Dactinomycin

FDA Drug Information • Also known as: Dactinomycin

Brand Names: Dactinomycin
Drug Class: Actinomycin [EPC]
Route: INTRAVENOUS
Dosage Form: INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION
Product Type: HUMAN PRESCRIPTION DRUG

Description

11 DESCRIPTION Dactinomycin USP is one of the actinomycins, a group of antibiotics produced by various species of Streptomyces . Dactinomycin USP is the principal component of the mixture of actinomycins produced by Streptomyces parvullus . Unlike other species of Streptomyces , this organism yields an essentially pure substance that contains only traces of similar compounds differing in amino acid content of the peptide side chains. The empirical formula is C 62 H 86 N 12 O 16 and the structural formula is: Dactinomycin for Injection, USP is a sterile, yellow to orange, lyophilized powder for injection by intravenous route or by regional perfusion after reconstitution. Each vial contains 0.5 mg (500 mcg) of dactinomycin USP and 20 mg of mannitol. Dactinomycin-str

What Is Dactinomycin Used For?

1 INDICATIONS AND USAGE Dactinomycin for injection is an actinomycin indicated for the treatment of: adult and pediatric patients with Wilms tumor, as part of a multi-phase, combination chemotherapy regimen. ( 1.1 ) adult and pediatric patients with rhabdomyosarcoma, as part of a multiphase, combination chemotherapy regimen. ( 1.2 ) adult and pediatric patients with Ewing sarcoma, as part of a multi-phase, combination chemotherapy regimen. ( 1.3 ) adult and pediatric patients with metastatic, nonseminomatous testicular cancer, as part of a multi-phase, combination chemotherapy regimen. ( 1.4 ) post-menarchal patients with gestational trophoblastic neoplasia, as a single agent or as part of a combination chemotherapy regimen. ( 1.5 ) adult patients with locally recurrent or locoregional solid malignancies, as a component of palliative or adjunctive regional perfusion. ( 1.6 ) 1.1 Wilms Tumor Dactinomycin for injection is indicated for the treatment of adult and pediatric patients with Wilms tumor, as part of a multi-phase, combination chemotherapy regimen. 1.2 Rhabdomyosarcoma Dactinomycin for injection is indicated for the treatment of adult and pediatric patients with rhabdomyosarcoma, as part of a multi-phase, combination chemotherapy regimen. 1.3 Ewing Sarcoma Dactinomycin for injection is indicated for the treatment of adult and pediatric patients with Ewing sarcoma, as part of a multi-phase, combination chemotherapy regimen. 1.4 Metastatic Nonseminomatous Testicular Cancer Dactinomycin for injection is indicated for the treatment of adult and pediatric patients with metastatic, nonseminomatous testicular cancer, as part of a multi-phase, combination chemotherapy regimen. 1.5 Gestational Trophoblastic Neoplasia Dactinomycin for injection is indicated for the treatment of post-menarchal patients with gestational trophoblastic neoplasia, as a single agent or as part of a combination chemotherapy regimen. 1.6 Regional Perfusion in Locally Recurrent and Locoregional Solid Malignancies Dactinomycin for injection is indicated for the treatment of adult patients with locally recurrent or locoregional solid malignancies, as a component of palliative or adjunctive regional perfusion.

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Wilms Tumor: The recommended dose is 45 mcg/kg intravenously once every 3 to 6 weeks for up to 26 weeks, as part of a multi-agent combination chemotherapy regimen. ( 2.1 ) Rhabdomyosarcoma: The recommended dose is 15 mcg/kg intravenously once daily for 5 days every 3 to 9 weeks for up to 112 weeks, as part of a multi-agent combination chemotherapy regimen. ( 2.2 ) Ewing Sarcoma: The recommended dose is 1250 mcg/m 2 intravenously once every 3 weeks for 51 weeks, as part of a multi-agent combination chemotherapy regimen. ( 2.3 ) Metastatic Nonseminomatous Testicular Cancer: The recommended dose is 1000 mcg/m 2 intravenously every 3 weeks, as part of cisplatin-based, multi-drug chemotherapy regimen. ( 2.4 ) Gestational Trophoblastic Neoplasia: o Non-metastatic and Low-risk Metastatic Disease: The recommended dose is 12 mcg/kg intravenously daily for 5 days, as a single agent. ( 2.5 ) o High-risk Metastatic Disease: The recommended dose is 500 mcg intravenously on Days 1 and 2 every 2 weeks for up to 8 weeks, as part of a multi-agent combination chemotherapy regimen. ( 2.5 ) Regional Perfusion in Locally Recurrent and Locoregional Solid Malignancies: o Lower Extremity or Pelvis: The recommend dose is 50 mcg/kg once with melphalan. ( 2.6 ) o Upper Extremity: The recommended dose is 35 mcg/kg once with melphalan. ( 2.6 ) 2.1 Recommended Dosage for Wilms Tumor The recommended dose of dactinomycin for injection, as part of a multi-agent combination chemotherapy regimen, is 45 mcg/kg intravenously once every 3 to 6 weeks for up to 26 weeks. 2.2 Recommended Dosage for Rhabdomyosarcoma The recommended dose of dactinomycin for injection, as part of a multi-agent combination chemotherapy regimen, is 15 mcg/kg intravenously once daily for 5 days every 3 to 9 weeks for up to 112 weeks. 2.3 Recommended Dosage for Ewing Sarcoma The recommended dose of dactinomycin for injection, as part of a multi-agent combination chemotherapy regimen, is 1,250 mcg/m 2 intravenously once every 3 weeks for 51 weeks. 2.4 Recommended Dosage for Metastatic Nonseminomatous Testicular Cancer The recommended dose of dactinomycin for injection, as part of a cisplatin-based, multi-agent combination chemotherapy regimen, is 1,000 mcg/m 2 intravenously once every 3 weeks for 12 weeks. 2.5 Recommended Dosage for Gestational Trophoblastic Neoplasia The recommended dose of dactinomycin for injection for nonmetastatic and low-risk metastatic disease is 12 mcg/kg intravenously daily for five days as a single agent. The recommended dose of dactinomycin for injection, as part of a multi-agent combination chemotherapy regimen, for high-risk metastatic disease is 500 mcg intravenously on Days 1 and 2 every 2 weeks for up to 8 weeks. 2.6 Recommended Dosage for Regional Perfusion in Locally Recurrent and Locoregional Solid Malignancies The recommended dose of dactinomycin for injection, in combination with melphalan, is 50 mcg/kg once for lower extremity or pelvis. The...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling:

Secondary Malignancy and Leukemia [see Warnings and Precautions (5.1) ]

Veno-occlusive Disease [see Warnings and Precautions (5.2) ]

Extravasation [see Warnings and Precautions (5.3) ]

Myelosuppression [see Warnings and Precautions (5.4) ]

Immunizations [see Warning and Precautions (5.5) ]

Severe Mucocutaneous Reactions [see Warnings and Precautions (5.6) ]

Renal Toxicity [see Warnings and Precautions (5.7) ]

Hepatotoxicity [see Warnings and Precautions (5.8) ]

Potentiation of Radiation Toxicity and Radiation Recall [see Warnings and Precautions (5.9) ] Common adverse reactions are: infection, alopecia, rash, dysphagia, fatigue, fever, nausea, vomiting, anemia, neutropenia, thrombocytopenia, mucositis, and hepatotoxicity. The following adverse reactions have been identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Infections : infections including sepsis with fatal outcome Hematologic : anemia, leukopenia, thrombocytopenia, pancytopenia, reticulocytopenia, neutropenia, febrile neutropenia, disseminated intravascular coagulation Immune system : hypersensitivity Metabolism and nutrition : anorexia, hypocalcemia, tumor lysis syndrome Nervous system : peripheral neuropathy Ocular: optic neuropathy Vascular: thrombophlebitis, hemorrhage Respiratory, thoracic and mediastinal : pneumonitis, pneumothorax Gastrointestinal: nausea, vomiting, abdominal pain, diarrhea, constipation, gastrointestinal ulceration, cheilitis, dysphagia, esophagitis, ulcerative stomatitis, ascites, proctitis, mucositis Hepatobiliary : liver function test abnormalities, hepatomegaly, hepatitis, hepatic failure with reports of death, hepatic veno-occlusive disease Dermatologic: alopecia, rash, dermatitis, acne, erythema multiforme, Stevens Johnson Syndrome, radiation recall, toxic epidermal necrolysis Musculoskeletal and connective tissue: myalgia, growth retardation Renal and urinary: renal impairment, renal failure General: fatigue, fever, malaise Common adverse reactions are: infection, alopecia, rash, dysphagia, fatigue, fever, nausea, vomiting, anemia, neutropenia, thrombocytopenia, mucositis, and hepatotoxicity ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Eugia US LLC at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

Contraindications

4 CONTRAINDICATIONS None. None. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action dactinomycin can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . In animal reproduction studies, administration of dactinomycin to pregnant animals during the period of organogenesis was teratogenic, resulting in malformations at doses lower than the recommended human dose (see Data) . Advise pregnant women of the potential risk to a fetus [see Use in Special Populations (8.3) ]. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Dactinomycin was teratogenic in animals. Administration of dactinomycin to pregnant rats, rabbits, and hamsters during the period of organogenesis, increased the incidence of fetal malformations and caused embryotoxicity at doses (based on body surface area) as low as 0.2 times the clinical dose of 1,250 mcg/m 2 .

8.3 Females and Males of Reproductive Potential Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to initiating dactinomycin [see Use in Specific Population (8.1) ]. Contraception Dactinomycin can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ]. Females Advise females of reproductive potential to use effective contraception during treatment with dactinomycin and for at least 6 months after the final dose. Males Because of the potential for genotoxicity, advise males with female partners of reproductive potential to use effective contraception during treatment with dactinomycin and for 3 months after the final dose [ see Nonclinical Toxicology (13.1) ].

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING Dactinomycin for injection, USP is a lyophilized powder. In the dry form the compound is an amorphous yellow to orange powder. The solution is clear, gold or yellow to orange colored and essentially free from visible particles. Dactinomycin for injection, USP is supplied in vials containing 0.5 mg (500 micrograms) of dactinomycin USP and 20.0 mg of mannitol. NDC 55150-431-01: 0.5 mg/vial in 2 mL single-dose vial; individually boxed Storage: Store at 20º to 25ºC (68º to 77ºF); [see USP Controlled Room Temperature]. Protect from light and humidity. Special Handling: Animal studies have shown dactinomycin to be corrosive to skin, irritating to the eyes and mucous membranes of the respiratory tract and highly toxic by the oral route. It has also been shown to be carcinogenic, mutagenic, embryotoxic and teratogenic. Due to the drug’s toxic properties, appropriate precautions including the use of appropriate safety equipment are recommended for the preparation of dactinomycin for injection for parenteral administration. Inhalation of dust or vapors and contact with skin or mucous membranes, especially those of the eyes, must be avoided. Avoid exposure during pregnancy. The National Institutes of Health presently recommends that the preparation of injectable antineoplastic drugs should be performed in a Class II laminar flow biological safety cabinet. Personnel preparing drugs of this class should wear chemical resistant, impervious gloves, safety goggles, outer garments and shoe covers. Additional body garments should be used based upon the task being performed (e.g., sleevelets, apron, gauntlets, disposable suits) to avoid exposed skin surfaces and inhalation of vapors and dust. Appropriate techniques should be used to remove potentially contaminated clothing. Several other guidelines for proper handling and disposal of antineoplastic drugs have been published and should be considered. 1 Accidental Contact Measures: Should accidental...

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.