Dosage guidance:
Dosing: Dactinomycin may be prescribed in MICROgrams (eg, 150 mcg), although many regimens list the dose in MILLIgrams (eg, mg/kg or mg/m2). Calculate the dose for obese or edematous patients based on ideal body weight (Ref). Reduce the dactinomycin dose by 50% during concomitant radiation.
Clinical considerations: Dactinomycin is associated with a high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref).
Ewing sarcoma: IV:
VAIA regimen: Adults ≤35 years of age: 500 mcg/m2/dose for 3 days (dactinomycin alternates with doxorubicin) every 3 weeks for 14 cycles (in combination with vincristine, ifosfamide, and mesna). Local therapy was scheduled following the fourth cycle of chemotherapy (Ref).
VAC/IE regimen: Adults ≤30 years: 1,250 mcg/m2 on day 1 of each odd-numbered 21-day cycle (dactinomycin is substituted for doxorubicin after a maximum doxorubicin dose is reached; in combination with vincristine, cyclophosphamide, and mesna; alternating with IE [ifosfamide, mesna, and etoposide] on even-numbered cycles); continue through cycle 17 (Ref).
Manufacturer's labeling: 1,250 mcg/m2 once every 3 weeks for 51 weeks (as part of a multiagent, combination chemotherapy regimen).
Gestational trophoblastic neoplasia: IV:
Nonmetastatic or metastatic low-risk disease (WHO prognostic score <7): 1,250 mcg/m2 once every 2 weeks (as a single agent); continue until human chorionic gonadotropin (hCG) level normalizes (Ref) or 1,250 mcg/m2 (maximum dose: 2,000 mcg) once every 2 weeks (as a single agent); continue for 3 cycles after hCG <5 milliunits/mL or until disease progression or unacceptable toxicity (Ref) or 12 mcg/kg/day for 5 days (as a single agent) (Ref).
Metastatic high-risk disease (off-label dosing):
EMA-CO regimen: 500 mcg/dose on days 1 and 2 of a 14-day treatment cycle (in combination with etoposide, methotrexate, leucovorin, cyclophosphamide, and vincristine); continue for at least 2 treatment cycles after a normal hCG level (Ref).
EMA-EP regimen: 500 mcg/dose on days 1 and 2 of a 14-day treatment cycle (in combination with etoposide, methotrexate, leucovorin, and cisplatin); continue for 2 to 4 treatment cycles after a normal hCG level (Ref).
EP-EMA regimen: 500 mcg/dose on day 1 every 2 weeks (in combination with etoposide, methotrexate, and leucovorin); alternating weekly with EP (etoposide and cisplatin) (Ref).
Manufacturer's labeling: 500 mcg/dose on days 1 and 2 every 2 weeks (as part of a multiphase combination chemotherapy regimen) for up to 8 weeks.
Ovarian germ cell tumors, malignant (off-label use): IV: VAC regimen: 500 mcg daily for 5 days every 4 weeks (in combination with vincristine and cyclophosphamide) for ~1 year (Ref) or 300 mcg/m2/day for 5 days every 4 weeks (in combination with vincristine and cyclophosphamide) for at least 10 cycles (Ref).
Rhabdomyosarcoma: IV:
VAC regimen: Patients <50 years of age: 45 mcg/kg (maximum dose: 2,500 mcg) every 3 weeks; duration of therapy depends on risk status (in combination with vincristine and cyclophosphamide, and mesna); dose omission required following radiation therapy (Ref).
VA regimen: Patients <50 years of age: 45 mcg/kg (maximum dose: 2,500 mcg) every 3 weeks for ~1 year (in combination with vincristine); dose omission required following radiation therapy (Ref).
Manufacturer's labeling: Dosing in the prescribing information may not reflect current clinical practice; 15 mcg/kg/day for 5 days every 3 to 9 weeks for up to 112 weeks (as part of a multiagent combination chemotherapy regimen).
Solid tumors, locoregional or locally recurrent (regional perfusion); dosages and techniques may vary by institution: Manufacturer's labeling: Lower extremity or pelvis: 50 mcg/kg once in combination with melphalan); upper extremity: 35 mcg/kg once (in combination with melphalan).
Regional limb perfusion: Soft tissue sarcoma, locally advanced/unresectable: Isolated limb infusion protocol: 50 to 100 mcg/L of tissue in 400 mL warmed, heparinized NS (in combination with melphalan) over 20 to 30 minutes (Ref).
Wilms tumor: IV:
VAD regimen (preoperative induction): Patients <30 years of age: 45 mcg/kg/dose (maximum: 2,300 mcg/dose) on day 1 of weeks 1, 4, 7, and 10 (in combination with vincristine and doxorubicin) (Ref).
DD-4A regimen (postoperative): Patients <30 years of age: 45 mcg/kg/dose (maximum dose: 2,300 mcg/dose) on day 1 of weeks 1, 7, 13, 19, and 25 (in combination with vincristine, doxorubicin, and radiation). Note: The first dose of dactinomycin administered following whole lung or whole abdomen irradiation should be decreased by 50% (Ref).
EE-4A regimen (pre- or postoperative): Patients <30 years: 45 mcg/kg/dose (maximum dose: 2,300 mcg/dose) on day 1 of weeks 1, 4, 7, 10, 13, 16, and 19 (in combination with vincristine) (Ref).
Manufacturer's labeling: 45 mcg/kg once every 3 to 6 weeks for up to 26 weeks (as part of a multiagent combination chemotherapy regimen).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; however, based on the amount of urinary excretion, dosage adjustments may not be necessary (Ref).
Liver impairment prior to treatment initiation: There are no dosage adjustments provided in manufacturer's labeling.
Acute hepatotoxicity during treatment:
Any transaminase increase: Reduce dose by 50%; may increase by monitoring toxicities (Ref).
Sinusoidal obstruction syndrome (SOS, also known as veno-occlusive disease): If SOS develops, consider delaying the next dactinomycin dose. Resume, reduce dose, or permanently discontinue dactinomycin based on the severity and the disease being treated.
ASCO Guidelines for appropriate chemotherapy dosing in adults with cancer with a BMI ≥30 kg/m2 : Utilize patient's actual body weight for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full, weight-based dosing (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (Ref). Note: The manufacturer's labeling recommends using ideal body weight to calculate the dose for patients with obesity or who are edematous.
Mucocutaneous reaction, severe: Permanently discontinue dactinomycin.
Myelosuppression, severe: Consider treatment delay or dose reduction in patients with prolonged myelosuppression based on the severity and the disease being treated.
Refer to adult dosing.
(For additional information see "Dactinomycin: Pediatric drug information")
Note: Medication orders for dactinomycin are commonly written in MICROgrams (eg, mcg/kg, mcg/m2) although many regimens list the dose in MILLIgrams (eg, mg/kg or mg/m2); use extra precaution. The dose intensity per 2-week cycle for adults and children should not exceed 15 mcg/kg/day for 5 days or 400 to 600 mcg/m2/day for 5 days. The manufacturer recommends calculation of the dosage for obese or edematous adult patients on the basis of body surface area in an effort to relate dosage to lean body mass. Antiemetics are recommended to prevent nausea and vomiting; dactinomycin is associated with a moderate or high emetic potential (depending on dose) in pediatrics (Ref).
Ewing sarcoma: Children and Adolescents: VAIA regimen: Limited data available: IV: 500 mcg/m2/dose for 3 days (dactinomycin alternating with doxorubicin) every 3 weeks for 14 cycles (in combination with vincristine, ifosfamide, and mesna) (Ref)
Kaposi sarcoma: Limited data available: Children and Adolescents: IV: 420 mcg/m2/day for 5 days every 4 weeks (in various combination regimens) (Ref)
Rhabdomyosarcoma: VAC regimen: Limited data available:
Infants: IV: 25 mcg/kg every 3 weeks, weeks 0 to 45 (in combination with vincristine and cyclophosphamide, and mesna); dose omission required following radiation therapy (Ref)
Children and Adolescents: IV: 45 mcg/kg (maximum dose: 2,500 mcg/dose) every 3 weeks, weeks 0 to 45 (in combination with vincristine and cyclophosphamide, and mesna); dose omission required following radiation therapy (Ref)
Wilms tumor: Note: Regimen selection based on multiple factors including the extent of disease at diagnosis, response to induction chemotherapy, and extent of surgical resection.
EE-4A regimen: Note: If the radiation field includes the whole lung or whole abdomen, reduce dose 50% during irradiation therapy
Infants: IV: 23 mcg/kg/dose (maximum dose: 2,300 mcg/dose) over 1 to 5 minutes on day 1 of weeks 1, 4, 7, 10, 13, 16, and 19 (in combination with vincristine) (Ref)
Children and Adolescents: IV: 45 mcg/kg/dose (maximum dose: 2,300 mcg/dose) over 1 to 5 minutes on day 1 of weeks 1, 4, 7, 10, 13, 16, and 19 (in combination with vincristine) (Ref)
VAD regimen: Limited data available:
Infants: IV: 23 mcg/kg/dose (maximum dose: 2,300 mcg/dose) over 1 to 5 minutes on day 1 of weeks 1, 4, 7, and 10 (in combination with vincristine and doxorubicin) (Ref)
Children and Adolescents: IV: 45 mcg/kg/dose (maximum dose: 2,300 mcg/dose) over 1 to 5 minutes on day 1 of weeks 1, 4, 7, and 10 (in combination with vincristine and doxorubicin) (Ref)
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; however, based on the amount of urinary excretion, dosage adjustments may not be necessary.
There are no dosage adjustments provided in the manufacturer's labeling; however, the following adjustments have been recommended: Children and Adolescents: Any transaminase increase: Consider dose reduction by 50%; may increase by monitoring toxicities (Ref).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not defined:
Cardiovascular: Thrombophlebitis
Central nervous system: Fatigue, malaise, peripheral neuropathy
Dermatologic: Acne vulgaris, alopecia, cheilitis, dermatitis, erythema multiforme, skin rash, Stevens-Johnson syndrome, toxic epidermal necrolysis
Endocrine & metabolic: Growth suppression, hypocalcemia
Gastrointestinal: Abdominal pain, anorexia, aphthous stomatitis, constipation, diarrhea, dysphagia, esophagitis, gastrointestinal ulcer, mucositis, nausea, proctitis, vomiting
Hematologic & oncologic: Anemia, bone marrow depression, disseminated intravascular coagulation, febrile neutropenia, hemorrhage, leukopenia, neutropenia (nadir: 14 to 21 days), pancytopenia, reticulocytopenia, second primary malignant neoplasm (including leukemia), thrombocytopenia, tumor lysis syndrome
Hepatic: Abnormal hepatic function tests, ascites, hepatic failure, hepatic sinusoidal obstruction syndrome, hepatitis, hepatomegaly, hepatotoxicity, severe hepatic disease (hepatopathy-thrombocytopenia syndrome, Farruggia 2011)
Hypersensitivity: Hypersensitivity reaction
Infection: Infection, sepsis
Neuromuscular & skeletal: Myalgia
Ophthalmic: Optic neuropathy
Renal: Renal function abnormality, renal failure syndrome, renal insufficiency
Respiratory: Pneumonitis, pneumothorax
Miscellaneous: Fever, radiation recall phenomenon
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• Bone marrow suppression: Severe and fatal myelosuppression (neutropenia, thrombocytopenia, and anemia) may occur. The neutrophil nadir typically occurs 14 to 21 days after administration.
• Dermatologic toxicity: Severe mucocutaneous toxicity, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, may occur.
• Extravasation: Dactinomycin is a vesicant (Pérez Fidalgo 2012); ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation. Severe local tissue damage (blistering, ulcerations, and persistent pain) requiring wide excision surgery followed by split-thickness skin grafting may occur. Immediately interrupt the infusion if signs/symptoms of extravasation occur. Apply dry, cold compresses to the site of extravasation for 20 minutes, 4 times per day for 1 to 2 days (Pérez Fidalgo 2012). Monitor closely; plastic surgery consultation may be necessary if extravasation occurs.
• Hepatotoxicity: Dactinomycin may cause hepatotoxicity, including severe and fatal hepatic sinusoidal obstruction syndrome (SOS; formerly called veno-occlusive liver disease); risk factors include <4 years of age or concomitant radiotherapy. Use with caution in hepatobiliary dysfunction.
• Nephrotoxicity: Kidney function abnormalities may occur with dactinomycin.
• Secondary malignancies: The risk of secondary malignancies (including leukemia) is increased with dactinomycin.
Special populations:
• Radiation therapy recipients: Dactinomycin potentiates the effects of radiation therapy; use with caution in patients who have received radiation therapy. Combination with radiation therapy may result in increased toxicity (eg, GI toxicity, myelosuppression, or erythema and vesiculation of the skin or buccal and pharyngeal mucosa). Erythema from prior radiation therapy may be reactivated by dactinomycin. Radiation recall risk appears to be highest when administered within 2 months of prior radiation, although the risk can still occur with distant radiation exposure.
Other warnings/precautions:
• Vaccines: Avoid administration of live vaccines prior to and during dactinomycin treatment. The safety of live vaccines following dactinomycin treatment has not been studied.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution Reconstituted, Intravenous:
Cosmegen: 0.5 mg (1 ea [DSC])
Generic: 0.5 mg (1 ea)
Solution Reconstituted, Intravenous [preservative free]:
Generic: 0.5 mg (1 ea)
Yes
Solution (reconstituted) (DACTINomycin Intravenous)
0.5 mg (per each): $600.00 - $921.88
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Cosmegen: 0.5 mg (1 ea)
Dactinomycin is associated with a high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref).
IV: Infuse over 10 to 15 minutes; may also be administered as a slow IV push (off-label rate) in some protocols. Do not filter with cellulose ester membrane filters.
Regional perfusion: Technique may vary by institution; consult protocol for details. Local reactions including epidermolysis, erythema, and edema have been reported (may be severe).
Vesicant; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation.
Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity. Apply dry cold compresses for 20 minutes 4 times a day for 1 to 2 days (Ref).
Parenteral: May administer undiluted into the side-port of a free flowing IV infusion by slow IVP over a few minutes; or may further dilute and administer as IV infusion over 10 to 15 minutes; consider a D5W or NS flush before and after a dactinomycin dose to ensure venous patency. Cellulose ester membrane filters may partially remove dactinomycin from solution and should not be used during administration. Avoid extravasation; do not give IM or SubQ.
Antiemetics are recommended to prevent nausea and vomiting; dactinomycin is associated with a moderate or high emetic potential (depending on dose) in pediatrics (Ref).
Vesicant; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation. If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity. Apply dry cold compresses for 20 minutes 4 times a day for 1 to 2 days (Ref).
Hazardous agent (NIOSH 2024 [table 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Ewing sarcoma: Treatment (as part of a multiphase, combination chemotherapy regimen) of Ewing sarcoma in adults and pediatric patients.
Gestational trophoblastic neoplasia: Treatment (as a single agent or as part of a combination chemotherapy regimen) of gestational trophoblastic neoplasia in postmenarchal patients.
Rhabdomyosarcoma: Treatment (as part of a multiphase, combination chemotherapy regimen) of rhabdomyosarcoma in adults and pediatric patients.
Solid tumors, locoregional or locally recurrent: Palliative and/or adjunctive treatment (as a component of regional perfusion) of locally recurrent or locoregional solid malignancies in adults.
Wilms tumor: Treatment (as part of a multiphase, combination chemotherapy regimen) of Wilms tumor in adults and pediatric patients.
Ovarian germ cell tumors, malignant
DACTINomycin may be confused with dacarbazine, Dacogen, DAPTOmycin, DAUNOrubicin
Actinomycin may be confused with achromycin
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Substrate of OATP1B1/1B3, P-glycoprotein (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of BCG Products. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor
Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Cytotoxic Chemotherapy) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification
Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Lenograstim: Antineoplastic Agents may decrease therapeutic effects of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Lipegfilgrastim: Antineoplastic Agents may decrease therapeutic effects of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor
Palifermin: May increase adverse/toxic effects of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider Therapy Modification
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Piperacillin: May increase hypokalemic effects of Antineoplastic Agents. Risk C: Monitor
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification
Ritlecitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may decrease therapeutic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to starting chemotherapy when possible. Patients vaccinated less than 14 days before or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Verify pregnancy status prior to initiating dactinomycin therapy in patients who could become pregnant. Patients who could become pregnant should use effective contraception during therapy and for at least 6 months after the last dactinomycin dose.
When used for gestational trophoblastic neoplasm, unfavorable outcomes have been reported when subsequent pregnancies occur within 6 months of treatment. It is recommended to use effective contraception for 6 months to 1 year after therapy (Matsui 2004; Seckl 2013).
Patients with partners who could become pregnant should use effective contraception during therapy and for 3 months after the last dactinomycin dose.
Based on data from animal reproduction studies and its mechanism of action, in utero exposure to dactinomycin may cause fetal harm.
When used for gestational trophoblastic neoplasm, unfavorable outcomes have been reported when subsequent pregnancies occur within 6 months of treatment (Matsui 2004; Seckl 2013).
It is not known if dactinomycin is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and (based on limited data) for 14 days after the last dactinomycin dose.
CBC (prior to each treatment cycle), LFTs (eg, AST, ALT, total bilirubin, alkaline phosphatase; prior to and during treatment), kidney function tests (frequently during treatment), and electrolytes (frequently during treatment). Verify pregnancy status prior to therapy initiation (in patients that could become pregnant). Monitor for signs/symptoms of hepatic sinusoidal obstruction syndrome, including total bilirubin >1.4 mg/dL, unexplained weight gain, ascites, hepatomegaly, or unexplained right upper quadrant pain (Arndt 2004). Monitor for signs/symptoms of secondary malignancy, extravasation, mucocutaneous reactions, myelosuppression, and radiation recall.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Dactinomycin binds to the guanine portion of DNA intercalating between guanine and cytosine base pairs inhibiting DNA and RNA synthesis and protein synthesis
Distribution: Children: Extensive extravascular distribution (59 to 714 L) (Veal 2005); does not penetrate blood-brain barrier
Metabolism: Minimally hepatic (Perry 2012)
Half-life elimination: 30 to 40 hours (Perry 2012); Children: Range: 14 to 43 hours (Veal 2005)
Excretion: ~30% in urine and feces within 1 week