Dactinomycin

Name: Dactinomycin

Dactinomycin Dosage

Dactinomycin is injected into a vein through an IV. You will receive this injection in a clinic or hospital setting. Dactinomycin is usually given only on certain days during a treatment cycle. How often you receive this medication depends on the condition being treated.

Tell your caregivers if you feel any burning, pain, or swelling around the IV needle when dactinomycin is injected.

Dactinomycin can be harmful if it gets in your eyes, mouth, or nose, or on your skin. If skin contact occurs, rinse with plain water for at least 15 minutes.

Dactinomycin can lower blood cells that help your body fight infections and help your blood to clot. Your blood will need to be tested often. Your cancer treatments may be delayed based on the results of these tests.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Call your doctor for instructions if you miss an appointment for your dactinomycin injection.

Dactinomycin Usage

Dactinomycin comes as a liquid to be infused into a vein (IV) by a healthcare provider in a hospital or other medical facility. In some cases, the medication must be injected directly into a specific part of the body or the organ where the tumor is located.

The length of treatment depends on a number of factors including:

  • the type of cancer being treated
  • other medications you are receiving
  • your body's response to treatment
  • side effects

Dactinomycin treatment may be delayed or stopped if certain side effects occur.

Dactinomycin Dosage

The dactinomycin dose your doctor recommends will be determined by the type of cancer you have, your height and weight, other medicines and treatments you are receiving, as well as other factors.

Dactinomycin Overdose

Dactinomycin is usually administered by a healthcare provider in a medical setting making it unlikely for an overdose to occur. However, if overdose is suspected, seek emergency medical attention.

Dactinomycin FDA Warning

WARNING

Dactinomycin for injection should be administered only under the supervision of a physician who is experienced in the use of cancer chemotherapeutic agents.

This drug is HIGHLY TOXIC and both powder and solution must be handled and administered with care. Inhalation of dust or vapors and contact with skin or mucous membranes, especially those of the eyes, must be avoided. Avoid exposure during pregnancy. Due to the toxic properties of dactinomycin (e.g., corrosivity, carcinogenicity, mutagenicity, teratogenicity), special handling procedures should be reviewed prior to handling and followed diligently. Dactinomycin is extremely corrosive to soft tissue. If extravasation occurs during intravenous use, severe damage to soft tissues will occur. In at least one instance, this has led to contracture of the arms.

What should I avoid while using dactinomycin?

Avoid getting this medicine on your clothes. Destroy any clothing the medicine has leaked onto if an accidental spill occurs.

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

This medicine can pass into body fluids (urine, feces, vomit). For at least 48 hours after you receive a dose, avoid allowing your body fluids to come into contact with your hands or other surfaces. Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

Do not receive a "live" vaccine while using dactinomycin, and avoid coming into contact with anyone who has recently received a live vaccine. There is a chance that the virus could be passed on to you. Live vaccines include measles, mumps, rubella (MMR), rotavirus, typhoid, yellow fever, varicella (chickenpox), zoster (shingles), and nasal flu (influenza) vaccine.

Cautions for Dactinomycin

Contraindications

  • Current or recent infection with chickenpox or herpes zoster.100 (See Immunosuppression under Cautions.)

  • Known hypersensitivity to dactinomycin or any ingredient in the formulation.100

Warnings/Precautions

Warnings

Carcinogenic Effects

Secondary malignancies (e.g., leukemias) reported in patients receiving dactinomycin in combination with radiation therapy.100 Long-term observation for occurrence of secondary malignancy is necessary in patients receiving combined modality treatment for cancer.100

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; teratogenicity and embryotoxicity demonstrated in animals.100 Avoid pregnancy during therapy.100 If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.100

Immunosuppression

Do not administer at or near the time of infection with chickenpox or herpes zoster.100 Risk of severe and possibly fatal generalized disease.100

Concurrent administration of live virus vaccines not recommended.100

Sensitivity Reactions

Hypersensitivity Reactions

Possible serious hypersensitivity reactions, including anaphylaxis. 100

Major Toxicities

Hematologic Effects

Risk of dose-limiting myelosuppression, manifested primarily by leukopenia and thrombocytopenia; anemia, pancytopenia, reticulopenia, agranulocytosis, and aplastic anemia also may occur.100 a

Leukocyte and platelet nadirs generally occur 14–21 days following completion of a course of therapy.a Leukocyte and platelet counts usually return to normal levels within 21–25 days.100

Monitor hematologic function frequently.100 If severe myelosuppression develops, discontinue therapy until blood counts return to an acceptable level;100 administer supportive therapy, anti-infectives for complicating infections, and blood product transfusions as indicated.a

Use with extreme caution in patients with impaired bone marrow function.a

GI Effects

Nausea and vomiting; generally occur within hours of administration and last up to 24 hours.100 a Antiemetics may be effective in preventing or treating nausea and vomiting.100 a

Risk of stomatitis or diarrhea; if stomatitis or diarrhea develops, discontinue therapy until symptoms resolve. 100

Hepatic Effects

Potentially fatal hepatic failure and hepatic veno-occlusive disease reported.100 Veno-occlusive disease may be associated with intravascular clotting disorder and multiorgan failure and may be fatal, particularly in children <4 years of age.100

Abnormal liver function tests, ascites, hepatomegaly, and hepatitis reported.100

Local Effects

Extravasation may produce severe local tissue damage, necrosis, cellulitis, phlebitis, and inflammation; contracture of the arms reported.100 a Follow precautions to avoid extravasation.100 (See IV Administration under Dosage and Administration.)

Epidermolysis, erythema, and edema, sometimes severe, reported with regional limb perfusion.100

General Precautions

Toxicity and Adequate Patient Monitoring

Highly toxic drug with a low therapeutic index; therapeutic response is not likely to occur without some evidence of toxicity.100 a Handle and administer cautiously; administer only under the supervision of qualified clinician experienced in the use of cancer chemotherapy agents.100 (See IV Administration under Dosage and Administration.)

Closely observe patient and frequently assess bone marrow, hepatic, and renal function.100

Toxicity Potentiation with Concomitant Radiation Therapy

Appears to potentiate effects of radiation therapy.100 Severe reactions possible if high doses of both dactinomycin and radiation are used or if patient is especially sensitive to such combination therapy.100

Increased incidence of GI toxicity (e.g., severe oropharyngeal mucositis) and myelosuppression reported.100

Erythema at the site of irradiation may occur early in normal skin and buccal and pharyngeal mucosa and may be followed rapidly by hyperpigmentation and/or edema, desquamation, vesiculation, and rarely necrosis.100 a

Possible reactivation of radiation effects (e.g., erythema) in previously irradiated tissues.100

Hepatomegaly, elevated serum AST concentrations, and ascites reported in the first 2 months after radiation therapy in patients with right-sided Wilms’ tumor; administer dactinomycin with particular caution in the first 2 months after radiation therapy.100 a Do not administer concomitantly with radiation therapy for treatment of Wilms’ tumor unless benefit outweighs risk.100 103

Specific Populations

Pregnancy

Category D.100 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether dactinomycin is distributed into human milk.100 Discontinue nursing or the drug.100

Pediatric Use

Increased incidence of adverse effects in infants; use only in infants older than 6–12 months of age.100

Increased incidence of fatal veno-occlusive disease in children <4 years of age.100 (See Hepatic Effects under Cautions.)

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults; consider the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly.100

Possible increased incidence of myelosuppression compared with younger adults.100

Common Adverse Effects

With IV therapy, myelosuppression, nausea, vomiting, anorexia, abdominal pain, diarrhea, GI ulceration, dysphagia, stomatitis, alopecia, rash, malaise, fatigue, lethargy, liver function test abnormalities, hepatitis, growth retardation, fever, infection, myalgia.100

With regional isolation perfusion, edema of involved extremity, regional soft tissue damage, myelosuppression, infection, impaired wound healing.100

What do I need to tell my doctor BEFORE I take Dactinomycin?

  • If you have an allergy to dactinomycin or any other part of dactinomycin.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have or had chickenpox or shingles lately.
  • If you are breast-feeding or plan to breast-feed.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take dactinomycin with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

What are some other side effects of Dactinomycin?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

  • Upset stomach or throwing up.
  • Not hungry.
  • Stomach pain.
  • Feeling tired or weak.
  • Muscle pain.
  • Hair loss.
  • Dry lips.
  • Pimples (acne).

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

If OVERDOSE is suspected

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Consumer Information Use and Disclaimer

  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else's drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.
  • Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about dactinomycin, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about dactinomycin. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using dactinomycin.

Review Date: October 4, 2017

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous:

Cosmegen: 0.5 mg (1 ea)

Dosing Pediatric

Note: Medication orders for dactinomycin are commonly written in MICROgrams (eg, 150 mcg) although many regimens list the dose in MILLIgrams (eg, mg/kg or mg/m2). The dose intensity per 2-week cycle should not exceed 15 mcg/kg/day for 5 days or 400 to 600 mcg/m2/day for 5 days. Dactinomycin is associated with a high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Dupuis 2011).

Ewing sarcoma: Children >6 months: IV: 15 mcg/kg/day for 5 days (in various combination regimens and schedules)

Off-label dosing: VAIA regimen: IV: 500 mcg/m2/dose for 3 days (dactinomycin alternates with doxorubicin) every 3 weeks for 14 cycles (in combination with vincristine, ifosfamide, and mesna) (Paulussen 2008)

Rhabdomyosarcoma: Children >6 months: IV: 15 mcg/kg/day for 5 days (in various combination regimens and schedules)

Off-label dosing: IV:

VAC regimen:

Children <1 year: 25 mcg/kg every 3 weeks, weeks 0 to 45 (in combination with vincristine and cyclophosphamide, and mesna); dose omission required following radiation therapy (Raney 2011)

Children ≥1 year: 45 mcg/kg (maximum dose: 2,500 mcg) every 3 weeks, weeks 0 to 45 (in combination with vincristine and cyclophosphamide, and mesna); dose omission required following radiation therapy (Raney 2011)

Wilms tumor: Children >6 months: IV: 15 mcg/kg/day for 5 days (in various combination regimens and schedules)

Off-label dosing: IV:

DD-4A regimen: 45 mcg/kg on day 1 every 6 weeks for 54 weeks (in combination with doxorubicin and vincristine) (Green 1998)

EE-4A regimen: 45 mcg/kg on day 1 every 3 weeks for 18 weeks (in combination with vincristine) (Green 1998)

VAD regimen:

Children <1 year: 750 mcg/m2 every 6 weeks for 1 year (stage III disease) (in combination with vincristine and doxorubicin) (Pritchard 1995)

Children ≥1 year: 1500 mcg/m2 every 6 weeks for 1 year (stage III disease) (in combination with vincristine and doxorubicin) (Pritchard 1995)

Osteosarcoma (off-label use): IV: 600 mcg/m2 on days 1, 2, and 3 of weeks 15, 31, 34, 39, and 42 (as part of a combination chemotherapy regimen including cyclophosphamide, bleomycin, methotrexate [high dose], leucovorin, doxorubicin, and cisplatin; refer to protocol for specific details) (Goorin 2003)

Dosing Hepatic Impairment

There are no dosage adjustments provided in manufacturer's labeling.

The following adjustments have also been recommended: Any transaminase increase: Reduce dose by 50%; may increase by monitoring toxicities (Floyd 2006).

Administration

Dactinomycin is associated with a high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Basch 2011, Dupuis 2011).

For IV administration; do not administer IM or SubQ. Administer by slow IV push or infuse over 10 to 15 minutes. 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 1-2 days (Perez Fildago 2012).

ALERT U.S. Boxed Warning

Experienced physician:

Administer dactinomycin only under the supervision of a health care provider who is experienced in the use of cancer chemotherapeutic agents.

Hazardous agent:

This drug is highly toxic and both powder and solution must be handled and administered with care. Inhalation of dust or vapors and contact with skin or mucous membranes, especially those of the eyes, must be avoided. Because of the toxic properties of dactinomycin (eg, corrosivity, carcinogenicity, mutagenicity, teratogenicity), review special handling procedures prior to handling and follow diligently.

Pregnancy:

Avoid exposure during pregnancy.

Extravasation:

Dactinomycin is extremely corrosive to soft tissue. If extravasation occurs during intravenous (IV) use, severe damage to soft tissues will occur. In at least one instance, this has led to contracture of the arms

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Dose Adjustments

Data not available

(web3)