Dactinomycin


Generic Medicine Info
Indications and Dosage
Intravenous
Childhood rhabdomyosarcoma, Ewing's sarcoma, Wilm's tumour
Adult: 15 mcg/kg daily for 5 days, in combination regimens. Max: 15 mcg/kg or 400-600 mcg/m2 daily for 5 days per 2-wk cycle.
Child: ≥6 mth Same as adult dose.

Intravenous
Metastatic nonseminomatous testicular cancer
Adult: 1 mg/m2 on day 1 of combination regimens. Max: 15 mcg/kg or 400-600 mcg/m2 daily for 5 days per 2-wk cycle.

Intravenous
Gestational trophoblastic tumours
Adult: 12 mcg/kg daily for 5 days as a single agent or 500 mcg daily on days 1 and 2 of combination regimens. Max: 15 mcg/kg or 400-600 mcg/m2 daily for 5 days per 2-wk cycle.
Reconstitution
Add 1.1 mL of sterile water for inj (w/o preservative), using aseptic precautions to make a soln containing approx 500 mcg/mL. The reconstituted soln can be added to infusion soln of dextrose 5% inj or NaCl inj either directly or to the tubing of a running IV infusion.
Incompatibility
Filgrastim.
Contraindications
Hypersensitivity. Patient w/ varicella or herpes zoster infection.
Special Precautions
Patient w/ impaired bone marrow. Renal and hepatic impairment. Pregnancy and lactation.
Adverse Reactions
Nausea, vomiting, cheilitis, oesophagitis, GI ulceration, proctitis, fever, malaise, hypocalcaemia, myalgia, alopecia, pneumonitis, kidney and liver abnormalities, eruptions, acne, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, severe tissue damage, oedema, neutropenia and febrile neutropenia.
Potentially Fatal: Hepatic failure, hepatic veno-occlusive disease, particularly in childn <4 yr, myelosuppression, sepsis, including neutropenic sepsis.
IV/Parenteral: D
Patient Counseling Information
Avoid inhalation of vapours or contact w/ skin, mucous membrane or eyes.
Monitoring Parameters
Monitor blood counts, renal, hepatic and bone marrow functions frequently.
Overdosage
Symptoms: Nausea, vomiting, diarrhoea, mucositis including stomatitis, GI ulceration, severe skin disorders including skin exfoliation, exanthema, desquamation and epidermolysis, severe haemopoietic depression, veno-occlusive disease, acute renal failure, sepsis (including neutropenic sepsis). Management: Symptomatic and supportive treatment.
Drug Interactions
Combination w/ radiation therapy may result in increased toxicity esp when w/in 2 mth of radiation treatment for right-sided Wilm's tumour. May diminish the therapeutic effect of live vaccines.
Lab Interference
May interfere w/ bioassay procedures for the determination of antibacterial drug levels.
Action
Description:
Mechanism of Action: Dactinomycin binds to the guanine portion of DNA forming a complex which interferes w/ DNA and RNA synthesis as well as protein synthesis. It is also immunosuppressive and possesses some hypocalcaemic activity.
Pharmacokinetics:
Absorption: Poorly absorbed from the GI tract.
Distribution: Rapidly distributed w/ high concentrations in bone marrow and nucleated cells. Crosses the placenta.
Metabolism: Minimal metabolism.
Excretion: Via urine and bile. Terminal plasma half-life: Approx 36 hr.
Chemical Structure

Chemical Structure Image

Source: National Center for Biotechnology Information. PubChem Database. Dactinomycin, CID=457193, https://pubchem.ncbi.nlm.nih.gov/compound/Dactinomycin (accessed on Jan. 20, 2020)

Storage
Store between 20-25°C. Protect from light and humidity.
MIMS Class
Cytotoxic Chemotherapy
References
Anon. Dactinomycin. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 17/06/2014.

Buckingham R (ed). Dactinomycin. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 17/06/2014.

Cosmegen (Dactinomycin) for Injection. U.S. FDA. https://www.fda.gov/. Accessed 17/06/2014.

Cosmegen Injection (Recordati Rare Diseases, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 17/06/2014.

McEvoy GK, Snow EK, Miller J et al (eds). Dactinomycin. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 17/06/2014.

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