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New primary malignancy has been reported (e.g., leukemia) following treatment with radiation and chemotherapy, including dactinomycin. Patients receiving multimodal therapy require long-term and careful observation. DNA damage and cytogenetic effects have been demonstrated in the animal studies.
Extravasation resulting in severe soft tissue damage has been reported with intravenous dactinomycin use; surgery and skin grafting may be necessary in severe cases. Extravasation may occur with or without a burning or stinging sensation and even if there is good blood return on needle aspiration. Immediately discontinue the injection or infusion if any signs or symptoms of extravasation occur; restart dactinomycin administration in another vein. Apply intermittent ice to the site for 15 minutes 4-times daily for 3 days if extravasation is suspected. If severe extravasation occurs, observe the patient closely and consult a plastic surgeon. 
Dactinomycin is highly toxic and its administration requires an experienced clinician knowledgeable in the use of chemotherapy agents. Dactinomycin demonstrates toxic properties such as corrosivity, carcinogenicity, mutagenicity, and teratogenicity; exercise usual cautions for handling, preparing, and administering cytotoxic drugs. Use care to avoid accidental exposure to dactinomycin such as inhaling dust vapors, contact with skin or mucous membranes, or ocular exposure. If accidental exposure occurs, seek medical attention immediately. For ocular exposure, rinse the eyes immediately and thoroughly for at least 15 minutes with water, normal saline, or balanced salt ophthalmic irrigation solution; promptly obtain an ophthalmologic consultation. For accidental skin contact, irrigate the affected area immediately with large amounts of water for at least 15 minutes; remove contaminated clothing and shoes.
Dactinomycin is classified as FDA pregnancy risk category D. Due to its potential for teratogenesis, dactinomycin should be avoided during pregnancy. Dactinomycin may cause fetal harm when administered during pregnancy, based on its mechanism of action and data from animal studies. Females of reproductive potential should avoid pregnancy during and after treatment with dactinomycin. Advise pregnant women of the potential risk to the fetus. Embryotoxicity and fetal malformations were observed in pregnant rats, rabbits, and hamsters following dactinomycin administered during organogenesis at doses that were as low as 0.2-times the clinical dose of 1,250 mcg/m2.
A cytotoxic antitumor antibioticUsed in Wilms tumor, rhabdomyosarcoma, Ewing sarcoma, testicular cancer, gestational trophoblastic neoplasia, and certain locally recurrent or locoregional solid malignanciesFatal sinusoidal obstruction syndrome has been reported
Cosmegen/Dactinomycin Intravenous Inj Pwd F/Sol: 500mcg
12 mcg/kg IV daily for 5 days.
500 mcg IV daily on days 1 and 2 repeated every 2 weeks for up to 8 weeks in combination with multi-agent chemotherapy. Dactinomycin has been evaluated in combination with methotrexate, leucovorin, etoposide, cyclophosphamide, and vincristine (EMA-CO regimen) in clinical studies; cure rates have ranged from 70% to 90% in women with high-risk gestational trophoblastic disease. Results are typically better in women who receive EMA-CO as primary therapy and in women without metastatic disease. Growth-factor support should be considered to maintain dose-intensity and prevent hematological toxicity. Complete response is typically defined as three consecutive weekly human chorionic gonadotropin (hCG) levels that are undetectable or less than the upper limit of normal. In studies, treatment was continued for 2 to 3 additional courses after complete hCG response. 
500 mcg IV daily on days 1 and 2 repeated every 2 weeks for up to 8 weeks in combination with multi-agent chemotherapy. Dactinomycin has been evaluated in combination with methotrexate, leucovorin, etoposide, and cisplatin (EMA-EP regimen) in a clinical study. Studies in patients with chemotherapy-refractory, high-risk gestational trophoblastic disease have shown response rates of more than 90% with salvage treatment with EMA-EP. Growth-factor support should be considered to maintain dose-intensity and prevent hematological toxicity.
1,000 mcg/m2 IV once every 3 weeks for 12 weeks in combination with cisplatin-based, multi-agent chemotherapy. Dactinomycin has been evaluated in combination with cyclophosphamide, bleomycin, vinblastine, and cisplatin (VAB-6 regimen).
45 mcg/kg IV once every 3 to 6 weeks for up to 26 weeks in combination with multi-agent chemotherapy. An alternative regimen is dactinomycin 15 mcg/kg IV daily for 5 days in combination with other chemotherapy agents.
1.2 mg/m2 IV on day 1 every 3 weeks has been given in combination with a single-dose of dacarbazine 800 mg/m2 IV on day 1 of the first course. In a small study of 18 patients, the ORR was 22% with this combination.Single-agent dacarbazine alone has produced response rates of 20%. In another study, dactinomycin in combination with bleomycin, dacarbazine, and vindesine produced an ORR of 33%.
50 mcg/kg for the legs or 35 mcg/kg for the arms in combination with hyperthermia has been utilized.
15 mcg/kg IV once daily for 5 days every 3 to 9 weeks for up to 112 weeks in combination with multi-agent chemotherapy. An alternative regimen is dactinomycin 15 mcg/kg IV daily for 5 days in combination with other chemotherapy agents.
Ifosfamide 6,000 mg/m2 continuous IV infusion (CIV) over 48 hours on days 1, 29, and 50 in combination with mesna 6,000 mg/m2/day CIV over 48 hours on days 1, 29, and 50, doxorubicin 40 mg/m2/day IV on days 29 and 30, dactinomycin 0.5 mg/m2/day IV on days 1 through 3 and 50 through 52, and vincristine 1.5 mg/m2 IV on days 1, 8, 15, and 22. The duration of therapy was dependent on stage at diagnosis (stage I: 16 weeks; II: 26 weeks; III: 40 weeks; IV: 48 weeks).
0.6 mg/m2/day IV on days 1 and 2 or on days 1, 2, and 3 in combination with bleomycin and cyclophospamide (BCD regimen) has been incorporated into multiple treatment protocols. In the POG-8651 protocol, 106 patients (younger than 30 years old) with previously untreated nonmetastatic high-grade osteogenic sarcoma were randomized to receive 3 days of BCD each cycle as part of a multiagent chemotherapy regimen in sequence with doxorubicin and cisplatin, and high-dose methotrexate, either before or after surgical resection. Event-free survival (EFS), the primary endpoint, was not significantly different between the treatment arms, and reached 69% at 5 years in the post-operative group. In a comparison of the Memorial Sloan-Kettering Cancer Center T-10 and T-12 protocols, 73 patients (ages 4.6 to 36.4 years) with previously untreated, high-grade osteogenic sarcoma received BCD on days 1 and 2 of each cycle as part of a multiagent chemotherapy regimen in sequence with doxorubicin and cisplatin, high-dose methotrexate, and surgical resection. The 5-year EFS was 78% and 73% in the T-12 and T-10 protocols, respectively. The use of BCD alone has also been studied in 8 patients (ages 9.1 to 16.4 years) with previously treated metastatic osteogenic sarcoma. Patients received 1 to 5 courses of BCD. No tumor regression could be measured for any of the patients, and progressive tumor enlargement was demonstrated in 2 patients. Use in patients older than 40 years of age has not been adequately assessed.
0.42 mg/m2/day IV on days 1 through 5, every 3 or 4 weeks (after recovery from myelosuppression) has been studied. Dactinomycin has been given with or without vincristine 1.4 mg/m2 IV weekly until the end of the second course of dactinomycin, then vincristine was given on days 1 and 5 of each subsequent course. In a small study, 9/10 patients (5 CR, 4 PR) receiving dactinomycin achieved a response, and 13/14 patients (10 CR, 3 PR) receiving dactinomycin/vincristine achieved a response.
†Indicates off-label use
NOTE: The correct dose of dactinomycin will vary based on specific protocol used. Clinicians should consult the appropriate references to verify the dose.
15 mcg/kg or 400 to 600 mcg/m2 IV daily for 5 days; 45 mcg/kg or 1,250 mcg/m2 IV as a single dose.
15 mcg/kg IV daily for 5 days; 45 mcg/kg or 1,250 mcg/m2 IV as a single dose.
Specific guidelines for dosage adjustments in hepatic impairment are not provided by the manufacturer; however, a 50% dactinomycin dosage reduction has been suggested in patients with hepatic impairment (e.g., any level of elevated hepatic enzymes).
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
Hazardous Drugs ClassificationNIOSH 2016 List: Group 1 NIOSH (Draft) 2020 List: Table 1Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.Emetic RiskDoses of 1.35 mg/m2/dose or greater: HighDoses of 10 mcg/kg/dose: ModerateAdminister routine antiemetic prophylaxis prior to treatment.Extravasation RiskVesicantAdminister drug through a central venous line.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Monitor patients for signs or symptoms of extravasation; stop the injection or infusion immediately if extravasation occurs.Reconstitution:Add 1.1 mL of preservative-free sterile water for injection to the 500-mcg lyophilized, single-dose vial for a final vial concentration of 500 mcg/mL.The reconstituted vial solution should be clear and gold-colored.Discard any unused portion of the vial.Storage: store reconstituted vials or the diluted solution at room temperature (20 to 25 degrees C; 68 to 77 degrees F) for up to 4 hours from vial reconstitution (includes infusion time). Intravenous (IV) Injection:Withdraw the appropriate amount of dactinomycin and directly inject it into the tubing of a running IV infusion of 5% dextrose injection or 0.9% sodium chloride injection.If dactinomycin is injected directly into a vein, use a two-needle technique; use one sterile needle to remove the calculated dose from the vial and another sterile needle for direct injection into the vein.IV Infusion:Withdraw the appropriate amount of dactinomycin and dilute it in 5% dextrose injection or 0.9% sodium chloride injection for a final concentration greater than 10 mcg/mL.Administer as an IV infusion over 10 to 15 minutes.Do not use an in-line filter with a cellulose ester membrane.
Cosmegen:- Avoid excessive humidity- Discard product if it contains particulate matter, is cloudy, or discolored- Discard unused portion. Do not store for later use.- Keep away from heat and flame- Protect from moisture- Reconstituted product must be used within 4 hours- Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F- Store in a cool, well ventilated, dry place- Store in the original carton to protect from light
Use is contraindicated in patients with a history of hypersensitivity with dactinomycin or any component of the product. Serious rash, such as Steven-Johnson syndrome and toxic epidermal necrolysis have been reported with dactinomycin use. Permanently discontinue therapy in patients who experience a severe mucocutaneous reaction.
Severe myelosuppression/bone marrow suppression (e.g., anemia, neutropenia, and thrombocytopenia) has been reported with dactinomycin therapy; some cases were fatal. Monitor complete blood counts prior to each treatment cycle; delay the next dactinomycin dose if severe myelosuppression persists. Consider a dose reduction in patients who with prolonged myelosuppression based on the severity of the reactions and disease being treated. Geriatric patients may have an increased risk of myelosuppression compared with younger patients based on a published meta-analysis of all studies performed by the Eastern Cooperative Oncology Group (ECOG) over a 13-year period.
Use of dactinomycin is contraindicated in patients with an active herpes infection (i.e., chickenpox or herpes zoster infection), due to a risk of death from these infections.
Veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) and hepatotoxicity (e.g., hepatic failure) have been reported with dactinomycin therapy; some cases were fatal. Obtain liver function tests prior to and during therapy; monitor patients for symptoms of VOD (e.g., weight gain and ascites). Consider delaying the next dactinomycin dose if VOD occurs. Resume, dose reduce, or permanently discontinue dactinomycin therapy based on the severity of the reactions and disease being treated. Children younger than 4 years of age may be at increased risk for developing VOD. Consider using dactinomycin only in infants older than 6 to 12 months due to the risk of increased toxicity.
Concomitant use of dactinomycin and radiation therapy may increase the risk of gastrointestinal toxicity, myelosuppression, skin or mucous membrane toxicity, and veno-occlusive disease/sinusoidal obstruction syndrome. Therefore, reduce the dactinomycin dose by 50% if it is used together with radiation. Use dactinomycin with caution in patients who have had prior radiation therapy due to a risk of a radiation recall reaction in the previously treated radiation fields; this risk appears highest if dactinomycin is administered within 2 months of prior radiation therapy. Administer dactinomycin concomitantly with radiotherapy in patients with Wilms' tumor only after risk versus benefit of therapy assessment.
Nephrotoxicity (e.g., renal failure) has been reported with dactinomycin therapy. Monitor renal function tests (i.e., serum creatinine) and serum electrolytes frequently during dactinomycin therapy.
Avoid vaccination with live viral vaccines prior to and during dactinomycin therapy.
Dactinomycin may cause laboratory test interference for the determination of antibacterial drug levels.
Counsel patients about the reproductive risk and contraception requirements during dactinomycin treatment. Pregnancy testing should be performed prior to starting dactinomycin in female patients of reproductive potential. These patients should use effective contraception and avoid pregnancy during and for at least 6 months after dactinomycin therapy. Women who become pregnant while receiving dactinomycin should be apprised of the potential hazard to the fetus. Additionally, male patients with a female partner of reproductive potential should use effective contraception during and for 3 months after dactinomycin therapy due to the risk of male-mediated teratogenicity.
It is not known if dactinomycin or its metabolites are secreted in human milk or if it has effects on the breast-fed infant or milk production. Due to the risk of serious adverse reactions in nursing infants, women should discontinue breast-feeding during dactinomycin therapy and for 14 days after the last dose.
pancytopenia / Delayed / Incidence not knownagranulocytosis / Delayed / Incidence not knownaplastic anemia / Delayed / Incidence not knownsinusoidal obstruction syndrome (SOS) / Delayed / Incidence not knownhepatic failure / Delayed / Incidence not knowndisseminated intravascular coagulation (DIC) / Delayed / Incidence not knownveno-occlusive disease (VOD) / Delayed / Incidence not knownpeptic ulcer / Delayed / Incidence not knownerythema multiforme / Delayed / Incidence not knownthrombosis / Delayed / Incidence not knowntoxic epidermal necrolysis / Delayed / Incidence not knowntissue necrosis / Early / Incidence not knownStevens-Johnson syndrome / Delayed / Incidence not knownnew primary malignancy / Delayed / Incidence not knownleukemia / Delayed / Incidence not knownpneumothorax / Early / Incidence not knowntumor lysis syndrome (TLS) / Delayed / Incidence not knownnephrotoxicity / Delayed / Incidence not knownrenal failure (unspecified) / Delayed / Incidence not knownvisual impairment / Early / Incidence not known
neutropenia / Delayed / Incidence not knownthrombocytopenia / Delayed / Incidence not knownanemia / Delayed / Incidence not knownleukopenia / Delayed / Incidence not knownelevated hepatic enzymes / Delayed / Incidence not knownascites / Delayed / Incidence not knownhepatitis / Delayed / Incidence not knownhepatomegaly / Delayed / Incidence not knownhyperbilirubinemia / Delayed / Incidence not knownproctitis / Delayed / Incidence not knownesophagitis / Delayed / Incidence not knowndysphagia / Delayed / Incidence not knownoral ulceration / Delayed / Incidence not knownstomatitis / Delayed / Incidence not knownskin ulcer / Delayed / Incidence not knownerythema / Early / Incidence not knownedema / Delayed / Incidence not knownimpaired wound healing / Delayed / Incidence not knownradiation recall reaction / Delayed / Incidence not knownhypocalcemia / Delayed / Incidence not knownpneumonitis / Delayed / Incidence not knowngrowth inhibition / Delayed / Incidence not knownbleeding / Early / Incidence not knownphlebitis / Rapid / Incidence not knownperipheral neuropathy / Delayed / Incidence not known
weight gain / Delayed / Incidence not knownabdominal pain / Early / Incidence not knownnausea / Early / Incidence not knownanorexia / Delayed / Incidence not knownvomiting / Early / Incidence not knowncheilitis / Delayed / Incidence not knowndiarrhea / Early / Incidence not knownpharyngitis / Delayed / Incidence not knownalopecia / Delayed / Incidence not knowninjection site reaction / Rapid / Incidence not knownrash / Early / Incidence not knownacne vulgaris / Delayed / Incidence not knownskin hyperpigmentation / Delayed / Incidence not knownlethargy / Early / Incidence not knownmalaise / Early / Incidence not knownfatigue / Early / Incidence not knownfever / Early / Incidence not knownmyalgia / Early / Incidence not knowninfection / Delayed / Incidence not known
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine. Digoxin: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy. Palifermin: (Moderate) Palifermin should not be administered within 24 hours before, during infusion of, or within 24 hours after administration of antineoplastic agents. Penicillamine: (Major) Do not use penicillamine with antineoplastic agents due to the increased risk of developing severe hematologic and renal toxicity. SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine. Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Dactinomycin is a cell cycle-phase nonspecific, antibiotic that is more active in actively proliferating cells. It complexes with DNA by intercalating between DNA residues, causing the helix to uncoil and thereby inhibiting DNA synthesis and DNA-dependent RNA synthesis. Dactinomycin selectively inhibits messenger RNA synthesis.
Dactinomycin is administered intravenously (IV); additionally, it may be administered via regional perfusion. Radiolabeled dactinomycin did not penetrate the blood-brain barrier in 3 adult patients with malignant melanoma. It is minimally metabolized and is concentrated in nucleated cells. Approximately 30% of radiolabeled dactinomycin was recovered in urine and feces within 1 week. The terminal plasma half-life was about 36 hours. Affected cytochrome P450 isoenzymes or drug transporters: P-gp, OATP1B3Dactinomycin is a substrate of P-glycoprotein and OATP1B3 transporters in vitro.