DACTINomycin

Brand names Cosmegen

Medication error ISMP high-alert medication that has an increased risk of causing significant patient harm potential if it is used in error.(1) Look-alike, sound-alike drug names ISMP and USP report that DACTINomycin has been confused with DAPTOmycin; no patient harm resulted.(2,3)

Contraindications U.S. boxed warning: Dactinomycin should be administered under the supervision of an and warnings experienced physician. The drug is highly toxic; both the powder and solution should be handled with care. Inhalation of vapors or dust and contact with skin and mucous mem- branes should be avoided. Do not use or handle during pregnancy. Special precautions should be in place and reviewed prior to handling due to the toxic properties of dactinomy- cin (corrosivity, carcinogenicity, mutagenicity, and teratogenicity). Dactinomycin is highly corrosive and will damage soft tissue if extravasation occurs (see the Infusion-Related Cautions section); dactinomycin extravasation has resulted in contracture of the arm in at least one case.(4) Contraindications: Known hypersensitivity to the drug or to any component of this product. Should not be administered around the time of infection with chicken pox or herpes zoster.(4) Other warnings: Veno-occlusive disease (especially in children <48 months), myelosup- pression, dermatological reactions, emesis, and secondary malignancies.(4,5) Dactinomycin should not be used in infants <6 months based on a higher incidence of side effects.(4) (See the Comments section.)

Infusion-related Extravasation will result in severe soft tissue damage. If extravasation is suspected, cautions discontinue infusion and apply, ice to the affected area intermittently for 15 minutes 4 times daily for 3 days.(4) (See Appendix E for additional information regarding extravasa- tion treatment.)

Dosage Consult individual protocols for complete dosing information. Dactinomycin is used as a component of combination therapy for several malignant pedi- atric solid tumors. Dactinomycin has also been used in patients with nephroblastoma, malignant melanoma, and osteosarcoma. Dosage should be based on body surface area for obese or edematous patients.(4) (See Appendix A.) Suggested regimens for different disease states include the following: Wilms tumor: 15 mcg/kg/day IV for 5 days in combination with chemotherapeutic agents(4-10) Alternate dosing, children and adolescents(11) With doxorubicin and vincristine: 45 mcg/kg on day 1 q 6 wk for 54 weeks With vincristine: 45 mcg/kg on day 1 q 3 wk for 18 weeks Alternate dosing, VAD (with vincristine and doxorubicin)(12) Infants >6 months: 750 mcg/m2 q 6 wk for 1 year (Stage III) Children and adolescents: 1500 mcg/m2 q 6 wk for 1 year (Stage III) Rhabdomyosarcoma: 15 mcg/kg/day for 5 days in combination with chemotherapeutic agents(4) Alternate dosing: VAC (with vincristine, cyclophosphamide and mesna)(13) Infants >6 months: 25 mcg/kg q 3 wk, weeks 0 to 45  252 DACTINomycin

Children and adolescents: 45 mcg/kg q 3 wk, weeks 0 to 45 Alternate dosing, accelerated schedule(14) Infants <12 months: 25 mcg/kg q 4 wk for 22 weeks in combination with che- motherapeutic agents Children and adolescents: 45 mcg/kg (maximum dose 2500 mcg) q 4 wk for 22 weeks in combination with chemotherapeutic agents Ewing sarcoma: 15 mcg/kg/day for 5 days in combination with chemotherapeutic agents(4) Osteosarcoma: 600 mcg/m2 IV days 1, 2 and 3, in combination with chemotherapeutic agents(15)

Dosage adjustment Not established in organ dysfunction

Maximum dosage The manufacturer recommends that dosages should not exceed 15 mcg/kg/day or 400–600 mcg/m2/day for 5 days per 2-week cycle.(4)

Additives Mannitol 20 mg(4)

Suitable diluents Reconstitute with SW; further dilution with D5W, NS.(4,16)

Maximum 500 mcg/mL(4,15) concentration

Preparation and Preparation: Both the powder and solution can cause severe damage when in direct delivery contact with the skin or through inhalation. Use caution when preparing. Reconstitute by adding 1.1 mL of SW (without preservative). Use of SW containing preservatives is not recommended as it results in precipitation formation.(4,16) Once reconstituted the solution (500 mcg/mL) can be added to a suitable infusion solution.(4) Delivery: Binds to cellulose filters; therefore, avoid inline filtration. Adsorbs to glass and plastic so dactinomycin should not be given by continuous infusion.(4,16)

IV push The desired dose of reconstituted drug may be injected into the tubing of a running infu- sion of D5W or NS.(4,16)

Intermittent infusion The desired dose of reconstituted drug may be further diluted with D5W or NS or may be injected into the tubing of a running infusion of D5W or NS.(4,16)

Continuous infusion Not reported

Other routes of Dactinomycin is highly corrosive and will damage soft tissue. Do not administer as IM or administration sub-Q injection.(16)

Comments Significant adverse effects: Dactinomycin has been associated with the development of hepatic sinusoidal obstruction syndrome in children <48 months.(4,17) Dactinomycin has been associated with an increased risk of dermatological adverse effects when used concomitantly with or after radiation.(4) Risks may be increased when radiation involves mucous membranes or when dactinomycin is administered within 2 months of radiation for right-sided Wilms tumors.  253