Dactinomycin

No dactinomycin drug interactions have been identified, however, you should tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Not all drug interactions are known or reported and new drug interactions are continually being reported.

Before receiving dactinomycin, tell your doctor about all of your medical conditions including if you:

• are allergic to dactinomycin or any other medicines
• have kidney or liver problems
• have blood disorders
• have previously, or are currently being treated with other cancer medicines or radiation therapy
• have recently had chickenpox or herpes zoster (shingles)
• are pregnant or breastfeeding

Talk to your doctor if you plan to receive vaccinations.

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Usual Adult Dose for Wilms' Tumor:

15 mcg/kg/day or 400 to 600 mcg/m2/day intravenously for 5 days as a part of a combination regimen. Dosage for obese or edematous adult patients may be calculated on the basis of body surface area to relate dosage to lean body mass. Dosage may be repeated every 3 to 6 weeks.

Usual Adult Dose for Ewing's Sarcoma:

15 mcg/kg/day or 400 to 600 mcg/m2/day intravenously for 5 days as a part of a combination regimen. Dosage for obese or edematous adult patients may be calculated on the basis of body surface area to relate dosage to lean body mass. Dosage may be repeated every 3 to 6 weeks.

Usual Adult Dose for Rhabdomyosarcoma:

15 mcg/kg/day or 400 to 600 mcg/m2/day intravenously for 5 days as a part of a combination regimen. Dosage for obese or edematous adult patients may be calculated on the basis of body surface area to relate dosage to lean body mass. Dosage may be repeated every 3 to 6 weeks.

Usual Adult Dose for Testicular Cancer:

For use in the treatment of metastatic nonseminomatous testicular cancer:

1000 mcg/m2 intravenously on day 1 as part of a combination regimen with cyclophosphamide, bleomycin, vinblastine, and cisplatin.

Usual Adult Dose for Trophoblastic Disease:

For use in the treatment of gestational trophoblastic neoplasia:

12 mcg/kg intravenously daily for five days as a single agent.

or

500 mcg intravenously on days 1 and 2 as part of a combination regimen with etoposide, methotrexate, folinic acid, vincristine, cyclophosphamide and cisplatin.

Usual Adult Dose for Malignant Disease:

For use as a component of regional perfusion in the palliative and/or adjunctive treatment of locally recurrent or locoregional solid malignancies:

50 mcg/kg for lower extremity or pelvis

or

35 mcg/kg for upper extremity.

(Please note that the dosage schedules and the technique itself vary from one investigator to another. Please consult the published literature for details.)

Usual Adult Dose for Osteosarcoma:

600 mcg/m2/day on days 1, 2, and 3 as part of a combination chemotherapy regimen

Usual Adult Dose for Ovarian Cancer:

For use in the treatment of ovarian (germ cell) tumor:

500 mcg/day for 5 days every 4 weeks

or

300 mcg/m2/day for 5 days every 4 weeks

Usual Pediatric Dose for Wilms' Tumor:

Greater than 6 months:

15 mcg/kg/day or 400-600 mcg/m2/day intravenously for 5 days (in various combination regimens and schedules). Dosage may be repeated every 3 to 6 weeks.

Usual Pediatric Dose for Ewing's Sarcoma:

Greater than 6 months:

15 mcg/kg/day or 400-600 mcg/m2/day intravenously for 5 days (in various combination regimens and schedules). Dosage may be repeated every 3 to 6 weeks.

Usual Pediatric Dose for Rhabdomyosarcoma:

Greater than 6 months:

15 mcg/kg/day or 400-600 mcg/m2/day intravenously for 5 days (in various combination regimens and schedules). Dosage may be repeated every 3 to 6 weeks.

Usual Pediatric Dose for Testicular Cancer:

For use in the treatment of metastatic nonseminomatous testicular cancer:

1000 mcg/m2 intravenously on day 1 as part of a combination regimen with cyclophosphamide, bleomycin, vinblastine, and cisplatin.

Usual Pediatric Dose for Trophoblastic Disease:

For use in the treatment of gestational trophoblastic neoplasia:

12 mcg/kg intravenously daily for five days as a single agent.

or

500 mcg intravenously on days 1 and 2 as part of a combination regimen with etoposide, methotrexate, folinic acid, vincristine, cyclophosphamide and cisplatin.

Usual Pediatric Dose for Malignant Disease:

For use as a component of regional perfusion in the palliative and/or adjunctive treatment of locally recurrent or locoregional solid malignancies:

50 mcg/kg for lower extremity or pelvis

or

35 mcg/kg for upper extremity.

(Please note that the dosage schedules and the technique itself vary from one investigator to another. Please consult the published literature for details.)

Usual Pediatric Dose for Osteosarcoma:

600 mcg/m2/day on days 1, 2, and 3 as part of a combination chemotherapy regimen

General

• Consult specialized references for procedures for proper handling and disposal of antineoplastics.100

Administration

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by IV infusion (preferred) or IV injection.100 May also be adminstered by regional isolation perfusion.100

Do not administer IM, sub-Q, or orally.100

Avoid extravasation; extremely irritating to tissues.100 Pain and burning or stinging sensation during IV administration may be a symptom, but extravasation may occur without these symptoms and even when blood returns well on aspiration of the infusion needle.100 If manifestations of extravasation occur, immediately stop administration and restart at another site; apply ice intermittently to affected area for 15 minutes 4 times daily for 3 days. 100 Because of the progressive nature of extravasation reactions, close observation and plastic surgery consultation recommended.100 Blistering, ulceration, and/or persistent pain are indications for wide excision surgery, followed by split-thickness skin grafting.100 (See Local Effects under Cautions.)

Prepare and handle cautiously (by trained nonpregnant personnel); use protective equipment (e.g., latex gloves, protective eyewear) and wash hands after removal of latex gloves.100 Avoid exposure by inhalation or by direct contact of the skin or mucous membranes.100 If drug powder or solution comes in contact with skin or mucosa, immediately irrigate affected area with water for ≥15 minutes; flush affected eye(s) with water or saline for ≥15 minutes and obtain prompt ophthalmologic consultation.100 Remove contaminated clothing and shoes; destroy clothing and and thoroughly clean shoes before reuse.100 (See Toxicity and Adequate Patient Monitoring under Cautions.)

Administer desired dose directly into any suitable vein or preferably into tubing or sidearm of a freely flowing IV infusion to reduce the risk of severe local reactions.100 (See Local Effects under Cautions.)

Following injection, flush vein with the running IV solution for 2–5 minutes and/or inject 5–10 mL of IV solution into sidearm to flush any remaining drug from the tubing.a

For direct IV injection, withdraw dose from the vial with one sterile needle and use another sterile needle for injection into vein.100

Do not use an inline cellulose ester membrane filter during administration.a

Use strict aseptic technique since drug product contains no preservative.100

Reconstitute vial containing 500 mcg of dactinomycin powder with 1.1 mL of sterile water for injection without preservatives, to provide a solution containing 500 mcg/mL.100

Do not use diluents with preservatives (benzyl alcohol or parabens) which may cause precipitation.100

Reconstituted solution may be added to IV infusions of 0.5% dextrose or 0.9% sodium chloride injection.100

For direct IV injection, administer desired dose over a few minutes directly into any suitable vein.a

Regional Isolation Perfusion

Techniques for administration by regional isolation perfusion may vary; consult specialized references.100

Possible systemic and local adverse effects associated with drug that escapes into systemic circulation (e.g., myelosuppression, increased susceptibility to infection, impaired wound healing, ulceration of GI mucosa, absorption of toxic products accompanying extensive tumor destruction, edema of extremity, soft tissue damage, venous thrombosis).100 (See Major Toxicities under Cautions.)

Dosage

Calculate dosage carefully before administration of each dose.100

Base dosage on the clinical and hematologic response, patient tolerance, and other chemotherapy or irradiation being used.100

Base dosage on body surface area in obese or edematous patients.100

Consult published protocols for dosages in combination regimens and method and sequence of administration.100

Pediatric Patients

Children >6 months of age: 15 mcg/kg daily for 5 days administered in various combinations and schedules with other chemotherapeutic agents.100

Children >6 months of age: 15 mcg/kg daily for 5 days administered in various combinations and schedules with other chemotherapeutic agents.100

Children >6 months of age: 15 mcg/kg daily for 5 days administered in various combinations and schedules with other chemotherapeutic agents.100

Adults

12 mcg/kg daily for 5 days.100

500 mcg on days 1 and 2 as part of a combination regimen with etoposide, methotrexate, folinic acid, vincristine, cyclophosphamide, and cisplatin.100 110

1000 mcg/m2 on day 1 as part of a combination regimen with cyclophosphamide, bleomycin, vinblastine, and cisplatin.100

Dosage by regional isolation perfusion may vary; consult specialized references.100

Pelvis or lower extremity: Usual dose is 50 mcg/kg.100

Upper extremity: Usual dose is 35 mcg/kg.100

Consider dosage reduction in obese patients or those who have received prior chemotherapy or irradiation.100

Prescribing Limits

Pediatric Patients

Maximum 15 mcg/kg daily or 400–600 mcg/m2 IV daily for 5 days for each 2-week course of therapy.100

Adults

Maximum 15 mcg/kg daily or 400–600 mcg/m2 IV daily for 5 days for each 2-week course.100

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.100

Renal Impairment

No specific dosage recommendations at this time.100

Geriatric Patients

Start at lower end of dosage range because of age-related decreases in hepatic, renal, or cardiac function and concomitant disease and drug therapy.100

Absorption

Bioavailability

Poorly absorbed from the GI tract.a

Distribution

Extent

Rapidly distributed into tissues, with highest concentrations in bone marrow and nucleated cells (i.e., granulocytes, lymphocytes).a 100 Does not cross the blood-brain barrier.100 a

Appears to cross placenta; not known whether distributed into milk.a 100

Elimination

Metabolism

Minimally metabolized.100

Elimination Route

Excreted in urine and feces; excreted in urine primarily as unchanged drug.a 100

Half-life

Biphasic; terminal half-life is approximately 36 hours.100 a

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

• It is used to treat cancer.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• This medicine may have effects on the bone marrow. The bone marrow may not be able to make cells found in the blood as well as it used to for a few weeks.
• You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor.
• You may have more of a chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu. Some infections have been very bad and even deadly.
• This medicine may add to the chance of getting some types of cancer. Talk with the doctor.
• If you have upset stomach, throwing up, loose stools (diarrhea), or are not hungry, talk with your doctor. There may be ways to lower these side effects.
• Very bad blood vessel problems have happened with dactinomycin. Most of the time, these blood vessel problems have been in the liver and may sometimes lead to death. The chance of death may be higher in children younger than 48 months of age. Talk with your doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take this medicine.
• Talk with your doctor before getting any vaccines. Use with dactinomycin may either raise the chance of an infection or make the vaccine not work as well.
• If you have had or will be having radiation treatment, talk with your doctor. Worse side effects from radiation treatment have happened with this medicine.
• Use with care in children. Talk with the doctor.
• This medicine may affect growth in children and teens in some cases. They may need regular growth checks. Talk with the doctor.
• If you are 65 or older, use dactinomycin with care. You could have more side effects.
• This medicine may cause harm to the unborn baby if you take it while you are pregnant.
• Use birth control that you can trust to prevent pregnancy while taking this medicine.
• If you are pregnant or you get pregnant while taking dactinomycin, call your doctor right away.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as a shot into a vein over a period of time.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

• ACT-D
• Actinomycin
• Actinomycin Cl
• Actinomycin D
• DACT

Osteosarcoma

Data from a multicenter randomized phase III trial supports the use of dactinomycin (as part of a combination chemotherapy regimen) in the management of non-metastatic osteosarcoma [Goorin 2003].

Ovarian germ cell tumors (malignant)

Data from two phase II studies supports the use of dactinomycin (in combination with vincristine and cyclophosphamide) for the treatment of malignant ovarian germ cell cancers [Gershenson 1985], [Slayton 1985].

Soft tissue sarcoma of the extremities (locally advanced or unresectable)

Data from a small study suggest that isolated limb infusion (ILI) with melphalan and dactinomycin may be effective in the management of locally advanced or unresectable soft tissue sarcoma of the extremities [Moncrieff 2008]. Additional data may be necessary to further define the role of dactinomycin in the treatment of this condition.

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience lack of appetite, muscle pain, hair loss, dry lips, or acne. Have patient report immediately to prescriber severe injection site redness, burning, pain, edema, or irritation, signs of infection, signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), severe abdominal pain, severe nausea, vomiting, excessive weight loss, signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), signs of low calcium (muscle cramps or spasms, numbness and tingling, or seizures), severe loss of strength and energy, diarrhea, mouth sores, difficulty swallowing, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Applies to dactinomycin: intravenous powder for solution

Along with its needed effects, dactinomycin may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking dactinomycin:

• Black, tarry stools
• blood in the urine or stools
• cough or hoarseness accompanied by fever or chills
• diarrhea (continuing)
• difficulty with swallowing
• fever or chills
• heartburn
• lower back or side pain accompanied by fever or chills
• painful or difficult urination accompanied by fever or chills
• pinpoint red spots on the skin
• sores in the mouth and on the lips
• stomach pain (continuing)
• unusual bleeding or bruising
• unusual tiredness or weakness

• Joint pain
• pain at the injection site
• swelling of the feet or lower legs
• wheezing
• yellow eyes or skin

• Abdominal or stomach cramps
• blisters
• body aches or pain
• chapped, red, or swollen lips
• confusion
• congestion
• convulsions
• cough
• difficulty with breathing
• difficulty with moving
• difficulty with swallowing
• dryness or soreness of the throat
• flushing or redness of the skin
• growth retardation
• irregular heartbeats
• muscle aching or cramping
• muscle cramps in the hands, arms, feet, legs, or face
• muscle pains or stiffness
• numbness and tingling around the mouth, fingertips, or feet
• runny nose
• scaling, redness, burning, pain, or other signs of inflammation of the lips
• shortness of breath
• swollen joints
• tender, swollen glands in the neck
• tremor
• unusually warm skin
• voice changes

Some side effects of dactinomycin may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Darkening of the skin
• general feeling of discomfort or weakness
• nausea and vomiting
• skin rash or acne
• unusual feeling of dullness or sluggishness

Greater than 6 months:

15 mcg/kg/day or 400-600 mcg/m2/day intravenously for 5 days (in various combination regimens and schedules). Dosage may be repeated every 3 to 6 weeks.

Greater than 6 months:

15 mcg/kg/day or 400-600 mcg/m2/day intravenously for 5 days (in various combination regimens and schedules). Dosage may be repeated every 3 to 6 weeks.

600 mcg/m2/day on days 1, 2, and 3 as part of a combination chemotherapy regimen