Dosing and uses of Dactinomycin (Cosmegen)
Adult dosage forms and strengths
powder for injection
- 500mcg/vial
Wilms Tumor/Ewing Sarcoma
15 mcg/kg IV qDay for 5 days
Locally Recurrent/Locoregional Solid Malignancies (Regional Perfusion Therapy)
Dosing schedule & technique varies
Pelvis/lower extremity: 50 mcg/kg IV
Upper extremity: 35 mcg/kg IV
May need to reduce dose in obese patients or patients who received chemotherapy/radiation therapy
Trophoblastic Neoplasms
12 mcg/kg IV for 5 days
Repeat course after 2 weeks
Testicular Cancer (Metastatic Nonseminomatous)
1000 mcg/m² IV on day 1 in combo with cyclophosphamide, bleomycin, vinblastine, & cisplatin
Ewing Sarcoma (Orphan)
Orphan desigantion of ANA-conjugated dactunomycin nanoemulsion for treatment of Ewing sarcoma
Sponsor
- NanoSmart Pharmaceuticals, Inc; 27071 Cabot Road, Suite 104; Laguna Hills, CA 92653
Administration
Not to exceed15 mcg/kg/day or 400-600 mcg/m²/day for 5 days per 2-week cycle
Pediatric dosage forms and strengths
powder for injection
- 500mcg/vial
Ewing Sarcoma
< 6 years: Safety and efficacy not established
≥6 years: 15 mcg/kg IV qDay for 5 days in various chemotherapy combinations and schedules
Rhabdomyosarcoma
< 1 year: 25 mcg/kg IV q3weeks; weeks 0-45 in combination with vincristine, cyclophosphamide, and mesna; omit dose following radiation
≥1 year: 45 mcg/kg IV q3weeks; weeks 0-45 in combination with vincristine, cyclophosphamide, and mesna; omit dose following radiation
Wilms Tumor
15 mcg/kg/day IV for 5 days; repeat q3-6 weeks if necessary; not to exceed 15 mcg/kg/day IV for 5 days per 2-week cycle
DD-4A regimen: 45 mcg/kg on day 1 q6weeks for 54 weeks (in combination with vincristine and doxorubicin)
EE-4A regimen: 45 mcg/kg on day 2 q3weeks for 18 weeks (in combination with vincristine)
Dactinomycin (Cosmegen) adverse (side) effects
Frequency not defined
Fatigue
Fever
Diarrhea
Malaise
Chills
Nausea
Vomiting
Stomatitis
Mucositis
Hypocalcemia
Hyperpigmentation of previously radiated areas
Acne
Alopecia
Erythema
Rash
Fertility impairment
Aplastic anemia
Febrile neutropenia
Neutropenia
Pancytopenia
Thrombocytopenia
Hepatotoxicity
Liver failure
Veno-occlusive disease of the liver
Anaphylaxis
Warnings
Black box warnings
The drug should be administered under the supervision of an experienced cancer chemotherapy physician
If extravasation occurs, it may cause severe soft tissue damage. Contracture of the arms has occurred (rare).
Avoid inhalation of vapors or contact with skin mucous membrane or eyes
Handle and dispose agent using appropriate precautions
Avoid exposure during pregnancy
Contraindications
Hypersensitivity
Active chickenpox or herpes zoster
Cautions
Vesicant
Caution in hepatic/renal impairment, elderly
May cause hepatic sinusoidal obstruction syndrome
Toxic effects may take 1-2 weeks to reach maximum severity following treatment; discontinue treatment if severe diarrhea, myelosuppression, or stomatitis occur
Avoid pregnancy
Avoid use within 2 weeks of radiation treatment for right-sided tumor (may increase risk of hepatotoxicity)
Avoid use of concomitant live virus vaccines
Use in myelosuppressive patients not recommended
Pregnancy and lactation
Pregnancy category: d
Lactation: not known if excreted in breast milk, do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Dactinomycin (Cosmegen)
Mechanism of action
Actinomycin antibiotic; intercalates into DNA base pairs preventing RNA , DNA, and protein synthesis
Pharmacokinetics
Half-Life: 36 hr (adults); 14-43 hr (children)
Protein Bound: 5%
Vd: 59-714 L (extensive extravascular distribution)
Metabolism: Minimal hepatic
Excretion: Urine (30%), feces
Administration
IV Incompatibilities
Y-site: filgrastim
IV Compatibilities
Solution: D5W, Ns
Y-site: allopurinol, amifostine, aztreonam, cefepime, etoposide PO4, fludarabine, gemcitabine, granisetron, melphalan, ondansetron, sargramostim, teniposide, thiotepa, vinorelbine
IV Preparation
Reconstitute with 1.1 mL of preservative-free SWI to yield a final concentration of 500 mcg/mL
Do not use preservative diluent as precipitation may occur
Solution is chemically stable or 24 hr at room temp
Significant binding of drug occurs with micrometer nitrocellulose filter materials
Standard dilution
- IV push: dose/syringe (500 mcg/mL)
- IVPB: dose/50 mL D5W or NS
IV Administration
Vesicant
Infuse over 10-15 min
Do not use in-line cellulose membrane filter
Do not give IM or SC
Extravasation Management
Apply ice immediately for 30-60 min
Then alternate off/on q15min for 1 day
Storage
Store intact vials at room temp
Protect from light
