Dactinomycin is a cytotoxic antitumor antibiotic that is indicated for the treatment of adult and pediatric patients with Wilms tumor, rhabdomyosarcoma, Ewing sarcoma, and testicular cancer in combination with chemotherapy. It is also indicated in postmenarchal patients with gestational trophoblastic neoplasia and in adult patients with locally recurrent or locoregional solid malignancies as a component of palliative or adjunctive regional perfusion. Hepatotoxicity has been reported with dactinomycin therapy, including fatal sinusoidal obstruction syndrome previously termed veno-occlusive disease.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Hazardous Drugs Classification
-NIOSH 2016 List: Group 1
-NIOSH (Draft) 2020 List: Table 1
-Observe 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 Risk
-Doses of 1.35 mg/m2/dose or greater: High
-Doses of 10 mcg/kg/dose: Moderate
-Administer routine antiemetic prophylaxis prior to treatment.
Extravasation Risk
-Vesicant
-Administer drug through a central venous line.
Route-Specific Administration
Injectable Administration
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
-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.
Severe myelosuppression has been reported with dactinomycin therapy in clinical trials or postmarketing surveillance, including pancytopenia, agranulocytosis, leukopenia, neutropenia/febrile neutropenia, anemia/aplastic anemia, reticulocytopenia, and thrombocytopenia; 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. Neutrophil nadirs typically occur 14 to 21 days after dactinomycin therapy.
Hepatotoxicity has been reported with dactinomycin therapy in clinical trials or postmarketing surveillance, including elevated hepatic enzymes, hyperbilirubinemia, hepatomegaly, hepatitis, and ascites; fatal cases of hepatic failure and hepatic veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) have also been reported. Obtain liver function tests prior to and during therapy; monitor patients for symptoms of VOD/SOS (e.g., weight gain and ascites). Consider delaying the next dactinomycin dose if VOD/SOS occurs. Resume, dose reduce, or permanently discontinue dactinomycin therapy based on the severity of the reactions and disease being treated. Hepatomegaly and increased AST levels occurred in patients with right-sided Wilms tumor who received dactinomycin within 2 months of radiation therapy; perform a risk/benefit analysis in these patients before administering dactinomycin in combination with radiation in these patients. Hepatic VOD/SOS may be associated with intravascular clotting disorder (e.g., disseminated intravascular coagulation (DIC)) and multi-organ failure.
Gastrointestinal (GI) toxicity has been reported with dactinomycin therapy in clinical trials or postmarketing surveillance, including nausea, vomiting, abdominal pain, anorexia, diarrhea, constipation, GI/peptic ulcer, cheilitis, dysphagia, esophagitis, pharyngitis, ulcerative stomatitis, proctitis, and mucositis/oral ulceration. Nausea and vomiting may occur within the first few hours following dactinomycin administration; prophylactic antiemetics may prevent these adverse events. If stomatitis or diarrhea occurs during therapy, discontinue dactinomycin until the patient has recovered. GI toxicity may be increased when dactinomycin is combined with radiation therapy. Patients who receive dactinomycin in combination with regional perfusion therapy may have an increased risk of developing superficial ulceration of the gastric mucosa.
Dermatologic toxicity has been reported with dactinomycin therapy in clinical trials or postmarketing surveillance, including alopecia, rash, dermatitis, hypersensitivity, acne vulgaris, erythema multiforme, Stevens-Johnson Syndrome, and toxic epidermal necrolysis. Permanently discontinue therapy in patients who experience a severe mucocutaneous reaction. A severe injection site reaction (i.e., extravasation) has occurred with IV dactinomycin resulting in severe tissue damage (tissue necrosis). Immediately discontinue dactinomycin in patients who develop signs or symptoms of extravasation; restart therapy in another vein. To treat extravasation or suspected extravasation, apply ice to the site for 15 minutes 4-times daily for 3 days. Also, closely observe the affected site and consult a plastic surgeon; wide excision surgery followed by skin grafting may be warranted for blistering, skin ulcer, and/or persistent pain. Contracture of the arms was reported in at least one patient. Cases of severe epidermolysis, erythema, and edema have occurred with regional limb perfusion. Patients who receive dactinomycin in combination with regional perfusion therapy may have an increased risk of impaired wound healing; additionally, extremity edema, soft tissue damage, and potential venous thrombosis have occurred.
A radiation recall reaction has been reported with dactinomycin therapy in patients who have had prior radiation therapy. This syndrome presents as erythema or skin hyperpigmentation of previously irradiated skin.
Hypocalcemia has been reported with dactinomycin therapy in clinical trials or postmarketing surveillance.
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. The International Agency on Research on Cancer has judged that dactinomycin is a positive carcinogen in animals. Dactinomycin has also been reported to be mutagenic.
Pneumonitis and pneumothorax have been reported with dactinomycin therapy in clinical trials or postmarketing surveillance.
Fatigue and malaise have been reported with dactinomycin therapy in clinical trials or postmarketing surveillance. Lethargy has also been reported with dactinomycin use.
Growth inhibition has been reported with dactinomycin therapy in clinical trials or postmarketing surveillance.
Fever has been reported with dactinomycin therapy in clinical trials or postmarketing surveillance.
Myalgia has been reported with dactinomycin therapy in clinical trials or postmarketing surveillance.
Tumor lysis syndrome (TLS) has been reported with dactinomycin therapy in clinical trials or postmarketing surveillance.
Nephrotoxicity/renal impairment and renal failure (unspecified) have been reported with dactinomycin therapy in clinical trials or postmarketing surveillance.
Thrombo-phlebitis and bleeding have been reported with dactinomycin therapy in clinical trials or postmarketing surveillance.
Visual impairment, particularly optic neuropathy, has been reported with dactinomycin therapy in clinical trials or postmarketing surveillance.
Peripheral neuropathy has been reported with dactinomycin therapy in clinical trials or postmarketing surveillance.
Infection has been reported with dactinomycin use, including neutropenic sepsis resulting in death. Do not administer dactinomycin in patients with an active infection herpes infection (i.e., chickenpox or herpes zoster infection).
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.
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.
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.
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.
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.
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.
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.
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.
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.
For the treatment of gestational trophoblastic disease:
-for the treatment of nonmetastatic or low-risk metastatic gestational trophoblastic disease, as a single-agent:
Intravenous dosage:
Female Adults and Post-Menarchal Adolescents and Children: 12 mcg/kg IV daily for 5 days.
-for high-risk gestational trophoblastic disease in combination with methotrexate, leucovorin, etoposide, cyclophosphamide, and vincristine (EMA-CO regimen):
Intravenous dosage:
Female Adults and Post-Menarchal Adolescents and Children: 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.
-for high-risk gestational trophoblastic disease in combination with methotrexate, leucovorin, etoposide, and cisplatin (EMA-EP regimen):
Intravenous dosage:
Female Adults and Post-Menarchal Adolescents and Children: 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.
For the treatment of metastatic nonseminomatous testicular cancer, as part of a multiphase combination chemotherapy regimen:
Intravenous dosage:
Male Adults, Adolescents, and Children: 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).
For the treatment of Wilms' tumor, as part of a multiphase combination chemotherapy regimen:
Intravenous dosage:
Adults, Adolescents, Children, and Infants: 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.
For the treatment of osteogenic sarcoma*:
Intravenous dosage:
Adults, Adolescents, and Children: 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.
For the treatment of malignant melanoma:
Intra-arterial dosage (isolated limb perfusion):
Adults: 50 mcg/kg for the legs or 35 mcg/kg for the arms in combination with hyperthermia has been utilized.
-for the treatment of malignant melanoma as a single-agent or in combination with other chemotherapy*:
Intravenous dosage:
Adults: 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%.
For the treatment of Kaposi's sarcoma*:
Intravenous dosage:
Adults and Adolescents: 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.
For the treatment of rhabdomyosarcoma:
-for the treatment of rhabdomyocarcoma, as part of a multiphase combination chemotherapy regimen:
Intravenous dosage:
Adults, Adolescents, Children, and Infants: 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.
-for the first-line treatment of rhabdomyosarcoma, in combination with vincristine, ifosfamide, and doxorubicin:
Intravenous dosage:
Adolescents and Children: 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).
Maximum Dosage Limits:
NOTE: The correct dose of dactinomycin will vary based on specific protocol used. Clinicians should consult the appropriate references to verify the dose.
-Adults
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.
-Geriatric
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.
-Adolescents
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.
-Children
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.
-Infants
15 mcg/kg IV daily for 5 days; 45 mcg/kg or 1,250 mcg/m2 IV as a single dose.
Patients with Hepatic Impairment Dosing
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).
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
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.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure 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.
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.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (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.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (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.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (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, OATP1B3
Dactinomycin is a substrate of P-glycoprotein and OATP1B3 transporters in vitro.
-Special Populations
Pediatrics
In a population analyses, increased systemic dactinomycin clearance was associated with increasing body weight in patients with cancer who were 21 years and younger.