dactinomycin (Rx)

Brand and Other Names:Cosmegen
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injection, powder for reconstitution

  • 500mcg/vial

Wilms Tumor

Indicated for Wilms tumor as part of a multiphase, combination chemotherapy regimen

45 mcg/kg IV every 3-6 weeks for up to 26 weeks  

Rhabdomyosarcoma

Indicated for rhabdomyosarcoma as part of a multiphase, combination chemotherapy regimen

15 mg/kg IV on Days 1-5 every 3-9 weeks for up to 112 weeks  

Ewing Sarcoma

Indicated for Ewing sarcoma as part of a multiphase, combination chemotherapy regimen

1250 mcg/m² IV q3Week for 51 weeks  

Gestational Trophoblastic Neoplasms

Indicated for postmenarchal patients with gestational trophoblastic neoplasia, as a single agent or as part of a combination chemotherapy regimen

Nonmetastatic and low-risk metastatic disease: 12 mcg/kg IV qDay for 5 days as a single agent  

High-risk metastatic disease: 500 mcg IV on Days 1 and 2 q2Weeks for up to 8 weeks  

Testicular Cancer

Indicated for metastatic, nonseminomatous testicular cancer, as part of a multiphase, combination chemotherapy regimen

1000 mcg/m² IV once q3Weeks for 12 weeks as part of a cisplatin-based, multi-agent combination regimen  

Locoregional Solid Malignancies

Indicated for locally recurrent or locoregional solid malignancies, as a component of palliative or adjunctive regional perfusion

Calculate dose for obese or edematous patients based on ideal body weight

Pelvis/lower extremity: 50 mcg/kg IV once in combination with melphalan  

Upper extremity: 35 mcg/kg IV once in combination with melphalan  

Malignant Germ Cell Tumors of the Ovary (Off-label)

Palliative therapy only

300 mcg/m²/day IV for 5 days q4Weeks (in combination with vincristine and cyclophosphamide) (Slayton 1985)

Dosage Modifications

Reduce dose by 50% during concomitant radiation; use caution when administering within 2 months of radiation

Dosing Considerations

Verify the pregnancy status of females of reproductive potential prior to initiating (see Pregnancy)

Dosage Forms & Strengths

injection, powder for reconstitution

  • 500mcg/vial

Wilms Tumor

Indicated for Wilms tumor as part of a multiphase, combination chemotherapy regimen

45 mcg/kg IV every 3-6 weeks for up to 26 weeks  

Rhabdomyosarcoma

Indicated for rhabdomyosarcoma as part of a multiphase, combination chemotherapy regimen

15 mg/kg IV on Days 1-5 every 3-9 weeks for up to 112 weeks  

Ewing Sarcoma

Indicated for Ewing sarcoma as part of a multiphase, combination chemotherapy regimen

1250 mcg/m² IV q3Week for 51 weeks  

Gestational Trophoblastic Neoplasms

Indicated for postmenarchal patients with gestational trophoblastic neoplasia, as a single agent or as part of a combination chemotherapy regimen

Nonmetastatic and low-risk metastatic disease: 12 mcg/kg IV qDay for 5 days as a single agent  

High-risk metastatic disease: 500 mcg IV on Days 1 and 2 q2Weeks for up to 8 weeks  

Testicular Cancer

Indicated for metastatic, nonseminomatous testicular cancer, as part of a multiphase, combination chemotherapy regimen

1000 mcg/m² IV once q3Weeks for 12 weeks as part of a cisplatin-based, multi-agent combination regimen  

Malignant Germ Cell Tumors (Off Label)

Palliative therapy only

≥14 years: 300 mcg/m²/day IV for 5 days q4Weeks (in combination with vincristine and cyclophosphamide) (Slayton 1985)

Dosage Modifications

Reduce dose by 50% during concomitant radiation; use caution when administering within 2 months of radiation

Dosing Considerations

Verify the pregnancy status of females of reproductive potential prior to initiating (see Pregnancy)

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Interactions

Interaction Checker

and dactinomycin

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            Frequency Not Defined

            Also see Cautions

            Common adverse effects include infection, alopecia, rash, dysphagia, fatigue, fever, nausea, vomiting, anemia, neutropenia, thrombocytopenia, mucositis, and hepatotoxicity

            Secondary malignancy and leukemia

            Veno-occlusive disease

            Extravasation

            Myelosuppression

            Severe mucocutaneous reactions

            Renal toxicity

            Hepatotoxicity

            Potentiation of radiation toxicity and radiation recall

            Postmarketing Reports

            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

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            Warnings

            Contraindications

            None

            Cautions

            Increased risk of secondary malignancy or leukemia following treatment

            Severe and fatal veno-occlusive disease reported; risk increased with young age (ie, <4 yr) or concomitant radiotherapy; monitor for increased AST, ALT, total bilirubin, hepatomegaly, weight gain, or ascites; consider delaying next dose; resume, reduce dose, or permanently discontinue based on severity of reaction and disease being treated

            If extravasation occurs, immediately interrupt the injection or infusion and apply ice (see Administration)

            Severe and fatal myelosuppression reported; monitor blood cell counts before each cycle; delay next dose if severe myelosuppression has not improved; consider dose reduction for patients with prolonged myelosuppression based on severity of reaction and disease being treated

            Severe mucocutaneous reactions (eg, Steven-Johnson syndrome, toxic epidermal necrolysis) can occur; permanently discontinue

            Renal toxicity reported; monitor creatinine and electrolytes frequently

            Hepatotoxicity reported; monitor transaminases, alkaline phosphatase and bilirubin before and during treatment

            Reduce dose by 50% during concomitant radiation; use caution when administering within 2 months of radiation

            Can cause fetal harm; inform patients of potential risk to a fetus and to use effective contraception (see Pregnancy)

            Drug interaction overview

            • Vaccination with live viral vaccines is not recommended before or during treatment; not studied
            • Published in vitro studies report that dactinomycin may be a P-glycoprotein and OATP1B3 substrate
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            Pregnancy & Lactation

            Pregnancy

            Based on findings from animal studies and its mechanism of action, can cause fetal harm when administered to pregnant women

            In animal reproduction studies, administration to pregnant animals during the period of organogenesis was teratogenic, resulting in malformations at doses lower than the recommended human dose

            Verify the pregnancy status of females of reproductive potential prior to initiating

            Contraception

            • Females of reproductive: Use effective contraception during treatment and for at least 6 months after the final dose
            • Males with female partners of reproductive potential: Use effective contraception during treatment and for 3 months after the final dose

            Lactation

            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

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Actinomycin antibiotic; intercalates into DNA base pairs preventing RNA, DNA, and protein synthesis

            Distribution

            Protein bound: Low

            Concentrates in nucleated cells and does not penetrate the blood-brain barrier

            Metabolism

            Minimally metabolized

            Elimination

            Excretion: 30% in urine and feces over 1 week

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            Administration

            IV Incompatibilities

            Y-site: diazepam, filgrastim, pantoprazole, phenytoin

            IV Compatibilities

            Solution: D5W, NS

            Y-site: acyclovir, alfentanil, allopurinol, amifostine, amikacin, aminophylline, amphotericin B, ampicillin, aztreonam, bleomycin, buprenorphine, calcium chloride, calcium gluconate, cefepime, cimetidine, cyclophosphamide, dacarbazine, daptomycin, daunorubicin, dexamethasone sodium phosphate, ephedrine, etoposide PO4, fludarabine, furosemide, ganciclovir, gemcitabine, granisetron, ifosfamide, magnesium sulfate, melphalan, mesna, midazolam, ondansetron, sargramostim, teniposide, thiotepa, topotecan, vancomycin, vinblastine, vincristine, vinorelbine, voriconazole

            IV Preparation

            Follow cytotoxic handling and disposal guidelines

            Reconstitute with 1.1 mL of preservative-free sterile water for injection to yield a final concentration of 500 mcg/mL

            Resulting solution should appear clear, gold-colored

            Further dilute reconstituted product with D5W or 0.9% NaCl to yield concentration >10 mcg/mL

            Contains no preservative, discard any unused portions

            IV Administration

            Vesicant

            Administer diluted reconstituted product IV over 10-15 minutes

            Do not use in-line cellulose ester membrane filter

            Do not give IM or SC

            Extravasation Management

            Discontinue for burning or stinging sensation or other evidence indicating perivenous infiltration or extravasation

            Confirmed or suspected extravasation

            • Terminate injection or infusion immediately and restart in another vein
            • Apply ice to the site intermittently for 15 minutes, 4 times a day for 3 days
            • Observe closely and consult plastic surgery if necessary based on severity of reaction

            Storage

            Unopened vials

            • Store at 20-25°C (68-77°F); excursions permitted between 15-30°C (59-86°F)
            • Protect from light and humidity

            Reconstituted vials

            • Store at 20-25°C (68-77°F); for no more than 4 hr from reconstitution to completion of administration
            • Cytotoxic drug; follow applicable special handling and disposal procedures
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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.