dactinomycin

High Alert

Wilms tumor (in combination with other chemotherapy drugs).
Rhabdomyosarcoma (in combination with other chemotherapy drugs).
Ewing sarcoma (in combination with other chemotherapy drugs).
Metastatic nonseminomatous testicular cancer (in combination with other chemotherapy drugs).
Gestational trophoblastic neoplasia (as monotherapy or in combination with other chemotherapy drugs).
As a component of regional perfusion for treatment of locally recurrent and locoregional solid malignancies.

Action ⬆ ⬇

Inhibits RNA synthesis by forming a complex with DNA (cell-cycle phase-nonspecific).

Therapeutic effects:

Death of rapidly replicating cells, particularly malignant ones.
Also has immunosuppressive properties.

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Widely distributed, with extensive tissue binding; does not cross the blood-brain barrier. Crosses the placenta.

Metabolism/Excretion: Excreted in bile (50%) and feces (14%) as unchanged drug; small amounts excreted unchanged by the kidneys (10%).

Half-Life: 36 hr.

Time/Action Profile ⬆ ⬇

(effects on blood counts)

ROUTE	ONSET	PEAK	DURATION
IV	7 days	14–21 days	21–28 days

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Patients with concurrent or recent chickenpox or herpes zoster infection;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Active infections;
Immunosuppressed patients;
Concurrent radiation therapy (↑ risk of veno-occlusive disease);
Hepatic impairment;
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Children 4 yr ( risk of hepatic veno-occlusive disease).

Adv. Reactions/Side Effects ⬆ ⬇

Derm: acne, alopecia, erythema (especially of previously irradiated skin), hyperpigmentation (especially of previously irradiated skin), rash, skin eruptions, photosensitivity

EENT: pharyngitis

F and E: hypocalcemia

GI: anorexia, nausea, vomiting, ulceration, abdominal pain, ascites, diarrhea, dysphagia, esophagitis, HEPATIC VENO-OCCLUSIVE DISEASE, hepatotoxicity, stomatitis

Hemat: anemia, leukopenia, thrombocytopenia, febrile neutropenia, neutropenia

Local: phlebitis at IV site, tissue injury (due to extravasation)

MS: myalgia

Neuro: lethargy, malaise

Resp: pneumonitis

Misc: fever

Interactions ⬆ ⬇

Drug-drug:

↑bone marrow depression with other antineoplastics or radiation therapy.
May ↓ antibody response to live-virus vaccines and ↑ risk of adverse reactions (avoid concurrent use).

Route/Dosage ⬆ ⬇

Dose in obese or edematous patients should be based on body surface area

Wilms Tumor

IV (Adults and Children ): 45 mcg/kg every 3–6 wk for up to 26 wk.

Rhabdomyosarcoma

IV (Adults and Children ): 15 mcg/kg once daily for 5 days every 3–9 wk for up to 112 wk.

Ewing Sarcoma

IV (Adults ): 1250 mcg/m² every 3 wk for 51 wk.

Metastatic Nonseminomatous Testicular Cancer

IV (Adults ): 1000 mcg/m² every 3 wk for 12 wk.

Gestational Trophoblastic Neoplasms

IV (Adults ): Nonmetastatic or low-risk metastatic disease (as monotherapy): 12 mcg/kg once daily for 5 days; High-risk metastatic disease (in combination with other chemotherapy drugs): 500 mcg once daily on Days 1 and 2 given every 2 wk for a total of 8 wk.

Regional Perfusion in Locally Recurrent Solid Malignancies

Regional perfusion
(Adults ): Lower extremity/pelvis (in combination with melphalan): 50 mcg/kg as single dose; Upper extremity (in combination with melphalan): 35 mcg/kg as single dose.

Availability ⬆ ⬇

(Generic available)

Powder for injection: 500 mcg/vial

Assessment ⬆ ⬇

Monitor vital signs before and frequently during therapy.
Monitor for bone marrow depression. Assess for bleeding (bleeding gums; bruising; petechiae; guaiac stools, urine, and emesis) and avoid IM injections and rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia. Anemia may occur. Monitor for increased fatigue, dyspnea, and orthostatic hypotension.
Assess IV site frequently for inflammation or infiltration. Dactinomycin is a vesicant. Patient should notify nurse if burning or stinging at injection site occurs; may cause blistering, ulceration, and persistent pain, requiring wide excision surgery followed by split-thickness skin grafting. If extravasation occurs, infusion must be stopped and restarted in another vein to avoid damage to SUBQ tissue. If extravasation occurs, apply ice compresses to the site for 15 min four times daily for 3 days.
Monitor intake and output, appetite, and nutritional intake. Assess for nausea and vomiting; usually begin a few hr after administration and persist for up to 20 hr. Administration of an antiemetic before and periodically during therapy and adjustment of diet as tolerated may help maintain fluid and electrolyte balance and nutritional status.
Monitor for signs and symptoms of hepatic veno-occlusive disease (elevations in AST, ALT, total bilirubin, hepatomegaly, weight gain, ascites) frequently during therapy. If signs occur, consider delaying next dose. Based on severity of reaction and disease being treated, resume at reduced dose or permanently discontinue therapy.
Side effects other than nausea and vomiting may be delayed in onset (2–4 days after course of treatment) and may not peak until 1–2 wk after treatment.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.
- Monitor CBC and differential before and periodically during therapy. Platelets and leukocyte counts begin to drop 7–10 days after beginning therapy. The nadirs of thrombocytopenia and leukopenia occur in 3 wk. Recovery occurs 3 wk later.
- Monitor for hepatotoxicity (↑ AST, ALT, LDH, and serum bilirubin).
- Monitor renal function (BUN and serum creatinine).

Implementation ⬆ ⬇

Fatalities have occurred with chemotherapeutic agents. Before administering, clarify all ambiguous orders; double-check single, daily, and course-of-therapy dose limits; have second practitioner independently double-check original order, calculations and infusion pump settings.
Do not confuse dactinomycin with daptomycin.
Avoid contact with skin; highly toxic; 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. Review special handling procedures prior to handling and follow diligently. If spillage occurs, irrigate skin with copious amount of water for at least 15 min and remove all contaminated clothing and shoes. If splashed into eye, irrigate with water for at least 15 min and consult ophthalmologist.

IV Administration:

Prepare solution for IV administration in a biologic cabinet. Wear gloves, gown, and mask while handling IV medication. Discard IV equipment in specially designated containers.
Intermittent Infusion: Reconstitution: Reconstitute each 0.5-mg vial with 1.1 mL of sterile water for injection without preservatives. Do not reconstitute with water containing preservatives (benzyl alcohol or parabens), as this causes precipitation. Reconstituted solution is clear, gold-colored; do not administer solutions that are cloudy, discolored, or contain particulate matter. Discard any unused solution.Concentration: 500 mcg/mL (0.5 mg/mL).Diluent: Dilute further with D5W, or 0.9% NaCl. 10 mcg/mL. Solution is stable for up to 4 hr at room temperature from reconstitution to completion of infusion.
Rate: Infuse over 10–15 min.

Patient/Family Teaching ⬆ ⬇

Explain purpose of dactinomycin to patient and family.
Instruct patient to notify health care professional if fever; chills; sore throat; signs of infection; bleeding gums; bruising; petechiae; or blood in urine, stool, or emesis occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor. Caution patient not to drink alcoholic beverages or take products containing aspirin or NSAIDs; may increase GI irritation.
Instruct patient to inspect oral mucosa for erythema and ulceration. Notify health care professional for new skin lesions, mouth sores, or oropharyngeal lesions. If ulceration occurs, advise patient to use sponge brush and rinse mouth with water after eating and drinking. Stomatitis may require treatment with opioid analgesics.
Discuss with patient the possibility of hair loss, which usually occurs 7–10 days after administration. Explore coping strategies.
Instruct patient not to receive any vaccinations without advice of health care professional.
Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for at least 6 mo after last dose and to avoid breastfeeding during and for 14 days after final dose. Advise males with female partners of reproductive potential to use effective contraception during and for 3 mo after last dose.
Emphasize the need for periodic lab tests to monitor for side effects.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇