NAME OF DRUG
dactinomycin

CLASSIFICATION

Cytotoxic Agent - vesicant
Antibiotic

ALTERNATE NAMES

ACTINOMYCIN D, COSMEGEN

INDICATIONS

• treatment of Wilm's tumor, rhabdomyosarcoma, Ewing's sarcoma in children, carcinoma of the testes, uterus and various sarcomas, other carcinomas, adenocarcinomas and leukemia

PHARMACOLOGY

• dactinomycin inhibits the DNA-dependent RNA-synthesis by forming a complex with DNA and impairing its template activity
• protein and DNA synthesis are also inhibited
• immunosuppressive
• half-life after IV administration is about 36 hrs
• slightly metabolized; excreted in the urine and the bile; in the urine it is excreted primarily as unchanged dactinomycin

• ALL cytotoxic agents are prepared in pharmacy and will be sent to the ward with a label indicating storage conditions and the expiry date.  All cytotoxic waste including bags, sets, tubing, gloves, etc. must be properly disposed of in the cytotoxic waste containers on the nursing unit.

• compatible with D5W, NS
• incompatible with bacteriostatic agents
• significantly adsorbed to cellulose filters; avoid in-line filtration

• PERIPHERAL ROUTE
  • via syringe using side arm method into the tubing of a free-flowing IV of D5W or NS at a rate of 100mg/minute (refer to PCG C-396)
     
• CENTRAL ROUTE
  • IV intermittent - administered in 50-100 mL D5W or NS over a period of 10-15 minutes
     
• isolation perfusion technique

A Parenteral Chemotherapy/Immunotherapy pre-printed order form (PPO # 45) must be used for prescribing if this cytotoxic agent
is not already on an existing PPO.

G - Cytotoxic Agents - See Drug Table G for specific administration guidelines.
H - Central route: the IV infusion rate must be controlled by an automated infusion control device.

DOSAGE

Dose and schedule depend on protocol and patient response.

• usual IV dose for each course of therapy should not exceed 15 mcg/kg or 600 mcg/m² daily for 5 days
• additional courses of therapy can be given at 2-4 week intervals
• isolation perfusion - usual dose
  • pelvis or lower extremity: 50 mcg/kg
  • upper extremity: 35 mcg/kg

POTENTIAL HAZARDS OF PARENTERAL ADMINISTRATION

• pain and erythema may occur at the injection site
• extravasation may cause tissue necrosis -  (see Appendix VII for extravasation protocol)

IMPORTANT IMPLICATIONS

• severe and often dose-limiting bone marrow depression occurring from the first day and up to 2 weeks after a course of therapy; hematologic status must be carefully monitored
• GI and mucosal toxicities are major and dose-limiting side effects
• nausea and vomiting usually occur within a few hours after administration:  antiemetics can be used
• skin and mucosal reactions (glossitis, stomatitis, dermal reactions, acne) are quite common, and may be dose-limiting
• "radiation recall" toxicity - this can be severe depending on the area radiated and the length of time between radiation and drug administration
• reduce dosage when radiation or other cytotoxic agents are used concomitantly, or in hepatic dysfunction
• renal and hepatic function should be monitored frequently

VGH Site only:
Notify security-84 immediately upon accidental spillage.
DO NOT ATTEMPT CLEAN-UP

• See also Appendix VI

Rev. Nov 2007