DACTINOMYCIN
Clinical safety rating: avoid
Contraindicated (not allowed)
Binds to DNA at guanine-cytosine base pairs, inhibiting RNA synthesis by preventing RNA polymerase elongation, thereby blocking transcription.
| 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. |
| Molecular Weight | 1255.42 |
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. |
| 1st trimester | Contraindicated due to teratogenicity; risk of neural tube defects and other malformations. |
| 2nd trimester | Contraindicated; can cause fetal harm and may lead to intrauterine growth restriction. |
| 3rd trimester | Contraindicated; risk of neonatal toxicity including myelosuppression and infection. |
Clinical note
Radiation therapy can recall skin reactions Can cause severe myelosuppression and extravasation injury.
| Placental transfer | Crosses the placenta rapidly and efficiently, achieving fetal concentrations comparable to maternal plasma levels. |
| Breastfeeding | Excreted into human milk; potential for serious adverse reactions in nursing infants, including immunosuppression and growth retardation. Discontinue breastfeeding or discontinue drug, taking into account importance of drug to mother. |
■ 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.
| Common Effects | Myelosuppression |
| Serious Effects |
PregnancyBreastfeedingSevere infection (active or recent)Hypersensitivity to dactinomycinConcurrent therapy with live vaccines
| 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. |
| Food/Dietary |
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| Lactation Rating |
| L5 (Contraindicated) |
| 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 | Complete blood count, liver function tests, renal function tests, uric acid levels, and pregnancy status before each cycle. Fetal ultrasound for growth and amniotic fluid volume. |
| Fertility Effects | May cause ovarian suppression, premature ovarian failure, and azoospermia. Use of contraception recommended during therapy. |
| Avoid grapefruit and grapefruit juice due to potential CYP3A4 inhibition. Maintain adequate nutrition; small, frequent meals may help reduce gastrointestinal side effects. No specific food restrictions otherwise. |
| Clinical Pearls | Dactinomycin is a potent vesicant; administer IV via central line to prevent extravasation. Extravasation causes severe tissue necrosis. Use with caution in hepatic impairment due to extensive liver metabolism. Monitor for myelosuppression, especially thrombocytopenia and leukopenia. Combination with radiation increases toxicity risk. |
| Patient Advice | Avoid sun exposure; use sunscreen and protective clothing as dactinomycin may cause photosensitivity. · Report any signs of infection (fever, sore throat) or bleeding (easy bruising, petechiae) immediately. · Maintain adequate hydration to prevent tumor lysis syndrome. · Do not receive live vaccines during treatment. · Contact healthcare provider if you experience severe nausea, vomiting, or mouth sores. |