Dactinomycin by is a Prescription medication manufactured, distributed, or labeled by Prasco Laboratories, Baxter Oncology GmbH. Drug facts, warnings, and ingredients follow.
Dactinomycin is an actinomycin indicated for the treatment of:
For injection: 500 mcg as a lyophilized powder in a single-dose vial. ( 3)
None. ( 4)
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 Recordati Rare Diseases at 1-800-575-8374 or FDA at 1-800-FDA-1088 orwww.fda.gov/medwatch.
Lactation: Advise not to breastfeed. ( 8.2)
See 17 for PATIENT COUNSELING INFORMATION.
Revised: 12/2019
Dactinomycin is indicated for the treatment of adult and pediatric patients with Wilms tumor, as part of a multi-phase, combination chemotherapy regimen.
Dactinomycin is indicated for the treatment of adult and pediatric patients with rhabdomyosarcoma, as part of a multi-phase, combination chemotherapy regimen.
Dactinomycin is indicated for the treatment of adult and pediatric patients with Ewing sarcoma, as part of a multi-phase, combination chemotherapy regimen.
Dactinomycin is indicated for the treatment of adult and pediatric patients with metastatic, nonseminomatous testicular cancer, as part of a multi-phase, combination chemotherapy regimen.
The recommended dose of Dactinomycin, 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.
The recommended dose of Dactinomycin, 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.
The recommended dose of Dactinomycin for injection, as part of a multi-agent combination chemotherapy regimen, is 1250 mcg/m 2 intravenously once every 3 weeks for 51 weeks.
The recommended dose of Dactinomycin for injection, as part of a cisplatin-based, multi-agent combination chemotherapy regimen, is 1000 mcg/m 2 intravenously once every 3 weeks for 12 weeks.
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.
The recommended dose of Dactinomycin, in combination with melphalan, is 50 mcg/kg once for lower extremity or pelvis.
The recommended dose of Dactinomycin, in combination with melphalan, is 35 mcg/kg once for upper extremity.
Calculate the dose for obese or edematous patients based on ideal body weight.
Preparation
Administration
Management of Extravasation
The risk of developing secondary malignancies, including leukemia, is increased following treatment with Dactinomycin.
Severe and fatal hepatic veno-occlusive disease (VOD) can occur with Dactinomycin. Risk factors for the development of VOD include age younger than 4 years or concomitant radiotherapy. After treatment with Dactinomycin, monitor frequently for signs and symptoms of VOD; these include elevations in AST, ALT, total bilirubin, hepatomegaly, weight gain, or ascites. If patients develop VOD, considering delaying next dose of Dactinomycin. Resume, reduce dose or permanently discontinue based on severity of reaction and disease being treated.
Extravasation of Dactinomycin can result in severe local tissue injury manifesting as blistering, ulcerations and persistent pain requiring wide excision surgery followed by split-thickness skin grafting. If any signs or symptoms of extravasation occur, immediately interrupt the injection or infusion. Apply ice to the site intermittently for 15 minutes, 4 times a day for 3 days [see Dosage and Administration ( 2.7)] . Observe closely and consult plastic surgery if necessary based on severity of reaction.
Severe and fatal myelosuppression, which may include neutropenia, thrombocytopenia and anemia, can occur with Dactinomycin. The nadir in neutrophil counts generally occurs 14 to 21 days after administration. Obtain complete blood counts prior to each treatment cycle. Delay next dose of Dactinomycin if severe myelosuppression has not improved. Consider dose reduction for patients with prolonged myelosuppression based on severity of reaction and disease being treated.
The safety with live viral vaccines following Dactinomycin has not been studied and vaccination with live virus vaccines is not recommended before or during treatment.
Severe mucocutaneous reactions, such as Steven-Johnson syndrome and Toxic Epidermal Necrolysis (TEN), can occur with Dactinomycin. Permanently discontinue Dactinomycin in patients who experience a severe mucocutaneous reaction.
Abnormalities of renal function can occur with Dactinomycin. Monitor creatinine and electrolytes frequently during Dactinomycin therapy.
Hepatotoxicity can occur with Dactinomycin. Monitor AST, ALT, alkaline phosphatase, and bilirubin prior to and during Dactinomycin therapy.
Dactinomycin can increase radiation-induced gastrointestinal toxicity, myelosuppression, or erythema and vesiculation of the skin or buccal and pharyngeal mucosa. Reduce the dose of Dactinomycin by 50% during concomitant radiation.
Radiation recall, affecting previously treated radiation fields, can occur in patients who receive Dactinomycin after prior radiation therapy. Although the risk can occur with distant radiation exposure, the risk appears highest when Dactinomycin is administered within two months of prior radiation.
Based on findings from animal studies and its mechanism of action, Dactinomycin can cause fetal harm when administered to a pregnant woman. 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.
Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with Dactinomycin and for at least 6 months after the final dose. 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 Use in Specific Populations ( 8.1, 8.3)].
The following serious adverse reactions are described elsewhere in the labeling:
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
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 1250 mcg/m 2.
Risk Summary
There are no data on the presence of dactinomycin or its metabolites in human milk or their effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in breastfed infants from Dactinomycin, advise women not to breastfeed during treatment with Dactinomycin and, based on limited published data regarding the dactinomycin half-life, for 14 days after the final dose.
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)].
The safety and effectiveness of dactinomycin have been established in pediatric patients with Wilms tumor, rhabdomyosarcoma, Ewing sarcoma, and metastatic nonseminomatous testicular cancer.
The safety and effectiveness of dactinomycin have been established in post-menarchal pediatric patients with gestational trophoblastic neoplasia.
The safety and effectiveness of Dactinomycin have not been established in pediatric patients undergoing regional perfusion for locally recurrent or locoregional solid malignancies.
Dactinomycin is an actinomycin. Dactinomycin is produced by Streptomyces parvullus. The chemical name is 8-amino-N-(2-amino-4,6-dimethyl-3-oxo-phenoxazin-1-yl)carbonyl-N’-[8-amino-4,6-dimethyl-7-oxo-9-[[3,6,10-trimethyl-7,14-bis(1-methylethyl)-2,5,8,12,15-pentaoxo-9-oxa-3,6,13,16-tetrazabicyclo[14.3.0]nonadec-11-yl]carbamoyl]phenoxazin-1-yl]carbonyl-4,6-dimethyl-7-oxo-N,N’-bis[3,6,10-trimethyl-7,14-bis(1-methylethyl)-2,5,8,12,15-pentaoxo-9-oxa-3,6,13,16 tetrazabicyclo[14.3.0]nonadec-11-yl]-1,9-bis[[3,6,10-trimethyl-7,14-bis(1-methylethyl)-2,5,8,12,15-pentaoxo-9-oxa-3,6,13,16-tetrazabicyclo[14.3.0] nonadec-11-yl]carbamoyl]phenoxazine-1,9-dicarboxamide. The molecular formula is C 62H 86N 12O 16 and the molecular weight is 1255.42 daltons. The structural formula of dactinomycin is shown below:
Dactinomycin for injection for intravenous use is a sterile, amorphous yellow to orange, lyophilized powder in a single-dose vial. Each vial contains 500 mcg of dactinomycin and 20 mg of mannitol.
Dactinomycin is a cytotoxic actinomycin that binds DNA and inhibits RNA synthesis. The cytotoxic activity of dactinomycin has been demonstrated in animal models of different human cancers.
Dactinomycin exposure-response relationships and the time course of pharmacodynamics response are unknown.
The distribution and excretion of radiolabeled dactinomycin ( 3H actinomycin D) were assessed in three adult patients with malignant melanoma.
Distribution
3H actinomycin D is concentrated in nucleated cells and does not penetrate the blood-brain barrier.
Elimination
Excretion
Following administration of radiolabeled dactinomycin, approximately 30% was recovered in urine and feces in one week.
Specific Populations
Pediatric Patients
Published studies and population analyses in patients ≤ 21 years of age with cancer report a trend of increasing systemic dactinomycin clearance with increasing body weight.
Drug Interaction Studies
Published in vitro studies report that dactinomycin may be a substrate of the P-glycoprotein and OATP1B3 transporter systems.
Dactinomycin is a carcinogen in animals. Local sarcomas were produced in mice and rats after repeated subcutaneous or intraperitoneal injections. Mesenchymal tumors occurred in male rats given intraperitoneal injections of 50 mcg/kg, 2 to 5 times per week, for 18 weeks, at doses (based on body surface area) 0.5 times the clinical dose of 1250 mcg/m 2.
Dactinomycin was mutagenic in several in vitro and in vivo test systems including human fibroblasts and leukocytes, and HeLa cells. DNA damage and cytogenetic effects have been demonstrated in the mouse and the rat.
Dactinomycin (dactinomycin for injection) for intravenous use is supplied as a sterile, amorphous yellow to orange, lyophilized powder in a single-dose vial. Each Dactinomycin vial (NDC: 66993-489-35) contains 0.5 mg of dactinomycin and 20 mg of mannitol.
Store at 20 to 25ºC (68 to 77ºF); excursions permitted between 15 to 30ºC (59 to 86ºF) [see USP Controlled Room Temperature].
Protect Dactinomycin from light and humidity.
Store the reconstituted Dactinomycin at room temperature for no more than 4 hours from reconstitution to completion of administration [see Dosage and Administration ( 2.7)].
Dactinomycin is a cytotoxic drug. Follow applicable special handling and disposal procedures. 1
Secondary Malignancy or Leukemia
Advise patients of the increased risk of secondary malignancies [see Warnings and Precautions ( 5.1)] .
Veno-occlusive Disease
Advise patients about the symptoms of VOD and to seek medical attention if they develop new onset jaundice, abdominal distention, or right upper quadrant pain [see Warnings and Precautions ( 5.2)] .
Myelosuppression
Advise patients to contact their healthcare provider for any signs or symptoms of myelosuppression or infection [see Warnings and Precautions ( 5.4)] .
Severe Mucocutaneous Reactions
Advise patients of the risk of severe mucocutaneous reactions and to contact their health care provided for new skin lesions, mouth sores or oropharyngeal lesions [see Warnings and Precautions ( 5.5)] .
Renal Toxicity or Hepatotoxicity
Advise patients of the need for periodic laboratory testing to monitor for renal toxicity and hepatotoxicity [see Warnings and Precautions ( 5.7, 5.8)] .
Potentiation of Radiation Toxicity and Radiation Recall
Advise patients of the risk of increased radiation-induced gastrointestinal, myelosuppression and skin toxicity [see Warnings and Precautions ( 5.9)] .
Embryo-Fetal Toxicity
Advise females of reproductive potential of the potential risk to a fetus. Advise females to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions ( 5.10), Use in Specific Populations ( 8.1)] .
Advise females of reproductive potential to use effective contraception during treatment with Dactinomycin and for 6 months after final dose [see Use in Specific Populations ( 8.3)] .
Advise male patients with female partners of reproductive potential to use effective contraception during treatment with Dactinomycin and for 3 months after final dose [see Use in Specific Populations ( 8.3)] .
Lactation
Advise females not to breastfeed during treatment with Dactinomycin and for 14 days after the final dose [see Use in Specific Populations ( 8.2)].
Manufactured by: Baxter Oncology GmbH, 33790 Halle/Westfalen, Germany
Manufactured for: Prasco Laboratories, Mason, OH 45040 USA
Revised: August 2018
APX1015/1
NDC: 66993-489-83
Single Dose Vial
Rx Only
PRASCO
Dactinomycin for Injection
500 mcg (0.5 mg)
For Preparation of Intravenous Solutions
NDC: 66993-489-35
12 Single Dose Vials
Rx Only
PRASCO
Dactinomycin for Injection
500 mcg (0.5 mg)
Store at 20-25ºC (68-77ºF).
See USP controlled room temperature.
Protect from light and humidity.
Manufactured by: Baxter Oncology GmbH
33790 Halle/Westfalen, Germany
For: Prasco Laboratories
Mason, OH 45040 USA
DACTINOMYCIN
dactinomycin injection, powder, lyophilized, for solution |
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Labeler - Prasco Laboratories (065969375) |
Establishment | |||
Name | Address | ID/FEI | Business Operations |
---|---|---|---|
Baxter Oncology GmbH | 344276063 | manufacture(66993-489) |