reversible). Other: Malaise, fatigue, lethargy, fever, myalgia, anaphylaxis, gonadal suppression, hypocalcemia, hyperuricemia, thrombophlebitis; necrosis, sloughing, and contractures at site of extravasation; hepatitis, hepatomegaly.

Interactions

Drug: Elevated uric acid level produced by dactinomycin may necessitate dose adjustment of antigout agents; effects of both dactinomycin and other myelosuppressants are potentiated; effects of both radiation and dactinomycin are potentiated, and dactinomycin may reactivate erythema from previous radiation therapy; vitamin K effects (antihemorrhagic) decreased, leading to prolonged clotting time and potential hemorrhage.

Pharmacokinetics

Distribution: Concentrated in liver, spleen, kidneys, and bone marrow; does not cross blood–brain barrier; crosses placenta. Elimination: 50% unchanged in bile and 10% in urine; only 30% in urine over 9 d. Half-Life: 36 h.

Nursing Implications

Assessment & Drug Effects

  • Observe injection site frequently; if extravasation occurs, stop infusion immediately. Restart infusion in another vein. Report to physician. Institute prompt local treatment to prevent thrombophlebitis and necrosis.
  • Monitor for severe toxic effects that occur with high frequency. Effects usually appear 2–4 d after a course of therapy is stopped and may reach maximal severity 1–2 wk following discontinuation of therapy.
  • Use antiemetic drugs to control nausea and vomiting, which often occur a few hours after drug administration. Vomiting may be severe enough to require intermittent therapy. Observe patient daily for signs of drug toxicity.
  • Lab tests: Frequent renal, hepatic, and bone marrow function tests are advised. Perform WBC counts daily, and platelet counts every 3 d to detect hematopoietic depression.
  • Monitor temperature and inspect oral membranes daily for stomatitis.
  • Monitor for stomatitis, diarrhea, and severe hematopoietic depression. These may require prompt interruption of therapy until drug toxicity subsides.
  • Report onset of unexplained bleeding, jaundice, and wheezing. Also, be alert to signs of agranulocytosis (see Appendix F). Report to physician. Antibiotic therapy, protective isolation, and discontinuation of the antineoplastic are indicated.
  • Observe and report symptoms of hyperuricemia (see Appendix F). Urge patient to increase fluid intake up to 3000 mL/d if allowed.

Patient & Family Education

  • Note: Infertility is a possible, irreversible adverse effect of this drug.
  • Learn preventative measures to minimize nausea and vomiting.
  • Note: Alopecia (hair loss) is an anticipated reversible adverse effect of this drug. Seek appropriate supportive guidance.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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