DACTINOMYCIN

Clinical safety rating: avoid

Contraindicated (not allowed)

How it works

Binds to DNA at guanine-cytosine base pairs, inhibiting RNA synthesis by preventing RNA polymerase elongation, thereby blocking transcription.

What the body does with it

Metabolism	Primarily hepatic metabolism via CYP3A4; excreted in bile and urine with a half-life of approximately 36 hours.
Excretion	Primarily biliary/fecal (≈50–60% as unchanged drug); renal excretion is minimal (<10%).
Half-life	Terminal elimination half-life ≈ 36 hours (range 24–48 h) in adults; prolonged in hepatic impairment.
Protein binding	Highly bound (≈95%) primarily to albumin, with minor binding to α1-acid glycoprotein.
Volume of Distribution	Apparent Vd ≈ 0.5–1.0 L/kg, indicating extensive tissue binding and distribution into body water.
Bioavailability	Not orally bioavailable (<5%); only administered intravenously.
Onset of Action	IV: clinical effects (antitumor activity) within 2–4 days; no other routes used clinically.
Duration of Action	Duration of myelosuppression typically 2–4 weeks; antineoplastic effect persists for weeks after administration.

Classification & Brands

Dosing & administration

Intravenous, 15 mcg/kg (max 500 mcg) daily for 5 days every 3-6 weeks; may repeat every 3 weeks.

Dosage form	INJECTABLE
Renal impairment	No adjustment required for GFR > 10 mL/min; avoid use in severe renal impairment (GFR < 10 mL/min) due to limited data.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated.
Pediatric use	15 mcg/kg/day (max 500 mcg/dose) intravenously for 5 days every 3-6 weeks.
Geriatric use	No specific dose adjustment; monitor for increased toxicity (myelosuppression, hepatotoxicity) and consider lower end of dosing range.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Radiation therapy can recall skin reactions Can cause severe myelosuppression and extravasation injury.

Breastfeeding	No human data on excretion in breast milk. M/P ratio unknown. Dactinomycin may cause serious adverse reactions in breastfed infants; discontinue breastfeeding or drug based on importance to mother.
Teratogenic Risk	Dactinomycin is teratogenic. First trimester: High risk of major malformations including craniofacial, CNS, and limb defects. Second and third trimesters: Increased risk of fetal growth restriction, oligohydramnios, and fetal death.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Dactinomycin is highly toxic and should be administered only by physicians experienced in cancer chemotherapy. It is a vesicant and can cause severe tissue necrosis if extravasation occurs. Monitor for myelosuppression, hepatotoxicity, and severe gastrointestinal adverse effects.

Side Effect Profile

Common Effects	Myelosuppression
Serious Effects

Absolute Contraindications

Hypersensitivity to dactinomycin, concurrent infection, severe hepatic impairment, pregnancy (FDA category D; teratogenic), and recent or concurrent radiation therapy (especially to the chest).

Clinical Precautions

Precautions

Severe myelosuppression (leukopenia, thrombocytopenia, anemia), hepatotoxicity including veno-occlusive disease (especially in children), gastrointestinal toxicity (nausea, vomiting, diarrhea, mucositis), extravasation causing tissue necrosis, radiation recall reactions, and increased risk of secondary malignancies.

Clinical Tips & Counseling

Drug interactions

Loading safety data…