dactinomycin (Rx)

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

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

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.

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

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